Biomedical subjects

B Mao

Publications and source records attributed to B Mao.

At least 19 recordsLinked to original sources

PubMed2003

Superior mesenteric arterial embolism: a retrospective study of local thrombolytic treatment with urokinase in West China.

Embolism of the superior mesenteric artery (SMA) is a rare disorder. To explore the selective criteria of local thrombolysis, evaluate its efficacy and discuss the therapeutic protocol of SMA embolism, a retrospective case control study was undertaken. Sixteen cases were divided into two groups: nine cases (group A) from May 1995 to April 1999 were given traditional treatment, while seven cases (group B) from November 1999 to June 2002 received comprehensive therapy including local thrombolysis. The local thrombolytic treatment was performed without procedure-related complications and the embolus was successfully lysed in four patients. The time between admission and diagnosis (or treatment) was shorter in group B than in group A (2.3 +/- 1.2 vs 12.3 +/- 9.2 hr, p = 0.013). Gangrenous bowel segments in group A were much longer than in group B (159.4 +/- 87.7 vs 45.7 +/- 61.6 cm, p = 0.009). However, mortality between the two groups was the same (p = 0.282, OR = 0.32, 95% CI = 0.039, 2.618) perhaps because of the small sample size. Angiography could shorten the duration from the onset of SMA embolism to therapy and certainly lowers the risk of mortality. Local fibrinolytic infusion may be an effective alternative to embolectomy in patients with SMA embolism but without intestinal infarction.

Adult↗

PubMed2001

Calcium imaging of epileptiform events with single-cell resolution.

Epileptic discharges propagate through apparently normal circuits, although it is still unclear how this recruitment takes place. To understand the role of different classes of neurons in neocortical epilepsy, we have developed a novel imaging assay that detects which neurons participate in epileptiform discharges. Using calcium imaging of neuronal populations during bicuculline-induced spontaneous epileptiform events in slices from juvenile mouse somatosensory cortex, we find that fast calcium transients correlate with epileptiform field potentials and intracellular depolarizing shifts and can be used as an optical signature that a given neuron has participated in an epileptiform event. Our results demonstrate a novel method to characterize epileptiform events with single-cell resolution. In addition, our data are consistent with an important role for layer 5 in generating neocortical seizures and indicate that subgroups of neurons are particularly prone to epileptiform recruitment.

Action Potentials↗

PubMed2001

LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.

Wnt glycoproteins have been implicated in diverse processes during embryonic patterning in metazoa. They signal through frizzled-type seven-transmembrane-domain receptors to stabilize beta-catenin. Wnt signalling is antagonized by the extracellular Wnt inhibitor dickkopf1 (dkk1), which is a member of a multigene family. dkk1 was initially identified as a head inducer in Xenopus embryos but the mechanism by which it blocks Wnt signalling is unknown. LDL-receptor-related protein 6 (LRP6) is required during Wnt/beta-catenin signalling in Drosophila, Xenopus and mouse, possibly acting as a co-receptor for Wnt. Here we show that LRP6 (ref. 7) is a specific, high-affinity receptor for Dkk1 and Dkk2. Dkk1 blocks LRP6-mediated Wnt/beta-catenin signalling by interacting with domains that are distinct from those required for Wnt/Frizzled interaction. dkk1 and LRP6 interact antagonistically during embryonic head induction in Xenopus where LRP6 promotes the posteriorizing role of Wnt/beta-catenin signalling. Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists.

Adaptor Proteins, Signal Transducing↗

PubMed2001

[Inhibitory effects of phosphorothioate antisense oligonucleotides on gene expression controlled by HCV 5'NCR in nude mice xenograft].

OBJECTIVE: To evaluate the activity in vivo of 3 phosphorothioate antisense oligonucleotides, HCV363, HCV279 and HCV349 using nude mice xenograft models based on the establishment of HCV 5' NCR transgenic cellular model (HepG2.9706). METHODS: Female BALB/C nude mice, aged 4 to 6 weeks and weighing around 20g, were implanted s.c. with 100mul (106 cells) of the HepG2.9706 cells suspension in the lower-back region. In approximate 1 weeks, the animals were randomly grouped and intraperitoneally administrated the antisense drugs at 10 mg/kg body weight. RESULTS: HCV363, HCV279 and HCV349 had obvious sequence-specific inhibitory effects on luciferase expression controlled by HCV 5' NCR in xenograft cells with the inhibitory rates of 80.4%, 78.6% and 47.9%, respectively. The effects of three different concentrations (5, 10, 20 mg/kg body weight) of HCV363 indicated that HCV363 increased the inhibitory activities on luciferase expression following the concentration raise and its inhibitory rate was up to 82.7%. CONCLUSIONS: This study suggests that antisense oligonucleotides may provide a novel therapeutic approach to the treatment of HCV infection.

Animals↗

PubMed2001

[The CPBC types used for clinical choice and observation on their microstructure].

UNLABELLED: According to the primary properties of calcium phosphate bone cement (CPBCs), we have chosen certain types of them for use in cranioplasty and have observed the microstructure of their set bodies by means of SEM. Five kinds of CPBCs powder have been prepared, including: octacalcium phosphate precipitated hydroxyapatite (OCP-PHA) type, octacalcium phosphate hydroxyapatite (OCP-HA) type, octacalcium phosphate (OCP) type, calcium deficient hydroxyapatite (CDHA) type and hydroxyapatite (HA) type. The mixing liquids were deionized water and 0.25 M Na2HPO4/NaH2PO4 buffer solution. The setting time was measured by Gillmore method. The compressive strengths were measured using the TS-14 automatically measured instrument-II of single granule's compressive strength. The CPBC types used for clinical cranioplasty were defined according to Ginebra's Criteria of the CPBCs, and the ultrastructure of the set-bodies of the defined CPBC type was observed by SEM before and after its immersion in Ringer's Solution. RESULT: Two out of five CPBCs, OCP-PHA-CPBC and CDHA-CPBC were selected for clinical cranioplasty. Before and after they were immersed in Ringer's Sol., the SEM found their set-bodies to be structurally porous and to dissolve with the increase of immension time. These data indicate that OCP-PHA-CPBC and CDHA-CPBC are sufficient for the reconstruction of non-stress-bearing bone, and the porous structure of their set-bodies is advantageous to fibroplasty or fibrovasculization in their set bodies.

Bone Cements↗

PubMed2001

Clinical features of diffuse axonal injury.

OBJECTIVE: To analyze the mechanism of diffuse axonal injury (DAI) and study the relationship between DAI and brain concussion, brain contusion, and primary brain stem injury. METHODS: The clinical data and iconographic characteristics of 56 patients with DAI were analyzed retrospectively. RESULTS: Traffic accidents were the main cause of DAI. Among t he 56 cases, 34 were injured for at least twice, and 71.43% of the patients were complicated with contusion. CONCLUSIONS: It is considered that DAI is a common pattern of primary brain injury, which is often underestimated. And DAI includes cerebral concussion and primary brain injury, and is often complicated by cerebral cortex contusion. Therefore, it is very simple and practical to divide primary brain injuries into local and diffuse injuries.

Adolescent↗

PubMed2001

Association of HIF-1alpha expression and cell apoptosis after traumatic brain injury in the rat.

OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and the correlation between HIF-1alpha and apoptosis after traumatic brain injury. METHODS: Using experimental traumatic brain injury in the rats, the expression of HIF-1alpha was studied by immunohistochemistry in cerebral tissue, apoptotic cell death was evaluated with TUNEL (transferase-mediated X-dUTP nick end labeling), and double-labeled immunohistochemistry and TUNEL methods were used to investigate the relationship between HIF-1alpha and apoptosis. RESULTS: There was remarkable difference in the expression of H IF-1alpha between the experimental groups and the control groups (P<0.01), in the experimental groups, the expression of HIF-1alpha at 48 hours was highest; the evidence of apoptotic cell death after experimental traumatic brain injury was found by TUNEL; the apoptotic percentage increased or decreased according to the changes of the positive expression of HIF-1alpha (r=0.99). CONCLUSIONS: The results suggest that secondary brain ischemia plays a crucial role in apoptotic cell death after traumatic brain injury; HIF-1alpha can prompt apoptotic cell death after experimental traumatic brain injury.

Animals↗

PubMed2001

[Expression of KDR in medulloblastoma and its clinical implication].

OBJECTIVE: To gain an insight into the possible relationship between the expression of kinase insert domain-containning receptor (KDR) and the prognosis of medulloblastoma. METHODS: Fifty cases of medulloblastoma of the posterior fossa and ten cases of normal cerebellar tissue were studied via a combination of immunnohistochemical staining in formalin fixed paraffin-embedded sections. RESULTS: KDR was expressed weakly in 1 of 10 normal cerebellar tissues, while KDR was either moderately or strongly expressed in most of the medulloblastomas (49 of 50 cases). Moreover, KDR was expressed not only in the endothelial cells of tumor vasculature, but also in tumor cells. Correlation analysis indicated that expression of KDR was correlated significantly with survival time (r = -0.527, P < 0.01). CONCLUSION: KDR was expressed in most of the medulloblastomas, not only in the endothelial cells of tumor vasculature, but also in tumor cells. The expression level of KDR had a negative correlation with the survival time, thus it might be used as one of the prognosticators of medulloblastoma.

Adolescent↗

PubMed2001

[Expression and significance of urokinase-type plasminogen activator in medulloblastoma].

OBJECTIVE: To detect the expression and evaluate the clinical significance of urokinase-type plasminogen activator (uPA) in medulloblastoma. METHODS: LSAB (labelled streptavidin biotin method) immunohistochemical technique was applied for detecting the expression of uPA in 50 patients with medulloblastoma, and a follow-up survey with Cox regression analysis was made. RESULTS: The staining for uPA was localized on tumor cells and endothelial cells. Cox regression analysis showed that uPA was an independent prognostic factor affecting survival and it had a negative correlation with the prognosis. CONCLUSION: uPA appears to be an independent marker for predicting the prognosis of medulloblastoma.

Adolescent↗

PubMed2001

[Expression of C-myc and N-myc protein in adulthood and childhood medulloblastomas and prognostic analysis].

OBJECTIVE: To detect the expression of C-myc and N-myc in medulloblastomas, the difference between adults and children, and the relation between expression and prognosis. METHODS: ABC immunostaining was used to detect C-myc and N-myc protein expression in 21 cases of adulthood medulloblastomas and 14 childhood cases. Follow-up materials were obtained to perform survival curve analysis. RESULTS: Of these 35 cases, 5 (4 children, 1 adult) showed C-myc positive expression. No N-myc expression was found. There was no relationship between expression and survival. CONCLUSION: C-myc may play a role in the tumorgenesis of medulloblastoma, especially in children, but it is of no prognostic significance. N-myc antigen may be lost during the fixation of specimens.

Adolescent↗

PubMed2000

[Effect of hypoxia and carbon monoxide on rat pulmonary arterial smooth muscle cell].

OBJECTIVE: To investigate the effect of carbon monoxide on rat pulmonary arterial smooth muscle cell (VSMC). METHODS: Three groups were randomly divided, (1) Normoxia group(N), (2) Hypoxia group(H), (3) 3% CO + 1% O2 group (CO + H), then tested by immunocytochemical analysis 3H-TdR in incorporation. RESULTS: (1) Hypoxia initiated the chang of VSMC from contractile phenotype to synthetic phenotype, the endoplasmic reticulum became dilated, the mitochondria became swollen and myelin figure appeared. alpha-actin and muscle fiber decreased. The form of VSMC in CO + H was similar to that in N. (2) Intracellular Ca2+ level of VSMC in H [4 h, 8 h, 12 h, 24 h, 36 h were (382.00 +/- 37.92) mmol/L, (456.00 +/- 53.76) mmol/L, (517.00 +/- 47.34) mmol/L, (608.00 +/- 35.92) mmol/L, (567.00 +/- 46.72) mmol/L, respectively] increased significantly(P < 0.01) than in N[4 h was(319.00 +/- 47.45) mmol/L], but that in CO + H increased slightly. (3) cAMP and cGMP level of VSMC in H increased significantly, cAMP of VSMC in CO + H increased significantly [2 h, 8 h, 12 h, 24 h were (1.87 +/- 0.36) pmol/mg protein, (2.16 +/- 0.36) pmol/mg protein, (2.36 +/- 0.41) pmol/mg protein, (2.12 +/- 0.39) pmol/mg protein, respectively] but cGMP of VSMC in CO + H increased slightly[2 h, 8 h, 12 h, 24 h were (0.52 +/- 0.21) pmol/mg protein, (0.58 +/- 0.21) pmol/mg protein, (0.60 +/- 0.24) pmol/mg protein, (0.68 +/- 0.29) pmol/mg protein, respectively]. CONCLUSION: Hypoxia may promote the proliferation of VSMC by second messenger system and CO in low desities can depress the action of hypoxia partly by Ca(2+)-cGMP system or by the expression of E2F-1 gene.

Animals↗

PubMed2000

[Effects of dexamethasone on apoptosis and expression of Fas/FasL system in lung tissues of ALI rats].

OBJECTIVE: To determine whether apoptosis occurs in the lung tissues from rats with acute lung injury (ALI), and observe protective effects of dexamethasone by regulating apoptosis of lung tissues in rats with ALI. METHODS: By using TUNEL, in situ hybridization, SqRT-PCR and immunocytochemistry techniques, apoptosis and Fas, FasL expression were studied during early phase of ALI in rats. RESULTS: LPS leads to the rapid appearance of apoptosis in alveolar epithelial cells and pulmonary vascular endothelial cells at early stage of ALI in rats. The expression of Fas, FasL mRNA and protein was up-regulated in lung tissues of rats with ALI. The administration of dexamethasone suppressed apoptosis as well as expression of Fas, FasL mRNA and protein, inhibited TNF-alpha production and abated lung injury. CONCLUSIONS: The excessive apoptosis and Fas/FasL system may play a role in the pathogenesis of LPS-induced ALI in rats. The protective effects of dexamethasone include inhibiting inflammatory mediators production, suppressing the activation of Fas/FasL system and apoptosis in lung tissues of ALI rats.

Animals↗

PubMed2000

[Malignant transformation of mouse embryonic fibroblast induced by mitochondrial DNA fragments].

OBJECTIVE: To investigate the malignant transforming effect and mechanism of mitochondrial DNA (mtDNA) fragments. METHODS: Tumorigenicity of mtDNA-transformed mouse embryonic fibroblast (NIH3T3) in nude mice was studied using transgenic techniques. Transformed tumors were detected by pathological examination and hybridization signals of mtDNA probe were analyzed by fluorescence in situ hybridization (FISH) techniques. RESULTS: Hybridization signals were observed on the nuclei of 18% - 20% NIH 3T3 cells 1 week after mtDNA fragments transforming. Tumor from mtDNA-transformed NIH 3T3 cells was developed in all 8 nude mice (8/8) respectively 2 weeks after the transformation. The pathological characteristics of the tumors developed were similar to that of fibrosarcoma. CONCLUSIONS: Auto-integration of mtDNA fragments into nuclear genome is a new factor involved in carcinogenesis.

Animals↗

PubMed2000

[Study on sensitivity of neuroglioma to chemotherapeutic drugs].

In this study, the chemosensitivity of 36 cases' fresh neuroglioma specimens was examined in vitro with MTT assay. The separation method for single tumor cell, the number of planting of cells, and the dosage and acting time of drugs, which have effects on the results of MTT assay, were studied systematically. On the basis of this experiment, we established a screening method for the chemosensitivity of neuroglioma; it is accurate, rapid, and simple. At the same time, the results showed that neuroglioma was more sensitive to the chemotherapeutic drugs Vm26, DDP and MMC, and the sensitivity varied with not only the drugs but also the individuals.

Antineoplastic Agents↗

PubMed2000

[An experimental study on traumatic brain injury for inducing neuronal apoptosis in rats].

This study was designed to explore the effect of traumatic brain injury and its mechanism for inducing neuronal apoptosis. The model of experimental traumatic brain injury was used. The rats were dispatched at different times(3 h, 12 h, 24 h, 48 h, 72 h) after traumatic brain injury, and the neuronal apoptosis was evaluated with microscope (HE staining), TUNEL method, flow cytometry, gel electrophoresis and immunohistochemistry assay. The results showed that the brain tissue neurons treated by traumatic brain injury underwent morphological changes of apoptosis, the DNA presented "ladder" break, the rate of neuronal apoptosis at different times ranged from 9.8% to 14.0%, but that of the control group was 1.7% and the expressions of related apoptosis genes(c-myc, fas and fasL) were increased. The findings of this study indicate that traumatic brain injury can induce neuronal apoptosis, and its molecular mechanism might be related to the expression of some apoptosis genes.

Animals↗

PubMed1999

Solution conformation of the (+)-trans-anti-benzo[g]chrysene-dA adduct opposite dT in a DNA duplex.

The solution structure of the adduct derived from the covalent bonding of the fjord region (+)-(11S, 12R, 13R, 14S) stereoisomer of anti -11,12-dihydroxy-13,14-epoxy-11,12,13, 14-tetrahydrobenzo[g]chrysene, (+)- anti -B[g]CDE, to the exocyclic N(6)amino group of the adenine residue dA6, (designated (+)- trans-anti -(B[g]C)dA6), positioned opposite a thymine residue dT17 in the DNA sequence context d(C1-T2-C3-T4-C5-(B[g]C)A6-C7-T8-T9-C10-C11). d(G12-G13-A14-A15-G16-T17-G18-A19-G20++ +-A21-G22) (designated (B[g]C)dA. dT 11-mer duplex), has been studied using structural information derived from NMR data in combination with molecular dynamics (MD) calculations. The solution structure of the (+)- trans-anti -(B[g]C)dA.dT 11-mer duplex has been determined using an MD protocol where both interproton distance and dihedral angle restraints deduced from NOESY and COSY spectra are used during the refinement process, followed by additional relaxation matrix refinement to the observed NOESY intensities to account for spin diffusion effects. The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5.dG18 and (B[g]C)dA6.dT17 base-pairs. All base-pairs, including the modified (B[g]C)dA6.dT17 base-pair, are aligned through Watson-Crick pairing as in normal B -DNA. In addition, the potential strain associated with the highly sterically hindered fjord region of the aromatic portion of the benzo[g]chrysenyl ring is relieved through the adoption of a non-planar, propeller-like geometry within the chrysenyl ring system. This conformation shares common structural features with the related (+)- trans-anti -(B[c]Ph)dA adduct in the identical base sequence context, derived from the fjord region (+)-(1S,2R,3R,4S)-3, 4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene stereoisomer, in which intercalation is also observed towards the 5'-side of the modified dA6.dT17 base-pair.

Binding Sites↗

PubMed1999

Solution structure of the (+)-cis-anti-benzo[a]pyrene-dA ([BP]dA) adduct opposite dT in a DNA duplex.

Minor adducts, derived from the covalent binding of anti-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide to cellular DNA, may play an important role in generating mutations and initiating cancer. We have applied a combined NMR-computational approach including intensity based refinement to determine the solution structure of the minor (+)-cis-anti-[BP]dA adduct positioned opposite dT in the d(C1-T2-C3-T4-C5-[BP]A6-C7-T8-T9-C10-C11). (d(G12-G13-A14-A15-G16-T17-G18-A19-G20+ ++-A21-G22) 11-mer duplex. The BP ring system is intercalated toward the 5'-side of the [BP]dA6 lesion site without disrupting the flanking Watson-Crick dC5.dG18 and [BP]dA6.dT17 base pairs. This structure of the (+)-cis-anti-[BP]dA.dT 11-mer duplex, containing a bay region benzo[a]pyrenyl [BP]dA adduct, is compared with the corresponding structure of the (+)-trans-anti-[BPh]dA.dT 11-mer duplex (Cosman et al., Biochemistry 32, 12488-12497, 1993), which contains a fjord region benzo[c]phenanthrenyl [BPh]dA adduct with the same R stereochemistry at the linkage site. The carcinogen intercalates toward the 5'-direction of the modified strand in both duplexes (the adduct is embedded within the same sequence context) with the buckling of the Watson-Crick [BP]dA6.dT17 base pair more pronounced in the (+)-cis-anti-[BP]dA.dT 11-mer duplex compared to its Watson-Crick [BPh]dA.dT17 base pair in the (+)-trans-anti-[BPh]dA.dT 11-mer duplex. The available structural studies of covalent polycyclic aromatic hydrocarbon (PAH) carcinogen-DNA adducts point toward the emergence of a general theme where distinct alignments are adopted by PAH adducts covalently linked to the N(6) of adenine when compared to the N(2) of guanine in DNA duplexes. The [BPh]dA and [BP]dA N(6)-adenine adducts intercalate their polycyclic aromatic rings into the helix without disruption of their modified base pairs. This may reflect the potential flexibility associated with the positioning of the covalent tether and the benzylic ring of the carcinogen in the sterically spacious major groove. By contrast, such an intercalation without modified base pair disruption option appears not to be available to [BP]dG N(2)-guanine adducts where the covalent tether and the benzylic ring are positioned in the more sterically crowded minor groove. In the case of [BP]dG adducts, the benzopyrenyl ring is either positioned in the minor groove without base pair disruption, or if intercalated into the helix, requires disruption of the modified base pair and displacement of the bases out of the helix.

Adenine↗

PubMed1999

Strategies toward predicting peptide cellular permeability from computed molecular descriptors.

The therapeutic efficacy of an orally administered drug is dictated not only by its pharmacological properties such as potency and selectivity, but also its pharmacokinetic properties such as its access to the site of activity. Thorough evaluation of the physicochemical and biological barriers to drug delivery is essential to the selection and successful development of drug candidates. We have demonstrated previously that cellular permeability, as a primary component of drug delivery, is principally dependent upon the desolvation potential of the polar functionalities in the molecule and, secondarily, upon the solute lipophilicity [Conradi, R.A., Hilgers, A.R., Ho, N.F.H., Burton, P.S. (1992). The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability. Pharm. Res. 9, 473-479]. Increasingly sophisticated computational methods are becoming available for describing molecular structural features proposed to correlate with such molecular physicochemical determinants of permeability. Herein we examine the relationships of various computationally derived molecular geometric descriptors for a set of peptides and peptidomimetics, in the context of experimentally measured hydrogen-bond potentials and lipophilicities, with their cellular permeabilities. These descriptors include molecular volume, polar and non-polar surface areas and projected molecular cross-sectional areas. Particular attention is paid to the roles of solvation treatments and other computational factors in descriptor generation, deconvolution of cellular transport mechanisms and statistical analyses of the resulting data for the development of valid, structure-based and mechanistically meaningful models of cellular permeability. No significant correlation of cellular permeability with computed descriptors was found. This was primarily because of our inability to identify surrogates for hydrogen-bond desolvation potential for the solutes from among these descriptors.

Adenocarcinoma↗