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Biomedical subjects

X Liang

Publications and source records attributed to X Liang.

At least 19 recordsLinked to original sources

Lingual foramina on the mandibular midline revisited: a macroanatomical study.

The purpose of the present study was to determine the incidence, size, location, course, and content of the foramina and bony canals located on the lingual side of the mandibular midline. Fifty dry human mandibles were morphometrically analyzed by measuring the distances of these midline foramina from the mandibular base and the dimensions of these foramina and their bony canals. In addition, macro- and microanatomical dissection was performed on 12 intact cadaver mandibles. The macroanatomic midline foramina were classified into superior and inferior genial spinal foramina according to their vertical location with respect to the genial spines. This study showed that out of 50 dry mandibles, 49 (98%) had at least one midline lingual foramen; only one lacked a true midline foramen. Evaluation of the microanatomical dissections indicated a clear neurovascular bundle in both superior and inferior genial spinal foramina and canals. For the superior canal, the content was found to derive from the lingual artery and the lingual nerve. For the inferior canal, however, the arterial origin was submental and/or sublingual, while the innervation derived from a branch of the mylohyoid nerve. In conclusion, different kinds of lingual foramina have been identified according to their location. The superior and inferior genial spinal foramina have different neurovascular contents, determined by their anatomical location above or below the genial spines.

Arteries↗

Nanosphere dispersed liquid crystals for tunable negative-zero-positive index of refraction in the optical and terahertz regimes.

An analysis of aligned nematic liquid crystal cells containing core-shell nanospheres shows that it is possible to devise a new type of metamaterial whose index of refraction is tunable from negative, through zero, to positive values. The design parameters for the constituents can be scaled for application in the optical as well as very long wavelength (e.g., terahertz and microwave) regions.

Journal Article↗

Laparoscopic hepatectomy by curettage and aspiration. Experiences of 62 cases.

BACKGROUND: This article introduces a new technique for hepatectomy. Its purpose is to describe the details of laparoscopic hepatectomy by curettage and aspiration (LHCA) and develop a new instrument for this technique. METHODS: We have performed laparoscopic hepatectomy by curettage and aspiration (LHCA) in 62 patients in our institute between 1998 and 2005: 34 men and 28 women, mean age 47.8 years (range: 26-71 years). Their diagnoses included 18 primary hepatic carcinoma, 2 metastatic carcinoma, 19 intrahepatic duct calculus, and 23 benign entities. RESULTS: The LHCA operation was completed in 60 patients. In two, the procedure had to be converted to open operation. The mean operative time was 146 min and the mean operative blood loss was 458 ml. Complications occurred in two patients, one with bile leakage and the other with pneumothorax. All the patients were ambulatory within 24 hours of operation. The average length of hospital stay was 1 week. CONCLUSIONS: Our experience leads us to believe that laparoscopic hepatectomy by curettage and aspiration (LHCA) is a safe and effective technique for resection of liver lesions.

Adult↗

Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern.

Administration of non-steroidal anti-inflammatory agents reduces the risk of developing Alzheimer's disease in normal aging populations, an effect that may occur from inhibition of the cyclooxygenases, the rate-limiting enzymes in the formation of prostaglandins. In this study, we investigated whether increased activity of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, potentiates disease progression in a transgenic mouse model of Alzheimer's disease. To study the functional effects of COX-2 activity, male and female bigenic mice (amyloid precursor protein with Swedish mutation [APPswe]-presenilin-1 protein with deletion of exon 9 [PS1dE9] and trigenic COX-2/APPswe-PS1dE9) were behaviorally tested +/-administration of the selective COX-2 inhibitor celecoxib. Behavioral testing included a three-trial Y maze that measures spatial working and recognition memories and an open field task that tested levels of hyperactivity. Overexpression of COX-2 in APPswe-PS1dE9 mice resulted in specific deficits in spatial working memory in female but not male mice. These sex-specific deficits were abolished by pharmacological inhibition of COX-2 activity. Importantly, COX-2-associated deficits were dependent on co-expression of all three transgenes since COX-2 single transgenic and APPswe-PS1dE9 bigenic mice showed normal memory. Quantification of amyloid plaque load and total Abeta 40 and 42 peptides did not reveal significant differences in trigenic versus bigenic mice treated with either vehicle or celecoxib. Taken together, these data indicate an interaction between the effects of COX-2 and Abeta peptides on cognition that occurs in a sex-specific manner in the absence of significant changes in amyloid burden. These findings suggest that pathological activation of COX-2 may potentiate the toxicity of Abeta peptides, particularly in females, without significantly affecting Abeta accumulation.

Alzheimer Disease↗

Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase.

Mer (MerTK) is a receptor tyrosine kinase important in platelet aggregation, as well as macrophage cytokine secretion and clearance of apoptotic cells. Mer is not normally expressed in thymocytes or lymphocytes; however, ectopic Mer RNA transcript and protein expression is found in a subset of acute lymphoblastic leukemia cell lines and patient samples, suggesting a role in leukemogenesis. To investigate the oncogenic potential of Mer in vivo, we created a transgenic mouse line (Mer(Tg)) that expresses Mer in the hematopoietic lineage under control of the Vav promoter. Ectopic expression and activation of the transgenic Mer protein was demonstrated in lymphocytes and thymocytes of the Mer(Tg) mice. At 12-24 months of age, greater than 55% of the Mer(Tg) mice, compared to 12% of the wild type, developed adenopathy, hepatosplenomegaly, and circulating lymphoblasts. Histopathological analysis and flow cytometry were consistent with T-cell lymphoblastic leukemia/lymphoma. Mer may contribute to leukemogenesis by activation of Akt and ERK1/2 anti-apoptotic signals, which were upregulated in Mer(Tg) mice. Additionally, a significant survival advantage was noted in Mer(Tg) lymphocytes compared to wild-type lymphocytes after dexamethasone treatment. These data suggest that Mer plays a cooperative role in leukemogenesis and may be an effective target for biologically based leukemia/lymphoma therapy.

Animals↗

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Age of Onset↗

A phase II randomized controlled trial of a novel male contraception, an intra-vas device.

The aim of this study was to introduce a novel male contraceptive method, an intra-vas device (IVD), and to assess the efficacy, safety and satisfaction of recipients compared with no-scalpel vasectomy (NSV). A phase II randomized controlled trial was conducted in China in 2003. Two hundred and eighty-eight male subjects seeking vasectomy were randomly assigned to the IVD or NSV group. Follow up included a telephone questionnaire on the 14th postoperative day and visits at the third and 12th postoperative months. The follow-up rates at the three time points were 100%, 100% and 96.5% respectively. There was no technical failure in any subject. The surgical conditions were similar in both groups, but the IVD group experienced an additional 5 min of operative time (p<0.001). The IVD group recovered normal activity and sexual intercourse more rapidly (both p<0.05). The azoospermia rate was lower in the IVD group than in the NSV group at the third and 12th postoperative months. The rate of contraceptive success based on semen analyses was similar in both groups, especially at the 12th postoperative month (94.3% in the IVD group vs. 98.6% in the NSV group; p=0.054). The IVD group had less risk of complications (i.e. pain, congestive epididymitis and sperm granuloma). More subjects reported satisfaction with IVD sterilization than with NSV. The two procedures were similar in terms of surgical complications. The IVD was slightly less effective, but had a lower risk of later adverse events than the NSV technique. The IVD group also reported a higher level of satisfaction.

Adult↗

An assessment on spiral CT scan of the superior and inferior genial spinal foramina and canals.

To characterise the superior as well as the inferior genial spinal foramen and their bony canal using a large CT data sample. The study included 555 mandibular spirals CT scans, taken from patients for pre-operative implant planning. Basic observation by three observers included the number of canals, their respective anatomical location and morphological variations. Furthermore, linear measurements were performed to describe the foramina and canal characteristics. On spiral CT scans, the superior and inferior genial spinal foramina were detected in 448 CT scans (81%). In 29% of the mandibular CTs, two or more midline canals were noted. 47% of the foramina were located in a position inferior to the genial spines; the others were located in a superior position. The mean (SD) lingual and buccal diameters of the canal structures were 0.73 (0.27) and 0.54 (0.29) mm, respectively with an average length of 3.94 (1.29) mm. The canal was located on average 7.40 (5.31) mm from the mandibular base at the lingual entrance and 7.96 (3.47) mm at the buccal canal end point. The average canal extended towards the buccal bone for an average 37% of the bone width. The results demonstrated the presence of both superior and inferior genial spinal foramina, with 29% of the individuals having double foramina. About 53% of the foramina was located superior to the genial spines. Considering its neurovascular content, these foramina should be carefully evaluated during pre-operative planning.

Adult↗

Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice.

Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption.

Animals↗

Microanatomical and histological assessment of the content of superior genial spinal foramen and its bony canal.

OBJECTIVES: To assess histologically the true content of the superior genial spinal foramen and to match these findings to the microanatomical canal content observed using high-resolution magnetic resonance images of the same region. METHODS: Ten human mandibular specimens were imaged using a 9.4 Tesla MRI unit. Afterwards, eight specimens were decalcified, embedded in paraffin and serially sectioned (7 microm) for histological examination; the remaining two were embedded in methylmethacrylate and sectioned (50-60 microm). All sections were examined using routine light microscopy to inspect the superior genial spinal foramen region and its content. RESULTS: Histological observations of the superior genial spinal foramen confirmed the presence of a well-defined neurovascular bundle, with branches of the lingual nerve and lingual artery. The canal had an average diameter exceeding 1 mm and could thus be considered significant. CONCLUSIONS: The present study confirms the existence of a true superior genial spinal foramen's bony canal with neural and blood vessel content. These findings imply that surgical procedures should consider a proper preoperative assessment of the neurovascular trajectory of the superior genial spinal foramen.

Arteries↗

Anisotropic metal-insulator transition in epitaxial thin films.

By comparing the properties of In and Pb quantum wells in a scanning tunneling microscopy subsurface imaging experiment, we found the existence of lateral bound states, a 2D Mott-Hubbard correlation gap, induced by transverse confinement. Its formation is attributed to spin or charge overscreening of quasi-2D excitations. The signature of the 2D confinement-deconfinement transition is also experimentally observed, with the correlation gap being pinned in the middle of the conduction band. A self-organized 2D Anderson lattice is suggested as a new ground state.

Journal Article↗

HIV-1 vaccine development: constrained peptide immunogens show improved binding to the anti-HIV-1 gp41 MAb.

The human immunodeficiency virus type I (HIV-1) transmembrane glycoprotein gp41 mediates viral entry through fusion of the target cellular and viral membranes. A segment of gp41 containing the sequence Glu-Leu-Asp-Lys-Trp-Ala has previously been identified as the epitope of the HIV-1 neutralizing human monoclonal antibody 2F5 (MAb 2F5). The 2F5 epitope is highly conserved among HIV-1 envelope glycoproteins. Antibodies directed at the 2F5 epitope have neutralizing effects on a broad range of laboratory-adapted HIV-1 variants and primary isolates. Recently, a crystal structure of the epitope bound to the Fab fragment of MAb 2F5 has shown that the 2F5 peptide adopts a beta-turn conformation [Pai, E. F., Klein, M. H., Chong, P., and Pedyczak, A. (2000) World Intellectual Property Organization Patent WO-00/61618]. We have designed cyclic peptides to adopt beta-turn conformations by the incorporation of a side-chain to side-chain lactam bridge between the i and i + 4 residues containing the Asp-Lys-Trp segment. Synthesis of extended, nonconstrained peptides encompassing the 2F5 epitope revealed that the 13 amino acid sequence, Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn, maximized MAb 2F5 binding. Constrained analogues of this sequence were explored to optimize 2F5 binding affinity. The solution conformations of the constrained peptides have been characterized by NMR spectroscopy and molecular modeling techniques. The results presented here demonstrate that both inclusion of the lactam constraint and extension of the 2F5 segment are necessary to elicit optimal antibody binding activity. The ability of these peptide immunogens to stimulate a high titer, peptide-specific immune response incapable of viral neutralization is discussed in regard to developing an HIV-1 vaccine designed to elicit a 2F5-like immune response.

AIDS Vaccines↗

Molecular characterization of a distinct potyvirus from whitegrass in China.

Apotyvirus isolated from perennial whitegrass ( Pennisetum centrasiaticum Tzvel.) in North China was characterized at the molecular level. The 3' terminal nucleotide (nt) sequence of 1669 nt of the viral RNA genome has been determined, which covered the coding region of the C-terminal part of the large nuclear inclusion protein (NIb, RNA polymerase), capsid protein (CP) gene and the 3' nontranslated region (NTR). The CP gene consisted of 909 nt (including the stop codon) encoding 302 amino acid residues, and the 3' NTR was 241 nt in length excluding the polyadenylated tract. Sequence comparison of the amino acids of CPs showed that this virus was most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus with percent identities of 77% to 78% while that of the 3' NTRs suggested that it was most closely related to Zea mosaic virus with identity of 72%. This virus isolate was to some extent closely related to other members of the Sugarcane mosaic virus subgroup of potyviruses for the CP amino acid sequences. Phylogenetic analyses of the sequences indicated that this virus isolate represented a distinct potyvirus, and the name Pennisetum mosaic virus (PenMV) is proposed.

Capsid Proteins↗

Protein kinase C is involved in clozapine's facilitation of N-methyl-D-aspartate- and electrically evoked responses in pyramidal cells of the medial prefrontal cortex.

We have previously shown that the atypical antipsychotic drug clozapine facilitates N-methyl-D-aspartate (NMDA)- and electrically evoked responses in pyramidal cells of the medial prefrontal cortex (mPFC). In the present study, we investigated the role of protein kinase C (PKC) in the action of clozapine. Bath administration of the PKC activator phorbol-12-myristate 13-acetate (PMA), but not the inactive isomer 4alpha-PMA, significantly enhanced the NMDA-evoked inward current and electrically evoked excitatory postsynaptic currents. Chelerythrine, a selective blocker of PKC, completely prevented the potentiating action produced by either clozapine or PMA on these currents in the mPFC cells. Intracellular injection of the PKC inhibitor PKC-I, but not the control substance PKC-S, through the recording electrode totally blocked clozapine's potentiating effect, indicating that a post-synaptic expressed PKC is critically involved in the augmenting action of clozapine on NMDA-evoked currents. Of the PKC inhibitor PKC-I, but not the control substance PKC-S, through the recording electrode totally blocked clozapine's potentiating effect, indicating that a post-synaptic expressed PKC is critically involved in the augmenting action of clozapine on NMDA-evoked currents. To further test the role of PKC in mediating the augmenting action of clozapine, we performed experiments in PKCgamma mutant and wild-type mice. In contrast to results in pyramidal cells from rats or wild-type mice, neither clozapine nor PMA was able to potentiate NMDA-induced currents in the mPFC from the PKCgamma mutant mice. Taken together, these results suggest that the PKC signal transduction pathway is critically involved in the facilitating action of clozapine on the NMDA-induced responses in pyramidal cells of the mPFC.

Alkaloids↗

Correct identification of polychlorinated biphenyls in temperature-programmed GC with ECD detection.

A method has been developed for peak identification of PCBs in GC with ECD detection under different temperature programs and isothermal conditions on two commonly used columns (DB-5 and DB-1701). This was achieved by means of accurate calibration of retention times based on the concept of the relative retention index P (i) and retention times of the selected PCB internal standards. The P (i) was calculated from the predicted retention times with the database of the retention parameters (A, B) and the migration equations. Through comparison of the calibrated and experimental retention times of PCBs in technical samples, it was shown that the developed method was effective for correct PCB comprehensive, quantitative, congener-specific (CQCS) analyses.

Journal Article↗

A potent small molecule, nonpeptide inhibitor of cathepsin K (SB 331750) prevents bone matrix resorption in the ovariectomized rat.

Inhibition of the cyteine proteinase, cathepsin K (E.C. 3.4.22.38) has been postulated as a means to control osteoclast-mediated bone resorption. The preferred animal models for evaluation of antiresorptive activity are in the rat. However, the development of compounds that inhibit rat cathepsin K has proven difficult because the human and rat enzymes differ in key residues in the active site. In this study, a potent, nonpeptide inhibitor of rat cathepsin K (K(i) = 4.7 nmol/L), 5-(2-morpholin-4-yl-ethoxy)-benzofuran-2-carboxylic acid ((S)-3-methyl-1-(3-oxo-1-[2-(3-pyridin-2-yl-phenyl)-ethenoyl]-azepan-4-ylcarbanoyl)-butyl)-amide (SB 331750), is described, which is efficacious in rat models of bone resorption. SB 331750 potently inhibited human cathepsin K activity in vitro (K(i) = 0.0048 nmol/L) and was selective for human cathepsin K vs. cathepsins B (K(i) = 100 nmol/L), L (0.48 nmol/L), or S (K(i) = 14.3 nmol/L). In an in situ enzyme assay, SB 331750 inhibited osteoclast-associated cathepsin activity in tissue sections containing human osteoclasts (IC(50) approximately 60 nmol/L) and this translated into potent inhibition of human osteoclast-mediated bone resorption in vitro (IC(50) approximately 30 nmol/L). In vitro, SB 331750 partially, but dose-dependently, prevented the parathyroid hormone-induced hypercalcemia in an acute rat model of bone resorption. To evaluate the ability of SB 331750 to inhibit bone matrix degradation in vivo, it was administered for 4 weeks at 3, 10, or 30 mg/kg, intraperitoneally (i.p.), u.i.d. in the ovariectomized (ovx) rat. Both 10 and 30 mg/kg doses of compound prevented the ovx-induced elevation in urinary deoxypyridinoline and prevented the ovx-induced increase in percent eroded perimeter. Histological evaluation of the bones from compound-treated animals indicated that SB 331750 retarded bone matrix degradation in vivo at all three doses. The inhibition of bone resorption at the 10 and 30 mg/kg doses resulted in prevention of the ovx-induced reduction in percent trabecular area, trabecular number, and increase in trabecular spacing. These effects on bone resorption were also reflected in inhibition of the ovx-induced loss in trabecular bone volume as assessed using microcomputerized tomography (microCT; approximately 60% at 30 mg/kg). Together, these data indicate that the cathepsin K inhibitor, SB 331750, prevented bone resorption in vivo and this inhibition resulted in prevention of ovariectomy-induced loss in trabecular structure.

Animals↗

Anthrax, MEK and cancer.

The MEK family of protein kinases plays key roles in regulating cellular responses to mitogens as well as environmental stress. Inappropriate activation of these kinases contributes to tumorigenesis. In contrast, anthrax lethal factor, the principal virulence factor of anthrax toxin, has been demonstrated to selectively inactivate MEKs. In this article we will discuss recent advances in our understanding of molecular aspects of the pathogenesis of anthrax, emphasizing the potential role of MEK signalling in this disease, and outline novel strategies to use anthrax lethal toxin in the treatment of cancer.

Animals↗