Biomedical subjects

Y Cao

Publications and source records attributed to Y Cao.

At least 181 records · Page 10Linked to original sources

PubMed2000

A property concept frame representation for flexible image-content retrieval in histopathology databases.

In histopathology databases, images descriptions are collections of properties provided by experts. Image content retrieval implies comparison of such properties. The objective of this work is to enrich the traditional attribute-value representation of properties in order to take into account the polymorphism and subjectivity of properties and to manage the comparison process. In this paper we define a property concept frame (PCF) representation based on fuzzy logic to handle both representation and comparison. Seven quantifiable morphological characteristics were selected from histopathological reports to illustrate the variety of fuzzy predicates and linguistic terms in properties. The PCF representation has been tested in the context of breast pathology. It is concluded that the PCF representation provides a unification scheme to retrieve in images morphological characteristics that are described in different ways. It may enhance the relevancy of applications in various contexts such as image content-based retrieval or case-based reasoning from images.

Breast↗

PubMed2000

Detection of prostate-specific membrane antigen expressing cells in blood obtained from renal cancer patients: a potential biomarker of vascular invasion.

Originally, prostate-specific membrane antigen (PSMA) was described in benign and malignant prostate cells. On the basis of recent reports that this antigen also is expressed in normal renal proximal tubular cells and in the neovascular endothelium associated with renal carcinoma, we used a nested reverse transcriptase-polymerase chain reaction assay to evaluate whether PSMA-expressing cells might be present in specimens of peripheral blood obtained from renal cancer patients, benign renal tumor patients, and healthy volunteers. Our reverse transcriptase-polymerase chain reaction PSMA assay had a sensitivity of detecting 1 lymph node prostate cancer (LNCaP) per 10(7) lymphocytes. None of the 20 non-renal cancer controls were positive for PSMA mRNA, whereas 11 of 50 patients (22%) with diagnosed renal cancer were positive. Despite a comparative increase of PSMA positivity with stage, no statistical correlation was found. However, 44% of PSMA-positive patients had tumor size greater than 12 cm, versus only 9% in patients negative for PSMA (P = .03), and 67% of positive PSMA patients were found to have vascular invasion versus only 16% of patients negative for PSMA (P = .006; odds ratio, 10.8). This preliminary study suggests the possibility that PSMA expression in peripheral blood might be a useful biomarker for detecting or monitoring the progression of renal cancer in patients.

Adenoma, Oxyphilic↗

PubMed2000

[Mutagenic analysis on the polyhedrin gene (polh) of Bombyx mori nuclear polyhedrosis virus (BmNPV)].

In our early studies, the abnormal shape of the polyhedra of Bombyx mori nuclear polyhedrosis virus (BmNPV) induced by chemical mutagens of MMC. 9-AA and EMS occurred, and the genome of the mutated BmNPV obtained from the successive test had some change in the restriction endonuclease partners of EcoRI, BglII and BamHI. The present studies showed that the arrangement of the crystal lattice of the polyhedrin was disorderly, and the SDS-PAGE electropherogram of the polyhedrin depicted distinct change in comparison with control group. The results of sequencing analysis showed that many point mutations with characteristics of the base substitution had occurred at some sites of the BmNPV polh gene in three mutated groups, and these results funther revealed molecular mutagenesis of the mutagens effective to BmNPV. It was not confirmable that the point mutations of polh gene in the mutated BmNPV have relationship to abnormal shape of the polyhedra.

Amino Acid Sequence↗

PubMed2000

Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor.

AIM: To do theoretical study about solvation effect and interaction mechanism of fentanyl analogs (FA) to mu opioid receptor (microOR). METHODS: Flexible docking (FlexiDock) was performed by using the possible active conformations of FA and optimized 3D structure of mu opioid receptor. Binding energies were calculated. Comparative molecular force field analysis (CoMFA) and quantitative structure activity relationship (QSAR) studies were carried out based on results of flexible docking. Solvation effects were considered by studying interaction of FA with water molecules. Partial least square (PLS) analysis was used to calculate regression equation for analgesic activities using binding energies as descriptive factor. RESULTS: 1) Binding conformations of these analogs derived by flexible docking were reasonable. 2) It was most possible for the FA to exist in water solution in the form of binding conformations. 3) Energetic calculation and QSAR analysis showed a good correlation between the calculated binding energies of FA and their analgesic activities. 4) Based on the 3D-model, the possible interaction mechanism of FA with mu opioid receptor can be illustrated reasonably. CONCLUSION: The nature of the correlation between the binding affinities and analgesic activities of FA was explained by our modeling result.

Analgesics↗

PubMed2000

Building three-dimensional structures of HIV-1 coreceptor CCR5 and its interaction with antagonist TAK779 by comparative molecular modeling.

AIM: To study the mechanism of interaction of CCR5 receptor with its antagonist TAK779. METHODS: Comparative molecular modeling has been used to develop the 3D-structural models of CCR5 receptor and its complex with TAK779. Molecular mechanics has been applied to optimize the above molecular models. Quantum mechanics has been utilized to calculate the structural information of TAK779. DOCK4.0 program is employed to dock the TAK779 molecular into the binding site of CCR5 receptor. RESULTS: The 3D-structural model of CCR5 receptor is constructed using the 3D-model of frog rhodopsin as a template. The binding pocket is situated in the transmembrane helices 3, 5, 6, and 7, and it is composed of conserved residues of Tyr108, Gly111, Ser114, Glu283, Gly286, and Cys290, and conservatively varied residues including Thr105, Leu107, Phe112, Gly115, Lys197, and Met287. O1, N7, N17, and O19 of TAK779 are the active center of TAK779. The pyran cycle and the aminium group of TAK779 interact with residues in the binding pocket of CCR5 receptor, the other part of TAK779 interacts with residues from the extracellular loops of CCR5. The binding energy of TAK779 with CCR5 is -51.606 kcal/mol. CONCLUSION: The model constructed and the interaction mode reported in the present study are useful in further understanding the molecular mechanism of receptor-virus recognition and designing new inhibitors of HIV-1 infection.

Amides↗

PubMed2000

Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor.

AIM: To build the three-dimensional structure of opioid receptor-like 1 (ORL1) receptor. METHODS: Structural elements of ORL1 receptor were predicted from sequence alignments of opioid and related receptors of G protein-coupled receptor (GPCR) based on (i) the consensus, biophysical interpretations of alignment-derived properties, and (ii) tertiary structural homology to frog rhodopsin; The extracellular loops of ORL1 were built by self-constructed database searching based on geometrical constraints; initial model was refined computationally with energy minimization by molecular mechanics method. RESULTS: The calculated structure of ORL1 receptor has clusters of hydrogen bonds existing in interhelices and extracellular loops; the ORL1 receptor has a possible ligand-binding "crevice" situated on the extraside of the transmembrane domains between helices 3, 5, 6, and 7, which is partially covered by the extracellular loop 2 (EL-2); The binding cavity may consist of a "highly conserved region" involving the residues of Asp130, Tyr131, and an outer "conservatively variable region" containing the residues near the interface of transmembrane (TM) helices-EL loops; The molecular model obtained is qualitatively consistent with ligand affinities, hybrid peptide studies, and other experimental data. CONCLUSION: The structural model of ORL1 receptor from this study is helpful for clarifying experimental observations of ligands interacting with opioid receptors, and for designing new biological investigations.

Amino Acid Sequence↗

PubMed2000

Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor.

AIM: To study the mechanism of interaction of nociceptin and opioids with ORL1 receptor. METHODS: Molecular dynamics study was carried out before nociceptin was manually docked into the binding site of ORL1 receptor; DOCK4.0 program was applied to dock four stereoisomers of lofentanyl and etorphine into the binding pocket of ORL1 receptor; Binding energies were calculated, the relationship between binding energy and binding affinity was studied. RESULTS: Nociceptin fits well into the binding pocket, the N-terminal FGGF tetrapeptide is located in the inner region of the binding cavity, the nociceptin (5-7) interacts with the conservatively variable residues near the other end of binding pocket, and maybe determines selectivity of ORL1 receptor over dynorphin A, the positively charged core of nociceptin (8-13) binds predominantly with negatively charged EL-2 loop, which is thought to be able to mediate receptor activation. The shortest fully active analogue of nociceptin (1-13) is also discussed. The main difference between these two opioids and nociceptin exists in the kinds and the number of conserved and variable residues in the binding pocket and thereafter in the strength of their interaction. Prediction for binding affinities of four stereoisomers of lofentanyl has been performed based on their binding energies, the similar pharmacophore of lofentanyl and other fentanyl analogs, and the good correlation between binding energies and their experimental binding affinities (-log Ki values). CONCLUSION: Ligand docking results from this study are helpful in clarifying experimental observations of ligands interaction with opioid receptors, thus furthering biological investigations.

Binding Sites↗

PubMed2000

[An initial experiment study on allogenic tissue engineered cartilage].

OBJECTIVE: To investigate the formation of engineered cartilage in vivo with allogenic chondrocytes. METHODS AND MATERIALS: Joint cartilage from ewe embryos (Pregnancy: 100 days) was isolated and digested to obtain dissociated chondrocytes. Mixed chondrocytes with biomaterials (Pluronic 127) at the density 50 x 10(6)/ml, then implant the allograft complex subcutaneously. Collect the novel tissue every two weeks along for six months, weigh and stain (HE, Safranin O, Masson's trichrome) the sample tissues individually to evaluate the characteristics of novel tissue. RESULT: Novel cartilage can regenerate in allograft animals, with similar histological properties of chondrocytes, aminoglycin and collagen distribution to normal cartilage. The novel cartilage observed histologically showed apparent surrounding inflammatory cells in two and four week and the tissue of cartilage came to mature since the sixth week, with less inflammatory reaction, but not disappeared. CONCLUSION: Novel cartilage can generate in allograft animals with tissue engineering approach, with certain immunoreaction surrounding. Such reaction will be weakened gradually with time.

Animals↗

PubMed2000

[Clinical study on shenmai injection in promoting postoperative recovery in patients of breast cancer].

OBJECTIVE: To investigate the effect of Shenmai injection in promoting postoperative recovery of patients with breast cancer. METHODS: Eighty postoperative patients of breast cancer were selected and divided into two groups, the treated group (40 cases) was given intravenous Shenmai injection for 7 days and compared with the control group (40 cases) in wound healing time, postoperative drainage volume, complication and blood picture, and the NK cell, T-lymphocyte subsets (CD3, CD4, CD8), were compared before and after treatment. RESULTS: The wound healing time and postoperational complication in the treated group were less than those in the control group significantly. There was no difference between the two groups in WBC and platelet count, but the recovery of hemoglobin in the treated group was quicker than that in the control group significantly (P < 0.05), as comparing with the control group, the NK cell, CD4, CD4/CD8 ratio in the treated group were elevated faster than those in the control group significantly (P < 0.05). CONCLUSION: Shenmai injection was beneficial to the recovery of postoperative patients of breast cancer, to reducing the occurrence of complication and was favorable to conduct postoperative chemotherapy smoothly.

Adult↗

PubMed2000

[Repairing peripheral nerve defects by tissue engineering techniques:an experimental study].

OBJECTIVE: To develop a novel effective substitute material or technique to repair peripheral nerve gap. METHODS: We inoculated expanded Schwann cells (SCs) at re-arranged bio-absorbable polymer polyglycolic acid (PGA) fiber and incubated for two weeks, then we developed a novel tissue-engineered scaffolds. The scaffolds were used as cellular isografts to bridge 15 mm long gap of sciatic nerve in inbred strains of Wistar rats. In an autologous and pure PGA fiber control group, the same surgical procedure was used. Evaluation included general observation, electromyographic examination, muscle measurement, and histological observation of serial sections at 12 weeks after surgery. The total number and density of reinnervation and thickness of myelin sheath was measured by computerized image analysis. RESULTS: SCs put out a long and thin prominence and migrated along the PGA fibers in spirality or parallel when they divided and finally rank into a cell-chain formation similar to Büngner's band. TEM/SEM and immunohistochemical survey demonstrated that the SCs at PGA fiber also secreted a great deal of ECMs included laminin, which play a very important role in peripheral nerve regeneration. Non-tubular scaffold comprised SCs and laminin (LN) channel in three-dimensional longitudinal rank. Animal transplantation study indicated the sensory and motor functional results of hindlimbs of experimental group rats reached to similar level of those found in nerve autograft control group. The number of reinnervation in the experimental group rats was slightly fewer than that in nerve autograft control group; but the axonal density was just reversal between the two groups because of a large area ischemic necrosis in the center of nerve autografts. CONCLUSION: This new paradigm offers a potential solution to repairing a long gap of peripheral nerve.

Animals↗

PubMed2000

[The key enzymes of metabolisms of glycerol in Candida glycerolgenesis].

The specific enzymes for glycerol formation and dissimilation in Candida glycerolgenesis were studied. C. glycerolgenesis hardly assimilated glycerol without glucose and a little amount of glucose remarkably stimulated this dissimilation pathway and the activity and expression of mitochondrial glycerol-3-phosphate dehydrogenase was induced strongly by glycerol-3-phosphate and repressed by glucose metabolism. During glycerol production fermented by C. glycerolgenesis, the activity of cytoplasmic glycerol 3-phosphate dehydrogenase maintained at a higher level and existed two peaks of activity, which appeared at 36 h and 60 h, respectively. The activity level of the first activity peak determines glycerol productivity and becomes a key enzyme of glycerol formation. The activity of glycerol 3-phosphatase maintained at a higher level just between 18 h and 48 h and appeared on peak activity at 36 h. In that period, the activity of glycerol 3-phosphatase was up to more than two times of cytoplasmic glycerol 3-phosphate dehydrogenase and that was inosculated with the phase of rapid accumulation of glycerol during glycerol production by C. glycerolgenesis. In the phase of slowly accumulation of glycerol between 48 h and 72 h, the activity of glycerol 3-phosphatase decreased below that of cytoplasmic glycerol 3-phosphate dehydrogenase. So, cytoplasmic glycerol 3-phosphate dehydrogenase is a key enzyme of glycerol formation in the phase of rapid accumulation of glycerol and glycerol 3-phosphatase becomes a more effective factor after glycerol fermentation reached into slowly accumulation phase. In a conclusion, it is a fundamental for C. glycerolgenesis over-producing high level of glycerol that its cytoplasmic glycerol 3-phosphate dehydrogenase maintains at high activity and the activity of glycerol 3-phosphatase is much higher than that of cytoplasmic glycerol 3-phosphate dehydrogenase.

Candida↗

PubMed1999

Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro.

The telomere DNA polymerase (telomerase) and the tumor suppressor protein p53 are frequently associated with human cancers, and activation of telomerase and inactivation of p53 involved in cancer cell immortalization. In this report, we demonstrate a direct interaction of telomerase with p53 in the nuclear lysates of human breast cancer cells, and with recombinant human p53, by affinity chromatography and immunoprecipitation. On activity criteria, the interaction is between the carboxyl-terminal region of p53 and a region close to the amino-terminus of human telomerase-associated protein 1 (hTEP1). Incubation of recombinant p53 with nuclear telomerase extracts results in inhibition of telomerase activity, with the C-terminal region of p53 being essential for inhibition. This effect is not mediated by binding to telomerase substrate DNA, but requires the region near the N-terminus of hTEP1, in that a synthetic peptide derived from this region of hTEP1 similarly inhibits telomerase activity. Together, these in vitro interactions between telomerase and p53 suggest that the activity of telomerase may be regulated by p53, down-regulation of which in turn would favor up-regulation of telomerase activity in cancer cell development.

Amino Acid Sequence↗

PubMed1999

Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin A gene.

Epileptic seizures are associated with increases in hippocampal excitability, but the mechanisms that render the hippocampus hyperexcitable chronically (in epilepsy) or acutely (in status epilepticus) are poorly understood. Recent evidence suggests that substance P (SP), a peptide that has been implicated in cardiovascular function, inflammatory responses, and nociception, also contributes to hippocampal excitability and status epilepticus, in part by enhancing glutamate release. Here we report that mice with disruption of the preprotachykinin A gene, which encodes SP and neurokinin A, are resistant to kainate excitoxicity. The mice show a reduction in the duration and severity of seizures induced by kainate or pentylenetetrazole, and both necrosis and apoptosis of hippocampal neurons are prevented. Although kainate induced the expression of bax and caspase 3 in the hippocampus of wild-type mice, these critical intracellular mediators of cell death pathways were not altered by kainate injection in the mutant mice. These results indicate that the reduction of seizure activity and the neuroprotection observed in preprotachykinin A null mice are caused by the extinction of a SP/neurokinin A-mediated signaling pathway that is activated by seizures. They suggest that these neurokinins are critical to the control of hippocampal excitability, hippocampal seizures, and hippocampal vulnerability.

Animals↗

PubMed1999

Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

Several publicly funded large-scale sequencing efforts have been initiated with the goal of completing the first reference human genome sequence by the year 2005. Here we present the results of analysis of 11.8 Mb of genomic sequence from chromosome 16. The apparent gene density varies throughout the region, but the number of genes predicted (84) suggests that this is a gene-poor region. This result may also suggest that the total number of human genes is likely to be at the lower end of published estimates. One of the most interesting aspects of this region of the genome is the presence of highly homologous, recently duplicated tracts of sequence distributed throughout the p-arm. Such duplications have implications for mapping and gene analysis as well as the predisposition to recurrent chromosomal structural rearrangements associated with genetic disease.

Animals↗

PubMed1999

Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge.

HIV infection is accompanied by an early immune dysfunction limiting host control of virus and likely contributing to difficulties in achieving a successful vaccine against HIV. We report here that the HIV Tat protein is strongly immunosuppressive, both immediately after immunization of mice with soluble protein (sTat), and in seroconverting humans, and propose that Tat-induced suppression cripples immune surveillance to HIV infection. We show that macrophages are sensitive to sTat stimulation at concentrations 1,000-fold lower (500 pM) than T cells, and this stimulation is accompanied by the immunosuppressive induction of Fas ligand on the macrophage. T cell proliferative defects induced by sTat in vitro can be completely (at lower concentrations of sTat) or partially (at higher concentrations) reversed by antagonists to Fas/Fas ligand interaction. We further report a method to preserve immunogenicity while inactivating Tat immunosuppression through oxidation, which advances the use of oxidized Tat as a component of an anti-HIV vaccine. These observations define additional methods to study the immunosuppressive functions of sTat that now may be rapidly applied to primary isolates from individuals with differing clinical courses. Our findings have immediate relevance for vaccine development, by describing and supporting a strategy that includes inactivated sTat in a multicomponent, anti-HIV vaccine.

AIDS Vaccines↗

PubMed1999

Molecular cloning of a novel tissue-specific gene from human nasopharyngeal epithelium.

A novel cDNA of human nasopharyngeal epithelium was cloned. The cDNA fragment of the gene, termed NESG1, was originally isolated by mRNA differential display, and was not homologous to any of the known genes in the database. The complete sequence of NESG1 cDNA, 1850 bp, contains an open reading frame of 1575 nucleotides, and encodes a soluble basic protein of 386 amino acids containing multiple protein kinase phosphorylation sites. The deduced protein has no homology to any of the known proteins in the database. A homologous STS localized NESG1 to the chromosomal region of 1q22-24. Messenger RNA of this gene was expressed only in nasopharynx and trachea. These results suggest that the human NESG1 gene may be a specific gene of columnar ciliated epithelium.

Amino Acid Sequence↗

PubMed1999

Blood-based reverse transcriptase polymerase chain reaction assays for prostatic specific antigen: long term follow-up confirms the potential utility of this assay in identifying patients more likely to have biochemical recurrence (rising PSA) following radical prostatectomy.

Reverse transcriptase polymerase chain reaction (RT-PCR) assay is a sensitive technique to detect circulating cells expressing prostate-specific antigen (PSA) in blood or bone marrow from patients with prostate cancer. When applied to prostate cancer patients at our institution, this technique identifies those patients with a greater likelihood of extra-prostatic disease. We evaluated RT-PCR PSA as a predictor of PSA recurrence and compared it with pre-operative (serum PSA, digital rectal examination, Gleason score on biopsy) and post-operative parameters (pathological findings). Three hundred nineteen men scheduled for radical prostatectomy had an enhanced RT-PCR PSA assay before surgery. The enhanced RT-PCR PSA protocol has been previously described. PSA recurrence was defined as any serum PSA value above 0.2 microgram/l. Forty-six patients had PSA recurrence. The mean follow-up was 25.4 months. Recurrence free survival was 53% for patients with positive RT-PCR PSA vs. 84% if RT-PCR PSA was negative. By using multivariate analyses, RT-PCR PSA status was not an independent predictor of PSA recurrence compared to pathological stage pT3, Gleason score on prostate specimen and serum PSA. If only pre-operative parameters were studied, serum PSA and RT-PCR PSA status were 2 independent pre-operative predictors of PSA recurrence compared with Gleason score on biopsy and digital rectal examination. Int. J. Cancer (Pred. Oncol.) 84:360-364, 1999.

Disease-Free Survival↗

PubMed1999

Proteolytic processing of big endothelin-3 by the kell blood group protein.

Kell blood group protein shares a consensus sequence (H.E.X.X.H) with a large family of zinc-dependent endopeptidases. Kell has closest homology with neutral endopeptidase 24.11, endothelin converting enzyme-1 (ECE-1), and the PEX gene product that, as a group, comprise the M13 subfamily of mammalian neutral endopeptidases. The proteolytic activity of the M13 members, but not of Kell, has been previously demonstrated. A secreted form of wild-type Kell protein (s-Kell), devoid of the intracellular and transmembrane domains, was expressed in sf9 cells. As a negative control, an inactive mutant Kell protein (E582G) was expressed. As determined by N-terminal amino acid sequencing and mass spectrometry of the cleaved products, wild-type s-Kell, but not the control mutant protein, specifically cleaved big endothelin-3 (ET-3) at Trp(21)-Ile(22), yielding ET-3, and, to a much lesser extent, also cleaved big ET-1 and big ET-2 at Trp(21)-Val(22), yielding ET-1 and ET-2. Enzymatic activity was partially inhibited by phosphoramidon. s-Kell has an acidic pH optimum (pH 6.0 to 6.5). Like the recombinant protein, red blood cells of common Kell phenotype also preferentially process big ET-3, in contrast to Ko (null) cells that do not. These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.

Endothelin-3↗