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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 181 records · Page 10Linked to original sources
PubMed2001

Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice.

Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.

Animals↗
PubMed2001

mRNA expression of three glycosyltransferases in human hepatoma tissues.

BACKGROUND: The sugar-chain structures of many glycoproteins are altered in the hepatoma tissues. The molecular mechanism by which these alterations occur remains largely unknown. METHODS: Messenger RNA expression of N-acetylglucosaminyltransferase (GlcNAcT-V), N-acetylglucosaminyltransferase III (GlcNAcT-III) and alpha1-6 fucosyltransferase (alpha1-6 FucT), were investigated in normal liver tissues samples (n=7), primary hepatic cancer (PHC) tissues (n=15) and noncancerous tissues surrounding PHC (n=15) by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The mRNA expression of the three glycosyltransferases in PHC tissues were enhanced by 3- to 10-fold in comparison with that in normal liver tissues. There were significantly higher mRNA expressions of GlcNAcT-V in invasive PHC than non-invasive. CONCLUSIONS: The change of glycoprotein sugar-chain structures in PHC may be related to the abnormal mRNA expression of some glycosyltransferases and the levels of mRNA expression of GlcNAcT-V associated with PHC invasiveness.

Carcinoma, Hepatocellular↗
PubMed2001

Cytotoxic 7,20-epoxy ent-kauranoids from Isodon xerophilus.

Four 7,20-epoxy ent-kaurane diterpenoids, xerophilusins G (1) and I-K (2-4), were isolated from the leaves of Isodon xerophilus, along with four known ones, enanderianin C (5), rosthorin A (6), longikaurin B (7), and rabdoternin D (8). Their structures were determined primarily using NMR spectroscopic techniques. The structure and stereochemistry of 3 were confirmed by X-ray crystallography. Compounds 4 and 7 exhibited broad cytotoxicity against four kinds of human tumor cells (K562, HL-60, HCT, and MKN-28 cells) in the range of 2.23-15.35 and 0.30-8.61 microg/ml, respectively.

Antineoplastic Agents, Phytogenic↗
PubMed2001

The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy.

Breast and ovarian cancers exhibit similar epidemiologic, genotypic, and phenotypic characteristics. Phosphatidylinositol 3-kinase (PI3K) and the PTEN tumor suppressor gene product phosphorylate and dephosphorylate the same 3' site in the inositol ring of membrane phosphatidylinositols. Germ-line mutations in the PTEN tumor suppressor gene are causative of Cowden's breast cancer predisposition syndrome, and PTEN is frequently mutated in sporadic breast cancers. In contrast, amplification of multiple components of the PI3K pathway is a hallmark of serous epithelial ovarian cancers. The resultant activation of the PI3K pathway in both breast and ovarian cancers contributes to cell-cycle progression, decreased apoptosis, and increased metastatic capabilities. Strikingly, both ovarian and breast cancer cells are selectively sensitive to pharmacologic and genetic manipulation of the PI3K pathway, making molecular therapeutics targeting this pathway particularly attractive approaches for these cancers.

Animals↗
PubMed2001

Rapid acquisition of entire DNA polymerase gene of a novel herpesvirus from green turtle fibropapilloma by a genomic walking technique.

A 4837-bp sequence of a newfound green turtle herpesvirus (GTHV), implicated in the etiology of green turtle fibropapilloma, was obtained from tumor tissues of a green turtle with fibropapilloma using a genomic walking method based on restriction enzyme digestion, self-ligation and inverse polymerase chain reaction (IPCR). The 4837-bp sequence was 56.23% G/C rich and contained three nonoverlapping open reading frames (ORF). The largest ORF (3507-bp) encoded the DNA polymerase gene (pol gene), which exhibited a high degree of homology at both amino acid and nucleotide levels with the DNA pol genes of human and animal herpesviruses, with a predicted protein of 1169 amino acids and molecular weight of 132.6 kilodaltons. The ATG at 518 to 520 was the first initiation codon in the ORF and was presumed to be the first methionine codon of the pol gene. Phylogenetic analysis, based on the amino acid sequence of the GTHV DNA pol gene and the corresponding regions of other known human and animal herpesviruses, indicated that GTHV belonged to the Alphaherpesvirinae subfamily. The upstream ORF of the pol gene encoded the N-terminal region of the GTHV homologue of the DNA-binding protein gene, whereas the downstream ORF was the C-terminal region of a gene which was homologous to ORFs conserved in human and animal herpesviruses, i.e., herpes simplex virus 1 (HSV1) gene UL31, Epstein-Barr virus (EBV) gene BFLF2, equine herpesvirus 1 (EHV1) gene 29, and alcelaphine herpesvirus 1 (AHV1) hypothetical protein 69 gene. The arrangement of these three genes in GTHV genome was identical to that seen in other alphaherpesviruses. The sequence and location of the DNA pol gene in the GTHV genome should greatly facilitate future studies of the viral life cycle.

Alphaherpesvirinae↗
PubMed2001

Characterization of interaction between C-domain on HIV-1 gp41 and the putative receptor protein p62.

Based on the fact that the binding of HIV-1 gp41 to the putative cellular receptor protein p62 could be inhibited by the C-domain peptide of gp41, we wanted to confirm the interaction of the C-domain with p62 and to characterize the receptor-binding site on the C-domain. We attempted to isolate the putative receptor protein p62 from cell lysates of the human B cell line Raji by affinity chromatography using sepharose-columns which were conjugated with three different peptides of the C-domain respectively. A protein of 62 kDa was isolated by peptide (NP2)-sepharose-column, while none of the proteins was identified in eluates of the other two overlapped peptides of C-domain, indicating that HIV-1 gp41 by the region aa635-664 of C-domain binds to the putative receptor protein p62. Besides, CD spectroscopy analysis revealed that only a NP2 peptide could induce significant conformational change of P62. In addition, the interaction between P62 and three peptides of the C-domain was characterized by the surface plasma resonance (SPR) measurement. It was indicated that only the NP2 peptide significantly inhibited the interaction between rsgp41 and the putative receptor P62, confirming that the protein p62 may serve as a potential receptor for gp41 binding, and the peptide NP2 contains an integrate binding site for gp41 binding to p62.

Amino Acid Sequence↗
PubMed2001

Molecular and cytogenetic alterations in early stage of carcinogenesis of human lung.

In an attempt to reveal the genetic and epigenetic abnormalities in early stage of carcinogenesis of human lung cancer, a human bronchial epithelial cell line was immortalized by transfection with the Simian virus early region genes (SV40T); the biological features of the stable transfected cells were compared to human non-small cell lung cancer (NSCLC) specimens. The immortalized bronchial epithelial cells did not develop tumors but premalignant lesions in animal models. However, several genetic changes, including chromosome deletion and aneuploidy, altered expression of oncogenes and tumor suppressor genes occur not only in invasive NSCLC (human specimens) but also in the early stage of lung carcinogenesis (premalignant lesions) in this transfection model.

Animals↗
PubMed2001

Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin.

Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.

Aging↗
PubMed2001

Clinical isolates of Streptococcus pneumoniae resistant to levofloxacin contain mutations in both gyrA and parC genes.

Thirty Streptococcus pneumoniae clinical isolates resistant to levofloxacin were analyzed for the quinolone resistance-determining DNA sequences to identify point mutations and were tested for in vitro susceptibility to multiple drug classes. Of these isolates, 29 had mutations in both gyrA and parC genes of DNA gyrase and topoisomerase IV, respectively. In GyrA, an amino acid change from Ser-81-->Phe was detected in 27 isolates and a Glu-85-->Lys change was found in the remaining three. Of the 29 isolates for which ParC data were available, Ser-79-->Tyr or Phe were the predominant mutations observed. MICs for levofloxacin were 4-16 mg/l, whereas those for moxifloxacin were 1-2 mg/l. Twenty-four (80%) isolates were susceptible to erythromycin, 25 (83%) to azithromycin, 26 (87%) to clarithromycin, 27 (90%) to clindamycin, 20 (67%) to penicillin, 21 (70%) to ceftriaxone and 30 (100%) to amoxycillin/clavulanate. These results confirm the presence of double mutations among clinical isolates of S. pneumoniae from diverse geographical regions of North America and also suggest that quinolone resistance may develop independently of resistance to other drug classes.

Amino Acid Substitution↗
PubMed2001

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing pulmonary parenchyma and bronchial anastomoses.

OBJECTIVE: Despite advanced surgical techniques, major complications of bronchial anastomoses and parenchymal repair, including early leak, fistula formation and granulations still occur. The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue), CryoLife Inc., Kennesaw, GA) as a sealant for bronchial anastomoses and parenchyma lesions. METHODS: Twenty-four sheep were split into two surgical groups. The first group consisted of six control sheep receiving standard sutured bronchial anastomosis with a 4-week end-point. The second group included 18 sheep receiving both a bronchial anastomosis and parenchymal defect repair using the adhesive with 2, 4, and 12 week end-point. Histopathologic evaluation was conducted at the study end-points. RESULTS: Bronchial anastomosis and parenchymal tissue repair can be sealed successfully against air leakage with adhesive. Macroscopic evaluation revealed a tight closure of the anastomosis and parenchyma defect in all postoperative stages, initially by the adhesive layer, and later by connective tissue. On microscopic examination, an inflammatory tissue response consisting of polymorphonuclear neutrophils, macrophages, granulation tissue and foreign body giant cells were found surrounding the glued area after 2 weeks. After 4 weeks the tissue response presented a granulomatous character. No granulomatous or foreign body reaction was present in the hand sutured group. After 12 weeks few remnants of adhesive surrounded by fibrous scar tissue were detectable in bronchial anastomosis and parenchymal repair. Healing was not considerably complicated by foreign body reaction or tissue granulation. CONCLUSION: This study supports BioGlue to be effective as an adjunct in sealing bronchial anastomosis and lung parenchyma defects in sheep, with minimal secondary healing disruptions such as granuloma formation. The results of this study indicate that the use of BioGlue in human pulmonary surgery should be effective.

Anastomosis, Surgical↗
PubMed2001

Identification of confounders in the assessment of the relationship between lead exposure and child development.

PURPOSE: To explore the best approach to identify and adjust for confounders in epidemiologic practice. METHODS: In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models. RESULTS: The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4). CONCLUSIONS: Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the confounder and outcome. This study shows the complexities one can expect to encounter in the identification of and adjustment for confounders.

Bias↗
PubMed2001

Measuring the academic radiologist's clinical productivity: survey results for subspecialty sections.

RATIONALE AND OBJECTIVES: The purpose of this project was to understand better the academic radiologist's clinical workload in order to determine faculty staffing requirements more accurately. MATERIALS AND METHODS: Surveys performed by the Society of Chairmen of Academic Radiology Departments (SCARD) collected data for radiologists in 20 departments in 1996 and 1998; the data included work relative value units (RVUs) per full-time equivalent (FTE). Radiologists in each subspecialty were compared with their counterparts in other departments. The data were collected for each radiologist. Summary statistics showing averages, medians, and quartiles were used to describe workload (in RVUs per FTE) for each department and each subspecialty. RESULTS: Overall, the average clinical workload was 4,458 RVU/FTE, with 0.62 RVU per procedure. In those sections for which the faculty performed similar types of procedures across departments, the results were useful. The workload data, however, proved inadequate to compare across subspecialty sections. Between 1996 and 1998, the workload increased from 3,790 to 4,458 RVU/FTE. CONCLUSION: The SCARD survey provided very useful clinical workload data, measured in work RVUs per FTE for specific subspecialty sections. At practically all surveyed institutions, increasing clinical workload is competing with academic activities.

Academic Medical Centers↗
PubMed2001

Measuring the academic radiologist's clinical productivity: applying RVU adjustment factors.

RATIONALE AND OBJECTIVES: To improve understanding of academic radiologists' clinical workloads, the Society of Chairmen of Academic Radiology Departments (SCARD) performed surveys to collect workload data for radiologists in 20 departments; workload was measured in relative value units (RVUs) per full-time equivalent (FTE). Although they were useful for comparisons within some subspecialties, the workload data proved inadequate for comparisons across sections, and adjustment factors were needed for each Current Procedure Terminology (CPT) code. MATERIALS AND METHODS: All CPT codes for examinations were divided into groups with similar radiologist work effort. Focusing on radiologists who worked almost exclusively in each group, the authors created adjustment factors by using data from the individual radiologists at each institution. RESULTS: The adjustment factors are 0.50 for angiography, 0.58 for computed tomography and magnetic resonance imaging, and 1.0 for nuclear medicine, plain radiography, and special procedures (no adjustment needed for these groups). These factors are multiplied by the work RVUs for each examination to create the adjusted workload RVUs. CONCLUSION: The SCARD survey provided very useful clinical workload data, with workload measured in work RVUs per FTE for specific subspecialty sections. The new adjusted workload RVUs allow comparison of radiologists' workload across subspecialties.

Academic Medical Centers↗
PubMed2001

Reaction of fumonisin with glucose prevents promotion of hepatocarcinogenesis in female F344/N rats while maintaining normal hepatic sphinganine/sphingosine ratios.

The reaction of the primary amine of fumonisin B(1) (FB(1)) with glucose was hypothesized to detoxify this mycotoxin. Eighty 10-day-old female F344/N rats were injected intraperitoneally with diethylnitrosamine (DEN; 15 mg/kg of body weight). At 4 weeks of age, the weaned rats were randomly assigned to one of four treatment groups with 20 rats each. At 9 weeks of age, four rats from each treatment group were killed. At 12 weeks, another five rats from each group were killed. At 20 weeks of age, the remaining rats were killed. In comparison with the rats fed basal diet or FB(1)-glucose (containing 25 ppm of FB(1)), rats fed 8 ppm (residual amount of free FB(1) in the FB(1)-glucose mixture) or 25 ppm of FB(1) had greater alanine aminotransferase activity at 9 and 20 weeks of age (P < 0.001), greater endogenous hepatic prostaglandin E(2) production at 20 weeks of age (P < 0.05), and significantly lower plasma cholesterol at 20 weeks of age (P < 0.01). Placental glutathione S-transferase (PGST)-positive and gamma-glutamyltransferase (GGT)-positive altered hepatic foci (AHF) occurred only in rats fed 25 ppm of FB(1) at 20 weeks of age. Hepatic natural killer (NK) cell activities were similar among the four groups, but the percentage of total liver-associated mononuclear cells exhibiting the NKR-P1(bright) marker was significantly greater in rats fed FB(1)-glucose, FB(1) (8 ppm) and FB(1) (25 ppm) than in control rats at 9 weeks of age, and FB(1)-glucose-treated rats had significantly lower NKR-P1(bright) cells as a percentage of total liver-associated mononuclear cells than rats fed 25 ppm of FB(1) at 20 weeks of age (P < 0.05). PGST- or GGT-positive AHF were not detected in any treatment group at 9 or 12 weeks of age. At 20 weeks of age, half of the rats fed 25 ppm of FB(1) had PGST- and GGT-positive AHF. The sphinganine (Sa) concentration and the Sa/sphingosine (So) ratio were significantly greater in the rats fed 25 ppm of FB(1) diet as compared with the control groups at, respectively, 12 or 20 weeks of age. Therefore, modifying FB(1) with glucose seems to prevent FB(1)-induced hepatotoxicity and promotion of hepatocarcinogenesis. The Sa/So ratio was not the most sensitive biomarker of FB(1) toxicity.

Alkylating Agents↗
PubMed2001

Latent and active p53 are identical in conformation.

p53 is a nuclear phosphoprotein that regulates cellular fate after genotoxic stress through its role as a transcriptional regulator of genes involved in cell cycle control and apoptosis. The C-terminal region of p53 is known to negatively regulate sequence specific DNA-binding of p53; modifications to the C-terminus relieve this inhibition. Two models have been proposed to explain this latency: (i) an allosteric model in which the C-terminal domain interacts with another domain of p53 or (ii) a competitive model in which the C-terminal and the core domains compete for DNA binding. We have characterized latent and active forms of dimeric p53 using gel mobility shift assays and NMR spectroscopy. We show on the basis of chemical shifts that dimeric p53 both containing and lacking the C-terminal domain are identical in conformation and that the C-terminus does not interact with other p53 domains. Similarly, NMR spectra of isolated core and tetramerization domains confirm a modular p53 architecture. The data presented here rule out an allosteric model for the regulation of p53.

Allosteric Regulation↗