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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 343 records · Page 19Linked to original sources
PubMed2000

Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.

Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Receptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected with the human periodontal pathogen Porphyromonas gingivalis, with soluble RAGE (sRAGE). sRAGE is the extracellular domain of the receptor, which binds ligand and blocks interaction with, and activation of, cell-surface RAGE. Blockade of RAGE diminished alveolar bone loss in a dose-dependent manner. Moreover, we noted decreased generation of the proinflammatory cytokines TNF-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sRAGE, paralleling the observed suppression in alveolar bone loss. These findings link RAGE and exaggerated inflammatory responses to the pathogenesis of destructive periodontal disease in diabetes.

Alveolar Bone Loss↗
PubMed2000

A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women.

Raloxifene HCl, a selective estrogen receptor modulator, has been shown to increase bone mineral density (BMD) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus. However, it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level, nor how changes with raloxifene compare with estrogen. In this randomized, double blind study, we evaluated the effects of raloxifene (Evista, 60 mg/day) or conjugated equine estrogens (CEE; Premarin, 0.625 mg/day) on bone architecture, bone turnover, and BMD. Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for standard histomorphometric indexes. Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4, 10, 18, and 24 weeks of treatment. Total body, lumbar spine, and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry. Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE, but not in the raloxifene, group. Bone mineralization did not change in either group. Most markers of bone resorption and formation decreased in both groups, but to a greater degree in the CEE group (P < .05). Total body and lumbar spine BMD increased from baseline in both groups, with a greater increase in the CEE group (P < 0.05). Hip BMD significantly increased from baseline in the raloxifene group, but the change was not different from that in the CEE group. These results suggest that raloxifene reduces bone turnover and increases bone density, although to a lesser extent than CEE. Thus, raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women.

Aged↗
PubMed2000

Inhibition of X-ray and doxorubicin-induced apoptosis by butyrolactone I, a CDK-specific inhibitor, in human tumor cells.

Cell-cycle progression is coordinately regulated by cyclin-dependent kinases (CDKs). The inhibition of CDKs by p21Waf1/Cip1/Sdi1 prevents the apoptosis of cells treated with DNA-damaging agents. In this study, we found that butyrolactone I, a specific inhibitor of CDC2 family kinases, blocks the X-ray- or doxorubicin-induced apoptosis of DLD1 (p21+/+) human colorectal carcinoma cells in a dose-dependent manner. We also found that butyrolactone I inhibits the CDK2 activity and enhances cell survival after an X-ray irradiation or doxorubicin treatment in both DLD1 (p21-/-) and DLD1 (p21+/+) cells. These findings suggest that butyrolactone I prevents apoptosis by the direct inhibition of CDK and also, possibly, by CDK-inhibition through p53-independent p21-induction. Our findings indicate that CDK activity is required for DNA-damaging agent-induced apoptosis.

4-Butyrolactone↗
PubMed2000

Genotoxic effects of alpha-endosulfan and beta-endosulfan on human HepG2 cells.

alpha-Endosulfan and ss-endosulfan are isomers of endosulfan, a pesticide used worldwide. In this study, we examined the genotoxicity of [alpha]- and ss-endosulfan in vitro with a HepG2 cell line. We used sister chromatid exchanges (SCE), micronuclei (MN), and DNA strand breaks as detected by single-cell gel electrophoresis (SCG) assays as biomarkers to judge the genotoxicity of [alpha]- and ss-endosulfan at concentrations from 1 times 10(-12) M to 1 times 10(-3) M. After treating HepG2 cells for 48 hr with ss-endosulfan, SCE showed a significant increase at concentrations from 1 times 10(-7) M to 1 times 10(-5) M, and MN showed a significant increase at concentrations from 5 times 10(-5) M to 1 times 10(-3) M. [alpha]-Endosulfan failed to show significant effects in both the SCE and MN assays. After treating HepG2 cells with [alpha]- or ss-endosulfan for 1 hr, DNA strand breaks were significantly induced by [alpha]-endosulfan at concentrations from 2 times 10(-4) M to 1 times 10(-3) M, and by ss-endosulfan at 1 times 10(-3) M. The results of this study suggest that both [alpha]- and ss-endosulfan are genotoxic to HepG2 cells and that the genotoxicity of ss-endosulfan seems stronger than that of [alpha]-endosulfan.

Biomarkers↗
PubMed2000

Studies and syntheses of siderophores, microbial iron chelators, and analogs as potential drug delivery agents.

Siderophores (microbial iron chelators) play an extremely important role in microbial pathogenicity. Microbial uptake of siderophore-iron complexes through active transport systems allow microbes to survive and proliferate even under iron deficient environments during invasion of a host. Due to their structural complexity, unique iron (III) chelation, acquisition properties, and their therapeutic potential, siderophores have attracted much attention in a broad range of disciplines. Tremendous progress has been made in siderophore syntheses, in determination of the structures and functions of outer membrane receptors (e.g. FhuA and FepA), and in the mechanistic insight into siderophore-iron-mediated active transport processes. One of the important practical applications of this active transport system is development of species-selective active drug transport (the Trojan Horse approach) to potentially treat infections due to drug resistant strains of microbes. Siderophore-drug conjugates have shown great potential in active drug delivery to target pathogenic microbes.

Drug Carriers↗
PubMed2000

MR imaging of the breast in patients with positive margins after lumpectomy: influence of the time interval between lumpectomy and MR imaging.

OBJECTIVE: Postsurgical contrast enhancement resulting from inflammatory changes at the site of surgery limits the accuracy of MR imaging of the breast in diagnosing residual breast cancer. This study was undertaken to evaluate the influence of the time interval between lumpectomy and MR imaging on the diagnosis of residual breast cancer. MATERIALS AND METHODS: Sixty-eight patients who had undergone excisional biopsy with positive resection margins underwent MR imaging for evaluation of residual breast cancer and possible breast conservation. Patients were retrospectively stratified according to the time interval between lumpectomy and MR imaging. Dynamic and morphologic enhancement features were used for lesion characterization. Imaging findings were correlated with results of histopathology. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for patients waiting 7, 14, 21, 28, 35, and 42 days after initial surgery before undergoing MR imaging of the breast. RESULTS: The time interval between lumpectomy and MR imaging of the breast had the greatest influence on the specificity and negative predictive value of MR imaging, increasing progressively over time. A plateau of highest values of 75% specificity and 86% negative predictive value was reached at 28 and 35 days after surgery, respectively. Although the sensitivity and positive predictive value showed smaller variations over time, peak values of 95% sensitivity and 92% positive predictive value were obtained at 35 and 28 days after surgery, respectively. CONCLUSION: We recommend scheduling patients with positive resection margins no earlier than 28 days after initial surgery for evaluation of residual cancer using MR imaging of the breast.

Adult↗
PubMed2000

Epitope-vaccine induces high levels of ELDKWA-epitope-specific neutralizing antibody.

Based on the fact that mAb 2F5 recognizing ELDKWA-epitope on the C-domain of HIV-1 gp41 has significant neutralization potency against 90% of the investigated viruses of African, Asian, American and European strains, we attempted to characterise immunogenicity of the ELDKWA-epitope on an epitope-vaccine, and to produce ELDKWA-epitope-specific monoclonal antibodies (mAb) induced by the epitope-vaccine. The C-domain peptide (P2) and the ELDKWA-tetramer peptide [C-(ELDKWAG)4] were conjugated with BSA or P24-EC (GPKEPFRDYVDRFYK, a peptide of HIV-1 gag-protein P24, proved to be a good carrier peptide to induce an immune response to the hapten on the conjugates[18])by different methods. After the vaccination course, two P2-BSA peptide-vaccines both induced a strong antibody response against the P2-peptide by about 1:12800-25600 dilution, and a weak antibody response against the ELDKWA-epitope (1:1600-3200). The P2-P24EC and P2 (conjugated with itself) peptide-vaccines could also induce a weak antibody response against the ELDKWA-epitope (1:1600-3200), while an rgp160 subunit vaccine induced a very weak antibody response (1:400). Interestingly, the ELDKWA-tetramer epitope-vaccine [C-(ELDKWAG)4-BSA] could induce a strong antibody response against the ELDKWA-epitope (1:12800-25600), i.e. It increased the level of ELDKWA-antibody eight-fold, clearly better than the P2 peptide-vaccine, and much better than the rgp160 subunit vaccine, which indicates that the immunogenicities of the ELDKWA-epitope on the ELDKWA-tetramer peptide, the C-domain peptide and rgp160 are very different. These results suggest that the ELDKWA-epitope-vaccine may be a new strategy for inducing high levels of epitope-specific neutralizing antibodies against HIV-1. Using hybridoma-technique, a mouse monoclonal antibody recognizing the ELDKWA-epitope on ELDKWA-peptide and C-domain peptide was produced by immunization with the C-(ELDKWAG)4-BSA epitope-vaccine, which indicates a new way to produce an epitope-specific mAb, namely immunization with epitope-vaccine instead of a natural or recombinant protein immunogen.

Amino Acid Sequence↗
PubMed2000

[Genetic polymorphism of 5 STR loci on chromosome 14 in Chinese Han].

OBJECTIVE: To understand the distribution of genes and genotypes of 5 STR loci on chromosome 14 in Chinese Han. METHODS: PCR and polyacrylamide gel electrophoresis were used to analyze the polymorphism of 5 STR loci (D14S742, D14S306, D14S606, D14S617, D14S611) on chromosome 14 in Chinese Han. RESULTS: 5 alleles and 13 genotypes, 5 alleles and 13 genotypes, 6 alleles and 13 genotypes, 9 alleles and 21 genotypes, and 6 alleles and 13 genotypes were observed at D14S742, D14S306, D14S606, D14S617 and D14S611, respectively. The frequencies of the most common allele at these five loci were 0.31, 0.31, 0.47, 0.35 and 0.29 respectively. CONCLUSION: These five loci are highly polymorphic in Chinese Han and their allele distribution is in good agreement with Hardy-Weinberg equilibrium.

China↗
PubMed2000

[Development of a mouse cell line containing stably integrated copies of pMCLacI/Neo plasmid: a model for studying mutations in vitro].

OBJECTIVE: To establish a suitable model for studying the different mechanisms of mutation between expressed and non-expressed genes in mammalian cells. METHODS: The NIH3T3 cells were transfected with the linearized pMCLacI/Neo DNAs by liposome-mediated transfection, and grew in the presence of G418. One drug resistant cell clone was selected to proliferate and to be analyzed with Southern blot and RT-PCR analyses on its genomic DNAs. RESULTS: (1) Multiple copies of pMCLacI/Neo plasmid DNA were intactly integrated in the genomic DNAs of the cell clone. (2) One of lac I target genes in the integrated plasmid could be transcribed in the NIH3T3 cells while the other could not. (3) The pMCLacI/Neo plasmid DNA could be efficiently rescued from the genomic DNAs of the cell clone with the average rescue efficiency of 410 cfu/microg DNA. CONCLUSION: The NIH3T3 cell line containing copies of a stably integrated pMCLacI/Neo has been established. The two lacI target genes in the cell line could imitate the functional states of expressed and non-expressed genes in mammalian cells respectively. The cell line will be a useful model for studying the different mechanisms of mutation between expressed and non-expressed genes in mammalian cells.

3T3 Cells↗
PubMed2000

Genetic polymorphism of 4 STR loci on chromosome 17 in Chinese Han.

OBJECTIVE: To analyze genetic polymorphism of D17S1290, D17S1293, D17S1303 and D17S1308 in Chinese Hans. METHODS: Fifty unrelated individuals were analyzed by PCR amplification fragment length polymorphism analysis method. RESULTS: 9, 7, 5, 5 alleles were observed at these 4 STR loci respectively, the genotypes distributions in Chinese Hans were in accordance with Hardy-Weinberg equilibrium, the expected heterozygosities for these loci were 0.770, 0.828, 0.608, 0.669 respectively, the polymorphism information contents(PIC) were 0.763, 0.820, 0.602, 0.662 respectively. CONCLUSION: The results demonstrate these 4 STR loci can be used for genetic analysis.

China↗
PubMed2000

[Changes of collagenase activity in immune hepatic fibrosis following pig's serum injection and therapeutic effect of HanDanGanLe].

OBJECTIVE: To investigate the changes of collagenase activity in immune hepatic fibrosis following pig's serum injection and the therapeutic effect of HanDanGanLe. METHODS: Pig's serum was injected intraperitoneally to Wistar rats to duplicate the hepatic fibrosis model due to immunologic injury. HanDanGanLe was used as therapeutic medicine and colchicine as control. The animals were killed at 12th week to detect hepatic collagenase activity, the staining semiquantity of hepatic collagenous fibre, and the content of hepatic collagen. RESULTS: HanDanGanLe can increase collagenase activity, decrease the content of collagenous fibre and collagen in the liver. The beneficial effect achieved in HanDanGanLe-treatment group especially in high-dose group in comparison to colchicine-treatment group. CONCLUSION: HanDanGanLe can effectively increase collagenase activity, improve collagen degradation, and abate hepatic fibrosis.

Animals↗
PubMed2000

Sextant localization of prostate cancer: comparison of sextant biopsy, magnetic resonance imaging and magnetic resonance spectroscopic imaging with step section histology.

PURPOSE: We compared the accuracy of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging with that of sextant biopsy for the sextant localization of prostate cancer. MATERIALS AND METHODS: Sextant biopsy, MRI, magnetic resonance spectroscopic imaging and radical prostatectomy with step section histology were done in 47 patients with prostate cancer. For each sextant we categorized biopsy and imaging results as positive or negative for cancer. Step section histology was used as the standard of reference. RESULTS: For sextant localization of prostate cancer MRI and magnetic resonance spectroscopic imaging were more sensitive but less specific than biopsy (67% and 76% versus 50%, and 69% and 68% versus 82%, respectively). The sensitivity of sextant biopsy was significantly less in the prostate apex than in the mid prostate or prostate base (38% versus 52% and 62%, respectively). MRI and magnetic resonance spectroscopic imaging had similar efficacy throughout the prostate compared with biopsy only as well as better sensitivity and specificity in the prostate apex (60% and 75%, and 86% and 68%, respectively). A positive biopsy or imaging result had 94% sensitivity for cancer and concordant positivity by all 3 tests was highly specific at 98%. CONCLUSIONS: Overall MRI and magnetic resonance spectroscopic imaging have accuracy similar to biopsy for intraprostatic localization of cancer and they are more accurate than biopsy in the prostate apex. These 2 imaging modalities may supplement biopsy results by increasing physician confidence when evaluating intraprostatic tumor location, which may be important for planning disease targeted therapy.

Aged↗
PubMed2000

Clinical observation and experimental study on compound hypoglycemic decoction for hyperglycemia.

PURPOSE: To observe the clinical efficacy of Compound Hypoglycemic Decoction (CHD) and its effect on serum total cholesterol in model mice. METHOD: The paired t test was used to analyze the data recorded before and after administration of drugs for hyperglycemia induced by intraperitoneal injection of 75% egg yolk emulsion in experimental mice. CHD and Fenofibrate were administered as prevention measures. RESULTS: The total effective rate of serum total cholesterol (TC) decrease in 60 cases of hyperglycemia was 86.66% and that of serum total triglyceride (TG) decrease was 81.81%. The total effective rate of high-density lipoprotein-cholesterol (HDL-C) increase was 75%. The decrease in TC and TG, and the increase of HDL-C after treatment by in-group comparison were all significant (P < 0.05). 21.9% and 22.2% decrease in the total cholesterol was respectively found in the CHD and Fenofibrate groups (both P < 0.05), with no significant difference. CONCLUSION: The hypoglycemic action of Compound Hypoglycemic Decoction was remarkable in clinical practice, and it is very effective in preventing hyperglycemia in experimental mice.

Adult↗
PubMed2000

[Advances in the researches of DNA vaccines against tumors].

The injection of naked plasmid DNA directly into the muscle cells of hosts has been shown to induce potent immune responses, as well as to express large amounts of gene product; this has provided a new way of treatment for tumor. The past ten years have witnessed tremendous growth in the field of gene therapy for cancer using intramuscular injection of plasmid DNA. Many studies have suggested that the immunostimulatory DNA sequences(ISS) in vector backbone of plasmid DNA, delivering adjuvant and mitogenic activity, are necessary for effective intradermal gene immunization. It has been postulated that muscle cells serve as a reservoir of expressed antigen with subsequent transfer to bone marrow-derived APCs. Thus, immunization with plasmid DNA can trigger strong and persistent cell-mediated and humoral immune responses to the antigen encoded by the plasmid. Increasing evidence demonstrates that DNA immunization can prevent or inhibit tumor development. In this review, the present authors presented a discussion on the characteristics of immune response to DNA vaccines and a summary of the effects of immune response against tumors.

Animals↗
PubMed2000

Participation of MAP kinase p38 and IkappaB kinase in chromium (VI)-induced NF-kappaB and AP-1 activation.

Epidemiological studies demonstrate that environmental and occupational exposure of chromium(VI) [Cr(VI)] or Cr(VI)-containing particles can cause a number of human diseases, including inflammation and cancer. The biological mechanisms responsible for the initiation and progression of diseases resulting from exposure to Cr(VI) are not fully understood. The present studies evaluated the ability of Cr(IV) to induce activation of NF-kappaB and AP-1, two important transcription factors governing the expression of many early response genes involved in inflammation and carcinogenesis. The activation of NF-kappaB and AP-1 by Cr(IV) was dose dependent. Aspirin, a well-established antioxidant, substantially inhibited Cr(VI)-induced activation of both NF-kappaB and AP-1. SB202190, a specific inhibitor for p38, attenuated AP-1 activation induced by Cr(IV), whereas PD98059, a specific inhibitor for Erk, exhibited no effect on Cr(IV)-induced AP-1 activation. Blockage of NF-kappaB signaling pathway by a transient transfection of a dominant negative expressing vector for IkappaB kinase beta resulted in inhibition of Cr(IV)-induced NF-kappaB, but not AP-1 activation. These data suggest that the activation of AP-1 or NF-kappaB by Cr(IV) is through the involvement of MAP kinase or IKK pathway, respectively.

Animals↗
PubMed2000

Involvement of cyclin-dependent kinases in doxorubicin-induced apoptosis in human tumor cells.

Apoptotic cell death caused by doxorubicin, a chemotherapeutic agent, is suppressed by expression of p21 (waf1/cip1/sdi1), a cyclin-dependent kinase (cdk) inhibitor. To examine cdk activity required for doxorubicin-induced apoptosis, we transfected p21-deficient human tumor DLD1(p21-/-) cells with plasmids carrying wild-type p21 and mutated p21 unable to bind to cdks or proliferating cell nuclear antigen. The apoptosis induced at the G(2)/M phase after doxorubicin treatment was suppressed by transient expression of the p21 with cdk-binding activity but not by the p21 lacking the activity. We also transfected cells with plasmids carrying wild-type, dominant negative and constitutively active mutants of cdk2 or cdk4. The apoptosis was suppressed by transient expression of dominant negative mutants of cdk2 or cdk4. These findings indicate that cdk is involved in the doxorubicin-induced apoptosis pathway.

Antibiotics, Antineoplastic↗
PubMed2000

[A system of microcomputer analysis for biological oxygen consumption and its application].

This paper introduces a microcomputer system of data analysis and methods of measuring oxygen consumption for biological materials. The system overcame some disadvantages of operating inconvenience and difficulties of collective and analytic data by traditional means. The system possesses functions of automatic enactment, collection, save/take and analysis for many experimental data. It can be used to measure oxygen consumption of tissues, cells and mitochondria.

Animals↗