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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 73 records · Page 4Linked to original sources
PubMed2004

Micro and nano-fabrication of biodegradable polymers for drug delivery.

This paper presents state-of-the-art micro and nano-fabrication techniques for biodegradable polymers. Replication molding, using a rigid or elastic master, can pattern structures on a polymer surface in a submicron resolution at a low cost. Layer-by-layer rapid prototyping methods are promising in producing controlled release units with complicated geometries, release mechanisms and the ability to control microstructure and composition. Special attention is paid to the fast, flexible, and non-invasive laser fabrication techniques that have great potential in the fabrication of biodegradable polymer drug delivery devices in both a laboratory and industry scale.

Absorbable Implants↗
PubMed2004

Scd1ab-Xyk: a new asebia allele characterized by a CCC trinucleotide insertion in exon 5 of the stearoyl-CoA desaturase 1 gene in mouse.

We describe here a spontaneous, autosomal recessive mutant mouse suffering from skin and hair defects, which arose in the outbred Kunming strain. By haplotype analysis and direct sequencing of PCR products, we show that this mutation is a new allele of the asebia locus with a naturally occurring mutation in the Scd1 gene (a CCC insertion at nucleotide position 835 in exon 5), which codes for stearoyl-CoA desaturase 1. This mutation introduces an extra proline residue at position 279 in the Scd1 protein. The mutant mice, originally designated km/km but now assigned the name Scd1ab-Xyk (hereafter abbreviated as abXyk/abXyk), have a similar gross and histological phenotype to that reported for previously characterized allelic asebia mutations (Scd1ab, Scd1abJ, Scd1ab2J, and Scd1tm1Ntam). Histological analysis showed they were also characterized by hypoplasic sebaceous glands and abnormal hair follicles. In a cross between Kunming- abXyk/abXyk and ABJ/Le-abJ/abJ mice, all the progeny showed the same phenotype, indicating that the two mutations were non-complementing and therefore allelic. Comparisons with the other four allelic mutants indicate that the Scd1ab-Xyk mutation causes the mildest change in Scd1 function. This new mouse mutant is a good model not only for the study of scarring alopecias in humans, which are characterized by hypoplasic sebaceous glands, but also for studying the structure and function of the Scd1 protein.

Alleles↗
PubMed2004

Response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to cyclic fatigue loading.

Cyclic loading induces fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to cyclic fatigue (-6000 microepsilon) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after fatigue loading, and this did not change after the period of adaptation. In fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to cyclic loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to loading and influence targeted remodeling.

Adaptation, Physiological↗
PubMed2004

Germline mutational analysis of CDH1 and pathologic features in familial cancer syndrome with diffuse gastric cancer/breast cancer proband in a Chinese family.

AIMS: Hereditary non-polyposis colorectal cancer, thyroid medullary carcinoma, breast/ovarian cancer and gastric cancer/breast cancer syndrome are encountered in surgery. Some gastric cancer/breast cancer syndrome may be the result of a CDH1 germline mutation. This is the first report of CDH1 germline mutations gastric cancer/breast cancer syndrome in Chinese patients. METHODS: Peripheral blood from the proband, as well as, her first and second degree relatives was collected and CDH1 gene exon 1-16 mutations were screened. E-cadherin/beta-catenin proteins expression and histopathologic features were examined on gastric cancer/breast cancer tissues from the proband. RESULTS: A C-->T nucleotide substitution at exon 13 (mRNA 2200 locus, Accession number NM-004360) was found. This was a transition from GCC-->GCT in DNA sequence (Ala154Ala). Diffuse-type gastric cancer and infiltrating ductal breast carcinoma were present. Both tumours preserved E-cadherin/beta-catenin expression immunohistochemically. CONCLUSIONS: Familial cancer syndrome with diffuse-type gastric cancer/breast cancer proband in Chinese has a propensity of early onset during lifespan. No truncating or splice-site CDH1 mutations had been identified in this family. A silent nucleotide variation in exon 13 of the CDH1 gene may contribute to some forms of cancer susceptibility.

Adult↗
PubMed2004

Determination of hesperetin, cinnamic acid and nicotinic acid in propolis with micellar electrokinetic capillary chromatography.

Micellar electrokinetic capillary chromatography (MEKC) has been used to determine hesperetin, cinnamic acid and nicotinic acid in propolis. After systematically study the effect of buffer concentration and pH, micellar concentration, organic modifier, applied voltage and injection time, the analytical conditions were optimized. Under the optimized conditions, the three analytes could be well separated in 20 min. A good linearity between the peak current and the concentration was found in the range of 0.02-0.60 mg/ml, 0.05-1.20 mg/ml and 0.10-1.40 mg/ml with correlation coefficients of 0.9989, 0.9995 and 0.9990 for hesperetin, cinnamic acid and nicotinic acid, respectively. The detection limits were 0.006 mg/ml (hesperetin), 0.017 mg/ml (cinnamic acid) and 0.036 mg/ml (nicotinic acid). The validity of the method was verified by analyzing the three analytes in propolis oral liquids.

Anti-Infective Agents↗
PubMed2004

Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis.

OBJECTIVES: To describe a semi-quantitative scoring method for multi-feature, whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic resonance imaging (MRI) findings. To determine the inter-observer agreement of this scoring method. To examine associations among the features included in the scoring method. METHODS: Nineteen knees of 19 patients with knee OA were imaged with MRI using conventional pulse sequences and a clinical 1.5 T MRI system. Images were independently analyzed by two musculoskeletal radiologists using a whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular cartilage integrity, subarticular bone marrow abnormality, subarticular cysts, subarticular bone attrition, marginal osteophytes, medial and lateral meniscal integrity, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, synovitis/effusion, intraarticular loose bodies, and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were determined for each feature as a measure of inter-observer agreement. Associations among the scores for different features were expressed as Spearman Rho. RESULTS: All knees showed structural abnormalities with MRI. Cartilage loss and osteophytes were the most prevalent features (98% and 92%, respectively). One of the least common features was ligament abnormality (8%). Inter-observer agreement for WORMS scores was high (most ICC values were >0.80). The individual features showed strong inter-associations. CONCLUSION: The WORMS method described in this report provides multi-feature, whole-organ assessment of the knee in OA using conventional MR images, and shows high inter-observer agreement among trained readers. This method may be useful in epidemiological studies and clinical trials of OA.

Aged↗
PubMed2004

Gap junctions are required for trophoblast proliferation in early human placental development.

Little is known about the role of gap junctional intercellular communication (GJIC) in human trophoblast differentiation, particularly during the formation of extravillous trophoblast (EVT) cell columns and their subsequent differentiation into invasive cells. We have identified transcripts for five connexin gap junction proteins in the early human placenta (Cx32, Cx37, Cx40, Cx43 and Cx45). Of these, Cx40 and Cx45 proteins immunolocalize to EVT in anchoring cell columns. Cx40 expression is prominent in the anchoring column throughout the first trimester of pregnancy (6-14 weeks gestation). We used first trimester placental villous explant cultures to determine the functional significance of the inhibition of GJIC in EVT cell proliferation and differentiation using two known GJIC inhibitors, carbenoxolone (CBX) and heptanol. The morphology of EVT outgrowths changed dramatically upon GJIC-blockade, from compact and organized outgrowths into a scattered group of rounded individual trophoblast cells, reminiscent of an early invasive phenotype. Furthermore, the inhibition of GJIC in placental explants by CBX or heptanol induced a switch away from the proliferative and towards an invasive EVT phenotype, as evident from (a) the loss of the proliferation marker Ki67 and (b) an increase in the invasive marker alpha1 integrin. We also utilized antisense oligonucleotides to inhibit Cx40 protein expression in placental explants. Cx40 antisense treatment also resulted in the abolishment of outgrowth EVT cell proliferation (as determined by Ki67 immunostaining). Together, these results suggest that gap junctions composed particularly of Cx40 channels are required for the proliferation of EVT cells in anchoring cell columns, and that a loss of GJIC contributes to differentiation to the invasive EVT phenotype.

Carbenoxolone↗
PubMed2004

Screening and analysis of porcine endogenous retrovirus in Chinese Banna minipig inbred line.

Pigs have been the most likely animal as the source of cells, tissues, and organs for xenotransplantation. But the use of pigs in xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Previous studies have identified that the proviruses are integrated into the genome of normal pigs and that virus particles released from the porcine cells can infect human cells in vitro. As a unique inbred pig, Banna minipig inbred (BMI) has a huge potential value for xenotransplantation and medical research. It has been the focal experimental animal for pig-to-human xenotransplantation in China, due to its clear genetic background and tiny individual differences. To evaluate whether the potential risk of PERV exists in inbred pigs, a series of screening experiments were performed herein. The results of PCR with primers specific for gag, pol, and env showed that proviruses existed in the genome of BMI, and the PERV subtypes were PERV-A and PERV-B. PERV mRNA was expressed functionally in BMI. Positive results of an RT assay identified that PERV in BMI had potential infectivity, but the concentration of PERV reverse transcriptase in BMI was almost 20 times lower than that of HIV. These results suggested that gag, pol and env genes of PERV were not lost during inbreeding, which created favorable conditions to produce viral particles that could possibly infect human cells in xenotransplantation.

Animals↗
PubMed2004

Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a systematic review.

INTRODUCTION: To evaluate the safety of mycophenolate mofetil (MMF) versus azathioprine (Aza) in renal transplantation, we compared their side effects using evidence-based methods. METHODS: Medline, Embase, Cochrane library, and Chinese Biomedicine database (CBM) were searched to select randomized clinical trials that had one group using MMF and another group using Aza as an immunosuppressive drugs. Safety analysis consist of the following factors: diarrhea, abdominal pain, vomiting, nausea, constipation, CMV infection, leukopenia, anemia, thrombocytopenia or skin malignancy. RevMan 4.11 software was used for the systematic review analysis. RESULT: Twenty trials including 6387 patients were identified. The diarrhea incidence with MMF (3 g/d) was higher than for Aza at 1 and 3 years (P < .05). Diarrhea on MMF (2 g/d) was higher than for Aza within 6 months (P < .05). CMV infection incidence on MMF (3 g/d) was higher than for Aza's at 3 years (P < .05), but MMF (2 g/d) did not show a statistical significance compared with Aza. Leukopenia incidence on MMF (3 g/d) was higher than that on Aza, whereas the incidence with MMF (2 g/d) was not significantly different from Aza. Skin malignancy incidence showed no statistical difference between MMF 3 g/d, MMF 2 g/d, or Aza. CONCLUSION: The use of MMF is associated with slight increases in gastrointestinal adverse effects, some hematologic adverse events, and CMV infections compared with Aza. Larger sample sizes of randomized controlled trials are needed to evaluate the safety of MMF.

Azathioprine↗
PubMed2004

Efficacy of mycophenolate mofetil versus azathioprine after renal transplantation: a systematic review.

INTRODUCTION: Our objective was to evaluate the efficacy of mycophenolate acid (MMF) versus azathioprine (AZA) after renal transplantation. MATERIALS AND METHODS: The following electronic databases were searched: Medline, Embase, Cochrane library, and Chinese Biomedicine database (CBM). Randomized controlled trials (RCTs) were subjected to Revman 4.11 for statistical analyses. RESULTS: Twenty-three RCTs were identified to compare MMF and AZA for antirejection, prophylaxis after renal transplantation. The data showed that MMF (2 g/d) was more beneficial than AZA to improve graft and long-term patient survivals, but there was no statistical differences between MMF (3 g/d) and AZA. Whether at 6 months or at 1 year after renal transplantation, the use of MMF (2 g/d) or MMF (3 g/d) markedly reduced the incidence of biopsy-proven rejection. CONCLUSION: Compared with AZA, MMF is a more potent immunosuppressive drug, that is more efficient in reducing the incidence of acute rejection episodes after renal transplantation. MMF can improve the graft and patient survival rate. The 2 g per day dosage is more acceptable.

Azathioprine↗
PubMed2004

Engineering plants for elevated CO(2): a relationship between starch degradation and sugar sensing.

In the future, plants will have additional CO(2) for photosynthesis. However, plants do not take maximal advantage of this additional CO(2) and it has been hypothesized that end product synthesis limitations and sugar sensing mechanisms are important in regulating plant responses to increasing CO(2). Attempts to increase end product synthesis capacity by engineering increased sucrose-phosphate synthase activity have been generally, but not universally, successful. It was found that plants benefited from a two- to three-fold increase in SPS activity but a 10-fold increase did not increase yield. Despite the success in increasing yield, increasing SPS did not increase photosynthesis. However, carbon export from chloroplasts was increased during the day and reduced at night (when starch provides carbon for sucrose synthesis. We develop here a hypothesis that starch degradation is closely sensed by hexokinase because a newly discovered pathway required for starch to sucrose conversion that involves maltose is one of few metabolic pathways that requires hexokinase activity.

Biological Transport↗
PubMed2004

Genetic polymorphism of the accessory gene regulator (agr) locus in Staphylococcus epidermidis and its association with pathogenicity.

Staphylococcus epidermidis has become one of the most important causes of nosocomial infections in recent years. The staphylococcal accessory gene regulator (agr) is the most important locus responsible for the regulation of virulence factors, and it has been shown to be polymorphic. The aim of this study was to investigate the agr locus and its genetic polymorphisms in different Chinese S. epidermidis isolates and the relationship between genetic polymorphisms and pathogenicity. Specific PCR was used to amplify the different agr groups. Results were confirmed by restriction enzyme digestion and sequence analysis. agr mutations were detected and three agr groups of S. epidermidis were determined. Of the isolates, 12 % were pathogenic S. epidermidis and 17 % had naturally occurring agr mutations (P > 0.05). Pathogenic S. epidermidis isolates comprised 68.2 % agr group I, 19.3 % group II and 12.5 % group III, while isolates from healthy controls comprised 39 % agr group I, 51 % group II and 10 % group III (P < 0.01). The percentages of agr locus mutants and the three agr groups in different hospitals showed no significant differences (P > 0.05). The percentage of agr group I S. epidermidis isolated from catheters and blood was higher than that isolated from the other clinical specimens. This is the first study to investigate the genetic polymorphism of agr in S. epidermidis in China. The mean percentage of agr locus mutants was 14.9 % (12 % in clinical specimens; 17.7 % in controls). Genetic polymorphism of agr in S. epidermidis was linked to its pathogenicity; group I was associated with pathogenicity, while most isolates from healthy subjects were group II. The mechanism is to be investigated.

Bacterial Proteins↗
PubMed2004

Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians.

BACKGROUND: Osteoporosis, mainly characterised by low bone mineral density (BMD), is a serious public health problem. The collagen type I alpha 1 (COL1A1) gene is a prominent candidate gene for osteoporosis. Here, we examined whether genetic variants at the COL1A1 gene can influence BMD variation. METHODS: BMD was measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females. We screened four single nucleotide polymorphisms (SNPs) at the COL1A1 gene: PCOL2 (-1997 G/T) in the promoter, Sp1 (1546 G/T) in the intron 1, Gly19Cys (3911 G/A) in exon 8, and Ala897Thr (13 773 G/A) in exon 45. Univariate and multivariate association approaches were used in the analyses. RESULTS: In multivariate analyses, we found a strong association between the PCOL2 SNP and BMD (p = 0.007 to 0.024) and a suggestive association between the Sp1 SNP and BMD (p = 0.023 to 0.048) in elderly Caucasian females. Interestingly, the interaction of these two SNPs was highly significantly associated with BMD variation (p = 0.001 to 0.003). The haplotype GG at the two SNPs had, on average, 2.7% higher BMD than non-carriers (p = 0.006 to 0.026). CONCLUSIONS: Our data suggested that the common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to BMD variation in elderly Caucasian females. Further studies are necessary to delineate the mechanisms underlying the effects of these common variants on BMD variation and to test their clinical relevance for general populations. In addition, our study highlighted the importance of multivariate analyses when multiple correlated phenotypes are under study.

Binding Sites↗
PubMed2004

Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice.

The purpose of this study was to evaluate the effect of cationic charge of complexes after intravenous administration of cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiomannosyl-ethyl)amino]butyl]formamide (Man-C4-Chol) containing cationic liposomes/pDNA complexes in mice. Transfection efficiency after intravenous administration of complex at a charge ratio (- : +) of 1.0:2.3 and/or 1.0:3.1 in liver and spleen expressing a mannose receptor on the cell surface were higher than those in lung. When complexes were formed at a charge ratio (- : +) of 1.0:4.7, on the other hand, transfection efficiency in the lung was highest, suggesting a non-specific interaction. Although asialoglycoprotein receptors are expressed on hepatocytes, a liver-selective gene transfection was not achieved by the intravenous administration of pDNA complexed with cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiogalactosyl-ethyl)-amino]butyl]formamide (Gal-C4-Chol)/DOPE liposomes at a charge ratio (- : +) of 1.0 : 2.3. This information supports the design of pDNA/ligands-grafted cationic liposome complexes for cell-specific gene delivery after intravenous administration.

Animals↗
PubMed2003

Evidence for control of nitrogen metabolism by a START-dependent mechanism in Saccharomyces cerevisiae.

It is generally thought that cell growth and metabolism regulate cell division and not vice versa. Here, we examined Saccharomyces cerevisiae cells growing under conditions of continuous culture in a chemostat. We found that loss of G1 cyclins, or inactivation of the cyclin-dependent kinase Cdc28p, reduced the activity of glutamate synthase (Glt1p), a key enzyme in nitrogen assimilation. We also present evidence indicating that the G1 cyclin-dependent control of Glt1p may involve Jem1p, a DnaJ-type chaperone. Our results suggest that completion of START may be linked to nitrogen metabolism.

Base Sequence↗
PubMed2003

Sequencing and characterization of the full-length gene encoding the single-stranded DNA binding protein of a novel Chelonian herpesvirus.

Through 4 consecutive genomic walks employing a recently modified inverse polymerase chain reaction technique, a 4,054-bp DNA fragment of a newfound green turtle herpesvirus (GTHV) was obtained from tumor tissues of a green turtle with fibropapillomas. This newly identified viral DNA fragment contains two non-overlapping open reading frames (ORF) oriented in the 3' to 5' direction. The first ORF is 59% G+C rich and contains the full-length genomic sequence of the DNA binding protein (DBP) gene (3,585 bp) encoding a protein of 1,195 amino acid residues in length. The second ORF encodes a partial peptide of the UL28 gene. Phylogenetic analysis of the GTHV DBP gene confirmed and substantiated that this novel Chelonian herpesvirus is closely related to the subfamily Alphaherpesvirinae. Examination of the translated amino acid sequence further supports this categorization since GTHV DBP comprises a highly conserved zinc finger motif (CXLCX4RX2C) and a putative DNA binding domain, and exhibits high sequence homology to other alphaherpesviruses. Cloning and sequencing the genome of this putative herpesvirus will facilitate current understanding of its role in causing GTFP and the development of molecular- and immuno-based methods for the diagnosis and prevention of this devastating disease of green turtles.

Alphaherpesvirinae↗
PubMed2003

Measuring stem cell frequency in epidermis: a quantitative in vivo functional assay for long-term repopulating cells.

Epidermal stem cells play a central role in tissue homeostasis, wound repair, tumor initiation, and gene therapy. A major impediment to the purification and molecular characterization of epidermal stem cells is the lack of a quantitative assay for cells capable of long-term repopulation in vivo, such as exists for hematopoietic cells. The tremendous strides made in the characterization and purification of hematopoietic stem cells have been critically dependent on the availability of competitive transplantation assays, because these assays permit the accurate quantitation of long-term repopulating cells in vivo. We have developed an analogous functional assay for epidermal stem cells, and have measured the frequency of functional epidermal stem cells in interfollicular epidermis. These studies indicate that cells capable of long-term reconstitution of a squamous epithelium reside in the interfollicular epidermis. We find that the frequency of these long-term repopulating cells is 1 in 35,000 total epidermal cells, or in the order of 1 in 104 basal epidermal cells, similar to that of hematopoietic stem cells in the bone marrow, and much lower than previously estimated in epidermis. Furthermore, these studies establish a novel functional assay that can be used to validate immunophenotypic markers and enrichment strategies for epidermal stem cells, and to quantify epidermal stem cells in various keratinocyte populations. Thus further studies using this type of assay for epidermis should aid in the progress of cutaneous stem cell-targeted gene therapy, and in more basic studies of epidermal stem cell regulation and differentiation.

Animals↗