Biomedical subjects

Yan Lu

Publications and source records attributed to Yan Lu.

At least 109 records · Page 6Linked to original sources

PubMed2004

Test of linkage and/or association between the estrogen receptor alpha gene with bone mineral density in Caucasian nuclear families.

Extensive studies have been performed on the association between the estrogen receptor alpha (ER-alpha) gene and bone mineral density (BMD). Despite considerable efforts, the studies using limited markers and relatively small sample size have yielded largely inconsistent results. In this study, 1873 Caucasian subjects from 405 nuclear families containing 1512 sib pairs were recruited. BMD at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). Seven single-nucleotide polymorphisms (SNPs) spanning from exon 1 to 8 in the ER-alpha gene were genotyped. The program QTDT (quantitative transmission disequilibrium test) was applied to test linkage and/or association of the ER-alpha gene and BMD variation using individual SNP markers and reconstructed haplotypes. Linkage disequilibrium (LD) was generally detected for SNPs in the ER-a gene (P < 0.05). Associations were observed between SNP rs932477 and FN BMD (P = 0.028), and between the most predominant three-marker haplotype (GCG) containing SNP rs932477 and FN BMD (P = 0.010). Within-family association (present only with both linkage and association) between SNP rs2228480 (G2014A) and FN BMD (P = 0.015) was observed. The most predominant seven-SNP haplotype (TCGCGGG) was associated with higher LS BMD (P = 0.015). However, after correction for multiple testing, these associations did not reach statistical significance. Denser markers may be necessary to better define the relationship between the ER-alpha gene and BMD variation in our sample.

Absorptiometry, Photon↗

PubMed2004

1,25-Dihydroxyvitamin D downregulation of TGFalpha/EGFR expression and growth signaling: a mechanism for the antiproliferative actions of the sterol in parathyroid hyperplasia of renal failure.

Elevated serum levels of parathyroid hormone (PTH) contribute to the increased morbidity and mortality in renal failure patients. Parathyroid gland hyperplasia is a major cause of high serum PTH. The present studies used the rat model of renal failure to address the mechanisms underlying uremia-induced parathyroid hyperplasia and the antiproliferative properties of vitamin D therapy (1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) or its less calcemic analogs). Enhanced TGFalpha/EGFR co-expression is the major mitogenic signal in uremic parathyroid glands. At early stages of renal failure, vitamin D therapy efficiently counteracts uremia- and high phosphorus-induced hyperplasia by inhibiting the increases in parathyroid-TGFalpha/EGFR co-expression. In established hyperparathyroidism, characterized by highly enhanced-TGFalpha/EGFR co-expression, vitamin D therapy arrests growth by suppressing EGFR-growth signals from the plasma membrane and nuclear EGFR actions as a transactivator of the cyclin D1 gene, an important contributor to parathyroid hyperplasia in humans. In advanced renal failure, reduced-parathyroid vitamin D receptor levels limits the antiproliferative efficacy of vitamin D therapy. However, non-antiproliferative doses of 1,25-dihydroxyvitamin D enhance the anti-EGFR actions of EGFR-tyrosine kinase inhibitors (TKI). In fact, combined 1,25-dihydroxyvitamin D/TKI therapy inhibits parathyroid hyperplasia more efficiently than phosphorus restriction, the most powerful promoter of parathyroid growth arrest available at present.

Cell Division↗

PubMed2004

Estrogen induced changes in Akt-dependent activation of endothelial nitric oxide synthase and vasodilation.

OBJECTIVES: Acute administration of estrogen results in vasodilation and increased nitric oxide (NO) production. We examined the hypothesis that this is due to activation of Akt/PKB which subsequently increases eNOS activity. METHODS AND RESULTS: Treatment of bovine microvascular and human umbilical endothelial cells (HUVEC) with 17-beta-estradiol (E2) (10(-9) to 10(-5)M) increased phosphorylation of Akt within 1 min and this was followed by phosphorylation of eNOS. These effects were blocked by wortmannin, a PI(3)K inhibitor and the upstream activator of Akt. The estrogen receptor antagonist, ICI 182,780, inhibited eNOS phosphorylation. E2 increased calcium dependent NOS activity and nitrite production and this was inhibited by wortmannin and ICI 182,780. E2 increased the vasodilatory response of aortic rings to acetylcholine and wortmannin blocked the effect. E2 (10(-9)M) dilated cerebral microvascular vessels under conditions of no flow, constant flow and increasing flow and this was blocked by wortmannin. Tamoxifen, a partial estrogen receptor antagonist, also dilated the microvessels. CONCLUSIONS: : E2 increases NO production through an Akt/PKB dependent pathway. This is associated with increased sensitivity to endothelial dependent dilation. In cerebral microvessels, E2 and tamoxifen produce significant dilation at low concentrations with and without acetylcholine induced stimulation of endothelial vasodilation.

Acetylcholine↗

PubMed2004

Association between COL1A1 gene polymorphisms and bone size in Caucasians.

Bone size is an important determinant of bone strength and a risk factor of osteoporotic fracture. Several studies indicate that bone size has a high heritability. Thus, a better understanding of genetic factors regulating bone size might have important clinical implications. In the present study, we examined the relationship between the collagen type I alpha 1 (COL1A1) gene and bone size at the spine, hip and wrist in a sample of 1873 subjects of Caucasian origin from 405 nuclear families. Three single-nucleotide polymorphisms (SNPs) in the COL1A1 gene were analyzed. The minor allele frequencies were 15.4, 18.8, and 1.9% for SNP1, SNP2, and SNP3, respectively. Haplotypes were reconstructed based on the family information as well as marker genotypes using the program Genehunter. We did not find evidence of population stratification, within-family association, or linkage for either single SNPs or haplotypes at any skeletal site. Suggestive evidence of total association was observed for the wrist size at SNP2 (P=0.011). After adjusting age, sex, height, and weight, subjects with the T allele of SNP2 had, on average, 3.05% smaller wrist size than noncarriers. When the subjects were divided into families with only female offspring and families with male offspring only, similar total associations were found at the wrist size for SNP2 with P-values of 0.011 and 0.010, respectively. In conclusion, the COL1A1 gene may have some effects on bone size variation at the wrist, but not at the spine or hip in our Caucasian nuclear families.

Adult↗

PubMed2004

Central role for aldose reductase pathway in myocardial ischemic injury.

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on myocardial ischemia-reperfusion injury, we used transgenic mice broadly overexpressing human aldose reductase (ARTg) driven by the major histocompatibility complex I promoter. Hearts from these ARTg or littermate mice (WT) (n=6 in each group) were isolated, perfused under normoxic conditions, then subjected to 50 min of severe low flow ischemia followed by 60 min of reperfusion. Creatine kinase (CK) release (a marker of ischemic injury) was measured during reperfusion; left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and ATP were measured throughout the protocol. CK release was significantly greater in ARTg mice compared with the WT mice. LVDP recovery was significantly reduced in ARTg mice compared with the WT mice. Furthermore, ATP content was higher in WT mice compared with ARTg mice during ischemia and reperfusion. Infarct size measured by staining techniques and myocardial damage evaluated histologically were also significantly worse in ARTg mice hearts than in controls. Pharmacological inhibition of aldose reductase significantly reduced ischemic injury and improved functional recovery in ARTg mice. These data strongly support key roles for AR in ischemic injury and impairment of functional and metabolic recovery after ischemia. We propose that interventions targeting AR may provide a novel adjunctive approach to protect ischemic myocardium.

Adenosine Triphosphate↗

PubMed2004

RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

Animals↗

PubMed2004

Development of a circuit for functional electrical stimulation.

This paper examines the various design of a multiple-purpose portable functional electrical stimulator which is used in surface stimulation of paralyzed muscle of patients with stroke and results in limb activation. The functionality, circuit performance and reliability of the circuits will be examined. Analysis, design, and experimental results are presented.

Computer Simulation↗

PubMed2004

Comparison of surgical techniques for synovectomy in New Zealand White rabbits with induced inflammatory arthritis.

OBJECTIVE: To compare effects of synovectomy performed by use of monopolar radiofrequency energy (MRFE) versus mechanical debridement in rabbits with induced inflammatory arthritis. ANIMALS: 25 mature female New Zealand White rabbits. PROCEDURE: Inflammatory arthritis was induced in both femoropatellar joints of each rabbit. Joints then were treated by mechanical debridement or MRFE treatment or served as sham-operated controls. Rabbits were euthanatized 2 weeks or 3 months after surgery. Biopsy specimens of synovium were analyzed by use of light microscopy. RESULTS: At 2 weeks after surgery, samples from MRFE-treated joints had fewer plasma cells and more heterophils than the other 2 groups and more lymphocytes than sham-operated controls, whereas samples from mechanically debrided joints had greater numbers of lymphocytes and heterophils than sham-operated controls. At 3 months after surgery, samples from MRFE-treated joints had fewer plasma cells than sham-operated controls, more heterophils than mechanically debrided and sham-operated controls, and more macrophages than mechanically debrided joints. There was no difference in synovial ablation, synovial proliferation, or fibrosis among the 3 groups at 2 weeks or 3 months after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study documented a similar degree of synovial ablation when comparing use of MRFE to mechanical debridement. In rabbits with this method of induced inflammatory arthritis, there were no detectable benefits of MRFE or mechanical debridement on the synovium, compared with results for sham-operated control joints, at 2 weeks and 3 months after surgery for most of the synovial variables evaluated.

Animals↗

PubMed2004

[Apoptosis of peripheral blood cells of children with viral pneumonia].

BACKGROUND: To study apoptosis of peripheral blood cells of children with viral pneumonia, explore immunopathogenesis and the possibility of immunotherapy of patients with viral pneumonia. METHODS: Fresh peripheral blood samples were collected from 28 patients with viral pneumonia and 24 healthy children were treated and run through the flow cytometry. The data were acquired using Cell Quest software and the percentage of live cells, viable apoptotic cells, non-viable apoptotic cells and dead cells of neutrophils and lymphocytes were counted. The patients with viral pneumonia were hospitalized at our hospital. The average age of patients was 1.3 years; 24 healthy children were served as control group (age 1.8 years, on average). T-test and variance analysis by SPSS FOR WINDOWS 10.0 software was used for statistical analysis. RESULTS: The percentage of live neutrophils and lymphocytes in the acute stage and recovery stage in patients were significantly lower than that in control group (P < 0.01). The percentage of viable apoptotic neutrophils and lymphocytes in two stages in patients were significantly higher than that in control group (P < 0.05). Except for the percentage of live cells, non-viable apoptotic cells and dead lymphocytes, others had no difference between the patients and control groups. CONCLUSION: Apoptosis of neutrophils and lymphocytes of peripheral blood cells of children with viral pneumonia increased. Whereas the percentage of live cells decreased. Drugs that can accelerate apoptosis may be helpful in treatment of viral pneumonia.

Apoptosis↗

PubMed2004

[Study on the synthesis of a new reagent 3-(4'-fluorophenyl)-5-(2'-arsenoxylphenylazo)-rhodanine and the fluoresence determination of bismuth(III)].

A new fluorescence reagent, 3-(4'-fluorophenyl)-5-(2'-arsenoxylphenylazo)-rhodanine, was synthesized. The structure of the reagent was clarified by elemental analysis and IR. At pH 5.4, the reagent can react with trace bismuth (III) to form a chelate which reduces the fluorescence intensity greatly. And when lambdaex/lambdaem = 305/407 nm, the fluorescence is intensive. There is a linear relationship between the decrease of fluorescence intensity and the concentration of bismuth (III) in the range of 0-0.025 microg x mL(-1). The detection limit is 1.2 x 10(-10) g x mL(-1). A new method of fluorescence spectrophotometric determination of bismuth (III) was developed.

English Abstract↗

PubMed2003

Early growth response-1 promotes atherogenesis: mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation.

Early growth response-1 (Egr-1) regulates expression of proinflammatory and procoagulant genes in acute cell stress. Experimental evidence suggested that Egr-1 transcripts were upregulated in human atherosclerotic plaques versus adjacent unaffected tissue. To test the impact of Egr-1 in chronic vascular stress, we examined its role in a murine model of atherosclerosis. Real-time PCR analysis of aortae retrieved from apoE-/- mice demonstrated increased Egr-1 transcripts in an age-dependent manner, compared with aortae retrieved from C57BL/6 control animals. Therefore, homozygous Egr-1-/- mice were bred into the apoE-/- background. Homozygous double-knockout mice (Egr-1-/-/apoE-/-) in the C57BL/6 background were maintained on normal chow diet. At age 14 and 24 weeks, atherosclerotic lesion area and complexity at the aortic root were strikingly decreased in mice deficient in both Egr-1 and apoE compared with mice deficient in apoE alone. In parallel, transcripts for genes regulating the inflammatory/prothrombotic response were diminished in Egr-1-/-/apoE-/- aortae versus apoE-/-. In vitro, oxidized low-density lipoprotein (OxLDL), a key factor inciting atherogenic mechanisms in the vasculature, upregulated Egr-1 expression in monocytes via the MEK-ERK1/2 pathway. We conclude that Egr-1 broadly regulates expression of molecules critically linked to atherogenesis and lesion progression.

Animals↗

PubMed2003

Metal ion interactions with sugars. The crystal structure and FT-IR study of the NdCl3-ribose complex.

The single-crystal structure of neodymium chloride-ribopyranose pentahydrate, NdCl3.C5H10O5.5H2O was determined to have Mr=490.80, a=9.138(11), b=8.830(10), c=9.811(11) A, beta=94.087(18) degrees, V=789.7(16) A3, P2(1), Z=2, mu=0.71073 A and R=0.0198 for 2075 observed reflections. The ligand of the title complex was observed in a disordered state and two molecular configurations of NdCl3.C5H10O5.5H2O were found in the single crystal as a pair of isomers. Both ligand moieties of the two molecules are ribopyranose forms, providing three hydroxyl groups in ax-eq-ax orientation for coordination. One ligand of the pair of isomers is beta-D-ribopyranose in the 1C4 conformation, and the other is alpha-D-ribopyranose in the 4C1 conformation. The Nd3+ ion is nine-coordinated with five Nd-O bonds from water molecules, three Nd-O bonds from hydroxyl groups of the ribopyranose and one Nd-Cl bond from chloride ion. The hydroxyl groups, water molecules, chloride ions form an extensive hydrogen-bond network. The IR spectral C-C,O-H,C-O and C-O-H vibrations were observed to be shifted in the complex and the IR results are in accordance with those of X-ray spectroscopy.

Carbohydrate Conformation↗

PubMed2003

Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders.

The glycation and oxidation of proteins/lipids leads to the generation of a new class of biologically active moieties, the advanced glycation endproducts (AGEs). Recent studies have elucidated that carboxymethyllysine (CML) adducts of proteins/lipids are a highly prevalent AGE in vivo. CML-modified adducts are signal transduction ligands of the receptor for AGE (RAGE), a member of the immunoglobulin superfamily. Importantly, CML-modified adducts accumulate in diverse settings. In addition to enhanced formation in settings of high glucose, these adducts form in inflammatory milieu. Studies performed both in vitro and in vivo have suggested that the proinflammatory/tissue destructive consequences of RAGE activation in the diabetic/inflamed environment may be markedly attenuated by blockade of the ligand-RAGE axis. Here, we will summarize the known consequences of RAGE activation in the tissues and highlight novel areas for therapeutic intervention in these disease states.

Animals↗

PubMed2003

The role of amylomaltase in maltose metabolism in the cytosol of photosynthetic cells.

Transitory starch is stored during the day inside chloroplasts and then broken down at night for export. Recent data indicate that maltose is the major form of carbon exported from the chloroplast at night but its fate in the cytosol is unknown. An amylomaltase gene ( malQ) cloned from Escherichia coli is necessary for maltose metabolism in E. coli. We investigated whether there is an amylomaltase in the cytosol of plant leaves and the role of this enzyme in plants. Two mutants of Arabidopsis thaliana (L) Heynh. were identified in which the gene encoding a putative amylomaltase enzyme [ disproportionating enzyme 2, DPE2 (DPE1 refers to the plastid version of this enzyme)] was disrupted by a T-DNA insertion. Both dpe2-1 and dpe2-2 plants exhibited a dwarf phenotype and accumulated a large amount of maltose. In addition, dpe2 mutants accumulated starch and a water-soluble, ethanol/KCl-insoluble maltodextrin in their chloroplasts. At night, the amount of sucrose in dpe2 plants was lower than that in wild-type plants. These results show that Arabidopsis has an amylomaltase that is involved in the conversion of maltose to sucrose in the cytosol. We hypothesize that knocking out amylomaltase blocks the conversion from maltose to sucrose, and that the higher amount of maltose feeds back to limit starch degradation reactions in chloroplasts. As a result, dpe2 plants have higher maltose, higher starch, and higher maltodextrin but lower nighttime sucrose than wild-type plants. Finally, we propose that maltose metabolism in the cytosol of Arabidopsis leaves is similar to that in the cytoplasm of E. coli.

Arabidopsis↗

PubMed2003

A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input.

The spinal substantia gelatinosa (SG) is a major termination region for unmyelinated (C) primary afferent fibers; however, how the input it receives from these sensory fibers is processed by SG neurons remains primarily a matter of conjecture. To gain insight on connections and functional interactions between intrinsic SG neurons, simultaneous tight-seal, whole-cell recordings were made from pairs of neurons in rat spinal cord slices to examine whether impulses in one cell generated synaptic activity in the other. Most SG neuron pairs sampled lacked synaptic interaction. Those showing a linkage included a recurring pattern consisting of a monosynaptic, bicuculline-sensitive inhibitory connection from an islet cell to a transient central neuron, each of which received direct excitatory input from different afferent C-fibers. This newly defined inhibitory circuit is postulated to represent a SG neural module by which a nociceptive C-fiber input to transient central cells is modified by other C-fiber messages.

Action Potentials↗

PubMed2003

Sugar complexation with calcium ion. Crystal structure and FT-IR study of a hydrated calcium chloride complex of D-ribose.

The single crystal structure of CaCl(2).C(5)H(10)O(5).3H(2)O was determined with M(r)=315.16, a=7.537(3), b=11.426(5), c=15.309(6) A, beta=90 degrees, V=1318.3(9) A(3), P2(1)2(1)2(1), Z=2, mu=0.71073 A and R=0.0398 for 2322 observed reflections. The ribose moiety of the complex exists as a furanose with alpha-D configuration. All five oxygen atoms of the ribose molecule are involved in calcium binding. Each calcium ion is shared by two such sugar molecules, coordinating through O(1), O(2), O(3) of one molecule and O(4) and O(5) of the other. The C-C, O-H, C-O and C-O-H vibrations are shifted and the relative intensities changed in the complex IR spectrum, corresponding to the changes in bond distances and angles of the sugar structure. All the hydroxyl groups, water molecules and chloride ions are involved in forming an extensive hydrogen-bond network of O-H...Cl...O-H structure, and the chloride ions play an important role in the crystal packing.

Calcium Chloride↗

PubMed2003

Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice.

OBJECTIVE: Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on atherogenesis in hypercholesterolemic apolipoprotein E-null mice. METHODS AND RESULTS: In the absence of alterations in distinct risk factors, P gingivalis infection exacerbated the early stages of atherogenesis in this model. Infected animals displayed evidence of local periodontal infection, as the severity of alveolar bone loss, the hallmark of periodontitis, was increased. Generalized activation of host inflammatory responses was evident in infected mice, as demonstrated by serum IgG response to P gingivalis and elevated levels of interleukin-6. P gingivalis DNA was localized in the aortic tissue from a limited number of infected mice but not in any noninfected controls. Infected mice displayed enhanced vascular activation, as suggested by increased aortic expression of vascular cell adhesion molecule-1 and tissue factor. CONCLUSIONS: Oral infection with P gingivalis accelerates early atherosclerosis. Thus, uncovering the underlying mechanisms is critical for the design of preventive and therapeutic strategies targeting atherosclerotic vascular disease and its sequelae.

Alveolar Bone Loss↗

PubMed2003

Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury.

BACKGROUND: Receptor for advanced-glycation end products (RAGE) and its ligands AGEs and S100/calgranulins have been implicated in a range of disorders. However, the role of RAGE/ligand interaction in neointimal hyperplasia after vascular injury remains unclear. METHODS AND RESULTS: We examined the expression of RAGE and its ligands after balloon injury of the carotid artery in both Zucker diabetic and nondiabetic rats. Using a soluble portion of the extracellular domain of RAGE, we determined the effects of suppressing RAGE/ligand interaction on vascular smooth muscle cell (VSMC) proliferation and neointimal formation after arterial injury. We demonstrate a significantly increased accumulation of AGE and immunoreactivities of RAGE and S100/calgranulins in response to balloon injury in diabetic compared with nondiabetic rats. Blockade of RAGE/ligand interaction significantly decreased S100-stimulated VSMC proliferation in vitro and bromodeoxyuridine (BrdU)-labeled proliferating VSMC in vivo, and suppressed neointimal formation and increased luminal area in both Zucker diabetic and nondiabetic rats. CONCLUSIONS: These findings indicate that RAGE/ligand interaction plays a key role in neointimal formation after vascular injury irrespective of diabetes status and suggest a novel target to minimize neointimal hyperplasia.

Angioplasty, Balloon↗