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Y Lu

Publications and source records attributed to Y Lu.

At least 19 recordsLinked to original sources
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

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↗
PubMed2003

Roles of the PI-3K and MEK pathways in Ras-mediated chemoresistance in breast cancer cells.

Activated Ras utilises several downstream pathways, including the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway and the phosphoinositide 3-kinase (PI-3k)/Akt pathway, to promote cell proliferation and to inhibit apoptosis. To investigate which pathway plays a major role in Ras-induced drug resistance to chemotherapeutic agents in breast cancer cells, we transfected MCF7 breast cancer cells with a constitutively active H-RasG12V and examined the toxicities of three commonly used breast cancer chemotherapeutic agents, paclitaxel, doxorubicin, and 5-fluorouracil in these cells under the conditions that PI-3K or MEK were selectively inhibited by their respective specific inhibitors or dominant negative expression vectors. We found that Ras-mediated drug resistance is well correlated with resistance to apoptosis induced by anticancer agents in MCF7 breast cancer cells. Although inhibition of MEK/MAPK or PI-3K/Akt can each enhance the cytotoxicity of paclitaxel, doxorubicin, or 5-fluorouracil, inhibition of the PI-3K/Akt pathway seems to have a greater effect than inhibition of the MEK/MAPK pathway in reversing Ras-mediated drug resistance. Our results indicate that the PI-3K pathway may play a more important role in receptor tyrosine kinase-mediated resistance to chemotherapy and suggest that PI-3K/Akt might be a critical target molecule for anticancer intervention in breast cancer.

Antineoplastic Agents↗
PubMed2003

Palangeal quantitative ultrasound, phalangeal morphometric variables, and vertebral fracture discrimination.

The aim of this study was to evaluate the association among phalangeal morphometric parameters, amplitude-dependent speed of sound (AD-SOS), ultrasound bone profile index (UBPI), and spinal bone mineral density (BMD) and fracture status. One hundred women (controls, mean age 53 +/- 12 years) and 40 osteoporotic women (mean age 59 +/- 7 years) with atraumatic fractures, diagnosed by spinal radiographs, were investigated. Quantitative ultrasound (QUS) assessment was performed using the DBM Sonic 1200. Morphological properties of the phalanges were measured from a digitized X-ray image of the hand acquired using industrial film. Spinal BMD was assessed by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). An increase in medullary canal width and a decrease in cortical thickness with aging were observed from the morphometric analysis of the hand radiographs. This phenomenon can be attributed mainly to endosteal resorption. QUS measurements at the phalanges were not significantly related to finger thickness (r <0.20, n.s.). They were significantly correlated to medullary canal ratio (r = -0.57, P <0.0001, for AD-SOS and r = -0.64, P <0.0001, for UBPI) and to cortical thickness (r = +0.52, P <0.0001 for AD-SOS and r = +0.59, P <0.0001 for UBPI). In the discrimination analysis between nonfractured and atraumatic vertebral fracture subjects we found that cortical thickness at the level of the phalanges were similar to lumbar spine BMD. The age and BMI-adjusted odds ratio ranged from 2.0 to 3.1 for QUS, 4.28 for BMD by QCT, 4.1 for BMD by DXA, and 4.1 for cortical thickness. We conclude from these data that phalangeal QUS is related to cortical thickness, which in turn is influenced by endosteal bone resorption occurring in association with spinal osteoporosis.

Adult↗
PubMed2003

Loss of pigment epithelium derived factor expression in glioma progression.

BACKGROUND: Pigment epithelium derived factor (PEDF) was first isolated from medium conditioned by human fetal retinal pigment epithelial cells. PEDF was detected in a broad range of human fetal and adult tissues including almost all brain areas. It can also inhibit the proliferation of cultured rat astrocytes. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. AIMS: To investigate the expression of PEDF in gliomas to assess its "gliastatic" effects and its role in anti-angiogenesis. METHODS: PEDF mRNA values were measured by quantitative real time reverse transcription polymerase chain reaction (RT-PCR) analysis of normal brain tissue and tumour specimens from both low and high grade gliomas. In addition, immunohistochemical staining for PEDF and vascular endothelial growth factor (VEGF) was performed on 32 paraffin wax embedded glioma samples, 10 of them grade IV, 10 grade III, seven grade II, and five grade I. RESULTS: RT-PCR showed that PEDF mRNA values were 5.0 (p < 0.001) and 15.4 (p < 0.001) times higher in normal human brain specimens (n = 5) than in tumour tissue specimens of low grade glioma (grades I and II; n = 15) and high grade glioma (grades III and IV; n = 10), respectively. VEGF was strongly positive in 90% of grade IV, 70% of grade III, 43% of grade II, and 20% of grade I cases. In contrast, PEDF was positive in none of grade IV, 20% of grade III, 43% of grade II, and 60% of grade I tumours. There was an inverse correlation between VEGF and PEDF expression, and a lack of PEDF in advanced grade gliomas. CONCLUSIONS: It is possible that the absence of PEDF expression is a potent factor for the enhancement of angiogenesis in glioma.

Brain↗
PubMed2003

Olfactory deficits and sleep disturbances in Parkinson's disease: a case-control survey.

BACKGROUND: Olfactory and sleep disturbances are common in Parkinson's disease, and may be early disease indicators. OBJECTIVE: To obtain information about olfactory and sleep deficits preceding the onset of motor symptoms in Parkinson's disease. SUBJECTS: 38 community dwelling patients with Parkinson's disease (73% response rate) and 32 age matched controls (60% response rate). METHODS: Using a questionnaire survey, the frequencies, timing, and relations between olfactory and sleep disturbances, drug treatment, mood, and motor deficits in Parkinson's disease were compared with those in age matched controls. Reliability of information was validated by informant interview in 9% of the sample. Interdependency of factors was assessed using Fisher's fourfold table test, and differences between populations were analysed using chi(2) and unpaired t tests. RESULTS: Microsmia was reported by 26 patients (68%) (and only one control), on average within a year of the diagnosis of Parkinson's disease. More patients than controls had excessive daytime somnolence (45% v 6%), restless legs (50% v 19%), and abnormal movements during sleep (34% v 0%), which generally occurred three to five years after diagnosis and were independent of mood disorders and drug treatment. CONCLUSIONS: Many patients with Parkinson's disease have microsmia at the onset of motor deficits, but some sleep disorders are a subsequent occurrence.

Aged↗
PubMed2003

The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

Animals↗
PubMed2003

Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors.

Gene therapy is a promising approach for the treatment of neurological disorders. However, current approaches to gene transfer in the central nervous system (CNS) are limited by the lack of effective, but non-invasive methods to deliver transgenes across the blood-brain barrier (BBB). In an effort to begin to explore the use of migratory monocytes as vehicles for delivery of therapeutic and antiviral genes into the CNS, we have utilized three HIV-based transfer vectors encoding cis-acting elements but lacking either structural genes (gag/pol and env), most accessory genes (vif, vpr and nef) and/or rev. These defective lentiviral vectors (DLV) encode the green fluorescent protein (GFP), display potent antiviral activity in CD4+ lymphocytes and can be mobilized by wild-type HIV-1 DLV were generated by transient transfection of 293T cells. Vector titers ranged from 4.2-6.6 x 10(6) infectious units (IU)/ml prior to concentration (by ultracentrifugation) and were equal to or higher than 1 x 10(9) IU/ml after concentration. Primary human monocyte-derived macrophages (MDM) were exposed to DLV resulting in efficiencies of transduction ranging from 14 to 26%. GFP expression in transduced MDM remained stable for more than 8 weeks without apparent cytopathic effect. Given the previously reported antiviral activities of these DLV and their lack of cytopathic effects on primary MDM, it may be possible to use these vectors to inhibit HIV-1 replication within the CNS.

Cells, Cultured↗
PubMed2002

Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand.

PURPOSE: Cantharidin, a natural toxin, is the active substance of mylabris and has antitumor effects in man. Norcantharidin, the demethylated analogue of cantharidin, has been used in the treatment of patients with primary hepatoma and those with leukopenia in China. The present study was designed to investigate whether norcantharidin exerts cytotoxic activity against colorectal cancer cells by inducing apoptosis and to examine the possible mechanism in the phenomenon. METHODS: Inhibition of proliferation of norcantharidin on Colo205, HT-29, and SW480 colorectal cancer cells was determined by the trypan blue dye exclusion test. Apoptosis of norcantharidin-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis, and quantitated by flow cytometry after staining with propidium iodide. Cell cycle and the cell surface expression of the CD95/CD95 ligand were evaluated by flow cytometry. Caspase 8-like protease and protein phosphatase 1 and 2A activities were also analyzed. RESULTS: Treatment with norcantharidin of colorectal cancer cells not only inhibited cell proliferation, but also induced apoptosis. Norcantharidin induced apoptosis mainly in two phases: rapid apoptosis in S-phase cells and delayed apoptosis in G2/M arrested cells. Treatment with norcantharidin resulted in an upregulation of the CD95 receptor and CD95 ligand on the cell surface. Furthermore, stimulation with anti-CD95 monoclonal antibody (mAb) resulted in further induction of apoptosis after treatment with norcantharidin. In addition, the apoptosis-inducing effect of norcantharidin was almost completely inhibited by anti-CD95 ligand mAb. Norcantharidin-treated cells showed the activation of caspase 8. Both zVAD-FMK (a broad range caspase inhibitor) and IETD-FMK (a caspase-8 inhibitor) showed apparent inhibition of the apoptosis-inducing effect. Norcantharidin did not show an inhibitory effect on protein phosphatase. CONCLUSIONS: These results suggest that norcantharidin triggers apoptosis in colorectal cancer cell lines via the activation of the CD95 receptor/ligand system, and that this agent may be useful for developing new therapeutic regimens for the treatment of colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed2002

Trophoblast functions, angiogenesis and remodeling of the maternal vasculature in the placenta.

One of the most important local adaptations to pregnancy is the change in maternal blood flow to the implantation site. In rodents and primates, new blood vessels form through angiogenesis, dilate and then become modified such that the blood enters into trophoblast cell-lined sinuses (hemochorial). Evidence from gene knockout mice suggests that factors from the placenta regulate the uterine vasculature. Consistent with this, trophoblast giant cells produce a number of angiogenic and vasoactive substances that may mediate these effects. Teratocarcinomas containing large numbers of trophoblast giant cells (derived from Parp1 gene-deficient ES cells) show similar 'hemochorial' host blood flow, implying that the effects are not specific to the uterine vascular bed. As in primates, murine trophoblast cells also invade into the uterine arteries of the mother. However, in normal pregnancy, dilation of the uterine arteries may be largely mediated by the effect of uterine natural killer cells.

Angiogenesis Inducing Agents↗
PubMed2002

Changes in calcaneal trabecular bone structure assessed with high-resolution MR imaging in patients with kidney transplantation.

The purpose of this study was to use high-resolution magnetic resonance (HR-MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after renal transplantation and to compare this technique with bone mineral density (BMD) in predicting therapy-induced bone loss and osteoporotic fracture status. HR-MR imaging (voxel size: 0.195 x 0.195 x 1 mm) was performed at 1.5 T with an axial and sagittal orientation in 48 patients after transplantation, 12 patients before renal transplantation and 20 healthy controls. Structure measures analogous to standard histomorphometry and fractal dimension were determined in these images. BMD measurements of the lumbar spine and the proximal femur were obtained in the healthy female controls and the patients. Vertebral and peripheral fracture status were determined in all patients. The structural measures app.BV/TV, Tb.Sp, Tb.Th and Tb.N showed significant differences between controls and patients (p<0.05) while fractal dimension showed no significant differences. Neither the structural measures nor BMD showed significant differences between patients before and after transplantation. Correlations between time after transplantation versus structural measures and BMD were not significant. Differences between fracture and nonfracture patients were significant for the structural measures app.BV/TV, Tb.Sp and Tb.N (axial images) as well as for app.Tb.Th (sagittal images) and spine BMD (p<0.05) but not for hip BMD. Using odds ratios the strongest discriminators between patients with and without fractures were app. BV/TV, app.Tb.Sp (axial images) and app.Tb.Th (sagittal images), even after adjustment for age and BMD. Using receiver operating characteristic analysis the highest diagnostic performance was found for a combination of BMD and structural measures. In conclusion, our results indicate that structural measures obtained from HR-MR images may be used to characterize fracture incidence in kidney transplant patients; the best results, however, are obtained using a combination of BMD and structural measures.

Adult↗
PubMed2002

New model-independent measures of trabecular bone structure applied to in vivo high-resolution MR images.

Complementing measurements of bone mass with measurements of the architectural status of trabecular bone is expected to improve predictions of fracture risk in osteoporotic patients and improve the assessment of response to drug therapy. With high-resolution MRI the trabecular network can be imaged with 156 x 156 x 500 microm3 voxels, sufficient to depict individual trabeculae, albeit with inaccurate thickness. In this work, distance transformation techniques were applied to the three-dimensional image of the distal radius of postmenopausal patients. Structural indices such as trabecular number (app.Tb.N), thickness (app.Tb.Th) and separation (app.Tb.Sp) were determined without model assumptions. A new metric index, the apparent intra-individual distribution of separations (app.Tb.Sp.SD), is introduced. The reproducibility of the MR procedure and structure assessment was determined on volunteers, and the coefficient of variation was found to be 2.7-4.6% for the mean values of structural indices and 7.7% for app.Tb.Sp.SD. The distance transformation methods were then applied to two groups of patients: one of postmenopausal women without vertebral fracture and one of postmenopausal women with at least one vertebral fracture. It was found that app.Tb.Sp.SD discriminates fracture subjects from non-fracture patients as well as dual-energy X-ray absorptiometry (DXA) measurements of the radius and the spine, but not as well as DXA of the hip. Using receiver operating characteristic analysis, the area under the curve (AUC) values were 0.67 for app.Tb.Sp.SD, 0.72 for DXA radius, 0.67 for DXA spine and 0.81 for DXA of the hip. A combination of MR indices reached an AUC of 0.75. Age-adjusted odds ratio ranged from 1.85 to 2.03 for app.Tb.N, app.Tb.Sp and app.Tb.Sp.SD (p<0.003). We conclude that in vivo high-resolution MRI not only has the potential of imaging trabecular bone, but in combination with novel metrics may offer new insight into the structural changes occurring in postmenopausal women.

Absorptiometry, Photon↗
PubMed2002

Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from the MORE study. Multiple Outcomes of Raloxifene Evaluation.

Raloxifene reduces the risk of new vertebral fractures, but its effect on the severity of these new fractures has not been determined. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial studied the effects of placebo, raloxifene 60 or 120 mg/day in 7,705 postmenopausal women with osteoporosis. Radiologists assessed new vertebral fractures from radiographs and graded the fracture severity as normal (no fracture) or mild, moderate or severe. New clinical vertebral fractures were defined as new vertebral fractures associated with symptoms, such as back pain, and confirmed in radiographs. In the total study population, the majority (76.4%) of the women who experienced clinical vertebral fractures were diagnosed with new moderate/severe vertebral fractures. In turn, women with moderate/severe vertebral fractures in the overall population were more likely to experience clinical symptoms suggestive of fracture than were women who had new mild-only vertebral fractures. The incidence of new mild-only and moderate/severe fractures was the same in women without prevalent vertebral fractures, but the incidence of new moderate/severe fractures was 2 to 3 times higher than that for new mild-only fractures in women with prevalent vertebral fractures. Raloxifene 60 mg/day decreased the risk of at least 1 new moderate/severe vertebral fracture by 61% in women without prevalent vertebral fractures [RR 0.39 (95% CI 0.17, 0.69)], and by 37% in women with prevalent vertebral fractures [RR 0.63 (95% CI 0.49, 0.83)] at 3 years. The risk reductions for at least 1 new moderate/severe vertebral fracture were not significantly different between the raloxifene doses, in women with and without prevalent vertebral fractures. The effects of raloxifene on significantly decreasing the risk of new moderate/severe vertebral fractures may explain the risk reduction for new painful clinical vertebral fractures observed with raloxifene, and is particularly important in postmenopausal women with severe osteoporosis who are at higher risk for moderate or severe fractures.

Aged↗
PubMed2002

3-D echo planar (1)HMRS imaging in MS: metabolite comparison from supratentorial vs. central brain.

UNLABELLED: To determine if metabolite ratios as measured by 3-dimensional echo planar spectroscopy imaging (3D-EPSI) from central brain regions of interest (ROI) centered at the corpus callosum reflect imaging metrics of large volumes of supratentorial brain (STB) from patients with multiple sclerosis. METHODS: 48 MS patients with relapsing-remitting, secondary progressive, and primary progressive disease underwent a 3D-EPSI sequence covering large volumes of STB. Metabolite ratios were first estimated from all voxels within a STB mask using a linear regression of N-acetylaspartate (NAA) over Creatine (Cr), NAA over choline (Cho) and Cho over Cr. Secondly, spectroscopic voxels from a central brain (CB) ROI centered at the corpus callosum were selected within the STB. Ratios were compared using Bland-Altman regression analysis and Spearman's correlation coefficients between STB versus central brain. Ratios from studied ROIs were correlated with the EDSS and compared to normal controls. RESULTS: Very strong correlations ranging from 0.884 and 0.938 (p < 0.0001) were found for all metabolite ratios between STB versus central brain. NAA/Cr ratios were similarly and negatively correlated with the EDSS across all ROIs, trends ranging from -0.257 to -0.314 (p < 0.1). NAA/Cr from all MS patients was similarly decreased compared to controls across all ROIs (p < 0.01). CONCLUSION: Metabolite ratios from a central brain ROI were statistically equivalent and highly correlated with ratios from the STB. The study of NAA/Cr using (1)HMRS from a central brain ROI centered at the corpus callosum seems to be representative of brainwide axonal changes in patients with MS.

Adult↗
PubMed2002

Neuromuscular disorders associated with static lumbar flexion: a feline model.

Static flexion of the lumbar spine with constant load applied to the viscoelastic structures for 20 minutes and for 50 minutes resulted in development of spasms and inhibition in the multifidus muscles (e.g., deep erector spinae) and in creep of the supraspinous ligament in the feline model. The development of spasms and inhibition was not dependent on load magnitude. It is suggested that occupational and sports activities which require prolonged static lumbar flexion within the physiological range can cause a "sprain"-like injury to the ligaments, which in turn reflexively induce spasms and inhibition in some erector spinae muscles. Such disorder may take a long time to recover, in the order of days to weeks, depending on the level of creep developed in the tissues.

Animals↗