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Biomedical subjects

D Xie

Publications and source records attributed to D Xie.

At least 37 records · Page 2Linked to original sources
PubMed2001

Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in myelodysplastic syndromes.

To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by identifying target tumor suppressor genes, we performed a detailed deletional mapping of the short arm of chromosome 1 in 38 paired samples of bone marrow and peripheral blood obtained from individuals with MDS by PCR amplification of a total of 23 highly informative microsatellite sequences. We identified the commonly deleted region between D1S508 and D1S244. LOH of this region was found in five patients (13%). In addition, LOH at 1p was associated with a poor clinical outcome, suggesting that the deletion of a gene in this region may be involved in the course of this disease. By analyzing the chromosomal map of this region, we found TNFRSF12 as a candidate tumor suppressor gene. However, our search for mutations in this gene did not identify somatic mutations in MDS. Our findings are consistent with the possible existence of an as-yet unknown tumor suppressor gene in this region that is altered in MDS.

Adult↗
PubMed2001

Adenoviral-mediated transfer of tissue plasminogen activator gene into brain capillary endothelial cells in vitro.

Tissue plasminogen activator (tPA) has a critical role in fibrinolysis, converting plasminogen into active protease plasmin. Because intravenous tPA has only limited effectiveness as acute stroke therapy, enhancement of endogenous tPA represents a potential alternative to stroke treatment. Adenoviral-mediated gene transfer was used to enhance production of tPA in bovine brain capillary endothelial cells (BEC). Antigen and activity levels of tPA and plasminogen activator inhibitor-1 (PAI-1) in media from BEC infected with AdCMVtPA were analyzed. Conditioned media were analyzed for thrombomodulin, the integral membrane antithrombotic molecule that co-activates protein C. BEC infected with AdCMVtPA demonstrated enhanced expression of tPA antigen (40.2 +/- 0.4 ng/mL vs 1.1 +/- 1.5 ng/mL [p<0.001] and 0.3 +/- 0.5 ng/mL [p<0.0001], respectively) and increased tPA enzymatic activity (27.4 +/- 5.7 IU/mL vs 8.3 +/- 1.7 IU/mL [p<0.05] and 13.3 +/- 3.2 IU/mL [p<0.05], respectively) compared to BEC infected with the control adenovirus (Adl327) or uninfected BEC. There was a moderate increase in PAI-1 protein 4 days after transfection with AdCMVtPA, and the integral membrane protein thrombomodulin was released into media by transfected BEC. These results demonstrate that adenoviral-mediated delivery in vitro of the human tPA gene resulted in high levels of expression of tPA in BEC. Transient overexpression of tPA by gene transfer might be a useful strategy to protect against thrombotic occlusion during the period of risk of acute stroke.

Adenoviridae↗
PubMed2001

Multipulse feed strategy for glycerol fed-batch fermentation: a steady-state nonlinear optimization approach.

During glycerol fed-batch fermentation, the process could be divided into multiple equal subintervals, and the feed operation was performed in pulse form at the start of each subinterval. Based on the macrokinetic models, the multipulse feed strategy for both glucose and corn steep slurry was determined by a general nonlinear optimization approach to maximize the final glycerol productivity and still control the residual glucose at a low concentration. The experimental results in a 600-mL Airlift Loop Reactor showed that the tested data with this strategy agreed well with the corresponding model prediction, and that the feed mode with nonlinear optimization could improve the glycerol productivity significantly compared with those determined just by limited experimental optimization in previous studies.

Bioreactors↗
PubMed2001

Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk.

Sulfotransferase (SULT) 1A1 is involved in the inactivation of estrogens and bioactivation of heterocyclic amines and polycyclic aromatic hydrocarbons. A G--->A transition at codon 213 (CGC/Arg to CAC/His) of the SULT1A1 gene was reported recently, and individuals homozygous for the His allele have a substantially lower activity of this enzyme than those with other genotypes. We hypothesized that the His allele may be a risk factor for breast cancer, particularly among women who had risk factors related to higher endogenous estrogen exposure. This hypothesis was investigated in a case-control study conducted in a cohort of postmenopausal Iowa women who completed a mailed questionnaire in 1986 on lifestyle factors including information on major breast cancer risk factors. DNA samples and information related to well-done meat intake were obtained from breast cancer cases diagnosed between 1992 and 1994 and a random sample of cancer-free cohort members. Multivariate analysis was performed on data from 156 cases and 332 controls who donated a blood sample. The frequency of the His allele was 41.6% in cases and 34.1% in controls (P = 0.03), and the risk of breast cancer was increased with the number of His alleles (P for trend = 0.02). Compared with women with the Arg/Arg genotype, an 80% elevated risk was observed among women homozygous for the His allele (95% confidence interval, 1.0-3.2; P = 0.04). This positive association was more pronounced among women who drank alcohol and had a high body mass index, early age at menarche, and late age at menopause, factors related to high endogenous estrogen exposure, than among those who did not have these risk factors. The risk of breast cancer was elevated with increasing doneness level of red meat intake among women with the Arg/Arg genotype (P for trend, 0.01) or the Arg/His genotype (P for trend, 0.10), whereas this association was not evident for women with the His/His genotype. The results from this study suggest that homozygosity for the SULT1A1 His213 allele may be a risk factor for breast cancer, and its effect may be modified by the exposure level of endogenous estrogens and heterocyclic amines.

Age Distribution↗
PubMed2001

[The numerical simulation of the dynamic stress field from impacting head].

In order to study the mechanism of impact injury to the head, we have simulated the development of the stress field by using the numerical simulation method. The process of the head having been impacted vertically by an impactor can be described as a 2D problem, and the reactions of the head subjected to impacted force can be simulated and analyzed by the method based on the finite difference method (FDM). The model is subjected to applied force by an impactor with the initial velocity of 25 m/s (90 km/h). The pre-processing for the model is done on the microcomputer software. Once imported to the software, the nodes and elements are generated and material characteristics are assigned. The results demonstrate that the high resolution computer graphics can provide the dynamic distribution of the stress field, which can clearly show how the stress is developed, and how many its value is. The results are helpful to understanding the mechanism of impact injury to head.

Craniocerebral Trauma↗
PubMed2001

Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: characterization of in vivo efficacy, pharmacokinetics, and safety.

Apo2L/TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a member of the tumor necrosis factor gene family known to induce apoptosis in a number of cancer cell lines and may have broad-spectrum activity against human malignancies. These studies have evaluated the potency of recombinant soluble human Apo2L/TRAIL in a mouse xenograft model and the disposition and safety of Apo2L/TRAIL in rodents and nonhuman primates. Mice with established COLO205 tumors were given daily i.v. injections of Apo2L/TRAIL (30-120 mg/kg/day). Control tumors doubled in size every 2 to 3 days, while time to tumor doubling in the treatment groups was significantly longer and related to dose (14-21 days). For pharmacokinetic studies, Apo2L/TRAIL was given as an i.v. bolus to mice (10 mg/kg), rats (10 mg/kg), cynomolgus monkeys (1, 5, and 50 mg/kg), and chimpanzees (1 and 5 mg/kg). Apo2L/TRAIL was rapidly eliminated from the serum of all species studied. Half-lives were approximately 3 to 5 min in rodents and approximately 23 to 31 min in nonhuman primates. Allometric scaling provided estimates of Apo2L/TRAIL kinetics in humans, suggesting that on a milligram per kilogram basis, doses significantly lower than those used in xenograft studies could be effective in humans. Apo2L/TRAIL clearance was highly correlated with glomerular filtration rate across species, indicating that the kidneys play a critical role in the elimination of this molecule. Safety evaluations in cynomolgus monkeys and chimpanzees revealed no abnormalities associated with Apo2L/TRAIL exposure. In conclusion, these studies have characterized the disposition of Apo2L/TRAIL in rodents and primates and provide information that will be used to predict the pharmacokinetics of Apo2L/TRAIL in humans.

Algorithms↗
PubMed2001

[Expression of ADAM12 (Meltrin-alpha) gene in giant cell tumor of bone].

OBJECTIVE: To detect expression and location of ADAM12 (meltrin-alpha) gene in giant cell tumor of bone and to study its effect on the formation of multinucleated giant cells in the tumor. METHODS: ADAM12 mRNA was detected by RT-PCR and RNA in situ hybridization in 18 cases of giant cell tumors, 6 cases of cultured tumor cells, 2 specimens of embryonic muscle tissue and 5 specimens of adult muscle tissue. RESULTS: RT-PCR showed that 12/18 (67%) cases of giant cell tumor of bone expressed ADAM12 mRNA. RNA in situ hybridization demonstrated positive ADAM12 mRNA in 12 cases of the detected tumors. The ADAM 12 mRNA positive signal was localized in the cytoplasm of almost all multinucleated giant cells and mononuclear stromal cells. However, the expression of ADAM12 mRNA decreased gradually, and eventually lost with increased passages of tumor cells and the disappearance of multinucleated giant cells in the culture. CONCLUSION: Multinucleated giant cells probably originated from the fusion of mononuclear stromal cells and ADAM12 may participate in the fusion process.

ADAM Proteins↗
PubMed2000

High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R.

Immunoglobulin G (IgG) Fc receptors play a critical role in linking IgG antibody-mediated immune responses with cellular effector functions. A high resolution map of the binding site on human IgG1 for human Fc gamma RI, Fc gamma RIIA, Fc gamma RIIB, Fc gamma RIIIA, and FcRn receptors has been determined. A common set of IgG1 residues is involved in binding to all Fc gamma R; Fc gamma RII and Fc gamma RIII also utilize residues outside this common set. In addition to residues which, when altered, abrogated binding to one or more of the receptors, several residues were found that improved binding only to specific receptors or simultaneously improved binding to one type of receptor and reduced binding to another type. Select IgG1 variants with improved binding to Fc gamma RIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fc gamma RIIIA co-crystal structure (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). These engineered antibodies may have important implications for improving antibody therapeutic efficacy.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2000

Activation of insulin signal transduction pathway and anti-diabetic activity of small molecule insulin receptor activators.

We recently described the identification of a non-peptidyl fungal metabolite (l-783,281, compound 1), which induced activation of human insulin receptor (IR) tyrosine kinase and mediated insulin-like effects in cells, as well as decreased blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M. T. , Pelaez, F., Ruby, C., Kendall, R. L., Mao, X., Griffin, P., Calaycay, J., Zierath, J. R., Heck, J. V., Smith, R. G. & Moller, D. E. (1999) Science 284, 974-977). Here we report the characterization of an active analog (compound 2) with enhanced IR kinase activation potency and selectivity over related receptors (insulin-like growth factor I receptor, epidermal growth factor receptor, and platelet-derived growth factor receptor). The IR activators stimulated tyrosine kinase activity of partially purified native IR and recombinant IR tyrosine kinase domain. Administration of the IR activators to mice was associated with increased IR tyrosine kinase activity in liver. In vivo oral treatment with compound 2 resulted in significant glucose lowering in several rodent models of diabetes. In db/db mice, oral administration of compound 2 elicited significant correction of hyperglycemia. In a streptozotocin-induced diabetic mouse model, compound 2 potentiated the glucose-lowering effect of insulin. In normal rats, compound 2 improved oral glucose tolerance with significant reduction in insulin release following glucose challenge. A structurally related inactive analog (compound 3) was not effective on insulin receptor activation or glucose lowering in db/db mice. Thus, small molecule IR activators exert insulin mimetic and sensitizing effects in cells and in animal models of diabetes. These results have implications for the future development of new therapies for diabetes mellitus.

Animals↗
PubMed2000

Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk.

BACKGROUND: Alterations of the HER2 (also known as erbB-2 or neu) proto-oncogene have been implicated in the carcinogenesis and prognosis of breast cancer. A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer. We evaluated this hypothesis in a subgroup of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China. METHODS: Genomic DNA from 339 patients with breast cancer and 361 healthy control subjects was examined for the Val(655)Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All study subjects completed a structured questionnaire during an in-person interview. All P values are from two-sided tests. RESULTS: We found that 25.1% of the case patients and 21.7% of the control subjects were heterozygous for the Val allele and 3.2% of the case patients and 0. 3% of the control subjects were homozygous for this allele (P =.005). Compared with women with the Ile/Ile genotype, women who had the Ile/Val or Val/Val genotype had an elevated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.0-2.0; P =. 05) after adjustment for age, educational level, study period, history of breast fibroadenoma, leisure physical activity, and age at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% CI = 1.8-113.4). The association was more pronounced among younger women (</=45 years) than among older women (>45 years). The adjusted OR associated with the Val allele was 1.7 (95% CI = 1.1-2.6) for younger women and 1.0 (95% CI = 0.5-1.9) for older women. CONCLUSIONS: Results of this study suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.

Adult↗
PubMed2000

Density functional theory study on fundamental vibrational spectra of disilyl iodide and its isotopomer.

Density function theory calculations using B3' exchange functional and LYP' correlation functionals (B3LYP) with the 3-21G** basis set were carried out to study the molecular structure and fundamental vibrational frequencies of Si2H5Br, Si2H5I and their isotopomers. One scale factor used to scale Si-H(D) force constants for Si2H5Br is transferred from Si2H5Br to Si2H5I. Other scale factors of force constants for Si2H5I and Si2D5I are determined by a least-squares fitting to experimental vibrational frequencies. The predictions of fundamental vibrational frequencies for Si2H5I and its isotopomer are given. The scaled DFT force fields using B3LYP/3-21G** reproduced the observed fundamental vibrational frequencies of Si2H5I and its deuterium isotopomer with a mean absolute deviation of 6 cm(-1). Reassignment of some fundamental vibrational modes of Si2H5I and its isotopomer is discussed.

Silanes↗
PubMed2000

HIV protease: enzyme function and drug resistance.

HIV protease is responsible for processing of the gag and gag-pol polyproteins during virion maturation. The activity of this enzyme is essential for virus infectivity, rendering the protein a major therapeutic target for AIDS treatment. This articles reviews the biochemical and biophysical properties of the enzyme. The clinical and in vitro observations of resistance to protease inhibitors are discussed from the perspective of drug resistance mechanisms of HIV protease mutants.

Amino Acid Sequence↗
PubMed2000

Mechanical properties and microstructures of glass-ionomer cements.

OBJECTIVE: The objective of this study was to determine the flexural strength (FS), compressive strength (CS), diametral tensile strength (DTS), Knoop hardness (KHN) and wear resistance of ten commercial glass-ionomer cements (GICs). The fracture surfaces of these cements were examined using scanning electron microscopic (SEM) techniques to ascertain relationships between the mechanical properties and microstructures of these cements. METHODS: Specimens were fabricated according to the instructions from each manufacturer. The FS, CS, DTS, KHN and wear rate were measured after conditioning the specimens for 7 d in distilled water at 37 degrees C. One-way analysis of variance with the post hoc Tukey-Kramer multiple range test was used to determine which specimen groups were significantly different for each test. The fracture surface of one representative specimen of each GIC from the FS tests was examined using a scanning electron microscope. RESULTS: The resin-modified GICs (RM GICs) exhibited much higher FS and DTS, not generally higher CS, often lower Knoop hardness and generally lower wear resistance, compared to the conventional GICs (C GICs). Vitremer (3M) had the highest values of FS and DTS; Fuji II LC (GC International) and Ketac-Molar (ESPE) had the highest CS; Ketac-Fil (ESPE) had the highest KHN. Ketac-Bond (ESPE) had the lowest FS; alpha-Silver (DMG-Hamburg) had the lowest CS. Four GICs (alpha-Fil (DMG-Hamburg), alpha-Silver, Ketac-Bond and Fuji II) had the lowest values of DTS, which were not significantly different from each other; alpha-Silver and Ketac-Silver had the lowest values of KHN. The highest wear resistance was exhibited by alpha-Silver and Ketac-Fil; F2LC had the lowest wear resistance. The C GICs exhibited brittle behavior, whereas the RM GICs underwent substantial plastic deformation in compression. The more integrated the microstructure, the higher were the FS and DTS. Higher CS was correlated with smaller glass particles, and higher KHN was found where there was a combination of smaller glass particles and lower porosity. Larger glass particle sizes and a more integrated microstructure contributed to a higher wear resistance. SIGNIFICANCE: The mechanical properties of GICs were closely related to their microstructures. Factors such as the integrity of the interface between the glass particles and the polymer matrix, the particle size, and the number and size of voids have important roles in determining the mechanical properties.

Analysis of Variance↗
PubMed2000

Density functional theory studies on tautomeric stability and infrared spectra of 2-chloroadenine.

The tautomeric stability and vibrational IR spectrum of 2-chloroadenine were studied using density functional theory (DFT) at B3LYP/6-31G* level. The amino N(9)H tautomer of 2-chloroadenine was predicted to be most stable. A scaled quantum mechanical (SQM) force field approach was used to calculate the vibrational frequencies of amino N(9)H form of 2-chloroadenine. The force constant scale factors were transferred from those of purine. The mean deviation between the predicted vibrational frequencies and the observed ones is 8.0 cm(-1). The results made it possible to give complete assignments of the IR spectrum of this molecule.

Adenine↗
PubMed2000

Allelotype analysis of the myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype of chromosomal deletions associated with MDS. DNAs from both bone marrow and peripheral blood of 32 MDS patients were studied using 84 highly informative microsatellite markers on all autosomal arms, excluding the short arms of the acrocentric chromosomes. A high percentage of loss of heterozygosity (LOH) was identified on chromosome 5q (40% of informative cases), 7q (45%), 17p (23%) and 20q (20%), which corresponds to the most common cytogenetic abnormalities reported in MDS. In addition, a high incidence of LOH (> or =20%) was observed on chromosomal arms which had not been previously reported including 1p (36%), 1q (35%), and 18q (23%). This extensive allelotype analysis focuses attention on several novel genomic regions that probably contain novel tumor suppressor genes whose loss of function contributes to the development of MDS.

Adult↗
PubMed2000

Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41.

The novel virucidal protein cyanovirin-N (CV-N) binds with equally high affinity to soluble forms of either H9 cell-produced or recombinant glycosylated HIV-1 gp120 (sgp120) or gp160 (sgp160). Fluorescence polarization studies showed that CV-N is also capable of binding to the glycosylated ectodomain of the HIV-envelope protein gp41 (sgp41) (as well as SIV glycoprotein 32), albeit with considerably lower affinity than the sgp120/CV-N interaction. Pretreatment of CV-N with either sgp120 or sgp41 abrogated the neutralizing activity of CV-N against intact, infectious HIV-1 virions. Isothermal calorimetry and optical biosensor binding studies showed that CV-N bound to recombinant sgp120 with a K(d) value ranging from 2 to 45 nM and to sgp41 with a K(d) value of 606 nM; furthermore, they indicated an approximate 5:1 stoichiometry for CV-N binding to sgp120 and a 1:1 stoichiometry for CV-N binding to sgp41. Circular dichroism studies additionally illuminated the binding of CV-N with both sgp120 and sgp41, providing the first direct evidence that conformational changes are a consequence of CV-N interactions with both HIV-1 envelope glycoproteins.

Anti-HIV Agents↗
PubMed2000

[The expression of DNA mismatch repair genes and detection of DNA ploidy in young patients with colorectal carcinoma].

OBJECTIVE: To investigate the clinicopathologic characters and carcinogentic pathways of young (age < 36) colorectal carcinomas (CRCs) in Guangzhou, China. METHODS: Immunohistochemistry and flow cytometry methods were used to detect the expression of hMSH(2) and hMLH(1), status of DNA ploidy in 63 cases of young CRCs from Guangzhou, China, and analyze their correlations with patient's clinicopathological characters. RESULTS: Of the 63 young CRCs studied, forty-four (69.8%) tumors were non-mucinous carcinomas, thirty-nine (61.9%) patients were in Dukes' C or D stage. Of the 59 CRCs which were successfully detected by immunohistochemistry and flow cytometry, ten (16.9%) CRCs lost either hMSH(2) or hMLH(1) and showed DNA diploid or near-diploid, while twenty-six (44.1%) had aneuploid DNA content and all with the normal expression of hMSH(2) and hMLH(1). In addition, there existed a significant percentage (23/59, 39%) of young CRCs showing no loss of either of these two mismatch repair proteins and having a diploid or near diploid DNA content. CONCLUSION: The overall percentage of young CRCs in Guangzhou is significantly higher than those in Caucasian predominant countries and about seventy percent of young CRCs in Guangzhou are conventional carcinomas. 39% of young CRCs in Guangzhou showed no evidence of either chromosomal instability or microsatellite instability carcinogentic pathway, indicating that there must be at least a third pathway which triggers the CRCs in these special subgroups of young patients in Guangzhou, China.

Adaptor Proteins, Signal Transducing↗