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D Ye

Publications and source records attributed to D Ye.

At least 19 recordsLinked to original sources
PubMed2006

A novel single-nucleotide polymorphism of the Fcgamma receptor IIIa gene is associated with genetic susceptibility to systemic lupus erythematosus in Chinese populations: a family-based association study.

BACKGROUND: Systemic lupus erytematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complexes which are cleared by Fcgamma receptors. OBJECTIVES: Family-based association analysis was performed to investigate whether the FCGR3A-72S/R and FCGR3A-270T/R polymorphisms are risk factors for SLE in a Chinese population. METHODS: In total, 119 patients with SLE from 95 nuclear families, aged 14-78 years, who met the American College of Rheumatology 1997 criteria were recruited, as were 316 family members of these patients. We studied two single-nucleotide polymorphisms (SNPs) encoding nonsynonymous substitution in the FCGR3A gene with respect to genetic susceptibility to SLE in a collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR restriction fragment length polymorphism. RESULTS: Our results showed that FCGR3A-72R/S have an excess of transmission of the R allele from heterozygous parents to affected offspring (transmission disequilibrium test chi2 = 9.30, P = 0.0032). Univariate (single-marker) family-based association tests demonstrated that a variant allele at SNP rs403016 of the FCGR3A gene was significantly associated with genetic susceptibility to SLE (exon 3, Z = 2.5444, P = 0.01097) in an additive model. The R and S allele frequencies were 39.4% and 60.6%, respectively. The frequencies of FCGR3A 72R/R, R/S and SS genotypes were 9.1%, 60.6% and 30.3%, respectively. However, the FCGR3A-270T/S SNP was not found in this Chinese population. CONCLUSION: This study suggests a linkage disequilibrium of the FCGR3A-72R/S SNP with SLE, and supports the notion that a novel polymorphism of the FCGR3A-72R/S SNP is associated with genetic susceptibility to SLE in Chinese populations.

Adolescent↗
PubMed2005

Pneumoperitoneum does not influence trocar site implantation during tumor manipulation in a solid tumor model.

BACKGROUND: The purpose of this study was to assess tumor implantation at abdominal wound sites following manipulation of a solid abdominal tumor. METHODS: GW-39 human colon cancer cells were injected into the omentum of golden Syrian hamsters. At 2 weeks, an omental tumor was harvested and animals were randomized to bivalve (A), crush (B), strip (C), or excision (D), with or without pneumoperitoneum. Four 5-mm trocars were inserted into the abdomen, and the tumor was reinserted through the midline, swept through four quadrants, and removed. The incision was closed and pneumoperitoneum at 7 mmHg was maintained for 10 min. Tumor implantation at wound sites was documented at 7 weeks. RESULTS: Implantation at trocar sites was 53 and 49% with and without pneumoperitoneum in the manipulated groups (A, B, C), respectively (p = 0.993). Implantation at trocar sites was reduced in the control group (D) at 9 and 10% with and without pneumoperitoneum, respectively (p < 0.001). CONCLUSIONS: Tumor implantation at trocar sites is due to spillage of tumor during manipulation and not to pneumoperitoneum.

Animals↗
PubMed2004

Interleukin-7 and suppression of local peritoneal immunity in ovarian carcinoma.

OBJECTIVES: To investigate the epithelial ovarian carcinoma (EOC) secretion of interleukin-7 (IL-7). METHODS: Levels of IL-7 were assayed by enzyme-linked immunoadsorbent assay and IL-7 mRNA, and protein expression in tissues and cell lines were detected by RT-PCR and immunohistochemistry. RESULTS: The median serum IL-7 level in patients with EOC (32 cases; 32.49 pg/ml) was significantly higher than that of patients with benign tumors (16 cases; 7.59 pg/ml) and healthy women (16 cases; 10.64 pg/ml) (P<0.05). The median peritoneal fluid IL-7 level in patients with EOC (17.39 pg/ml) was slightly higher than that of patients with benign tumors (14.09 pg/ml), but not significantly so (P>0.05). There were positive correlations between the serum and peritoneal fluid IL-7 levels in both ovarian cancer and benign group (P<0.05, both). Only two EOC specimens expressed IL-7 mRNA, and no IL-7 protein positive was found in any specimens. CONCLUSIONS: Epithelial ovarian carcinoma cells rarely express IL-7, and IL-7 levels are decreased in the ascitic fluid of patients with EOC.

Adolescent↗
PubMed2003

Design of artificial transcription factors to selectively regulate the pro-apoptotic bax gene.

The tumor suppressor p53 is the most commonly mutated gene in human cancers. Active p53 is able to stimulate the transcription of a variety of genes including the pro-apoptotic gene bax, as well as p21, a cell cycle regulator. In this study we produced novel zinc finger transcription factors that would selectively increase the expression of bax, but not of other p53 targets. Reporter gene assays in p53-negative Saos-2 cells showed that the novel zinc finger proteins stimulated transcription driven by a minimal bax promoter, but not that driven by a minimal p21 promoter. Moreover, electromobility shift assays demonstrated that the novel transcription factors could bind the bax promoter sequence with high affinity and selectivity. Expression of a five zinc finger protein (5ZFAV) in COS-7 cells resulted in an increase in Bax protein levels, indicating that this novel transcription factor could act on endogenous gene expression. Expression of 5ZFAV also drastically reduced Saos-2 cell survival; this effect could be reversed by the general caspase inhibitor B-D-FMK. These data suggest that 5ZFAV is able to induce apoptosis through increased Bax expression. Further, while expression of 5ZFAV in p53-deficient Saos-2 cells reduced cell survival, there was little effect on U-2 OS cells which have wild-type p53. Thus the selective induction of the pro-apoptotic bax gene may be a valuable adjunct to cancer chemotherapy by diminishing survival of p53-deficient tumor cells.

Animals↗
PubMed2001

Investigation of the role of the domain linkers in separate site catalysis by Clostridium symbiosum pyruvate phosphate dikinase.

Pyruvate phosphate dikinase (PPDK) catalyzes the reversible reaction: ATP + P(i) + pyruvate <--> AMP + PP(i) + PEP using Mg2+ and NH4+ ions as cofactors. The reaction takes place in three steps, each mediated by a carrier histidine residue located on the surface of the central domain of this three-domain enzyme: (1) E-His + ATP <--> E-His-PP.AMP, (2) E-His-PP.AMP + P(i) <--> E-His-P + AMP + PP(i), (3) E-His-P + pyruvate <--> E-His + PEP. The first two partial reactions are catalyzed at an active site located on the N-terminal domain, and the third partial reaction is catalyzed at an active site located on the C-terminal domain. For catalytic turnover, the central domain travels from one terminal domain to the other. The goal of this work is to determine whether the two connecting linkers direct the movement of the central domain between active sites during catalytic turnover. The X-ray crystal structure of the enzyme suggests interaction between the two linkers that may result in their coordinated movement. Mutations were made at the linkers for the purpose of disrupting the linker-linker interaction and, hence, synchronized linker movement. Five linker mutants were analyzed. Two of these contain 4-Ala insertions within the solvated region of the linker, and three have 3-residue deletions in this region. The efficiencies of the mutants for catalysis of the complete reaction as well as the E-His + ATP <--> E-His-PP.AMP partial reaction at the N-terminal domain and the E-His + PEP <--> E-His-P + pyruvate reaction at the C-terminal domain were measured to assess linker function. Three linker mutants are highly active catalysts at both active sites, and the fourth is highly active at one site but not the other. These results are interpreted as evidence against coordinated linker movement, and suggest instead that the linkers move independently as the central domain travels between active sites. It is hypothesized that while the linkers play a passive role in central domain-terminal domain docking, their structural design minimizes the conformational space searched in the diffusion process.

Adenosine Monophosphate↗
PubMed2001

Investigation of the catalytic site within the ATP-grasp domain of Clostridium symbiosum pyruvate phosphate dikinase.

Pyruvate phosphate dikinase (PPDK) catalyzes the interconversion of ATP, P(i), and pyruvate with AMP, PP(i), and phosphoenolpyruvate (PEP) in three partial reactions as follows: 1) E-His + ATP --> E-His-PP.AMP; 2) E-His-PP.AMP + P(i) --> E-His-P.AMP.PP(i); and 3) E-His-P + pyruvate --> E.PEP using His-455 as the carrier of the transferred phosphoryl groups. The crystal structure of the Clostridium symbiosum PPDK (in the unbound state) reveals a three-domain structure consisting of consecutive N-terminal, central His-455, and C-terminal domains. The N-terminal and central His-455 domains catalyze partial reactions 1 and 2, whereas the C-terminal and central His-455 domains catalyze partial reaction 3. Attempts to obtain a crystal structure of the enzyme with substrate ligands bound at the nucleotide binding domain have been unsuccessful. The object of the present study is to demonstrate Mg(II) activation of catalysis at the ATP/P(i) active site, to identify the residues at the ATP/P(i) active site that contribute to catalysis, and to identify roles for these residues based on their positions within the active site scaffold. First, Mg(II) activation studies of catalysis of E + ATP + P(i) --> E-P + AMP + PP(i) partial reaction were carried out using a truncation mutant (Tem533) in which the C-terminal domain is absent. The kinetics show that a minimum of 2 Mg(II) per active site is required for the reaction. The active site residues used for substrate/cofactor binding/activation were identified by site-directed mutagenesis. Lys-22, Arg-92, Asp-321, Glu-323, and Gln-335 mutants were found to be inactive; Arg-337, Glu-279, Asp-280, and Arg-135 mutants were partially active; and Thr-253 and Gln-240 mutants were almost fully active. The participation of the nucleotide ribose 2'-OH and alpha-P in enzyme binding is indicated by the loss of productive binding seen with substrate analogs modified at these positions. The ATP, P(i), and Mg(II) ions were docked into the PPDK N-terminal domain crevice, in an orientation consistent with substrate/cofactor binding modes observed for other members of the ATP-Grasp fold enzyme superfamily and consistent with the structure-function data. On the basis of this docking model, the ATP polyphosphate moiety is oriented/activated for pyrophosphoryl transfer through interaction with Lys-22 (gamma-P), Arg-92 (alpha-P), and the Gly-101 to Met-103 loop (gamma-P) as well as with the Mg(II) cofactors. The P(i) is oriented/activated for partial reaction 2 through interaction with Arg-337 and a Mg(II) cofactor. The Mg(II) ions are bound through interaction with Asp-321, Glu-323, and Gln-335 and substrate. Residues Glu-279, Asp-280, and Arg-135 are suggested to function in the closure of an active site loop, over the nucleotide ribose-binding site.

Adenosine Triphosphate↗
PubMed2001

[Evaluation of diagnosis of endometrial hyperplasia by curettage].

OBJECTIVE: To evaluate the accuracy of diagnosing endometrial hyperplasia (EH) by curettage. METHODS: 150 cases who had been diagnosed as EH by curettage and received hysterectomy shortly after were studied retrospectively. All of the specimens obtained from curettage and operation underwent pathological examination. The results of pathological diagnosis of these two kinds of specimens were compared. Proliferating cell nuclear antigen (PCNA) expression was examined by immunohistochemistry in 38 cases diagnosed as complex atypical hyperplasia (CAH). RESULTS: Fifty-three cases were diagnosed as simple hyperplasia (SH), eleven cases as complex hyperplasia (CH), twenty-six cases as simple atypical hyperplasia (SAH), and sixty cases as CAH by curettage. Rediagnosis was made for all patients after hysterectomy. Pathological examination of the specimens from operation diagnosed 65 cases as SH, 7 cases as CH, 15 cases as SAH, 29 cases as CAH, and 34 cases as EC. The general accuracy of histological diagnosis by curettage was 76.7% approximately 92.6%. Coexistence with EC was more common in cases with SAH and CAH than in cases with SH and CH (chi(2) = 26.3, P < 0.01). Coexistence with EC was more common in cases with CAH than in cases with SAH (chi(2) = 9.78, P < 0.005). Among the CAH cases, coexistence with EC was more common in postmenopausal patients than in premenopausal patients (chi(2) = 3.93, P < 0.05). Among the CAH cases, the positive rate of PCNA expression was higher and strength of positivity greater in those cases with EC (Uc = 3.66, P < 0.05). CONCLUSION: The accuracy of curettage is rather high in diagnosing SH and relatively low in diagnosing CAH. CAH often coexists with EC. Examination of PCNA expression may help differentiate between CAH and EC.

Adult↗
PubMed2001

Differential splicing of Pneumocystis carinii f. sp. carinii inosine 5'-monophosphate dehydrogenase pre-mRNA.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in guanine nucleotide metabolism that has drawn attention as a drug target in several organisms. Pneumocystis carinii f. sp. carinii IMPDH mRNA (GeneBank Accession No: U42442) previously identified from cultured organisms yielded a predicted amino acid sequence about 70 amino acids shorter at the amino terminus than IMPDH from other species. Recent research has shown that the amino terminal region is important for enzyme activity, suggesting that the previous putative P. carinii IMPDH might not represent full length, functional enzyme. To test this hypothesis, RT-PCR was performed with total RNA isolated from P. carinii f. sp. carinii. Three IMPDH splicing variants were found and splicing preference was observed: P. carinii isolated from infected rat lung contained primarily splicing variant one (introns two and four deleted), but organisms from spinner flask culture contained primarily splicing variant three (all four introns deleted). Importantly, splicing variant one (GeneBank Accession No: AF196975) contained an open reading frame for 529 amino acids, a size comparable to that of other eukaryotic IMPDH forms. The other variants contained the same open reading frame (454 amino acids) previously reported. Sequence analysis and complementation studies suggest variant one represents the full length, catalytically active form of P. carinii IMPDH. The differential splicing of the enzyme may reflect a mechanism by which the organism regulates the expression of IMPDH in response to environmental stresses.

Alternative Splicing↗
PubMed2001

Conjugation of monoclonal antibodies with TETA using activated esters: biological comparison of 64Cu-TETA-1A3 with 64Cu-BAT-2IT-1A3.

A simple method for conjugation of monoclonal antibodies (mAbs) with the chelating agent 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), has been developed using commercially available reagents. This method involved activation of a single carboxyl group of TETA with N-hydroxysulfosuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. The resulting activated ester of TETA was reacted with the anti-colorectal carcinoma mAb 1A3 at molar ratios ranging from 10:1 to 100:1 to give immunoconjugates modified with an average of 0.4 to 2.0 functional chelators per antibody molecule. The TETA-1A3 conjugate was labeled with 64Cu at specific activities as high as 15.4 microCi/microgram, and the radiolabeled mAb exhibited high in vitro serum stability and minimal loss of immunoreactivity. The biodistribution of 64Cu-labeled TETA-1A3 in hamsters bearing GW39 human colon carcinoma xenografts was compared to that of 64Cu-BAT-2IT-1A3 (BAT = 6-(p-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8,11- tetraacetic acid; 2IT = 2-iminothiolane). Both conjugates showed high tumor uptake (6.60-9.05% injected dose/gram) from 24 to 48 h post-injection and generally similar blood clearance and non-target organ uptakes. Human absorbed dose estimates derived from the hamster biodistribution data showed the critical organs for both conjugates to be the large intestine and the red marrow. Our results suggest that the in vitro and in vivo performance characteristics of 64Cu-TETA-1A3 compare favorably with those of 64Cu-BAT-2IT-1A3 and that further evaluation of the diagnostic and therapeutic efficacy of 64Cu-TETA-1A3 is warranted.

Animals↗
PubMed2001

Growth inhibition of interleukin-2 receptor gene-transduced peripheral blood lymphocytes on human ovarian cancer cells.

OBJECTIVE: To investigate the growth inhibition of interleukin-2 receptor (IL-2R) gene-transduced peripheral blood lymphocytes (PBLs) on human ovarian cancer cells. METHODS: Interleukin-2 (IL-2) and IL-2R genes were transfected into human ovarian cancer cell line 3AO and PBLs, respectively, using the same Fugene vector. Twenty-four hours later transfected and nontransfected PBLs were cocultured with transfected and nontransfected 3AO for 48 hours. cytotoxicity of PBLs on 3AO was detected by the MTT assay. RESULTS: The morphology of IL-2-transduced 3AO and IL-2R-transduced PBLs remained unchanged. 3AO cells could be transfected with the IL-2 gene and expressed IL-2 mRNA, and PBLs could be transfected with the IL-2R gene and expressed IL-2R mRNA. IL-2 transduced 3AO cells enhanced their response to the cytotoxicity of PBLs. Furthermore, growth inhibition of PBLs to 3AO cells increased significantly when the IL-2R was transfected into PBLs and when the IL-2 gene was transfected into 3AO cells and the two were combined. CONCLUSIONS: IL-2R gene transduced PBLs are able to enhance their cytotoxicity on IL-2 gene transduced ovarian cancer cells. This method may be a new way to investigate IL-2 gene therapy for ovarian cancer.

Cell Count↗
PubMed2001

[Obesity, hypertension, and diabetes mellitus among school children in Ouagadougou (Burkina Faso)].

This paper deals with the findings of a survey conducted at the school environnement in Ouagadougou. Three factors of cardiovascular risks were identified: obesity, high blood pressure, and diabete millitus. The survey was based on a sample of 1470 students from primary and secondary schools consisted in taking their blood pressure, measuring they weight and height and glycaemia using dextrostix. Of the 1470 students targeted, 668 were girls and 782 were boys. Their age ranges between 4 and 25 years with average age of 13.8 years. 55 % of the students had an average socio-economic backgrounds. 58 students or 3.94% had high blood pressure including 50 cases of maximum high blood pressure and 8 cases of confirmed high blood pressure (HBP). A diastolic HBP predominance among 48 cases or 3.26% was also recorded. While 1 case showed systolic HBP, 6 were systolo-diastolic. The quetelet index used to determine obesity revealed 28 cases of excess in weight or 1.90% of the cases and 4 cases of obesity, or 0.28%. The predominance of excess in weight was statistically significant among girls. Only 1 case of obesity was associated with high blood pressure. No case of diabetes was identified. The factors of cardiovascular risk seem to be statistically important in school environnement in Ouagadougou. However, an muticentered study is recommended, as it will lead to an exhaustive knowledge of the prevalence of these factors of cardiovascular risk.

Adolescent↗
PubMed2000

Identification of domain-domain docking sites within Clostridium symbiosum pyruvate phosphate dikinase by amino acid replacement.

Potential domain-domain docking residues, identified from the x-ray structure of the Clostridium symbiosum apoPPDK, were replaced by site-directed mutagenesis. The steady-state and transient kinetic properties of the mutant enzymes were determined as a way of evaluating docking efficiency. PPDK mutants, in which one of two stringently conserved docking residues located on the N-terminal domain (Arg(219) and Glu(271)) was substituted, displayed largely unimpeded catalysis of the phosphoenolpyruvate partial reaction at the C-terminal domain, but significantly impaired catalysis (>10(4)) of the ATP pyrophosphorylation of His(455) at the N-terminal domain. In contrast, alanine mutants of two potential docking residues located on the N-terminal domain (Ser(262) and Lys(149)), which are not conserved among the PPDKs, exhibited essentially normal catalytic turnover. Arg(219) and Glu(271) were thus proposed to play an important role in guiding the central domain and, hence, the catalytic His(455) into position for catalysis. Substitution of central domain residues Glu(434)/Glu(437) and Thr(453), the respective docking partners of Arg(219) and Glu(271), resulted in mutants impaired in catalysis at the ATP active site. The x-ray crystal structure of the apo-T453A PPDK mutant was determined to test for possible misalignment of residues at the N-terminal domain-central domain interface that might result from loss of the Thr(453)-Glu(271) binding interaction. With the exception of the mutation site, the structure of T453A PPDK was found to be identical to that of the wild-type enzyme. It is hypothesized that the two Glu(271) interfacial binding sites that remain in the T453A PPDK mutant, Thr(453) backbone NH and Met(452) backbone NH, are sufficient to stabilize the native conformation as observed in the crystalline state but may be less effective in populating the reactive conformation in solution.

Adenosine Triphosphate↗
PubMed2000

The possible subduction of continental material to depths greater than 200 km.

Determining the depth to which continental lithosphere can be subducted into the mantle at convergent plate boundaries is of importance for understanding the long-term growth of supercontinents as well as the dynamic processes that shape such margins. Recent discoveries of coesite and diamond in regional ultrahigh-pressure (UHP) metamorphic rocks has demonstrated that continental material can be subducted to depths of at least 120 km (ref. 1), and subduction to depths of 150-300 km has been inferred from garnet peridotites in orogenic UHP belts based on several indirect observations. But continental subduction to such depths is difficult to trace directly in natural UHP metamorphic crustal rocks by conventional mineralogical and petrological methods because of extensive late-stage recrystallization and the lack of a suitable pressure indicator. It has been predicted from experimental work, however, that solid-state dissolution of pyroxene should occur in garnet at depths greater than 150 km (refs 6-8). Here we report the observation of high concentrations of clinopyroxene, rutile and apatite exsolutions in garnet within eclogites from Yangkou in the Sulu UHP metamorphic belt, China. We interpret these data as resulting from the high-pressure formation of pyroxene solid solutions in subducted continental material. Appropriate conditions for the Na2O concentrations and octahedral silicon observed in these samples are met at depths greater than 200 km.

Journal Article↗