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Biomedical subjects

Fang Zhang

Publications and source records attributed to Fang Zhang.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Refined mapping of loss of heterzygosity on 10q23-24 in sporadic colorectal carcinoma].

OBJECTIVE: Loss of heterozygosity (LOH) of tumor suppressor gene (TSG) is believed to play a key role in carcinogenesis of colorectal cancer (CRC). In this study, we performed refined mapping of LOH on 10q23-24 region and screened the candidate TSG related to sporadic CRC. METHODS: Seven fluorescent labeled polymorphic markers (encompassing D10S185 locus) were analyzed in 83 cases of colorectal carcinoma and normal tissues by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. GeneScan 3.1 and Genotyper 2.1 softwares were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by Chi-square test. RESULTS: The average LOH frequency was 36.11%. The highest frequency of LOH (D10S583 locus) and the lowest (D10S205 locus) were 54.84% and 21.3%, respectively. Two obviously high LOH regions were detected: one between D10S583 locus and D10S185 locus (about 0.9 cm, 10q23.33); another flanked by D10S1709 and D10S1265 locus (about 1.5 cm, 10q24.2-24.31). Furthermore, significant difference was observed between LOH frequency and Dukes stages only on D10S1265 locus. CONCLUSION: Two obviously high frequency LOH regions, 10q23.33 and 10q24.2-24.31, were detected in sporadic CRC. Besides PTEN gene, the above two regions may harbor candidate TSG involved in development and progression of sporadic CRC.

Adenocarcinoma↗
PubMed2005

Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network.

Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we show that OCRL1 is associated with clathrin-coated transport intermediates operating between the trans-Golgi network (TGN) and endosomes. OCRL1 interacts directly with clathrin heavy chain and promotes clathrin assembly in vitro. Interaction with clathrin is not, however, required for membrane association of OCRL1. Overexpression of OCRL1 results in redistribution of clathrin and the cation-independent mannose 6-phosphate receptor (CI-MPR) to enlarged endosomal structures that are defective in retrograde trafficking to the TGN. Depletion of cellular OCRL1 also causes partial redistribution of a CI-MPR reporter to early endosomes. These findings suggest a role for OCRL1 in clathrin-mediated trafficking of proteins from endosomes to the TGN and that defects in this pathway might contribute to the Lowe syndrome phenotype.

Animals↗
PubMed2005

CASK inhibits ECV304 cell growth and interacts with Id1.

Calcium/calmodulin-dependent serine protein kinase (CASK) is generally known as a scaffold protein. Here we show that overexpression of CASK resulted in a reduced rate of cell growth, while inhibition of expression of endogenous CASK via RNA-mediated interference resulted in an increased rate of cell growth in ECV304 cells. To explore the molecular mechanism, we identified a novel CASK-interacting protein, inhibitor of differentiation 1 (Id1) with a yeast two-hybrid screening. Furthermore, endogenous CASK and Id1 proteins were co-precipitated from the lysates of ECV304 cells by immunoprecipitation. Mammalian two-hybrid protein-protein interaction assays indicated that CASK possessed a different binding activity for Id1 and its alternative splicing variant. It is known that Id proteins play important roles in regulation of cell proliferation and differentiation. Thus, we speculate that the regulation of cell growth mediated by CASK may be involved in Id1. Our findings indicate a novel function of CASK, the mechanism that remains to be further investigated.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2005

Resolution of overlapping capillary electrophoresis peaks by using chemometric analysis: quantification of the components in compound reserpine tablets.

The application of multivariate curve resolution with alternating least squares (MCR-ALS) methods to second-order data from capillary electrophoresis with diode array detector (CE-DAD) is reported. Initial qualitative solutions obtained by evolving factor analysis (EFA) and pure-variable detection method can be further optimized by a simultaneous analysis of multiple electrophoresis run data with ALS regression. While unknown samples are analyzed simultaneously against the corresponding standards in different composition ratios, the exact amounts of common components in different CE runs can be determined by the traditional calibration curve method, and quantification can thus be achieved. The above methods are applied to the determination of the components in compound reserpine tablets in overlapping peaks from CE. The quantification results are compared with those of the first derivative of the electropherogram method and artificial neural network (ANN) method.

Electrophoresis, Capillary↗
PubMed2005

Trapidil enhances the slowly activating delayed rectifier potassium current and suppresses the transient inward current induced by catecholamine in Guinea pig ventricular myocytes.

We examined the electrophysiological effects of trapidil on the ionic currents influencing the repolarization and on the transient inward current (ITi) that can cause triggered arrhythmia using the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Trapidil shortened the action potential duration (APD) and increased the delayed rectifier potassium current (IK) in a concentration-dependent manner. The effect of trapidil on the rapidly and slowly activating components of IK (IKr and IKs, respectively) was studied by the envelope of tails test. Trapidil failed to affect IKr and selectively enhanced IKs. Trapidil increased the amplitude of the L-type Ca2+ current (ICa,L), with an acceleration of its inactivation, whereas isoproterenol, a beta-adrenoceptor agonist, increased the amplitude of the ICa,L in a different manner. Isoproterenol activated ITi; however, trapidil not only failed to facilitate ITi but also suppressed isoproterenol-induced ITi. The inhibitory effect of trapidil on isoproterenol-induced ITi is at least partly via a reduction of Ca2+ overload through an acceleration of ICa,L inactivation and/or a sarcoplasmic reticulum (SR) Ca channel modulation. These results suggest that trapidil does not prolong the QT interval and has an antiarrhythmic effect on arrhythmias elicited by triggered activity secondary to Ca2+ overload at much higher concentrations than clinical concentration.

Action Potentials↗
PubMed2005

Race differences in long-term diabetes management in an HMO.

OBJECTIVE: We examined race differences in diabetes outcomes over 4-8 years in a single HMO. RESEARCH DESIGN AND METHODS: We identified black and white adult diabetic patients who were continuously enrolled (1992-2001) and in whom diabetes was 1) diagnosed before 1994 (n = 1,686) or 2) newly diagnosed in 1994-1997 (n = 1,280). We used hierarchical models to estimate the effect of race on average annual HbA(1c) (A1C) controlling for baseline A1C, BMI, and age, as well as annual measures of type of diabetes medications, diabetes-related hospitalization, time and the number of A1C tests, physician visits, and nondiabetes medications. Stratifying by sex accounted for significant interactions between sex and race. RESULTS: At baseline, black and white patients had similar rates of A1C testing and physician visits, but blacks had higher unadjusted A1C values. In multivariate models, among patients with previously diagnosed diabetes, average A1C was nonsignificantly 0.11 higher (95% CI -0.12 to 0.34) in black than in white men but was 0.30 higher (0.14-0.46; P = 0.0007) in black than in white women. Among patients with newly diagnosed diabetes, the adjusted black-white gap was 0.49 among men (0.17-0.80; P = 0.007) and was 0.05 among women (-0.20 to -0.31), which was positive but not significant. CONCLUSIONS: Factors other than the quality of care may explain persistent race differences in A1C in this setting. Future interventions should target normalization of A1C by identifying potential psychosocial barriers to therapy intensification among patients and clinicians and development of culturally appropriate interventions to aid patients in successful self-management.

Adult↗
PubMed2005

Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis.

We investigated hepatitis B virus (HBV) DNA integration and expression of several proteins involved in the cell cycle and apoptosis, including cyclin A, retinoblastoma protein (pRB), Fas-associated death domain protein (FADD), tumor necrosis factor receptor-associated death domain protein (TRADD), and nuclear factor kappaB (NF-kappaB) in HBV-associated hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Archival HCC and LC specimens were obtained from 35 patients each with HBV infection; 5 normal liver specimens used as controls were also obtained. Polymerase chain reaction and Southern blot hybridization were used to detect the integration of HBV DNA in the HCC and LC specimens. The protein levels were determined by Western blot assay. The difference in HBV DNA integration between HCC and LC and correlation between HBV-encoded X protein (Hbx) integration and protein expression were analyzed statistically. HBV DNA was detected in 33 (94%) of the HCC and LC specimens. HBx integration differed in the HCC [24 (69%)] and LC [14 (40%)] specimens (p=0.015). Sixty percent of the HCC specimens and 6% of the LC specimens had increased cyclin A expression. Also, 34, 37, 69, and 77% of the HCC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression, whereas 80, 60, 100, and 100% of the LC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression. Significant correlations between HBx integration and the level of expression of cyclin A (r=0.452; p=0.006), pRB (r=-0.419; p=0.012), and TRADD (r=0.470; p=0.004) were discovered. Therefore, integration of HBV DNA occurred frequently in HCC and LC cases with chronic HBV infection, whereas HBx integration occurred more often in HCC than in LC cases (p=0.015). HBx integration and altered expression of genes is a key to apoptosis and may play important roles in HBV-induced hepatocarcinogenesis.

Apoptosis↗
PubMed2005

[Effects of various iodin-nutritional on activity of T4 5'-and 5-deiodinase in rat brain].

OBJECTIVE: To investigate the changing of T4 5'-and 5-deiodinase within rat brain under various iodin-nutritional states. METHODS: Animal model of iodine-deficiency rat was performed and the rats were divided into 4 groups by the intake of iodine-nutrition, and then killed at an age of 20 days. The thyroid hormones level in serum was measured by ELISA and the activity of T(4) 5'-and 5-deiodinase within brain was analyzed. RESULTS: In less-iodine (LI) group,TT4 and FT4 were accounting for 3.5% of the neutral-iodine (NI) group's, and FT3 was 174.0% of NI group's (P < 0.05). In NI group,TT4 and FT4 were 114.5% and 127.7% of NI group's (P < 0.05). In high-iodine (HI) group, TT4 and FT4 were 61.86% and 62.0% of NI group's, and FT3 was 184.9% of NI group's (P < 0.05). In LI group, the activity of T4 5'-deiodinase tissue of per gram (1.95 +/- 0.32) ngT3.microgT4(-1).h was significantly higher than that of NI group (P < 0.05), and the activity of 5-deiodinase (1.38 +/- 0.21) ngrT3.microg T4(-1).h(-1) is significantly less than that of NI group (1.59 +/- 0.23) (P < 0.05). In HI group the activity of T4 5'-and 5-deiodinase tissue of per gram (1.12 +/- 0.19 and 1.73 +/- 0.36) ngrT3.microgT4(-1).h(-1)was significantly less than that of NI group (P < 0.05). CONCLUSION: The activity of T4 5'-deiodinase in iodine deficiency heightens and that in iodine excess is debased, the activity of T4 5-deiodinase in iodine deficiency and in iodine excess is debased.

Animals↗
PubMed2005

Blockage of the ERK signaling pathway abrogates the SCAP ligand-induced transcriptional activation of the LDL receptor gene in HepG2 cells.

Previous studies identified the putative SCAP ligands including compound GW707 as a new class of up-regulators of LDL receptor (LDLR) transcription by activation of the sterol-regulatory element binding proteins (SREBP). These compounds increase LDLR expression in hepatoma cells in vitro and lower plasma LDL-c in hamsters. However, it is unknown, what signaling pathways are utilized by these agents that lead to the activation of LDLR transcription. Here, we report that the ERK signaling cascade is critically involved in GW707-mediated induction of LDLR expression. We show that: a) blocking ERK activation with U0126, the inhibitor of ERK upstream kinase MEK, completely abolishes the inducing effects of GW707 on LDLR promoter activity, LDLR mRNA expression, and DiI-LDL uptake in HepG2 cells; b) treating HepG2 cells with GW707 induces a dose-dependent conversion of SREBP-2 from the 125 kDa precursor form to the 68 kDa activated form and U0126 does not inhibit this cleavage process, but U0126 significantly reduces the total amount of SREBP-2 protein in GW707-treated cells without affecting the expression levels of other proteins involving in SREBP processing; and c) inhibition of ERK signaling pathway has no effects on the promoter activity or mRNA expression of SREBP-2. Collectively, these new findings establish an important role of ERK signaling pathway in SCAP ligand-induced transcription of LDLR and imply that the protein synthesis or turnover rate of SREBP-2 may be regulated by ERK.

Butadienes↗
PubMed2005

[Synthesis and DNA binding spectroscopy studies of Cu(II)-Thr-Phen].

A new complex [Cu (Thr)(Phen)H2O] SO4 . HO2 x CH3 OH (Thr = DL-Threonine, Phen = o-Phenanthroline), which has not been published, was synthesized and characterized by elemental analysis, IR spectroscopy, and TG-DTA. The interaction of the complex and sperm DNA was studied by electronic absorption and ethidium bromide (EB) fluorescence spectroscopy. The result indicates that the maximal absorption peaks of this complex are red-shifted and the intensity is weakened; At the same time, it can to some extent quench the emission intensity of EB-DNA system. Therefore, the authors come to a conclusion that the interaction of this complex and sperm DNA is intercalation.

Animals↗
PubMed2004

Identification and chemical profiling of monacolins in red yeast rice using high-performance liquid chromatography with photodiode array detector and mass spectrometry.

Monascus purpureus-fermented rice (red yeast rice) was one of the food supplements that had the ability of lowering the blood-lipid levels, and monacolins have been proved to be main active constituents. In total 14 monacolin compounds such as monacolin K (mevinolin), J, L, M, X, and their hydroxy acid form, as well as dehydromonacolin K, dihydromonacolin L, compactin, 3alpha-hydroxy-3,5-dihydromonacolin L, etc. were identified in red yeast rice, using high-performance liquid chromatography with photodiode array detector and tandem mass spectrometry. A chemical fingerprint profiling method to display bioactive monacolins in red yeast rice was established and could be used for the quality control of the target material and its related products. Ten finish products labeled as red yeast rice from different manufacturers in marketing were traced using the chromatographic chemical profiling method, and the results show that only two of them were similar while the other eight were significantly different from the reference red yeast rice. All of these materials including raw material powder and finished products available were quantified and the contents of monacolins were calculated with reference of monacolin K (mevinolin) as the standard.

Chromatography, High Pressure Liquid↗
PubMed2004

Benzodiazepine use and hip fractures in the elderly: who is at greatest risk?

BACKGROUND: It remains unclear whether benzodiazepine use increases hip fracture incidence. We studied this relationship in a large cohort, controlling for multiple potential confounders. METHODS: We analyzed 42 months of New Jersey Medicaid health care claims data for all enrollees. Each eligible person-day was assigned to categories of benzodiazepine exposure and categories of other predictors, based on prior and current medication dispensing and diagnosis information. Hip fractures were identified based on hospital claims with primary discharge diagnosis International Classification of Diseases, Ninth Revision (ICD-9) codes 820.xx. RESULTS: Cohort members (n = 125 203) contributed 194 071 person-years and had 2312 eligible hip fractures. After adjustment for age, sex, race, Medicaid nursing home residence, exposure to other psychoactive medications, including antiparkinsonian medications, diagnoses of epilepsy and dementia, and hospitalization in the previous 6 months, the incidence rate of hip fracture was significantly higher compared with no benzodiazepine use for exposure to any benzodiazepine (incidence rate ratio [IRR], 1.24; 95% confidence interval [CI], 1.06-1.44), to a short half-life, high-potency benzodiazepine (IRR, 1.27; 95% CI, 1.01-1.59), during the first 2 weeks after starting a benzodiazepine (IRR, 2.05; 95% CI, 1.28-3.28), during the second 2 weeks after starting a benzodiazepine (IRR, 1.88; 95% CI, 1.15-3.07), and for continued use (IRR, 1.18; 95% CI, 1.03-1.35). CONCLUSIONS: The incidence of hip fracture appears to be associated with benzodiazepine use. Contrary to several previous studies, short half-life benzodiazepines are not safer than long half-life benzodiazepines. Hip fracture risk is highest during the first 2 weeks after starting a benzodiazepine and declines thereafter.

Aged↗
PubMed2004

Loss of heterozygosity on chromosome 1 in sporadic colorectal carcinoma.

AIM: Loss of heterozygosity (LOH) on tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer. When it occurs at a tumor suppressor gene locus with abnormal allele, neoplastic transformation happens. In this study, we analyzed the LOH at 21 loci on chromosome 1 in sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis. METHODS: Twenty-one polymorphic micro-satellite DNA markers were analyzed with PCR both in 83 cases of colorectal cancer and in normal tissues. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. chi2 test was used to compare LOH frequency with clinicopathological data. P<0.05 was considered as statistically significant. RESULTS: The average LOH frequency of chromosome 1, short arm and long arm was 19.83%, 18.00% and 21.66%, respectively. The 2 highest LOH loci with a frequency of 36.54% and 32.50% were identified on D1S468 (1p36.33-p36.31) and D1S413 (1q31.3), respectively. On D1S2726 locus, LOH frequency of rectal cancer was 28.57% (6/21), which was higher than that of colon cancer (0.00%, 0/33) (P=0.002), suggesting that the mechanism of carcinogenesis was different in both groups. CONCLUSION: Putative tumor suppressor genes on chromosome 1 may relate to sporadic colorectal carcinomas. Tumor-suppressor-genes might locate on 1p36.33-36.31 and/or 1q31.3.

Adult↗
PubMed2004

Effects of health maintenance organization coverage of self-monitoring devices on diabetes self-care and glycemic control.

BACKGROUND: Increasingly, government mandates require insurance coverage of blood glucose monitors and test strips for patients with type 1 and type 2 diabetes. No data exist on the effects of such coverage on self-monitoring of blood glucose (SMBG), medication compliance, or blood glucose control. We evaluated whether a policy providing free blood glucose monitors increased SMBG and whether initiating SMBG was associated with increased regularity of medication use and improved glucose control (hemoglobin A(1c) [HbA(1c)] level). METHODS: Using interrupted time-series analysis and controlling for preintervention trends, we determined changes in rates of SMBG 2 years before and after the policy among 3219 continuously enrolled patients with diabetes receiving drug therapy within a multispecialty medical group (part of a health maintenance organization) serving approximately 300 000 patients. We also compared changes over time in regularity of medication use (mean days between dispensings) and mean HbA(1c) level among initiators and noninitiators of SMBG. RESULTS: The policy resulted in a small, significant increase in SMBG among insulin-treated patients (n = 1428). Among sulfonylurea-treated patients (n = 1791), the monthly initiation rate of SMBG increased by 14 new patients per 1000 (95% confidence interval [CI], 10 to 17), a doubling of the expected initiation rate. Test strip consumption increased during the first 6 months after the policy by 17.9 strips per cohort member (75% relative increase by 6 months; 95% CI, 50% to 101%). Compared with noninitiators of SMBG, initiators (n = 593) showed sudden, significant improvements in regularity of medication use by 6 months after initiation (-19.5 days between dispensings among those with low refill regularity [95% CI, -27.7 to -11.3]; -9.7 days among those with moderate regularity [95% CI, -12.3 to -7.1]), and in glucose control (-0.63% mean HbA(1c) level [as percentage of total hemoglobin] among those with poor baseline glycemic control [HbA(1c) >10%; 95% CI, -1.14% to -0.12%]). CONCLUSIONS: Providing free glucose monitors improved rates of self-monitoring in this health maintenance organization population, possibly by offering an initial incentive for patients to engage in more desirable patterns of care. Initiating SMBG was associated with increased regularity of medication use and a reduction in high blood glucose levels.

Adolescent↗
PubMed2004

Induction of S100A9 gene expression by cytokine oncostatin M in breast cancer cells through the STAT3 signaling cascade.

Cytokine oncostatin M (OM) strongly inhibits the growth of MCF-7 breast cancer cells through the STAT3 signaling pathway. We have performed cDNA microarray analyses to identify novel OM-regulated genes in MCF-7 cells that are downstream effectors of the STAT3 signaling cascade. We show that expression of the calcium-binding protein S100A9 is strongly induced by OM in MCF-7 cells and this induction is markedly reduced in MCF-7-dnStat3 cells that express a dominant negative mutant of STAT3. We further show the induction of S100A9 by OM in other breast cancer cell lines whose proliferations are inhibited by OM whereas S100A9 is not significantly induced in SKBR-3 or HepG2 cells that do not respond to OM with a growth repression. In addition, inhibition of S100A9 expression with siRNA decreased cell response to OM-induced growth repression. By analyzing a series of S100A9 promoter reporter constructs, we have defined two discrete regions in the S100A9 promoter responsible for OM-induced transcriptional activation. Together these studies identify S100A9 as a novel OM-regulated gene through the STAT3-signaling cascade and suggest its involvement in the growth regulation of breast cancer cells.

Animals↗
PubMed2004

Stability and fluctuation in adult attachment style over a 6-year period.

The present study investigates stability of adult attachment style and concurrent covariation between attachment security and coping and well-being within a 6-year longitudinal-sequential study, with a sample ranging from late adolescence to late adulthood. The findings indicate that attachment style was relatively stable over the six-year period; nevertheless, it was characterized more by fluidity than by stability. Fluctuation in attachment security showed a negative concurrent covariation with defensive coping and depressive symptoms, but a positive covariation with integrative coping and self-perceived well-being. At any point when participants were better copers and reported a better state of well-being (than their own average baseline), they were also more secure (than their own average baseline). An age effect in attachment change was also found. Over time, older individuals became more secure and more dismissing, but less preoccupied than young people.

Adaptation, Psychological↗
PubMed2004

Four rice genes encoding NADP malic enzyme exhibit distinct expression profiles.

In plants, the NADP malic enzymes (NADP-MEs) are encoded by small gene families. These NADP-ME gene families are relatively well described in C4 plants but not well studied in C3 plants. In this study, we investigated the NADP-ME gene family in a model C3 monocot plant (rice, Oryza sativa) based on its recently released genomic DNA sequence. We found that the rice NADP-ME family is composed of four members, one plastidic NADP-ME and three cytosolic versions. Although the rice NADP-ME genes identified share a high degree of similarity with one another, one cytosolic NADP-ME (OscytME3) contains several unique amino acid substitutions within highly conserved amino acid regions. Phylogenetic analysis showed that OscytME3 might be derived from a different evolutionary branch than the other three rice genes. Expression analysis of the four rice NADP-ME genes indicated that each had a different tissue-specific and developmental profile, although all four responded to stress stimuli.

Amino Acid Sequence↗