Biomedical subjects

Fang Zhang

Publications and source records attributed to Fang Zhang.

At least 73 records · Page 4Linked to original sources

PubMed2004

Peroxisome proliferator-activated receptors as attractive antiobesity targets.

The peroxisome proliferator-activated receptors (PPARs) alpha, delta and gamma are a group of ligand-activated transcription factors that function as lipid sensors and govern numerous biological processes, including energy metabolism, cell proliferation, differentiation and inflammation. It has been known for some time that both PPAR alpha and PPAR gamma play a role in lipid metabolism. Antidiabetic drugs of the thiazolidinedione (TZD) class are potent and selective activators of PPAR gamma known to promote adipocyte differentiation and lipid storage. Lipid-lowering agents of the fibrate class activate PPAR alpha. Until recently, the function of PPAR delta remained elusive, but recent progress has shown that PPAR delta plays a key role in lipid metabolism, as it regulates serum lipid profiles and fatty acid beta oxidation in muscle and adipose tissue. This suggests that PPAR delta agonists may play a beneficial role in the treatment of lipid disorders, in particular obesity. This review will highlight key new findings in PPAR delta biology and discuss the recent evidence linking PPAR alpha and PPAR gamma to adipose tissue biology and the development of obesity.

Adipose Tissue↗

PubMed2004

Study of trace elements in blood of thyroid disorder subjects before and after 131I therapy.

Both trace elements and thyroid hormones play essential roles in the human body. However, the previous results about the interaction between these two factors are often controversially given. In order to make clear the influence of thyroid hormones on the homeostasis of trace elements, we studied the variation of Fe, Cu, and Zn in erythrocyte and serum from patients with hyperthyroidism before and after 131I therapy by the X-ray fluorescence method. The different thyroid statuses of the patients before and after the therapy were assayed by determining the levels of thyroid hormones. The results showed that the homeostasis of metal ions in both serum and erythrocyte could be more or less influenced by the altered thyroid hormones. The serum Cu and Zn exhibited the significantly positive correlation with triiodothyronine (T3) and thyroxine (T4). Although the serum Cu and Zn differed significantly before and after the therapy, no difference was observed in the concentrations of Cu and Zn in erythrocyte, except that the erythrocyte Zn in the patients with hypothyroidism exhibited an obvious increase. Furthermore, the erythrocyte Zn showed a markedly negative correlation with T3.

Copper↗

PubMed2004

Length-of-stay policies and ascertainment of postdischarge problems in newborns.

OBJECTIVE: The purpose of this study was to evaluate the effects of an early postpartum discharge program and a subsequent legislative mandate for 48 hours of hospital coverage on incidence of newborn jaundice and feeding problems. We tested the hypothesis that heightened postdischarge ascertainment (rather than short stays) is responsible for apparent increases in these outcomes. METHODS: Interrupted time series analysis was conducted on retrospective data from the automated medical records of a large Massachusetts health maintenance organization (HMO). A population of 20,366 mother-infant pairs with normal vaginal deliveries between October 1990 and March 1998 was identified. The interventions included a new HMO protocol in 1994 of 1 hospital overnight after delivery, plus a nurse home visit, then the Massachusetts' 1996 minimum coverage law. Postpartum length of stay, clinical evaluation on day 3 or 4 of life, health center visits up to day 21, health center diagnoses of jaundice or feeding problems, bilirubin testing and test severity, rehospitalizations, and emergency department visits were measured. RESULTS: Postpartum stays <2 nights rose from 28% of newborns before implementation of the program to 70% immediately after implementation. Later, this rate fell from 66% before the mandate to 21% just after the law went into effect. Day 3 or 4 evaluation rose from 24.5% to 64% after the program, then dropped somewhat to 53% after the mandate. Controlling for longer-term trends in health center visits, implementation of the early discharge program was associated with approximately 1 extra visit for every 4 newborns within the first 21 days of life. The state mandate did not affect health center visit rates. Jaundice diagnoses were flat at 8% of newborns during the baseline, then rose to a constant 11% throughout the program and postmandate periods. Bilirubin testing of newborns also rose by 3.4 percentage points at the time of program implementation, and the proportion of tested newborns with results calling for at least consideration of phototherapy rose by 6 percentage points. Phototherapy use rose from a flat 1.8% to 2.4% of newborns after program implementation. Feeding problem diagnoses more than doubled at the time of program implementation and remained elevated after the mandate. Rehospitalizations overall and specifically for jaundice were constant over time, whereas more rare emergency department visits for jaundice dropped from 0.3% of newborns to 0 on program implementation. CONCLUSIONS: Sudden increases in jaundice-related measures and identification of infant feeding problems were not associated with changes in length of stay in this setting. Instead, these increases seem to be the result of more frequent evaluation of newborns during the critical day 3 to 4 period and may also have been elevated by a new climate of concern about neonatal vulnerability. "Ascertainment bias" may have confounded findings in previous reports that raised concerns about the safety of early discharge.

Breast Feeding↗

PubMed2004

Does antidepressant adherence have an effect on glycemic control among diabetic antidepressant users?

OBJECTIVE: To examine the relationship between adherence to antidepressant medications and HbA1c levels among patients with diabetes in a managed care setting. METHOD: The analysis included measures of HbA1c levels before, during, and after initial antidepressant use among 568 patients with diabetes enrolled in the Harvard Pilgrim Health Care insurance plan from 1991-1995. Adherence was defined as four refills in a six-month period after the first antidepressant prescription. General linear models using SAS PROC MIXED were used to estimate the effects of covariates including antidepressant adherence on HbA1c levels over time, comparing patients who were adherent to antidepressant medications to those patients who were non-adherent to antidepressant medications. RESULTS: Adherence to antidepressant treatment was not significantly associated with HbA1c levels among diabetic patients who are antidepressant users. Younger age, use of insulin and oral medications, and female gender were all significantly associated with HbA1c levels over time. CONCLUSIONS: Although we did not observe any association between level of adherence to antidepressant therapy among diabetic patients and levels of glucose control, our results confirm previously established associations between patient characteristics and glycemic control. Further research is needed to disentangle the complex relationship among antidepressant treatment adherence and diabetes outcomes.

Adolescent↗

PubMed2004

[Dynamic modeling of potato phenological development].

By means of systematic demonstration, this study found the mathematical relationship among several temperature driven nonlinear models for crop growth, and amended the limitation of the past nonlinear model in biological usage and the improved model with more general definition. Integrated with four years' field experimental data and Gauss function based temperature effectiveness model submitted in this study, the phenological development model for potato crop was established under different ecological conditions. The phenological development model explained the digital contribution of soil temperature increment on potato growth, and verified by the experimental data from different years and different conditions. There were strict co-relationships between modeling data and experimental data.

Computer Simulation↗

PubMed2003

Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord.

Following tail amputation in urodele amphibians, an ependymal tube, that resembles a developing neural tube, forms from ependymal cells that migrate from the cord stump and elongates by cell proliferation. Expression of the keratin pair 8 and 18 has been observed in the developing urodele nervous system and is maintained in the ependymal cells of the mature cord. We show here that expression of these keratins is not unique to urodeles, but is also observed in the radial glia of the human spinal cord, suggesting that these proteins might play a role both in neural development and regeneration. Analysis of their expression in the regenerating spinal cord following tail amputation shows that their expression, as well as that of glial fibrillary acidic protein (GFAP), is maintained in the ependymal tube during regeneration, though differences in their levels of expression are observed along the anteroposterior axis and appear to be related to the progression of morphogenesis. In addition, we show that following tail amputation the ependymal tube expresses the neural stem cell markers nestin and vimentin, which are undetectable in normal urodele spinal cord. This up-regulation of neural stem cell markers shows that the ependymal cells undergo a phenotypic change. Whereas maintenance of keratin and GFAP expression in the adult ependyma may reflect a higher plasticity of these cells in adult urodeles than in other vertebrates, re-expression of markers of early neural development suggests the occurrence of a dedifferentiation process in the spinal cord in response to injury.

Animals↗

PubMed2003

Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene.

The sterol-independent regulatory element (SIRE) of the LDL receptor (LDLR) promoter mediates oncostatin M (OM)-induced transcription of the LDLR gene through a cholesterol-independent pathway. Our prior studies have detected specific associations of the zinc finger transcription factor Egr1 with the SIRE sequence in OM-stimulated HepG2 cells. Because the SIRE motif is composed of a c/EBP binding site and a cAMP response element, both of which are quite divergent from the classical GC-rich Egr1 recognition sequences, we hypothesized that Egr1 may regulate LDLR transcription through interacting with members of the c/EBP and CREB families. Here, we show that treating HepG2 cells with OM specifically leads to prominent increases of the levels of c/EBPbeta and Egr1 bound to the LDLR promoter in vivo. In vitro, the binding of Egr1 to the SIRE sequence is weak, but is strikingly enhanced in the presence of HepG2 nuclear extract. Mammalian two-hybrid assays demonstrate that the N-terminal transactivation domain of Egr1 specifically interacts with c/EBPbeta but not with c/EBPalpha or CREB. The OM treatment further enhances this interaction, resulting in a large increase in the Egr1 transactivating activity. The direct protein to protein contact between Egr1 and c/EBPbeta is also demonstrated by co-immunoprecipitation experiments. Furthermore, we show that a mutation of the phosphorylation motif of c/EBPbeta diminished the OM-stimulated interaction of Egr1 and c/EBPbeta. Taken together, we provide strong evidence that Egr1 regulates LDLR transcription via a novel mechanism of protein-protein interaction with c/EBPbeta.

Binding Sites↗

PubMed2003

Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3.

Glycogen synthase kinase-3 (GSK-3) is a critical, negative regulator of diverse signaling pathways. Lithium is a direct inhibitor of GSK-3 and has been widely used to test the putative role of GSK-3 in multiple settings. However, lithium also inhibits other targets, including inositol monophosphatase and structurally related phosphomonoesterases, and thus additional approaches are needed to attribute a given biological effect of lithium to a specific target. For example, lithium is known to increase the inhibitory N-terminal phosphorylation of GSK-3, but the target of lithium responsible for this indirect regulation has not been identified. We have characterized a short peptide derived from the GSK-3 interaction domain of Axin that potently inhibits GSK-3 activity in vitro and in mammalian cells and robustly activates Wnt-dependent transcription, mimicking lithium action. We show here, using the GSK-3 interaction domain peptide, as well as small molecule inhibitors of GSK-3, that lithium induces GSK-3 N-terminal phosphorylation through direct inhibition of GSK-3 itself. Reduction of GSK-3 protein levels, either by RNA interference or by disruption of the mouse GSK-3beta gene, causes increased N-terminal phosphorylation of GSK-3, confirming that GSK-3 regulates its own phosphorylation status. Finally, evidence is presented that N-terminal phosphorylation of GSK-3 can be regulated by the GSK-3-dependent protein phosphatase-1.inhibitor-2 complex.

3T3 Cells↗

PubMed2003

Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: a cross sectional study.

BACKGROUND: Recent studies suggest that patients at greatest risk for diabetes complications are least likely to self-monitor blood glucose. However, these studies rely on self-reports of monitoring, an unreliable measure of actual behavior. The purpose of the current study was to examine the relationship between patient characteristics and self-monitoring in a large health maintenance organization (HMO) using test strips as objective measures of self-monitoring practice. METHODS: This cross-sectional study included 4,565 continuously enrolled adult managed care patients in eastern Massachusetts with diabetes. Any self-monitoring was defined as filling at least one prescription for self-monitoring test strips during the study period (10/1/92-9/30/93). Regular SMBG among test strip users was defined as testing an average of once per day for those using insulin and every other day for those using oral sulfonylureas only. Measures of health status, demographic data, and neighborhood socioeconomic status were obtained from automated medical records and 1990 census tract data. RESULTS: In multivariate analyses, lower neighborhood socioeconomic status, older age, fewer HbA1c tests, and fewer physician visits were associated with lower rates of self-monitoring. Obesity and fewer comorbidities were also associated with lower rates of self-monitoring among insulin-managed patients, while black race and high glycemic level (HbA1c>10) were associated with less frequent monitoring. For patients taking oral sulfonylureas, higher dose of diabetes medications was associated with initiation of self-monitoring and HbA1c lab testing was associated with more frequent testing. CONCLUSIONS: Managed care organizations may face the greatest challenges in changing the self-monitoring behavior of patients at greatest risk for poor health outcomes (i.e., the elderly, minorities, and people living in low socioeconomic status neighborhoods).

Adult↗

PubMed2003

Delineating an oncostatin M-activated STAT3 signaling pathway that coordinates the expression of genes involved in cell cycle regulation and extracellular matrix deposition of MCF-7 cells.

A number of studies have demonstrated that the STAT pathway is an important signaling cascade utilized by the IL-6 cytokine family to regulate a variety of cell functions. However, the downstream target genes of STAT activation that mediate the cytokine-induced cellular responses are largely uncharacterized. The aims of the current study are to determine whether the STAT signaling pathway is critically involved in the oncostatin M (OM)-induced growth inhibition and morphological changes of MCF-7 cells and to identify STAT3-target genes that are utilized by OM to regulate cell growth and morphology. We show that expression of a dominant negative (DN) mutant of STAT3 in MCF-7 cells completely eliminated the antiproliferative activity of OM, whereas expression of DN STAT1 had no effect. The growth inhibition of breast cancer cells was achieved through a concerted action of OM on cell cycle components. We have identified four cell cycle regulators including c-myc, cyclin D1, c/EBPdelta, and p53 as downstream effectors of the OM-activated STAT3 signaling cascade. The expression of these genes is differentially regulated by OM in MCF-7 cells, but is unaffected by OM in MCF-7-dnStat3 stable clones. We also demonstrate that the OM-induced morphological changes are correlated with increased cell motility in a STAT3-dependent manner. Expression analysis of extracellular matrix (ECM) proteins leads to the identification of fibronectin as a novel OM-regulated ECM component. Our studies further reveal that STAT3 plays a key role in the robust induction of fibronectin expression by OM in MCF-7 and T47D cells. These new findings provide a molecular basis for the mechanistic understanding of the effects of OM on cell growth and migration.

Breast Neoplasms↗

PubMed2003

Synergistic activation of human LDL receptor expression by SCAP ligand and cytokine oncostatin M.

OBJECTIVE: A recent study identified a new class of compounds designated as the sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) ligands that putatively bind to SCAP, leading to increased LDL receptor (LDLR) expression. In this study, we examined the effects of SCAP ligand GW707 in comparison with lovastatin and cytokine oncostatin M (OM) on the regulation of LDLR expression in cultured HepG2 cells. METHODS AND RESULTS: Our studies uncovered several new features that distinguish SCAP ligand from lovastatin, a classic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and from OM, which utilize an SREBP-independent regulatory pathway. We show that the induction of LDLR mRNA expression by GW707 is not affected by intracellular cholesterol but is completely abolished by blocking de novo protein synthesis. Moreover, the effects of GW707 but not lovastatin on LDLR promoter activity, mRNA expression, and uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanin perchlorate-LDL are markedly enhanced by OM. We further demonstrate that the amounts of the mature form of SREBP-2 translocated to the nucleus under GW707 treatment are increased by costimulating cells with OM. CONCLUSIONS: Our studies provide the first evidence that higher levels of LDLR expression and function can be achieved through simultaneous stimulation of the SREBP-dependent and SREBP-independent pathways, suggesting a strategy to develop an adjunct therapeutic intervention utilizing both pathways.

Active Transport, Cell Nucleus↗

PubMed2003

Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt.

Lower vertebrates, such as fish and amphibians, and developing higher vertebrates can regenerate complex body structures, including significant portions of their central nervous system. It is still poorly understood why this potential is lost with evolution and development and becomes very limited in adult mammals. In this review, we will discuss the current knowledge on the cellular and molecular changes after spinal cord injury in adult tailed amphibians, where regeneration does take place, and in developing chick and mammalian embryos at different developmental stages. We will focus on the recruitment of progenitor cells to repair the damage and discuss possible roles of changes in early response to injury, such as cell death by apoptosis, and of myelin-associated proteins, such as Nogo, in the transition between regeneration-competent and regeneration-incompetent stages of development. A better understanding of the mechanisms underlying spontaneous regeneration of the spinal cord in vivo in amphibians and in the chick embryo will help to devise strategies for restoring function to damaged or diseased nervous tissues in mammals.

Animals↗

PubMed2003

Recruitment of postmitotic neurons into the regenerating spinal cord of urodeles.

By using fluorescent tracers, we have investigated the origin of the cells that form the regenerating spinal cord after tail amputation in urodele amphibians. We show that spinal cord cells immediately adjacent to the amputation plane die and are removed by phagocytic cells. Spinal cells just anterior to these dying cells are destined to make the majority of the regenerating cord. The largest contribution is likely to come from the radial ependymal cells, but we also demonstrate that postmitotic neurons in this location can translocate into the regenerating cord. These neurons integrate into the regenerate structure and survive for at least 4 weeks. We find no evidence that these translocated neurons dedifferentiate and divide during this regeneration process. We discuss the possibility that these neurons survive long term in the regenerate cord and become part of the functional neuronal circuitry.

Ambystoma↗

PubMed2003

Quantification of analytes in overlapping peaks from capillary electrophoresis using multivariate curve resolution-alternating least squares methods.

Application of multivariate curve resolution with alternating least squares (ALS) methods to second-order data from capillary electrophoresis diode array detector (CE-DAD) is shown. Second-order data are easily obtained by setting individual data matrix of CE run one in top of the other. Initial qualitative solutions obtained by evolving factor analysis can be further optimized by simultaneous analysis of multiple electrophoresis run data with ALS regression. Quantification is achieved by the comparison of the analyte peak areas with that of pure standards. During the ALS regression procedure, the following constraints were applied: (i) both concentrations and unit pure spectra of the resolved components must be positive; (ii) elution profiles have an unimodal shape; (iii) correspondence exists between common species in the different data matrices; (iv) the pure spectrum of each species is the same in all runs where it is present. The above methods were applied for the determination of dinitrotoluene (DNT) isomeric compounds in overlapping peaks from CE.

Dinitrobenzenes↗

PubMed2003

Quantitative chiral analysis in capillary electrophoresis from unresolved peaks using derivative electropherograms, experimental design, and artificial neural networks.

Quantitative capillary electrophoretic analysis of chiral compounds might be difficult or even impossible when baseline separation is not reached. In this work, the use of n-th derivative of the electropherogram was studied and examined on model and experimental data. The electropherograms should be first smoothed using Savitzky-Golay method and the quantitative analysis is then possible using either a graphical method or multivariate calibration applying a combination of experimental design (ED) and artificial neural networks (ANNs). The best results were obtained for the first derivative, higher derivatives are not suitable because of noise accumulation. The method was applied to real experimental data to quantify chiral amino acids from unresolved peaks, but it is applicable for quantitative analysis of any other chiral analytes from poorly resolved peaks. Precision of analysis from partially resolved peaks reached was about +/- 3.2% relative standard deviation.

Amino Acids↗

PubMed2003

Extranodal imaging manifestations of non-Hodgkin's lymphoma.

A series of imaging features of extranodal, multi-systemic involvements in Non-Hodgkin's lymphoma (NHL) were investigated. The clinical data and imaging findings of 16 patients with pathologically proved NHL were retrospectively analyzed. The related literatures were reviewed. Of the 16 cases of NHL, skeletal involvement was found in 4, nasal cavity and nasal sinuses were involved in 4, too. Lesion in the thorax was seen in 3 patients, hepatic involvement occurred in one case, cerebral ventricle was affected in 3 cases, mesentery was involved in one case. Even though extranodal involvement of NHL exhibited extremely variable patterns, there were some relatively typical imaging findings. Emphasized in this report were the relatively specific imaging manifestations of different systems, which may mimic infectious or other neoplasms of different sites. The importance of imaging studies lies in the availability for diagnosis, staging and follow-up of NHL. Combined with the clinical and other related information, the diagnostic accuracy can be further improved, thus, providing reliable evidence in guiding clinical management.

Adolescent↗

PubMed2003

Effects of state surveillance on new post-hospitalization benzodiazepine use.

BACKGROUND: Benzodiazepines (BZD) effectively treat anxiety and insomnia accompanying major health events, including hospitalizations. Prescribing regulations to decrease BZD misuse may negatively impact therapeutic uses. OBJECTIVE: To assess the impact of a Triplicate Prescription Program (TPP) on initiation of post-hospitalization BZD prescribing, both overall and among cardiac and cancer patients in the United States. DESIGN: Interrupted time-series of post-hospitalization BZD dispensing events to enrollees in the US Medicaid program in the states of New York (intervention group) and New Jersey (control group), before and after implementation of a TPP. STUDY PARTICIPANTS: Community-dwelling Medicaid enrollees in New York State (n = 67 962) and New Jersey (n = 71 701), hospitalized between 1 January 1988 and 30 November 1990. INTERVENTION: The New York State TPP, implemented on 1 January 1989, requires physicians to prescribe BZD on triplicate prescription forms for state surveillance. OUTCOME MEASURES: Rates and duration of new post-hospitalization use of BZD and substitute medications. RESULTS: Overall, a sudden and sustained 63.5% decrease [95% confidence interval (CI) -58.6% to -68.3%] in new post-hospitalization BZD dispensing-from a baseline rate of 44 discharges with BZD dispensing per 1000 discharges per month-followed the TPP in New York State, without discontinuity in the control state. Patients hospitalized for acute ischemic cardiac events experienced a 72.5% reduction (95% CI -55.5% to -89.4%), and cancer patients a 69.4% reduction (95% CI -36.7% to -100.0%). The TPP did not preferentially reduce BZD use lasting >2 months. Increased substitute use did not offset reductions in BZD use. CONCLUSIONS: By decreasing new short-term post-hospitalization BZD use, the New York State TPP also had unintended effects.

Adult↗

PubMed2003

Genome-wide search for loss of heterozygosity in Chinese patients with sporadic colorectal cancer.

In an attempt to integrally investigate the loss of tumor suppressor genes and search for putative suppressor loci associated with tumor occurrence and progression, we conducted a genome-wide loss of hetero zygosity (LOH) study of 83 tumor samples obtained from Chinese patients with sporadic colorectal cancer. We employed 400 fluorescence-labeled microsatellite marker primers to amplify the corresponding loci of the genomic DNA and then electrophoresed the polymerase chain reaction products and analyzed the fluorescent signals. The LOH frequencies were high (>35%) but were not associated with the tumor stage and progression in 20 loci, including the regions where TP53, E-cadherin, deleted in colorectal carcinoma (DCC), phosphatase and tensin homolog deleted on chromosome 10 (PTEN), mothers against decapentaplegic, Drosophila, homolog of 2 (MADH2) and mothers against decapentaplegic, Drosophila, homolog of 4 (MADH4) reside. Loss of other loci, including two narrow regions on chromosome 2, was found to relate to the tumor stage, suggesting that this genomic instability may contribute to tumor progression.

Adult↗