Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 73 records · Page 4Linked to original sources

PubMed2005

Selection of novel mediators of E2F1-induced apoptosis through retroviral expression of an antisense cDNA library.

The E2F1 transcription factor is an essential mediator of p53-dependent and p53-independent apoptosis as part of an anti-tumour safeguard mechanism. In this study, a functional so-called technical knockout (TKO) approach was applied to Saos-2ERE2F1 cells that conditionally activate E2F1 by the addition of 4-hydroxytamoxifen to search for p53-independent pro-apoptotic E2F1 targets. The approach was based on random inactivation of genes after retroviral transfer of an antisense cDNA library enriched of E2F1-induced genes, followed by the selection of Saos-2ERE2F1 cells that survive in the presence of the apoptotic stimulus. We identified 13 novel E2F1 target genes encoding proteins of known cellular function, including apoptosis and RNA binding. FACS analysis revealed that E2F1-induced apoptosis was significantly attenuated in cell clones containing the antisense cDNA fragments of these genes, demonstrating their participation in E2F1 death pathways. Moreover, inactivation of the target genes resulted in a clear increase of cell viability (>80%) in response to E2F1 activation compared with controls (approximately 30%). Four genes showed an increase in expression intensity in the presence of cycloheximide, suggesting a direct effect of E2F1 on gene transcription, whereas one gene was identified as an indirect target. Our data provide new insight in the regulation of E2F1-induced apoptosis.

Apoptosis↗

PubMed2005

NMR measurements of the diffusional permeability of water in cultured colonic epithelial cancer cells.

The water residence time and diffusional water permeability in colonic epithelial T84 cancer cells was measured using (1)H NMR spectroscopy; the values estimated were 35.2+/-2.8 ms and (7.4+/-0.6)x10(-3)cms(-1), respectively. Water permeability was inhibited to approximately 10% of its original value by the mercurial diuretic, p-chloromercuribenzenesulfonate (PCMBS; 1mM), and fully restored by dithiothreitol (DTT; 1mM). The permeability was also inhibited reversibly to approximately 55%, by extracellular glibenclamide (1mM), an inhibitor of some ATP-binding cassette (ABC) transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR). Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IMBX; 0.1-1mM) and the adenylate cyclase activator, forskolin (0.1-1mM) did not alter water permeability. It is concluded that in T84 cells water diffuses through the membrane lipid bilayer and via channels that are inhibited by PCMBS, including the channels that are known to be inhibited by glibenclamide.

4-Chloromercuribenzenesulfonate↗

PubMed2005

Search for X(3872) in gammagamma fusion and radiative production at CLEO.

We report on a search for the recently reported X(3872) state using 15.1 fb(-1) of e(+)e(-) data taken in the sqrt[s] = 9.46-11.30 GeV region. Separate searches for the production of the X(3872) in untagged gammagamma fusion and e(+)e(-) annihilation following initial state radiation are made by taking advantage of the unique angular correlation between the leptons from the decay J/psi --> l(+)l(-) in X(3872) decay to pi(+)pi(-)J/psi. No signals are observed in either case, and 90% confidence upper limits are established as (2J+1)Gamma(gammagamma)(X(3872))B(X --> pi(+)pi(-)J/psi) < 12.9 eV and Gamma(ee)(X(3872))B(X- -> pi(+)pi(-)J/psi) < 8.3 eV.

Journal Article↗

PubMed2005

Observation of 1(-)0(-) final states from psi(2S) decays and e(+)e(-) annihilation.

Using CLEO data collected from CESR e(+)e(-) collisions at the psi(2S) resonance and nearby continuum at sqrt[s]=3.67 GeV, we report the first significantly nonzero measurements of light vector-pseudoscalar hadron pair production (including rhopi, omegapi, rhoeta, and K(*0)K0 ) and the pi(+)pi(-)pi(0) final state, both from psi(2S) decays and direct e(+)e(-) annihilation.

Journal Article↗

PubMed2005

Computational analysis of biomechanical contributors to possible endovascular graft failure.

This paper evaluates numerically coupled blood flow and wall structure interactions in a representative stented abdominal aortic aneurysm (AAA) model, leading potentially to endovascular graft (EVG) failure. A total of 12 biomechanical contributors to possible EVG migration were considered. The results show that after EVG insertion for the given model, the peak AAA sac-pressure was reduced to 14.2 mmHg (11.8% of p(lumen)), and hence the maximum von Mises wall stress and wall deformation dropped by factors of 20 and 10, respectively. Thus, an EVG can significantly reduce sac pressure, mechanical stress, pulsatile wall motion, and the maximum diameter in AAAs and hence prevent AAA rupture effectively. In the absence of endoleaks, elevated sac-pressure can still be caused by fluid-structure interactions between the EVG, stagnant blood, and AAA wall. EVG migration forces vary from 1.4 to 7 N for different EVG geometries, material properties, and hemodynamic conditions. AAA-neck angle, iliac bifurcation angle, neck aorta-to-iliac diameter ratio, EVG size, aorto-uni-iliac EVG, and hypertension play important roles in generating forces potentially leading to EVG migration.

Animals↗

PubMed2005

A new wall stress equation for aneurysm-rupture prediction.

Aneurysms, especially in the abdominal aorta (AAA), are prone to rupture, and hence a reliable and easy-to-use predictor is most desirable. Based on clinical observations and numerical analyses, a semi-empirical equation for the peak AAA-wall stress has been developed. It can be readily used for AAA-rupture predictions or can be integrated into more elaborate AAA-assessment models.

Animals↗

PubMed2005

Recruitment of multiple cell lines by collagen-synthetic copolymer matrices in corneal regeneration.

Collagen hydrogel matrices with high optical clarity have been developed from collagen I, cross-linked with a copolymer based on N-isopropylacrylamide, acrylic acid and acryloxysuccinimide. The controlled reaction of collagen amine groups with this copolymer under neutral pH and aqueous conditions gave robust, optically clear hydrogels and prevented the excessive collagen fibrillogenesis that can lead to collagen opacity. These sterile, non-cytotoxic hydrogels allowed epithelial cell overgrowth and both stromal cell and nerve neurite ingrowth from the host tissue. This regenerative ability appeared to result from the high glucose permeability, nanoporosity and the presence of cell adhesion factors, RGD in collagen and the laminin pentapeptide, YIGSR, grafted onto the copolymer. Under physiological conditions, optical clarity superior to the human cornea and tensile performance adequate for suturing were obtained from some formulations.

Animals↗

PubMed2005

Effects of injections of 8-hydroxy-2-(di-n-propylamino)tetralin or muscimol in the median raphe nucleus on c-fos mRNA in the rat brain.

Inhibition of the median raphe nucleus (MRN) by the local injection of 5-HT(1A) or GABA(A) receptor agonists produces strong activational effects on feeding, drinking and locomotor activity. Using an animal model of relapse, we have shown that intra-MRN injection of the 5-HT(1A) autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reinstates alcohol seeking in rats. The circuitry underlying the behavioral effects of intra-MRN injection of these drugs is not known. In order to identify the brain areas that may be involved, we measured levels of mRNA of the immediate early gene c-fos in discrete nuclei of the rat brain following intra-MRN infusions of these drugs. Male Wistar rats received intra-MRN infusions of 8-OH-DPAT (1 mug), muscimol (25 ng) or saline vehicle immediately prior to placement in locomotor activity chambers. Thirty minutes later, they were decapitated, and their brains processed for in situ hybridization of c-fos mRNA. In agreement with previous reports, injections of 8-OH-DPAT or muscimol into the MRN resulted in large increases in locomotor activity. Intra-MRN injections of these drugs increased c-fos in a number of brain nuclei previously shown to be involved in the rewarding effects of drugs of abuse in a regionally specific manner. Both drugs significantly increased the expression of c-fos mRNA in the medial frontal cortex, nucleus accumbens, lateral septum, dorsal bed nucleus of the stria terminalis and ventral tegmental area. In the ventral hippocampus, only 8-OH-DPAT increased c-fos, while in the basolateral nucleus of the amygdala and locus coeruleus, it was increased only by muscimol. These results are discussed in terms of the projections of the MRN and the pathways involved in relapse to alcohol and drug seeking.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2005

Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.

OBJECTIVE: The objective of this study was to assess the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Japanese renal transplant recipients. METHOD: The pharmacokinetic parameters of tacrolimus were calculated in steady-state on day 28 after transplantation. Polymerase chain reaction-restriction fragment length polymorphism and direct sequence methods were used for CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The dose-adjusted area under the concentration-time curve (AUC0-12) was significantly lower among CYP3A5*1 carriers than those bearing CYP3A5*3/*3. (0.570 +/- 0.105 vs 0.865 +/- 0.343 ng.h/mL per mg/kg, P = .00322). The daily tacrolimus dose per body weight was significantly higher in CYP3A5*1 carriers than those of CYP3A5*3/*3 carriers (0.271 +/- 0.110 vs 0.150 +/- 0.056 mg/kg, P = .00016). In this study, a distinction was made between carriers of CYP3A5*1/*1+*1/*3 and CYP3A5*3/*3 to investigate the influence of the MDR1 C3435T mutation on tacrolimus pharmacokinetics. The MDR1 C3435T polymorphisms did not affect any tacrolimus pharmacokinetic parameter in either group. CONCLUSIONS: Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC0-12 of tacrolimus. In contrast, MDR1 C3435T polymorphism was not an important factor in tacrolimus pharmacokinetics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein.

BACKGROUND: Achieving significant weight loss and glycemic control in diabetic patients remains a challenging task. OBJECTIVE: This study compared the effects of a soy-based meal replacement (MR) plan vs an individualized diet plan (IDP; as recommended by the American Diabetes Association) on weight loss and metabolic profile. DESIGN/SUBJECTS: A total of 104 subjects were randomized prospectively to the two treatments for a total of 12 months. RESULTS: In all, 77 of the 104 subjects completed the study. Percentage weight loss in MR group (4.57+/-0.81%) was significantly greater (P<0.05) than in IDP group (2.25+/-0.72%). Fasting plasma glucose was significantly reduced in MR group (126.4+/-4.9 mg/dl) compared with IDP group (152.5+/-6.6 mg/dl, P<0.0001) at 6 months but not at 12 months. Controlling for baseline levels, hemoglobin Alc level improved by 0.49+/-0.22% for those receiving MR when compared to IDP group (P<0.05). A greater number of subjects in MR group reduced their use of sulfonylureas (P<0.0001) and metformin (P<0.05) as compared to IDP group. High-sensitivity C-reactive protein (hs-CRP) decreased -26.3% (P = 0.019) in MR group compared to -7.06% (P = 0.338) in IDP group at 6 months. Similar changes were observed at 12 months with MR groups, with hs-CRP decreasing by -25.0% (P = 0.019) compared to -18.7% (P = 0.179) in IDP group. CONCLUSION: This study demonstrates that MR is a viable strategy for weight reduction in diabetic patients, resulting in beneficial changes in measures of glycemic control and reduction of medications.

Blood Glucose↗

PubMed2005

Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with and without metabolic syndrome.

OBJECTIVE: To evaluate the efficacy of very low calorie diet (VLCD) in black and white obese women. Changes in weight, metabolic profile, and body composition are assessed. METHOD: Patients are enrolled in a self-paid, university-based, outpatient weight loss program. All are prescribed VLCD (500-800 Cal/day), an exercise regimen, and group behavioral counseling. Black and white patients are matched for age, weight, body mass index, and by metabolic syndrome (MS) status. RESULTS: A total of 304 black and white women (152 in each group) were included the analysis. Approximately 40% of patients had MS (white women: 39.5%; black women: 41.2%). Mean baseline weights were similar. After 12 weeks, weight reduction of 9.97% was seen in white women and 9.02% drop was seen in black women (both P<0.0001). However, the degree of weight change was not different between the groups (P = 0.244). Marked improvements in fasting glucose, total cholesterol, LDL, triglyceride, and blood pressures (BP) were observed (all P<0.01); however, no difference between cohorts were seen. Patients with MS had higher baseline weight, BP, glucose and triglyceride levels when compared to patients without MS (all P<0.01). Significant reductions in % body fat were seen in white and black patients, independent of MS status. CONCLUSION: Obese patients, independent of race, were able to achieve significant weight loss when enrolled in a structured outpatient program. Weight loss significantly correlated with all aspects of MS. Our results suggest that differences seen in past studies may be influenced by socioeconomic and behavioral factors rather than differences in physiological response to dieting.

Adult↗

PubMed2005

Epigenetic changes in the repression and induction of asparagine synthetase in human leukemic cell lines.

In common with certain other lymphoid neoplasms, cells of the human lymphocytic leukemia lines 1873 and 1929 are asparagine (ASN) auxotrophs. Asparagine synthetase (ASY), which is a housekeeping gene, is repressed and the promoting region of the gene is highly methylated. We now demonstrate in these cells multiple levels in control of the expression of this gene, in a system of cocultivation with macrophages and other cell types. In this system, mediated by cell-to-cell contact, ASY becomes expressed by the leukemic cells and they become prototrophic. Demethylation of ASY occurs; it follows expression and is permanent over multiple cell generations, but the cells return to auxotrophy with rapid repression of ASY on removal from cell contact. With ASY expression, the associated histone H3 at lysine position 9 (H3K9) becomes acetylated and H3K4, methylated. In contrast to other systems, H3K9 methylation does not characterize the repressed state. The changes leading from repression to induction of ASY and demethylation parallel the physiological changes specific to functional maturation of normal lymphoid precursors. The lability of expression of ASY has potential significance in determining the sensitivity of leukemic cells to L-asparaginase.

Acetylation↗

PubMed2005

Power and related statistical properties of conditional likelihood score tests for association studies in nuclear families with parental genotypes.

Both population based and family based case control studies are used to test whether particular genotypes are associated with disease. While population based studies have more power, cryptic population stratification can produce false-positive results. Family-based methods have been introduced to control for this problem. This paper presents the full likelihood function for family-based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The likelihood of a family factors into the probability of parental mating type, conditional on offspring phenotypes, times the probability of offspring genotypes given their phenotypes and the parental mating type. The first factor can be influenced by population stratification, whereas the latter factor, called the conditional likelihood, is not. The conditional likelihood is used to obtain score tests with proper size in the presence of population stratification (see also Clayton (1999) and Whittemore & Tu (2000)). Under either the additive or multiplicative model, the TDT is known to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT-like procedures. The relative informativeness of the various mating types is assessed using the Fisher information, which depends on the number of affected and unaffected offspring and the penetrances. When the additive model is true, families with parental mating type Aa x Aa are most informative. Under the dominant (recessive) model, however, a family with mating type Aa x aa(AA x Aa) is more informative than a family with doubly heterozygous (Aa x Aa) parents. Because we derive explicit formulae for all components of the likelihood, we are able to present tables giving required sample sizes for dominant, additive and recessive inheritance models.

Case-Control Studies↗

PubMed2005

Results of surgical treatment of congenital cystic lung disease.

OBJECTIVE: To review the experience with surgical intervention for congenital cystic lung disease (CCLD). METHODS: From April 1988 to December 2001, 68 patients were diagnosed and treated surgically for CCLD. There were 27 males and 41 females ranging in age from 2 to 65 years. The majority of the cases were diagnosed by history, clinical manifestations and chest radiography or computerized tomography (CT). There were 25 (36.8 %) right-sided and 43 (63.2 %) left-sided cystic lung lesions. Four patients had massive bleeding and needed urgent or emergency operation. Pneumonectomy, lobectomy, and/or segmentectomy were performed. RESULTS: 29 (42.6 %) patients underwent lobectomy, 25 (36.8 %) had total pneumonectomy, 9 (13.2 %) lobectomy plus segmentectomy, and 5 (7.4 %) bilobectomy. During the operation, left-sided pulmonary sequestration was confirmed in 3 patients. No death occurred in this series. Diagnoses were confirmed by pathology in all cases. Two patients had malignant lesions arising from multicystic lung lesions. CONCLUSIONS: A history of recurrent pneumonia, often with hemoptysis and subsequent dyspnea, should raise the suspicion of CCLD. The diagnosis can be confirmed by chest X-ray and CT preoperatively, and early surgical intervention may avoid the development of serious complications. Delayed diagnosis and surgical management usually result in significant morbidity and mortality.

Adolescent↗

PubMed2005

Up-regulation of macrophage migration inhibitory factor in infants with acute neonatal necrotizing enterocolitis.

AIMS: To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in necrotizing enterocolitis (NEC). METHODS AND RESULTS: The expression of MIF mRNA and protein in NEC guts was assayed by in situ hybridization and immunohistochemistry, respectively. Concentrations of MIF, interleukin (IL)-6 and IL-8 in the serum and in the supernatant of macrophage cultures were examined by ELISA. Increased expression of MIF mRNA and protein was observed in the NEC guts, mainly in the infiltrating macrophages in the mucosa and submucosal layers. Up-regulation of MIF was associated with the accumulation of macrophages and T cells. In addition, serum levels of MIF, IL-6 and IL-8 in NEC patients during the acute stage of the disease were significantly increased. The expression of MIF decreased both locally and systemically after the disease was resolved. MIF was also found to increase the secretion of IL-6 and IL-8 by macrophages isolated from healthy individuals in vitro in NEC. CONCLUSIONS: MIF acts by stimulating macrophage production of IL-6 and IL-8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.

Acute Disease↗

PubMed2005

Peripheral B lymphocyte beta1,3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy.

PURPOSE: Aberrant O-glycosylation of serum IgA(1) is presumed to be one of the main pathogenesis of immunoglobulin A nephropathy (IgAN). beta1,3-galactosyltransferase (beta1,3GT), whose activity requires coexistence of a specific chaperone, is the main enzyme which participate in the glycosylation process. The current study was carried out to elucidate the expression level of beta1,3GT (C1GALT1) and its chaperone (Cosmc) in IgAN, and their relationships with clinical features as well as IgA glycosylation level. DESIGN, SETTING AND SUBJECTS: Forty-one patients with IgAN, 21 patients with non-IgAN glomerulonephritis and 26 normal controls were included in the present study. Peripheral B lymphocytes were isolated, and then expression level of C1GALT1 and Cosmc were quantitatively measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Serum IgA level and glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding method. Correlation analysis was performed between C1GALT1/Cosmc expression levels and clinical manifestations (severe proteinuria, renal dysfunction, gross haematuria). RESULTS: B-lymphocyte Cosmc gene expression level was significantly lower in IgAN patients than that of normal control and non-IgAN patients (P<0.05), whilst no apparent disparity was observed in C1GALT1 expression level. Cosmc expression showed a negative correlation with IgA O-glycosylation level indicated by VV lectin-binding assay. Statistical analysis also indicated that the level of Cosmc expression was negatively correlated with severe proteinuria (P<0.05) instead of gross haematuria (P>0.05). CONCLUSION: These data suggested that the aberrant IgA O-glycosylation in IgAN was resulted from a downregulation of beta1,3GT chaperone (Cosmc) expression in B lymphocyte, which is closely associated with clinical characteristics of the disease. This downregulation might be one of the fundamental pathogenic abnormalities in IgAN.

Adult↗

PubMed2005

Immobilization and condensation of DNA with 3-aminopropyltriethoxysilane studied by atomic force microscopy.

We used different methods to modify a mica surface with 3-aminopropyltriethoxysilane (APTES), and then used it as substrate to immobilize DNA for atomic force microscopy (AFM) observation. The evaporation method and solution modifying method were investigated and evaluated. The solution modifying method was found to be relatively simple and effective. Using an APTES solution-modified mica surface, DNA immobilization appeared more reproducible and it could be imaged in liquid. The mixed solution of APTES and DNA was dropped directly onto the mica surface for AFM imaging. We found that DNA can condense in APTES water solutions. Toroids, rods and intermediate structures of condensation were captured by AFM.

DNA↗

PubMed2005

A study of three measures of expressed emotion in a sample of Chinese families of a person with schizophrenia.

Emotional climate or expressed emotion (EE) has been examined in families of white descent who have a family member with schizophrenia but few studies have been conducted in Asian or Chinese families. This study tested the utility of the five-minute interview (FMI), adjective checklist (ACL) and family attitude scale (FAS) in a sample of Chinese family members in Beijing, in an attempt to introduce useful measures of EE into practice. A sample of 51 family members were interviewed and administered the three instruments. A total of 29.4% of families were found to be high-EE critical and 13.7% high-EE emotional over involvement using the FMI. The FAS and ACL prove internally consistent and were significantly correlated but not with the FMI. Cultural explanations for the discrepancies are offered. The measures have applicability in terms of understanding family relationships but further research and replication is necessary to deepen our understanding of EE in Chinese families.

Adaptation, Psychological↗