Biomedical subjects

J Cui

Publications and source records attributed to J Cui.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Relationship of vitamin D receptor polymorphism with breast cancer].

OBJECTIVE: To detect the association between vitamin D receptor polymorphism and breast cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used. Two restriction fragment length polymorphisms in the 3'region of vitamin D receptor (VDR) gene, Taq I and Apa I, were tested for association with breast cancer risk in 86 females with breast cancer and 134 healthy female controls. RESULTS: Allele frequencies of the 3'Taq I polymorphism showed a significant association (P=0.0004, OR:5.39,CI:1.81-17.20). The further study of genotype found the association of Tt, tt with breast cancer. The haplotype analysis of Apa I and Taq I showed a linkage disequilibrium between t-allele and A-allele. The frequency of tA haplotype was higher in breast cancer patients than in controls (P=0.001), indicating that tA haplotype is associated with breast cancer. The alleles and haplotype of the two loci had not any difference among the clinical subgroups. CONCLUSION: There is association between vitamin D receptor polymorphism and breast cancer.

Adult↗

PubMed2001

Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription.

Activation of brain natriuretic peptide (BNP) gene promoter activity represents one of the earliest and most reliable markers of ventricular cardiac myocyte hypertrophy. We recently demonstrated that mechanical strain increases immunoreactive BNP secretion, steady-state BNP mRNA levels and BNP gene transcriptional activity in neonatal rat myocyte cultures. We have also shown that strain-dependent BNP gene transcription is critically dependent on the functional integrity of a number of integrins (specfically beta1, beta3, and alpha(v)beta5 integrins) present on the surface of cardiac myocytes. When used alone, each of these antibodies resulted in a significant reduction in strain-dependent activation of a transfected hBNP-luciferase reporter and inhibition of a number of signaling pathways that have been linked to stimulation of this reporter (e.g., extracellular signal regulated kinase and c-Jun amino terminal kinase). The present study shows that combinations of these antibodies resulted in further reductions in hBNP gene promoter activity and inhibition of the relevant signaling cascades. These studies provide further support for the importance of integrin-matrix interactions in promoting strain-dependent changes in cardiac myocyte gene transcription.

Animals↗

PubMed2001

[Construction of c-fms antisense eukaryotic expressing vector bearing AFP enhancer and its clinical significance].

OBJECTIVE: To construct human c-fms antisense eukaryotic expressing vector that would express in human hepatoma cells efficiently and specifically and to observe its affection on biological behavior of hepatoma cells. METHODS: A c-fms fragment centered by TAC sequence coding for 571(st) tyrosine of CSF-1R was amplified with PCR. The fragment was cloned inversely into pcDNA(3) vector (constructed plasmid was named as 'pAS'). Amplified human AFP enhancer core region fragment was cloned into pAS (constructed plasmid was named as pAEAS). PcDNA(3), pAS and pAEAS were transfected into HepG(2) hepatoma cell line and HeLa cervical carcinoma cell line with calcium phosphate method, respectively. Growth rate and apoptosis of transfected cells were observed. RESULTS: Detected sequences of human c-fms antisense fragment and AFP enhancer core region fragment were both consistent with the sequences registered in Genbank. The growth rates of HepG(2) cells transfected with antisense gene were slower than control (P<0.05). The inhibitory effect of pAEAS was more remarkable than that of pAS (P<0.05). Apoptoic rates of pcDNA(3), pAS and pAEAS group cells in HepG(2) cells were 5.25%, 14.7% and 31.2%, respectively (P<0.01). Apoptoic DNA ladder was observed in pAEAS group. In HeLa cell groups, growth rates of cells in pAS and pAEAS groups were slower than control, while no difference was observed between them (P>0.05). Apoptoic rates of pcDNA(3), pAS and pAEAS group cells in HeLa cells were 3.99%, 8.27% and 8.66%, respectively (P<0.05). No apoptoic DNA ladder was observed in HeLa cells. CONCLUSIONS: Human c-fms antisense eukaryotic expressing vector bearing AFP enhancer selectively inhibit the growth of AFP positive hepatoma cells. It enables to induce apoptosis of hepatoma cells and is a new gene therapy method for hepatocellular carcinoma.

Apoptosis↗

PubMed2001

High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGFR) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo.

The epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases have been implicated in the development, progression, and severity of several human cancers and are attractive targets for therapeutic intervention. SU11925 was developed as a small molecule inhibitor of the tyrosine kinase activity of both EGFR and HER-2. In cellular assays, SU11925 exhibited similar potency against EGFR and HER-2, inhibiting EGF-stimulated EGFR autophosphorylation in A431 (human epidermoid carcinoma) cells with an IC(50) of 30 nM and HER-2 phosphorylation in SK-OV-3TP5 (human ovarian carcinoma) cells with an IC(50) of 38 nM. In contrast to its similar activity against the two targets in cellular assays, approximately 10-fold higher plasma concentrations of SU11925 were required to inhibit HER-2 phosphorylation in HER-2-overexpressing tumors compared with EGFR phosphorylation in EGFR-overexpressing tumors in vivo. Consistent with the proposed mechanism of action of this inhibitor, SU11925 inhibited the s.c. growth of EGFR- and HER-2-dependent tumors in athymic mice at doses that produced substantial inhibition of target receptor phosphorylation in vivo. An unexpected finding from these studies was that higher plasma concentrations of SU11925 were required to inhibit EGFR phosphorylation in vivo in tumors that also express high levels of HER-2 than in tumors that express EGFR alone. This observation, which suggests that it is more difficult to inhibit EGFR phosphorylation in vivo in cells that express high levels of HER-2, was confirmed with ZD1839 (Iressa), a selective EGFR inhibitor that also targets the tyrosine kinase catalytic site. The potential clinical implications of this observation are discussed.

Animals↗

PubMed2001

[Study on the protective effect of xinkang oral liquid on the isoproterenol-induced ischemic myocardial damage in rats].

OBJECTIVE: To study the protective effect of Xinkang oral liquid on the ischemic myocardial damage. METHODS: Ischemic myocardial damage model was obtained by i.p. 85 mg/kg isoproterenol. The level of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase (CK), lactic dehydrogenase (LDH) in the serum and endothelin (ET) in the plasma were detected. RESULTS: The level of ET, MDA, CK, LDH of Xinkang oral liquid group was much lower than that of model group (P < 0.01). The SOD activity was higher than that of model group (P < 0.01). The level of Xinkang oral liquid group was lower than that of Shuxin oral liquid group. The SOD activity of Xinkang oral liquid group was much higher than that of Shuxin oral liquid group (P < 0.01). CONCLUSION: Xinkang oral liquid can prevent the myocardium from ischemic damage.

Animals↗

PubMed2001

Influence of vestibulo-sympathetic reflex on muscle sympathetic outflow during head-down tilt.

To clarify the response of muscle sympathetic nerve activity (MSNA) to static stimulation of otolith organs in a craniocaudal direction (+Gz) in humans, we examined the effect of otolith stimulation on MSNA without changing the effect of cardiopulmonary baroreceptors using a 6-8.5 degrees head-down tilt (HDT) and lower body negative pressure (LBNP) device. Before the study, we established that 6-8.5 degrees HDT with 10 mmHg LBNP caused a fluid shift to the degree that the thoracic impedance was the same as the supine position without LBNP. Subjects were young male volunteers aged 22.1 +/- 3.8 years who gave informed consent. MSNA was recorded from the tibial nerve by microneurography simultaneously with heart rate (ECG), thoracic fluid volume (impedance method), and blood pressure (tonometric method). During 6-8.5 degrees HDT with 10 mmHg LBNP, MSNA was suppressed slightly without significantly changing heart rate, thoracic impedance, or mean arterial blood pressure. The results suggest that the sympathosuppression was related not to the result of cardiopulmonary [correction of cardioplumonary] loading but to the -Gz change (caudocranial direction [correction of dirction]) of 0.1 G. It is estimated that the vestibulo-sympathetic reflex may suppress sympathetic outflow to muscles in humans.

Adult↗

PubMed2001

[Advances on the biological effect indices for fine particles (PM2.5) in air].

Fine particles are complex mixture of air pollutants containing not only a great deal of organic compounds but also varied kind of metals, such as B(a)p, Pb, Cd, Cr etc. Most of those compounds are toxic. Some of them are the cause of lung inflammation and asthma, some are genotoxic with a potential of carcinogenesis. Because the fine particles can be inhaled into lung and deposit in lung tissue, which have adverse effects on human health. Epidemiological studies indicated that increased mortality and morbidity, especially for cardiovascular and lung diseases, was associated with the amount of ambient fine particles. Although some scientists thought fine particles damaging the body through oxidant stress, inflammation and genetic materials and so on, the mechanism for them is not known well. Therefore, it is necessary to explore the biological effects of fine particle on human health in the future.

Air Pollutants↗

PubMed2001

Effects of lower body positive pressure on muscle sympathetic nerve activity response [correction of respopnse] to head-up tilt.

The benefits of lower body positive pressure (LBPP) are generally accepted for clinical treatment in medical emergencies caused by massive bleeding to maintain the systemic blood pressure. They are also used by NASA post spaceflight for preventing orthostatic hypotension in the astronauts. However, controversy still exists concerning the mechanisms underlying LBPP benefits. The purpose of this study was to test the hypothesis that the baroreflex-mediated enhancement in sympathetic activity would be attenuated by LBPP during an orthostatic challenge in humans. Specifically, we studied 1) the sympathetic activity responses by the microneurographic technique, using direct intraneural measurement of muscle sympathetic nerve activity (MSNA); and 2) the contributions of preload and afterload to the chances in MSNA response during orthostasis on application of LBPP. To accomplish these issues, MSNA was recorded microneurographically along with noninvasive measurement of the cardiovascular variables in all the subjects during exposure to a 70 degrees HUT with 30-mm Hg LBPP.

Adult↗

PubMed2000

After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer.

Mutations in BRCA1 and BRCA2 that cause a dominantly inherited high risk of female breast cancer seem to explain only a small proportion of the aggregation of the disease. To study the possible additional genetic components, we conducted single-locus and two-locus segregation analyses, with and without a polygenic background, using three-generation families ascertained through 858 women with breast cancer diagnosed at age <40 years, ascertained through population cancer registries in Melbourne and Sydney, Australia. Extensive testing for deleterious mutations in BRCA1 and BRCA2, to date, has identified 34 carriers. Our analysis suggested that, after other possible unmeasured familial factors are adjusted for and the known BRCA1 and BRCA2 mutation carriers are excluded, there appears to be a residual dominantly inherited risk of female breast cancer in addition to that derived from mutations in BRCA1 and BRCA2. This study also suggests that there is a substantial recessively inherited risk of early-onset breast cancer. According to the best-fitting model, after excluding known carriers of mutations in BRCA1 and BRCA2, about 1/250 (95% confidence interval [CI] 1/500 to 1/125) women have a recessive risk of 86% (95% CI 69%-100%) by age 50 years and of almost 100% by age 60 years. Possible reasons that our study has implicated a novel strong recessive effect include our inclusion of data on lineal aunts and grandmothers, study of families ascertained through women with early-onset breast cancer, allowance for multiple familial factors in the analysis, and removal of families for whom the cause (i.e., BRCA1 or BRCA2) is known. Our findings may have implications for attempts to identify new breast cancer-susceptibility genes.

Age Factors↗

PubMed2000

Allosteric linkage between voltage and Ca(2+)-dependent activation of BK-type mslo1 K(+) channels.

The activation of BK type Ca(2+)-activated K(+) channels depends on both voltage and Ca(2+). We studied three point mutations in the putative voltage sensor S4 or S4-S5 linker regions in the mslo1 BK channels to explore the relationship between voltage and Ca(2+) in activating the channel. These mutations reduced the steepness of the open probability - voltage (P(o) - V) relation and increased the shift of the P(o) - V relations on the voltage axis in response to increases in the calcium concentration. It is striking that these two effects were reciprocally related for all three mutations, despite different effects of the mutations on other aspects of the voltage dependence of channel gating. This reciprocal relationship suggests strongly that the free energy contributions to channel activation provided by voltage and by calcium binding are simply additive. We conclude that the Ca(2+) binding sites and the voltage sensors do not directly interact. Rather they both affect the mslo1 channel opening through an allosteric mechanism, by influencing the conformational change between the closed and open conformations. The mutations changed the channel's voltage dependence with little effect on its Ca(2+) affinitiy.

Allosteric Regulation↗

PubMed2000

Spontaneous thrombosis in mice carrying the factor V Leiden mutation.

A polymorphism in coagulation factor V, factor V Leiden (FVL), is the major known genetic risk factor for thrombosis in humans. Approximately 10% of mutation carriers experience clinically significant thrombosis in their lifetime. In a small subset of patients, thrombosis is associated with coinheritance of other prothrombotic gene mutations. However, the potential contribution of additional genetic risk factors in the majority of patients remains unknown. To gain insight into the molecular basis for the variable expressivity of FVL, mice were generated carrying the homologous mutation (R504Q [single-letter amino acid codes]) inserted into the endogenous murine Fv gene. Adult heterozygous (FvQ/+) and homozygous (FvQ/Q) mice are viable and fertile and exhibit normal survival. Compared with wild-type mice, adult FvQ/Q mice demonstrate a marked increase in spontaneous tissue fibrin deposition. No differences in fetal development or survival are observed among FvQ/Q, FvQ/+ or control littermates on the C57BL/6J genetic background. In contrast, on a mixed 129Sv-C57BL/6J genetic background, FvQ/Q mice develop disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. These results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within FV among mammalian species and suggest an important contribution of other genetic factors to the thrombosis associated with FVL in humans. (Blood. 2000;96:4222-4226)

Activated Protein C Resistance↗

PubMed2000

CYP17 promoter polymorphism and breast cancer in Australian women under age forty years.

BACKGROUND: The cytochrome P450c17alpha enzyme functions in the steroid biosynthesis pathway, and altered endogenous steroid hormone levels have been reported to be associated with a T to C polymorphism in the 5' promoter region of the CYP17 gene. Because steroid hormone exposure is known to influence breast cancer risk, we conducted a population-based, case-control-family study to assess the relationship between the CYP17 promoter polymorphism and early-onset breast cancer. METHODS: Case subjects under 40 years of age at diagnosis of a first primary breast cancer, population-sampled control subjects, and the relatives of both case and control subjects were interviewed to record family history of breast cancer and other risk factors. CYP17 genotype was determined in 369 case subjects, 284 control subjects, and 91 relatives of case subjects. Genotype distributions were compared by logistic regression, and cumulative risk was estimated by a modified segregation analysis. All statistical tests were two-tailed. RESULTS: Compared with the TT genotype (i.e., individuals homozygous for the T allele), the TC genotype was not associated with increased breast cancer risk (P: =.7). Compared with the TT and TC genotypes combined, the CC genotype was associated with a relative risk of 1. 81 (95% confidence interval [CI] = 1.15-2.86; P: =.01) before adjustment for measured risk factors and 1.63 (95% CI = 1.00-2.64; P: =.05) after adjustment. There was an excess of CC genotypes in case subjects who had at least one affected first- or second-degree relative, compared with control subjects unstratified by family history of breast cancer (23% versus 11%; P: =.006), and these case subjects had a threefold to fourfold higher risk than women of other groups defined by genotype and family history of breast cancer. Analysis of breast cancer in first- and second-degree relatives of case subjects with the CC genotype, excluding two known carriers of a deleterious mutation in BRCA1 or BRCA2, gave a relative hazard in women with the CC genotype of 3.48 (95% CI = 1.13-10.74; P: =.04), which is equivalent to a cumulative risk of 16% to age 70 years. CONCLUSIONS: The CC genotype may modify the effect of other familial risk factors for early-onset breast cancer.

Adult↗

PubMed2000

Prothrombotic phenotype of protein Z deficiency.

Protein Z (PZ) is a vitamin K-dependent plasma protein whose function has been uncertain. The structure of PZ is very similar to that of the coagulation-related factors VII, IX, and X and PC, but PZ differs from these other proteins in that it is not the zymogen of a serine protease. We have shown recently that PZ forms a calcium ion-dependent complex with activated factor X at phospholipid surfaces and that this interaction leads to the inhibition of activated factor X activity through, in part, the action of a previously unidentified plasma protein named PZ-dependent protease inhibitor. Herein, we report that the presence of PZ dampens the coagulation response in human plasma and that concomitant PZ deficiency dramatically increases the severity of the prothrombotic phenotype of factor V(Leiden) mice. The results indicate that PZ plays a physiologically important role in the regulation of coagulation.

Animals↗

PubMed2000

An expressed sequence tag database of T-cell-enriched activated chicken splenocytes: sequence analysis of 5251 clones.

The cDNA and gene sequences of many mammalian cytokines and their receptors are known. However, corresponding information on avian cytokines is limited due to the lack of cross-species activity at the functional level or strong homology at the molecular level. To improve the efficiency of identifying cytokines and novel chicken genes, a directionally cloned cDNA library from T-cell-enriched activated chicken splenocytes was constructed, and the partial sequence of 5251 clones was obtained. Sequence clustering indicates that 2357 (42%) of the clones are present as a single copy, and 2961 are distinct clones, demonstrating the high level of complexity of this library. Comparisons of the sequence data with known DNA sequences in GenBank indicate that approximately 25% of the clones match known chicken genes, 39% have similarity to known genes in other species, and 11% had no match to any sequence in the database. Several previously uncharacterized chicken cytokines and their receptors were present in our library. This collection provides a useful database for cataloging genes expressed in T cells and a valuable resource for future investigations of gene expression in avian immunology. A chicken EST Web site (http://udgenome. ags.udel. edu/chickest/chick.htm) has been created to provide access to the data, and a set of unique sequences has been deposited with GenBank (Accession Nos. AI979741-AI982511). Our new Web site (http://www. chickest.udel.edu) will be active as of March 3, 2000, and will also provide keyword-searching capabilities for BLASTX and BLASTN hits of all our clones.

Animals↗

PubMed2000

Cyclic AMP regulates the HERG K(+) channel by dual pathways.

Lethal cardiac arrhythmias are a hallmark of the hereditary Long QT syndrome (LQTS), a disease produced by mutations of cardiac ion channels [1]. Often these arrhythmias are stress-induced, suggesting a relationship between beta-adrenergic activation of adenylate cyclase and cAMP-dependent alteration of one or more of the ion channels involved in LQTS. Second messengers modulate ion channel activity either by direct interaction or through intermediary kinases and phosphatases. Here we show that the second messenger cAMP regulates the K(+) channel mutated in the LQT2 form of LQTS, HERG [2], both directly and indirectly. Activation of cAMP-dependent protein kinase (PKA) causes phosphorylation of HERG accompanied by a rapid reduction in current amplitude, acceleration of voltage-dependent deactivation, and depolarizing shift in voltage-dependent activation. In a parallel pathway, cAMP directly binds to the HERG protein with the opposing effect of a hyperpolarizing shift in voltage-dependent activation. The summation of cAMP-mediated effects is a net diminution of the effective current, but when HERG is complexed with with the K(+) channel accessory proteins MiRP1 or minK, the stimulatory effects of cAMP are favored. These findings provide a direct link between stress and arrhythmia by a unique mechanism where a single second messenger exerts complex regulation of an ion channel via two distinct pathways.

Animals↗

PubMed2000

Coactivator-vitamin D receptor interactions mediate inhibition of the atrial natriuretic peptide promoter.

We have discovered a role for coactivators binding to the AF-2 surface of the vitamin D receptor (VDR) in its negative effects on gene transcription. We tested nine amino acid residues (Ser(235), Ile(242), Lys(246), Asp(253), Ile(260), Leu(263), Leu(417), Leu(419), and Glu(420)) in human VDR which, based on homology to the human thyroid hormone receptor, would be predicted to lie in or near the coactivator-binding site. Mutation of six of these residues in VDR resulted in loss of both the activation (assessed with a transfected DR3 TK luciferase reporter) and inhibition (assessed with an hANPCAT reporter) functions of the receptor when tested in cultured neonatal rat atrial myocytes and HeLa cells. Collectively, these mutations also suppressed association of VDR with the coactivators GRIP1 and steroid receptor coactivator 1 in vitro but had little or no effect on ligand binding, heterodimerization with the retinoid X receptor, or association with a VDR-specific DNA recognition element. Co-transfection with GRIP1 or steroid receptor coactivator 1 amplified both the positive and negative responses to wild type VDR but had little or no effect on the functionally impaired mutants described above. The interaction between VDR and GRIP1 proved to be heavily dependent upon the integrity of nuclear box III in the latter protein. Mutations in this region of GRIP1 impaired its ability to associate with VDR in vitro and to amplify VDR activity in intact cells. These studies establish a role for coactivators recruited to the same receptor surface in both the activating and inhibitory activity of the liganded receptor.

Amino Acid Sequence↗

PubMed2000

Estimating HIV incidence using dates of both HIV and AIDS diagnoses.

Knowledge of HIV incidence is important to formulate sensible strategies aimed at controlling the HIV/AIDS epidemic. Back-projection is one of the methods for reconstructing the HIV incidence curve from AIDS incidence data. However, because of the low risk of developing AIDS during the first few years after infection, precise estimates of HIV incidence for the recent past are unlikely if we use AIDS incidence data only. As a result there have been recent attempts to use, not only the date of AIDS diagnosis, but also to use the date of their first positive HIV test. The objective of this paper is to incorporate into back-projection the additional information provided by those individuals who have tested HIV positive but have not yet developed AIDS. This adds information on a very large number of other individuals, and provides the hope that the precision of back-projection is improved considerably. The date of a positive HIV test or an AIDS diagnosis of an individual, whichever comes first, is used in a generalized convolution equation for the purpose of back-projection. The method is illustrated by an application to Australian HIV and AIDS data. Study results show that dramatic improvement in precision is gained for estimates of HIV incidence in recent years when both HIV and AIDS diagnosis dates are used on all individuals.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[Study on the absorption of environmental contaminants in low-level exposure by pharmacokinetic analysis].

A dynamic generating toxic gas system and a nose-only exposure system were used for the pharmacokinetic study of inhaled environmental contaminants for benzene, toluene, xylene, ethylbenzene, chlorobenzene, styrene, isopropyl benzene, tetrachloroethylene, nonane and methylcyclohexane in male guinea pig. The change of these substances in blood with time was determined simultaneously by solid phase micro-extraction(SPME) gas chromatography (GC). The results showed that the fraction of absorption of benzene at low (121 micrograms/m3) exposure was 4.8 times higher than that at high(12.1 mg/m3) exposure. The pharmacokinetics of these substances were evaluated by using linear compartment models. The data showed that more styrene was absorbed than tetrachloroethylene at low-exposure. The metabolic elimination of these compounds at various exposure concentrations was extrapolated by using estimated pharmacokinetic parameters. Moreover, not only should the differences in absorption quantities be considered in evaluation of potential risk assessment, the metabolic elimination rates should also be considered although the exposure concentrations in gas for all chemicals were equal. The data presented in this paper was fundamental data used for risk assessment.

Air Pollutants↗