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X Xie

Publications and source records attributed to X Xie.

At least 91 records · Page 5Linked to original sources
PubMed1999

The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue.

BACKGROUND: Bax, Bcl-2, and p53 proteins are involved in the regulation of apoptosis and have been reported to correlate with prognosis in several tumor types. METHODS: Bax, Bcl-2, p53, and the level of spontaneous apoptosis were evaluated in formalin fixed, paraffin embedded pretreatment specimens from 85 T1-4 squamous cell carcinomas (SCCs) of the tongue by immunohistochemical methods. The percentage of apoptotic cells labeled by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP labeling (TUNEL) method was expressed as an apoptotic index (AI). For Bax and Bcl-2 evaluation, the fraction of tumor cells stained and the staining intensities were given scores that were added together, resulting in a final score. p53 immunostaining was expressed as a percentage of positive cells. RESULTS: High AI was significantly associated with high Bax expression (P = 0.0122) and highly differentiated tumors (P = 0.0062). No correlation was found between AI and Bcl-2 expression. There was no correlation between p53 positivity and any of the other apoptosis-related parameters. Whereas low AI scores and low Bax expression correlated significantly with poor prognosis (P = 0.0053 and P = 0.0012, respectively), a low Bcl-2 expression was associated with a favorable clinical outcome (P = 0.0262). Patients with a high Bcl-2/Bax expression ratio had a significantly poorer prognosis than those with a low ratio (P < 0.0001). Multivariate analysis revealed that Bax expression, the Bcl-2/Bax expression ratio, and the T and N classifications were significantly independent prognostic variables. The Bcl-2/Bax expression ratio was the strongest independent prognostic parameter. CONCLUSIONS: AI, individual Bax and Bcl-2 expression, and particularly the Bcl-2/Bax expression ratio have prognostic value in SCC of the tongue.

Adult↗
PubMed1999

Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays.

Evaluation of a biased "library" of pyrrolo[2,3-d]pyrimidines using yeast-based functional assays expressing human A1- and A2a-adenosine receptors, led to the A1 selective antagonist 4b. A direct correlation between yeast functional activity and binding data was established. Practical compounds with polar residues at C-4 of the pyrrolopyrimidine system required H-bond donor functionality for high potency.

Binding, Competitive↗
PubMed1999

Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide.

Joint immunization with two recombinant adenoviruses, one expressing hepatitis C virus (HCV) core and E1 proteins and another expressing IL-12 (RAdIL-12), strongly potentiates cellular immune response against HCV Ags in BALB/c mice when RAdIL-12 was used at doses of 1 x 105-1 x 107 plaque-forming units. However, cellular immunity against HCV Ags was abolished when higher doses (1 x 108 plaque-forming units) of RAdIL-12 were used. This immunosuppressive effect was associated with marked elevation of IFN-gamma and nitric oxide in the serum and increased cell apoptosis in the spleen. Administration of N-nitro-L -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, to mice that received high doses of RAdIL-12 was lethal, whereas no apparent systemic toxicity by L -NAME was observed in those immunized with lower doses of the adenovirus. Interestingly, in mice immunized with recombinant adenovirus expressing core and E1 proteins of HCV in combination with RAdIL-12 at low doses (1 x 107 plaque-forming units), L -NAME inhibited T cell proliferation and CTL activity in response to HCV Ags and also production of Abs against adenoviral proteins. In conclusion, gene transfer of IL-12 can increase or abolish cell immunity against an Ag depending of the dose of the vector expressing the cytokine. IL-12 stimulates the synthesis of NO which is needed for the immunostimulating effects of IL-12, but apoptosis of T cells and immunosuppression ensues when IFN-gamma and NO are generated at very high concentrations.

Adenoviridae↗
PubMed1999

Oligomerization and scaffolding functions of the erythropoietin receptor cytoplasmic tail.

Signal transduction by the erythropoietin receptor (EPOR) is activated by ligand-mediated receptor homodimerization. However, the relationship between extracellular and intracellular domain oligomerization remains poorly understood. To assess the requirements for dimerization of receptor cytoplasmic sequences for signaling, we overexpressed mutant EPORs in combination with wild-type (WT) EPOR to drive formation of heterodimeric (i.e. WT-mutant) receptor complexes. Dimerization of the membrane-proximal portion of the EPOR cytoplasmic region was found to be critical for the initiation of mitogenic signaling. However, dimerization of the entire EPOR cytoplasmic region was not required. To examine this process more closely, we generated chimeras between the intracellular and transmembrane portions of the EPOR and the extracellular domains of the interleukin-2 receptor beta and gammac chains. These chimeras allowed us to assess more precisely the signaling role of each receptor chain because only heterodimers of WT and mutant receptor chimeras form in the presence of interleukin-2. Coexpression studies demonstrated that a functional receptor complex requires the membrane-proximal region of each receptor subunit in the oligomer to permit activation of JAK2 but only one membrane-distal tail to activate STAT5 and to support cell proliferation. Thus, this study defines key relationships involved in the assembly and activation of the EPOR signal transduction complex which may be applicable to other homodimeric cytokine receptors.

Base Sequence↗
PubMed1999

Association of nonspecific minor ST-T abnormalities with cardiovascular mortality: the Chicago Western Electric Study.

CONTEXT: Minor electrocardiographic (ECG) ST-T abnormalities are common, but their prognostic importance has not been fully determined. OBJECTIVE: To examine associations of single (1 time only) and multiple (2 times only and > or =3 times) nonspecific minor ST-T abnormalities in 5 years with long-term mortality due to myocardial infarction (MI), coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in middle-aged men. DESIGN: Prospective cohort study (29-year follow-up after 5 annual examinations). SETTING AND PARTICIPANTS: A total of 1673 men employed at the Western Electric Company in Chicago, III, aged 40 to 55 years at entry, with no evidence of CHD and no major ECG abnormalities throughout the first 5-year period. MAIN OUTCOME MEASURES: Minor ST-T abnormalities identified from annual resting ECGs and mortality ascertained from death certificates. RESULTS: Of the 1673 men, 173 had evidence of isolated nonspecific minor ST-T segment abnormalities. During the follow-up period, there were 234 deaths due to MI, 352 deaths due to CHD, 463 deaths due to CVD, and 889 deaths due to all causes. For men with 3 or more annual recordings of minor ST-T abnormalities, risk of death due to MI, CHD, CVD, and all causes was significantly greater than for those with normal ECG findings. For men with 3 or more ECGs with minor ST-T abnormalities, relative risks (and 95% confidence intervals) adjusted for cardiovascular and other risk factors were 2.28 (1.16-4.49), 2.39 (1.39-4.12), 2.30 (1.44-3.68), and 1.60 (1.06-2.42), respectively, with a graded relationship between frequency of occurrence of ST-T abnormalities and mortality risk (linear trend, P< or =.007). CONCLUSIONS: Persistent, minor, nonspecific ST-T abnormalities are associated with increased long-term risk of mortality due to MI, CHD, CVD, and all causes; the higher the frequency of occurrence of minor ST-T abnormalities, the greater the risk. These data underscore the potential value of including nonspecific ECG findings in the overall assessment of cardiovascular risk.

Adult↗
PubMed1999

The economic consequences of smoking in Ontario.

Smoking causes health and social problems such as sickness, death, fire, injury, pain and suffering. This paper provides an estimate of the economic burden imposed by the adverse health and social consequences of smoking in Ontario in 1992. The cost-of-illness method, in particular, the human-capital approach is used to estimate the prevalence-based economic costs of smoking. The direct and indirect components of smoking-related costs are estimated and the total cost in Ontario is US$2.91 billion. Associated with these economic costs are health-related harms: 69,318 hospital separations; 1,007,647 days stay in hospitals; 11,648 deaths resulting in more than 171,443 person-years lost.

Adolescent↗
PubMed1999

Prognostic significance of proliferative and apoptotic markers in oral tongue squamous cell carcinomas.

The prognostic impact of proliferative and apoptotic markers was studied in 85 T1-4 oral tongue squamous cell carcinomas (SCCs). Ki67 immunoreactivity and AgNOR counts, including mean AgNOR counts (mAgNOR) and the percentage of nuclei with more than one AgNOR (pAgNOR > 1), were used as proliferative parameters. The apoptotic index (AI) was assessed using the TUNEL method. Bax expression was detected immunohistochemically and scored. Bax expression correlated positively with AI (p = 0.0122). Ki67 correlated with both pAgNOR > 1 (p = 0.0042) and mAgNOR (p = 0.0189). Low Bax expression and low AI correlated significantly with the disease-free period (p = 0.0001 and p = 0.0024, respectively). High values for Ki67, pAgNOR > 1 and mAgNOR correlated with poor prognosis (p = 0.0021, p = 0.0001 and p = 0.0244, respectively). Combinations of proliferative and apoptotic parameters were stronger predictors than individual parameters (p < 0.0001). pAgNOR > 1-Bax expression appeared to be the best combination (p < 0.0001). We conclude that proliferative and apoptotic markers, especially their combinations, have prognostic value in tongue SCC.

Adult↗
PubMed1999

Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling.

We describe genetic screens in Saccharomyces cerevisiae designed to identify mammalian nonreceptor modulators of G-protein signaling pathways. Strains lacking a pheromone-responsive G-protein coupled receptor and expressing a mammalian-yeast Galpha hybrid protein were made conditional for growth upon either pheromone pathway activation (activator screen) or pheromone pathway inactivation (inhibitor screen). Mammalian cDNAs that conferred plasmid-dependent growth under restrictive conditions were identified. One of the cDNAs identified from the activator screen, a human Ras-related G protein that we term AGS1 (for activator of G-protein signaling), appears to function by facilitating guanosine triphosphate (GTP) exchange on the heterotrimeric Galpha. A cDNA product identified from the inhibitor screen encodes a previously identified regulator of G-protein signaling, human RGS5.

Cloning, Molecular↗
PubMed1999

The anticonvulsant BW534U87 depresses epileptiform activity in rat hippocampal slices by an adenosine-dependent mechanism and through inhibition of voltage-gated Na+ channels.

1. The cellular and molecular actions of BW534U87 were studied using intracellular and extracellular recordings from the CA1 region of rat hippocampal slices and whole-cell voltage-clamp recordings of recombinant human brain type IIA Na+ channels expressed in Chinese hamster ovary (CHO) cells. 2. Normal excitatory and inhibitory postsynaptic potentials evoked in hippocampal slices were unaffected by BW534U87 or the adenosine deaminase inhibitor EHNA. However, epileptiform activity was depressed by BW534U87 (50 micronM) and this inhibition was reversed by the adenosine receptor antagonist 8-phenyl theophylline (8-PT, 30 micronM). EHNA (10 micronM) mimicked the effects of BW534U87. Furthermore, BW534U87 enhanced the inhibitory effects of exogenous adenosine on evoked synaptic potentials. BW534U87 (50 micronM) also voltage- and use-dependently inhibited action potentials elicited by current injection, independent of the adenosine system, since it was not affected by 8-PT. 3. In CHO cells expressing the recombinant human brain Na+ channel, BW534U87 produced a concentration- and voltage-dependent inhibition of Na+ currents with a half-maximal inhibitory concentration of 10 micronM at a Vh of -60 mV. Use-dependent inhibition was evident at high-frequencies (20x20 ms pulse train at 10 Hz). 4 In conclusion, BW534U87 blocks hippocampal epileptiform activity by a dual mechanism. The first action is similar to that produced by EHNA and is dependent on endogenous adenosine probably by inhibition of adenosine deaminase. Secondly, BW534U87 directly inhibits voltage-gated Na+ channels in a voltage- and frequency-dependent manner. Both actions of BW534U87 are activity-dependent and may synergistically contribute to its overall anticonvulsant effects in animal models of epilepsy.

Action Potentials↗
PubMed1999

Validation of a leg-to-leg bioimpedance analysis system in assessing body composition in postmenopausal women.

OBJECTIVES: To evaluate the validity of a leg-to-leg bioimpedance analysis (BIA) system in predicting body composition as measured by dual-energy X-ray absorptiometry (DXA) in postmenopausal women. SUBJECTS AND METHODS: Body fat mass (FM), %Fat and fat free mass (FFM) were measured in 124 postmenopausal women (age: 51-63 y, body mass index (BMI): 17-38 kg/m2) first by the leg-to-leg BIA system, and then by DXA as reference method. Bland-Altman analysis was used to determine the bias and 95% limits of agreement between the two methods for the assessment of the individual. Precision error (CV%) of the BIA system was obtained by repeated measurements with intermediate repositioning. RESULTS: The leg-to-leg BIA system had a high reproducibility with within-day CVs being 0.6% for FFM and 1.1% for FM, and between-day CVs about twice that. The impedance index (Ht2/Z) obtained by the leg-to-leg BIA was moderately correlated to FFM measured by DXA (r=0.66). A significant, systematic bias was observed between the two methods. The BIA system overestimated FM by a mean of 3.1 kg, and underestimated FFM by 2.7 kg. The analysis of 95% limits of agreement showed that for most individuals, %Fat estimated by the BIA might differ from that measured by DXA by 12% below to 45% above, indicating the lack of agreement between the two methods for the assessment of the individual. CONCLUSIONS: The leg-to-leg BIA system can provide simple, rapid and highly reproducible measurements of body composition for groups, but it has limited accuracy for the assessment of the individual. Population-specific equations will be needed to improve its accuracy in estimating body composition in postmenopausal women.

Absorptiometry, Photon↗
PubMed1999

Influence of local haemodynamics on leucocyte rolling and chemoattractant-induced firm adhesion in microvessels of the rat mesentery.

Tissue hyperaemia, oedema formation and leucocyte accumulation are characteristic features of the inflammatory process referable to changes at the microcirculatory level. Here, we used intravital fluorescence video microscopy to assess relationships among haemodynamical parameters, leucocyte rolling, and chemoattractant-induced firm adhesion in small venules (13-24 microM) of the rat mesentery. The rolling leucocyte flux in these vessels was directly proportional to the total leucocyte flux (r = 0.76, P < 0.001), which in turn closely correlated to the venular blood flow (r = 0.77, P < 0.001). Consequently, the rolling to total leucocyte flux fraction, averaging 39 +/- 15%, did not vary with the blood flow and showed no correlation to either blood flow velocity (r = -0.15, P = 0.42) or wall shear rate (r = -0.06, P = 0.77), indicating that the extent of leucocyte rolling is not primarily dependent on the fluid viscous drag at physiological blood flow rates in vivo. Stimulation of the mesentery with the chemoattractant fMLP (10(-6) M) induced firm adhesion of rolling leucocytes. It was found that the number of adherent leucocytes in individual vessels was directly related to the rolling leucocyte flux (r = 0.78, P < 0.001) and hence to the venular blood flow (r = 0.47, P < 0.05), while there was no correlation to the wall shear rate (r = 0.27, P = 0.24). The dependence of the firm adhesive response on the blood flow level and the delivery rate of leucocytes was confirmed at the whole organ level. Thus, leucocyte accumulation in rat skin lesions was markedly enhanced when a vasodilator was co-administered with the chemotactic stimulus compared with chemotactic stimulation alone. The data indicate that, within a physiological blood flow range, the leucocyte response to chemotactic stimulation is largely independent of the prevailing hydrodynamic shear forces. Instead, manifestation of the firm adhesive response, because of its dependence on the preceding rolling interaction, is clearly related to the blood flow level in the microvessels, which emphasizes the significance of tissue hyperaemia in inflammation.

Animals↗
PubMed1999

Assessment methods for alcohol consumption, prevalence of high risk drinking and harm: a sensitivity analysis.

BACKGROUND: There are no standardized ways to assess alcohol consumption in epidemiological studies. The main objective of the present study was to compare three widely used methods for assessing alcohol consumption with respect to resulting prevalence estimates for high risk drinking and harm as defined by morbidity and mortality indicators. METHODS: A within-subjects design was used to compare a quantity frequency, a graduated frequency, and a weekly drinking recall measure. Data consisted of a representative sample of 3961 adult residents of the province of Ontario, Canada, who participated in a multi-wave cross-sectional survey between 1990-1994. Cross-tabulation, Spearman correlation, and standard methodologies for prevalence-based cost-of-illness studies were used. RESULTS: The graduated frequency measure consistently yielded higher estimates of the prevalences of high risk drinking and harm. Differences were marked on all indicators, but were most pronounced for harmful drinking as defined by consuming an average of >60 g pure alcohol per day for males, and >40 g per day for females. Prevalence estimates of harmful drinking were almost five times higher for graduated frequency versus weekly drinking measures, and almost three times higher for graduated frequency versus quantity frequency measures. CONCLUSIONS: The characteristics of different measures of alcohol consumption should be considered in future research in epidemiology.

Adult↗
PubMed1999

Prognostic value of Le(y) and H antigens in oral tongue carcinomas.

OBJECTIVE: To investigate the prognostic significance of the carbohydrate epitopes H and Le(y) and their relationship with proliferation and apoptosis. STUDY DESIGN: Eighty randomly selected patients with T1-T4 oral tongue squamous cell carcinoma (SCC) were studied. Serial sections were cut from diagnostic, formalin-fixed, paraffin-embedded specimens. METHODS: Sections were stained immunohistochemically for H antigen and Le(y). RESULTS: Expression of H antigen was associated positively with Le(y) expression (P = .0001). Expressions of H antigen or Le(y) correlated with the proliferative markers Ki67 (P = .0442 and P = .0003, respectively) and pAgNOR > 1 (P = .0674 and P = .0047, respectively), but not with apoptotic markers such as Bax expression or the apoptotic index (AI). Tumors that expressed H antigen and high levels of Le(y) (> 50%) had a poor prognosis (P = .0006 and P = .0056, respectively). Combinations of expression of H antigen and Le(y), and either proliferative or apoptotic markers revealed an enhanced prognostic potential (P < .0001). The combination of pAgNOR score greater than 1 and H-antigen expression appeared to be the best combination to predict good prognosis. CONCLUSION: The expression of H antigen and Le(y), especially their combination with proliferative or apoptotic markers, has prognostic value in tongue SCC.

ABO Blood-Group System↗
PubMed1999

Detection of hypoxic cells in murine tumors using the comet assay: comparison with a conventional radiobiological assay.

The comet (single-cell electrophoresis) assay has been developed as a method for measuring DNA damage in single cells after irradiation. We have developed our own methods and image analysis system for the comet assay to identify hypoxic fractions. In vitro, we tested our system using a cultured tumor cell line (SCCVII). In vivo, we compared the hypoxic fractions detected by this assay with those determined by the in vivo-in vitro clonogenic assay using two rodent tumors (SCCVII/ C3H, EMT6/KU/balb/c), which exhibit different types of hypoxia: acute and chronic. In vitro, our method could differentiate hypoxic cells from oxic cells, using the parameter of tail moment. In vivo, there were good correlations between the hypoxic fractions determined by the comet assay and by the clonogenic assay, in SCCVII/C3H (r=0.85) and in EMT6/KU/balb/c (r=0.75) tumors. By comparison of the two methods in chronically hypoxic and acutely hypoxic tumors, we further confirmed that the comet assay is clinically useful for estimating hypoxic fractions of solid tumors.

Animals↗
PubMed1999

17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation.

Gonadal steroid hormones influence CNS functioning through a variety of different mechanisms. To test the hypothesis that estrogen modulates synaptic plasticity in the hippocampus, in vitro hippocampal slices from 2-mo-old Sprague-Dawley male rats were used to determine the effect of 17beta-estradiol on both N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potentials (EPSPs) through intracellular recordings and long-term potentiation (LTP) through extracellular recordings. Intracellular EPSPs and extracellular field EPSPs (fEPSPs) were recorded from CA1 pyramidal cells by stimulating Schaffer collateral fibers. In intracellular experiments, slices were perfused with medium containing bicuculline (5 microM) and low Mg2+ (0.1 mM) to enhance the NMDA receptor-mediated currents and 6, 7-dinitroquinoxaline-2,3-dione (DNQX) (10 microM) to block the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprianate (AMPA) receptor-mediated component. The effects of 17beta-estradiol on NMDA receptor-mediated activity were excitatory; concentrations >10 nM induced seizure activity, and lower concentrations (1 nM) markedly increased the amplitude of NMDA-mediated EPSPs (both the first and second responses increased during paired pulse stimulation by 180 and 197%, respectively). In extracellular experiments, slices perfused with 17beta-estradiol (100 pM) exhibited a pronounced, persisting, and significant enhancement of LTP of both the fEPSP slope (192%) and fEPSP amplitude (177%) compared with control slices (fEPSP slope = 155%; fEPSP amplitude = 156%) 30 min after high-frequency stimulation. These data demonstrate that estrogen enhances NMDA receptor-mediated currents and promotes an enhancement of LTP magnitude.

2-Amino-5-phosphonovalerate↗
PubMed1999

Morbidity and mortality attributable to alcohol, tobacco, and illicit drug use in Canada.

OBJECTIVES: This study estimated morbidity and mortality attributable to substance abuse in Canada. METHODS: Pooled estimates of relative risk were used to calculate etiologic fractions by age, gender, and province for 91 causes of disease or death attributable to alcohol, tobacco, or illicit drugs. RESULTS: There were 33,498 deaths and 208,095 hospitalizations attributed to tobacco, 6701 deaths and 86,076 hospitalizations due to alcohol, and 732 deaths and 7095 hospitalizations due to illicit drugs in 1992. CONCLUSIONS: Substance abuse exacts a considerable toll on Canadian society in terms of morbidity and mortality, accounting for 21% of deaths, 23% of years of potential life lost, and 8% of hospitalizations.

Adult↗
PubMed1999

Isolated tetrasomy 8 in minimally differentiated acute myeloid leukemia (AML-M0).

Tetrasomy 8 as a sole anomaly in hematological disorders is relatively rare. To the best of our knowledge, only 19 such cases have been described in the literature to date. Of them, acute myeloid leukemia (AML) in 13 (M1, one; M2, three; M4, one; M5, eight), acute lymphoblastic leukemia(ALL) in one, myelodysplastic syndrome(MDS) in 3, polycythemia vera(PV) and myelofibrosis(MF), one case each. Their median survival was 20 weeks. Here, we report the first case of a 29-year-old man with minimally differentiated AML (AML-M0) displaying a tetrasomy 8 clone. Immunophenotyping showed positivity with CD33, CD34 and intracellular MPO, but all lymphoid markers tested were negative. Conventional cytogenetics of bone marrow cells showed 84.9% of metaphases with tetrasomy 8 in addition to 15.1% with normal diploidy. However, Fluorescence in situ hybridization(FISH) using a centromeric probe specific for chromosome 8 revealed trisomy 8 in 14.2% of interphase nuclei besides tetrasomy 8 in 82.4%. The patient died four weeks after diagnosis without therapy. In conclusion, these findings suggest that tetrasomy 8 is associated with a heterogeneous group of myeloid disorders and heralds a bad prognosis. It may be a consequence of clonal evolution of trisomy 8.

Acute Disease↗