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S Liu

Publications and source records attributed to S Liu.

At least 145 records · Page 8Linked to original sources
PubMed2001

alpha4 integrin is expressed in a subset of cranial neural crest cells and in epicardial progenitor cells during early mouse development.

By RNA in situ hybridization and immunohistochemical analyses of early stage mouse embryos, we find that alpha 4 integrin gene is expressed in migratory cranial neural crest cells originating from the presumptive forebrain, midbrain, and rhombomeres 1 and 2 of the presumptive hindbrain. alpha 4 is also expressed in epicardial progenitor cells in the septum transversum that migrate to the heart.

Animals↗
PubMed2001

17beta-estradiol inhibits soluble guanylate cyclase activity through a protein tyrosine phosphatase in PC12 cells.

Besides its involvement in reproductive functions, estrogen protects against the development of cardiovascular diseases. The guanylate cyclase/cGMP system is known to exert potent effects on the regulation of blood pressure and electrolyte balance. We examined whether 17beta-estradiol can affect soluble guanylate cyclase in PC12 cells. The results indicate that 17beta-estradiol decreases cGMP levels in PC12 cells. 17beta-Estradiol decreases sodium nitroprusside (SNP)-stimulated, but not atrial natriuretic factor-stimulated cGMP formation in PC12 cells, indicating that 17beta-estradiol decreases cGMP levels by inhibiting the activity of soluble guanylate cyclase. 17beta-Estradiol also stimulates protein tyrosine phosphatase activities in PC12 cells and dephosphorylates at least three proteins. Addition of sodium vanadate, a protein tyrosine phosphatase inhibitor, blocks the inhibitory effects of 17beta-estradiol on soluble guanylate cyclase activity in PC12 cells. Furthermore, transfection of SHP-1, a protein tyrosine phosphatase, into PC12 cells inhibits both basal and SNP-stimulated guanylate cyclase activity. Amino acid analysis also reveals that the 70-kDa subunit of soluble guanylate cyclase contains the SHP-1 substrate consensus sequence. These results suggest that 17beta-estradiol inhibits soluble guanylate cyclase activity through SHP-1.

Animals↗
PubMed2001

Adverse outcomes in pregnancies of asthmatic women: results from a Canadian population.

PURPOSE: There has been little attention paid to asthma complicating pregnancy. This study is among the few studies that investigated this issue in a large Canadian population (more than two millions of Canadian pregnant women). METHODS: We carried out a historical cohort study using hospital discharge data collected by the Canadian Institute for Health Information for fiscal years 1989/90 to 1995/96. RESULTS: A total 2,017,553 obstetric deliveries were included in the analysis. Overall prevalence of asthma among these Canadian women were 0.43%, yielding a total of 8672 cases of asthmatic mothers. Maternal asthma was associated with all of the adverse pregnancy outcomes examined (including fetal death, preterm labour, hypertensive disorders of pregnancy, gestational diabetes, antepartum hemorrhage, infection of the amniotic cavity, premature rupture of membrane, cesarean delivery, as well as postpartum hemorrhage), and adjustment for important confounding factors by multiple logistic regression analysis did not change the overall results. These associations were consistently observed in teenage and adult mothers, although the associations in teenage mothers tended to be stronger than in adult mothers. CONCLUSIONS: This study confirms that pregnant women with asthma are at substantially increased risk for many adverse pregnancy outcomes. For this reason, pregnant women with asthma are a particularly high-risk group to which extra attention, including increased efforts at education, monitoring, and optimal asthma management, may be appropriate.

Adolescent↗
PubMed2001

Elucidation of CYP2E1 5' regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer.

The CYP2E1 gene, whose protein product plays an important role in the metabolism of various carcinogens, exhibits two polymorphisms recognized by the restriction enzymes RsaI and PstI in its transcriptional regulatory region that have been previously implicated in cancer susceptibility. In this study, we have examined these polymorphisms to elucidate CYP2E1 allelic haplotype, examining the prevalence of these CYP2E1 alleles in Caucasians and African Americans and their potential role in risk for oral cancer. In addition to the c1 (RsaI[+]/PstI[-]) and c2 (RsaI[-]/PstI[+]) alleles reported in previous studies, we have identified two new alleles, c3 (RsaI[+]/PstI[+]) and c4 (RsaI[-]/PstI[-]). The prevalence of the c2 and c3 alleles differs between racial groups, with African Americans exhibiting a lower prevalence of the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) than Caucasians (0.031 for c2 and 0.004 for c3). Of the 570 subjects screened in this study, the c4 allele was observed in one subject, a Caucasian case with the (c4/c4) genotype. A significant increase in the CYP2E1 (c1/c1) genotype was observed in oral cancer cases as compared to frequency-matched controls in subjects who smoked < or =24 pack-years (P=0.033). No association was observed between CYP2E1 genotype and risk for oral cancer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest that the c1 allele may contribute to increased risk for oral cancer.

Adult↗
PubMed2001

Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia.

The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.

Adolescent↗
PubMed2001

Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.

SUMMARY: DOC-2/hDab2 (DOC-2) has tumor suppressive functions in ovarian cancer and choriocarcinoma. In these tumors, it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. Pancreatic cancer exhibits a high frequency of K-ras gene mutations; however, it is not known whether DOC-2 expression is altered in these tumors. Therefore, we investigated DOC-2 expression in 22 pancreatic adenocarcinomas and in 6 pancreatic cancer cell lines. Findings in human tumors were compared with normal controls and correlated with clinicopathological data. Additionally, the influence of K-ras on DOC-2 transcription was investigated. Northern blot and Western blot analyses both demonstrated an increase of DOC-2 mRNA and protein levels in primary pancreatic cancers in comparison with normal controls. In situ hybridization showed DOC-2 mRNA expression in the majority of cancer cells of primary tumors, as well as in chronic pancreatitis-like lesions surrounding the cancer mass. Immunohistochemistry mirrored the in situ hybridization findings. In contrast, levels of expression of DOC-2 in lymph node metastases were markedly decreased in comparison with levels in primary tumors. In addition, in 5 metastatic pancreatic cancer cell lines, DOC-2 mRNA and protein levels were low, whereas quantitative RT-PCR demonstrated relatively higher levels in a nonmetastatic pancreatic cancer cell line. In conclusion, DOC-2 is overexpressed in primary pancreatic adenocarcinoma but down-regulated in metastatic disease, suggesting a tumor suppressor function of DOC-2 in the late steps of pancreatic carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Atrioventricular conduction: a determinant for the manifestation of ventricular preexcitation in patients with Wolff-Parkinson-White syndrome.

The relation between the atrioventricular conduction properties of the atrioventricular node and the anterograde conduction ability over the accessory pathway in the Wolff-Parkinson-White syndrome has never been studied. Atrioventricular nodal characteristics were studied in 285 patients with manifest and 204 with concealed accessory pathway who underwent radiofrequency ablation, and compared with 146 controls. First and second degree atrioventricular block was observed in 13 (5%) preexcitation patients after ablation, compared with none in concealed accessory pathway (P=0.001) and control patients (P=0.006). The atrial-His intervals in preexcitation patients (88 +/- 20 ms) was significantly longer than in concealed accessory pathway (76 +/- 15 ms, P<0.0001) and control patients (77 +/- 15 ms, P=0.0007), as was PR intervals (165 +/- 25 versus 149 +/- 20 and 150 +/- 21 ms, P<0.0001, respectively) even after excluding those with atrioventricular block. Significant differences in PR and atrial-His intervals were not observed between concealed accessory pathway and control patients. More preexcitation patients had ventriculoatrial dissociation than had patients in the other groups. The results indicate that atrioventricular block is not uncommon in preexcitation patients and a relatively long atrioventricular conduction time is an electrophysiological prerequisite for the manifestation of preexcitation in the Wolff-Parkinson-White syndrome.

Adult↗
PubMed2001

Molecular characterization and diversity of thermophilic iron-reducing enrichment cultures from deep subsurface environments.

AIMS: The objectives of this work were to explore the diversity in Fe (III)-reducing enrichment cultures from the deep subsurface and to identify strains involved in metal reduction. METHODS AND RESULTS: Analyses of 16S ribosomal RNA (rRNA) of enrichments, supplemented with hydrogen, acetate or pyruvate as an electron donor, identified three dominant operational taxonomic units (OTUs). All cultures exhibited considerable diversity (36-24 OTUs), even after being transferred at least nine times. Two OTUs were present in all three cultures, constituting about 65% of the total clones examined. CONCLUSION: Dominant OTUs appeared to be most closely related to Thermoanaerobacter ethanolicus or T. kivui. One OTU, which is potentially responsible for autotrophic Fe (III) reduction, was only about 95% similar to T. ethanolicus and may represent a new species. SIGNIFICANCE AND IMPACT OF THE STUDY: An unexpectedly high diversity was found in these enrichments and this diversity may be a feature that can be exploited.

Acetic Acid↗
PubMed2001

Contribution of androgens to chronic allograft nephropathy is mediated by dihydrotestosterone.

BACKGROUND: Donor and recipient gender influence long-term allograft outcome after kidney transplantation. Sex hormones are likely to contribute to these gender-related differences. The present study investigated the role of androgens and their inhibition on the development of chronic allograft nephropathy. METHODS: Male or female Fisher (F344) kidneys were orthotopically transplanted into intact male Lewis recipients. Animals were treated either with testosterone, the antiandrogen flutamide, the 5alpha-reductase inhibitor finasteride, or vehicle. Twenty weeks after transplantation animals were harvested for histology, immunohistology, and molecular analysis. RESULTS: Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-A and -B chain (PDGF-A and -B). In contrast, flutamide and finasteride reduced glomerulosclerosis as well as the inflammatory cell infiltration associated with decreased TGF-beta, PDGF-A, and -B chain mRNA expression. No gender-related donor differences were noted between the groups. CONCLUSIONS: Our data suggest that dihydrotestosterone mediates the adverse effects of androgens on chronic allograft nephropathy. The inhibition of androgens improves long-term allograft outcome after kidney transplantation.

Androgen Antagonists↗
PubMed2001

An unusual cause of tachycardiomyopathy: incessant atypical AV nodal reentrant tachycardia induced by 1:2 AV conduction.

We report a 62-year-old female with cardiomyopathy mediated by incessant atypical atrioventricular nodal reentrant tachycardia, which was induced by 1:2 atrioventricular conduction. Her arrhythmia was identified and cured by radiofrequency catheter ablation. Follow-up over the course of next 5 months the patient's cardiomyopathy dramatically improved.

Atrioventricular Node↗
PubMed2001

Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation.

The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.

Animals↗
PubMed2001

Gender and atrioventricular conduction properties of patients with symptomatic atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome.

The objective of this study was to delineate the sex distribution and atrioventricular conduction properties in patients with manifest or concealed Wolff-Parkinson-White syndrome (WPW) and atrioventricular nodal reentrant tachycardia (AVNRT). The study comprised 328 patients with AVNRT, 347 with manifest, and 220 with concealed WPW who underwent radiofrequency ablation. A male preponderance was observed in patients with manifest WPW (69%), but not in those with concealed WPW (52%) and female preponderance in AVNRT patients (67%). The PR (166 +/- 25 ms) and AH (88 +/- 20 ms) intervals obtained 30 minutes after ablation in manifest WPW patients were significantly longer than in concealed WPW patients (149 +/- 20, 76 +/- 15 ms, P <.0001). The PR (146 +/- 20 ms) and AH intervals (75 +/- 15 ms) measured before ablation in AVNRT patients were shorter than those obtained before ablation in concealed WPW patients (154 +/- 21, 80 +/- 17 ms, P <.05) and after ablation in manifest WPW patients (P <.0001). The PR interval in AVNRT patients was also shorter than those measured during follow-up in concealed (153 +/- 21 ms, P <.05) and manifest WPW patients (165 +/- 23 ms, P <.0001). The ventriculoatrial block cycle length in AVNRT patients was significantly shorter than in manifest and concealed WPW patients. When age-matched patients were assigned to each group, significant differences in PR interval were observed between men and women (159 +/- 22 vs. 151 +/- 22 ms, P <.0001). Differences in sex distribution exist among patients with manifest and concealed WPW and AVNRT. The atrioventricular conduction properties required for the manifestation of pre-excitation and induction of AVNRT and gender differences in atrioventricular conduction may account for the differences in sex distribution.

Adult↗
PubMed2001

Maternal asthma and pregnancy outcomes: a retrospective cohort study.

OBJECTIVE: We examined the relationship between asthma during pregnancy and selected infant and maternal outcomes. STUDY DESIGN: A retrospective cohort study was conducted on mother-infant dyads identified from a linked infant and maternal hospital discharge database in the Canadian province of Quebec between fiscal years 1991-1992 and 1995-1996. Mothers with asthma (n = 2193) were compared with a randomly selected control sample (n = 8772) from the remaining population of mothers. RESULTS: After important confounding variables were accounted for, maternal asthma was significantly associated with several adverse infant outcomes, including preterm birth and birth of infants who are very small for gestational age, and adverse maternal outcomes, such as idiopathic preterm labor, early idiopathic preterm labor, preeclampsia, transient hypertension of pregnancy, pregnancy-associated hypertension, chorioamnionitis, and cesarean delivery. CONCLUSION: Our results demonstrated that pregnant women with asthma are at substantially increased risk for several adverse infant and maternal outcomes and suggest the need for extra attention to mothers with asthma and their infants.

Abruptio Placentae↗
PubMed2001

Gender differences in the electrophysiological characteristics of atrioventricular conduction system and their clinical implications.

OBJECTIVE: The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff-Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. DESIGN: The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. RESULTS: The AH (83 +/- 15 ms) and His-ventricular intervals in men (42 +/- 6 ms) were significantly longer than in women (78 +/- 14, 38 +/- 6 ms, p < 0.05, respectively), as was the PR interval (160 +/- 17 vs 152 +/- 13 ms, p = 0.02). The effective refractory period of AV node in men (349 +/- 75 ms) was longer than in women (297 +/- 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 +/- 76 ms) than in women (330 +/- 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 +/- 107 vs 384 +/- 90 ms. p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). CONCLUSION: The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation.

Adult↗
PubMed2001

The cytoplasmic domain of the integrin alpha9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner.

The integrin alpha9 subunit forms a single heterodimer, alpha9beta1. The alpha9 subunit is most closely related to the alpha4 subunit, and like alpha4 integrins, alpha9beta1 plays an important role in leukocyte migration. The alpha4 cytoplasmic domain preferentially enhances cell migration and inhibits cell spreading, effects that depend on interaction with the adaptor protein, paxillin. To determine whether the alpha9 cytoplasmic domain has similar effects, a series of chimeric and deleted alpha9 constructs were expressed in Chinese hamster ovary cells and tested for their effects on migration and spreading on an alpha9beta1-specific ligand. Like alpha4, the alpha9 cytoplasmic domain enhanced cell migration and inhibited cell spreading. Paxillin also specifically bound the alpha9 cytoplasmic domain and to a similar level as alpha4. In paxillin(-/-) cells, alpha9 failed to inhibit cell spreading as expected but surprisingly still enhanced cell migration. Further, mutations that abolished the alpha9-paxillin interaction prevented alpha9 from inhibiting cell spreading but had no effect on alpha9-dependent cell migration. These findings suggest that the mechanisms by which the cytoplasmic domains of integrin alpha subunits enhance migration and inhibit cell spreading are distinct and that the alpha9 and alpha4 cytoplasmic domains, despite sequence and functional similarities, enhance cell migration by different intracellular signaling pathways.

Amino Acid Motifs↗
PubMed2001

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women.

BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In epidemiologic studies, dietary glycemic load (GL) is positively associated with risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both the physiologic relevance of GI and GL and the ability of dietary questionnaires to measure these variables. DESIGN: In the Nurses' Health Study, we measured plasma triacylglycerol concentrations in fasting blood samples from 185 healthy postmenopausal women and HDL-cholesterol concentrations in an additional 95 nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of semiquantitative food-frequency questionnaires. The cross-sectional associations between these 3 variables and plasma triacylglycerol and HDL were assessed, with adjustment for potential confounding factors. RESULTS: For the lowest and highest quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001). Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01) contributed independently to the strong positive association between GL and fasting triacylglycerol concentrations. GL was also inversely associated with HDL-cholesterol concentrations. For the lowest and highest quintiles of GL, the mean HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P for trend = 0.03). The relation between GL and fasting triacylglycerol concentrations differed significantly by body mass index (BMI; in kg/m(2)) categories (P < 0.001 for interaction). For the lowest to the highest quintiles of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and 198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001). CONCLUSION: These data support the physiologic relevance of the GL as a potential risk factor for coronary artery disease in free-living women, particularly those prone to insulin resistance. These findings also document the ability of a semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.

Aged↗
PubMed2001

Outcome in prostate cancer associations with skin type and polymorphism in pigmentation-related genes.

Epidemiological studies have suggested that UV exerts a protective effect on prostate cancer. Accordingly, we determined, in 210 prostate cancer cases, whether parameters of exposure, skin type and polymorphism in MC1R, VDR and TYR were associated with the outcome parameters, histological grade, clinical stage and presence of bone metastases. We used logistic regression analysis, with correction for age and metastases, stage and grade in the models, to determine if the frequencies of individual factors were different in the patient groups. The development of metastases was not associated with UV exposure parameters. Paradoxically, patients with skin type 1 were at significantly reduced risk [P = 0.027, odds ratio (OR) 0.17, 95% CI 0.03-0.82] of developing metastases compared with cases with skin type 4. MC1R Val92/Val92 and VDR ff were associated with increased risk of metastases (ORs 4.30 and 4.98, respectively). Further, cumulative exposure (P = 0.005, OR 0.85/year) and increasing proportion of outdoor occupation (P = 0.001, OR 0.84/unit) were associated with reduced risk of advanced stage tumours. Skin types, MC1R or VDR genotypes were not significantly associated with advanced stage. None of the exposure parameters, skin types or genotypes were associated with tumour grade. While MC1R Val92/Val92 and VDR ff were only associated with bone metastases, TYR genotypes were associated with each of the outcome parameters. Thus, in logistic regression models that included age, but not advanced stage and high grade histology, TYR A1A2 was significantly associated with reduced risk of metastases (P = 0.033, OR 0.41). Similarly, in models that included age but not the other outcome parameters, associations between TYR A2A2 and high-grade and advanced stage were significant (P = 0.040, OR 0.41) or approached significance (P = 0.052, OR 0.44), respectively. These data indicate for the first time that pigmentation response to UV is associated with outcome in prostate cancer.

Adenocarcinoma↗