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H Xi

Publications and source records attributed to H Xi.

At least 19 recordsLinked to original sources
PubMed2007

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer.

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.

Aged↗
PubMed2005

Patient characteristics and costs associated with dyslipidaemia and related conditions in HIV-infected patients: a retrospective cohort study.

BACKGROUND: Metabolic abnormalities are common in HIV-infected individuals and, although multifactorial in origin, have been strongly associated with antiretroviral therapy. METHODS: Using automated claims and clinical databases, combined with medical record data, we evaluated the burden of dyslipidaemia (DYS) and associated metabolic abnormalities among a cohort of 900 HIV-infected patients aged 18 years and older who received their care from a large multispecialty medical group between 1 January 1996 and 30 June 2002. A Cox proportional hazards model for DYS was developed. Resource use was compiled and subsequently costed with stratification to account for variable length of follow-up. RESULTS: Mean follow-up time was 3.3 years. DYS was present in 54% of the cohort and 3.4% experienced a cardiovascular (CV) event. Both unadjusted and adjusted results found patients with dyslipidaemia and cardiovascular events significantly more likely to have received protease inhibitor (PI) treatment for longer periods of time. In the Cox proportional hazards model the following factors were significantly associated with an increased risk for DYS: older age, white race, PI use and male sex. Diagnoses of hypertension, hepatitis C virus infection, depression or opportunistic infections were all negatively associated with a DYS diagnosis. When controlled for length of follow up, patients with DYS (and no CV-related events) incurred greater median and mean total average costs than patients without DYS or CV-related events. For patients with more than 2 years of follow up, these total cost differences were statistically significant (P<0.05). CONCLUSIONS: These findings indicate that DYS is common among patients with HIV infection and is associated with increased use of medical resources.

Adult↗
PubMed2005

Recognition of triple helical nucleic acids by aminoglycosides.

Aminoglycosides, traditional RNA binders, were found to be a new class of triple helical nucleic acid-stabilizing ligands. Neomycin, of all the aminoglycosides, has shown the most significant effects in stabilizing DNA, RNA, and hybrid triple helices. When compared with minor groove binders or intercalators, neomycin excels at triple helical stabilization in most cases. Molecular modeling studies suggest that neomycin reaches into the larger Watson-Hoogsteen groove. The charge and shape complementarity are the key factors in neomycin-triplex recognition. By conjugating neomycin with intercalators such as BQQ (a potent triple helix intercalating agent designed by Hélène), we have progressed in developing more potent triple helix stabilizing ligands. The design of such dual or even triple recognition ligands opens a new paradigm for recognition of triple helix nucleic acids. The article herein presents studies of neomycin as the first molecule that can selectively stabilize nucleic acid triplex structures. These studies are supported by our recent discovery that neomycin prefers to bind to A-like conformations, of which triple helix structures are known to display some characteristics. These findings will contribute to the development of a new series of triplex-specific ligands, and may contribute to either antisense or antigene therapies.

Aminoglycosides↗
PubMed2001

Impaired class II transactivator expression in mice lacking interferon regulatory factor-2.

Class II transactivator (CIITA) is required for both constitutive and inducible expression of MHC class II genes. IFN-gamma induced expression of CIITA in various cell types is directed by CIITA type IV promoter. The two transactivators, STAT1 and IRF-1, mediate the IFN-gamma activation of the type IV promoter by binding to the GAS and IRF-E of the promoter, respectively. In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays. IRF-1 and IRF-2 can co-occupy the IRF-E of the human CIITA type IV promoter. To understand the effect of loss of IRF-2 on the endogenous CIITA expression, we assayed for CIITA expression in IRF-2 knock-out mice. Both basal and IFN-gamma induced CIITA expression were reduced in IRF-2 knock-out mice. At least half of the amount of inducible CIITA mRNA depends on IRF-2. The reduction of IFN-gamma induced CIITA mRNA in IRF-2 knock-out mice was due to the reduction of the type IV CIITA mRNA induction. The reduction of basal CIITA mRNA was apparently due to the reduction of CIITA mRNA originating from other promoters. These data indicate that IRF-2, like IRF-1, plays a critical role in the regulation of the endogenous CIITA gene. The implications in understanding the previously described phenotypes of IRF-2 defective mice are discussed.

Animals↗
PubMed2001

Provider type and the receipt of general and diabetes-related preventive health services among patients with diabetes.

OBJECTIVE: Using a measure of provider type that includes "shared care" to determine the contribution of provider type on receipt of general and diabetes-related preventive health services. METHODS: Automated clinical and administrative data were used to identify adult patients with type 1 and 2 diabetes receiving care from a multispecialty, salaried group practice and enrolled in a large health maintenance organization between 3/97 and 2/98 (n = 10,991). Logistic regression models were fit using generalized estimating equation approaches to evaluate the contribution of provider type on service receipt. MEASURES: Preventive service receipt included receipt of glycated hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines, Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for age, sex, race, marital status, household income, diabetes-related comorbidities and complications, prescription drug use, laboratory testing results, and frequency of medical care contact. RESULTS: Patients seeing an endocrinologist and primary care physician (PCP) were more likely than those seeing endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR, 1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms (OR, 1.43). Compared with patients seeing PCPs only, patient's seeing endocrinologists only were more likely to receive retinal examinations (OR, 1.37) and less likely to receive Pap smears (OR, 0.46). CONCLUSIONS: Care delivered by no one single provider type is associated with greater receipt of all recommended services. Instead, patients seeing both an endocrinologist and a PCP are most likely to receive recommended services.

Adult↗
PubMed2001

Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines.

Melanoma cells commonly express MHC class II molecules constitutively. This is a rare, or possibly unique, phenotype for a nonprofessional antigen-presenting cell, where MHC class II expression ordinarily occurs only after IFN-gamma treatment. Despite the fact that constitutive expression of MHC class II on melanoma cells has been observed for decades and that the regulation of the MHC class II genes is well understood for many different cell types, there is no data regarding the basis for constitutive MHC class II expression in melanoma cells. Here we report that MHC class II expression in melanoma cells can be traced to constitutive expression of the class II transactivator protein (CIITA), which mediates both IFN-gamma-inducible and -constitutive MHC class II expression in all other cell types. In addition, we determined that constitutive CIITA expression is the result of the activation of both the B cell-specific CIITA promoter III and the IFN-gamma-inducible CIITA promoter IV, the latter of which previously has never been known to function as a constitutive promoter in any cell type. The recently described B cell-related ARE-1 activity is important for promoter III activation in the melanoma cells. Constitutive promoter IV activation involves the IFN regulatory factor element (IRF-E), which binds members of the IRF family of proteins, although the major, IFN-gamma inducible member of this family, IRF-1, is not constitutively expressed in these cells. In cells with constitutively active promoter IV, the promoter IV IRF-E is most likely activated by IRF-2. The relevance of these results to the pathway of melanoma development is discussed.

DNA-Binding Proteins↗
PubMed2000

Interferon regulatory factor-2 point mutations in human pancreatic tumors.

Interferon regulatory factor (IRF)-2, a member of the IRF family, is a transcription factor involved in the regulation of various interferon and virus-stimulated genes and other genes. For example, IRF-2 is an activator of the interferon (IFN)-gamma-inducible MHC class II transactivator (CIITA) type IV promoter. It cooperates with IRF-1 in the activation of the CIITA type IV promoter and can co-occupy the IRF-E of the promoter with IRF-1. In a previous study, we identified an inactivating point mutation in the DNA binding domain of IRF-2 expressed in a human pancreatic tumor cell line that does not express CIITA or MHC class II in response to IFN-gamma. To further assess the potential impact of IRF-2 mutations in tumorigenesis, we screened fresh pancreatic tumor explants and identified 2 IRF-2 point mutations in the 2 alleles of IRF-2 from a single tumor specimen. Both mutations occurred in the DNA binding domain of IRF-2. DNA binding assays demonstrated that the IRF-2 point mutations impaired IRF-2 DNA binding. The transactivation function of the mutant IRF-2s was similarly impaired. This is the first report of IRF-2 mutations in human tumor explants.

Alleles↗
PubMed2000

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China.

Fetal iodine deficiency disorder (FIDD) is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However not everyone at risk develops FIDD and familial aggregation is common. This suggests that genetic factors may also be involved. The Apolipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroid hormone binding domain, and APOE genotype may affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases with 154 local control subjects, recruited from three iodine deficiency areas in central China. We have also genotyped 42 FIDD family cases and 158 normal individuals from the families of local controls, and 375 population controls from Shanghai. APOE epsilon4 genotypes were significantly enriched in FIDD probands from each of the three iodine deficiency areas; the epsilon4 allele frequency was 16% vs 6% in controls. The same effect was also observed when we compared FIDD family cases with controls and control families. Our data suggest that in iodine-deficient areas, the APOE epsilon4 allele is a genetic risk factor for FIDD. The phenomenon may affect population selection and contribute to the low frequency of the epsilon4 allele in Chinese compared to Caucasian populations.

Adolescent↗
PubMed2000

Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol.

Sarcolemma integrity is stabilized by the dystrophin-associated glycoprotein complex that connects actin and laminin-2 in contractile machinery and the extracellular matrix, respectively. Interruption of the connection by the primary gene defect or acquired pathological burden can cause cardiac failure. The purposes of the present study were to verify whether dystrophin is disrupted in acute myocardial injury after the isoproterenol overload (10 mg/kg) and to examine its relation to myocardial cell apoptosis in rats. This injury from 4-16 h at the subendocardium was accompanied by dystrophin disruption and dislocation from subsarcolemma to cytoplasm, which were confirmed by immunohistology and Western blotting. However, delta-sarcoglycan was thoroughly preserved in sarcolemma. The dystrophin degradation preceded the appearance of apoptotic cells and exactly coincided with the transferase-mediated dUTP-biotin nick end labeling-positive cardiomyocytes (TUNEL), as was verified by double-staining. These data suggest that beta-adrenergic stimulation induces dystrophin breakdown followed by apoptosis.

Adrenergic beta-Agonists↗
PubMed2000

Purine catabolism in Escherichia coli and function of xanthine dehydrogenase in purine salvage.

Escherichia coli is not known to utilize purines, other than adenine and adenosine, as nitrogen sources. We reinvestigated purine catabolism because a computer analysis suggested several potential sigma(54)-dependent promoters within a 23-gene cluster whose products have homology to purine catabolic enzymes. Our results did not provide conclusive evidence that the sigma(54)-dependent promoters are active. Nonetheless, our results suggest that some of the genes are metabolically significant. We found that even though several purines did not support growth as the sole nitrogen source, they did stimulate growth with aspartate as the nitrogen source. Cells produced (14)CO(2) from minimal medium containing [(14)C]adenine, which implies allantoin production. However, neither ammonia nor carbamoyl phosphate was produced, which implies that purine catabolism is incomplete and does not provide nitrogen during nitrogen-limited growth. We constructed strains with deletions of two genes whose products might catalyze the first reaction of purine catabolism. Deletion of one eliminated (14)CO(2) production from [(14)C]adenine, which implies that its product is necessary for xanthine dehydrogenase activity. We changed the name of this gene to xdhA. The xdhA mutant grew faster with aspartate as a nitrogen source. The mutant also exhibited sensitivity to adenine, which guanosine partially reversed. Adenine sensitivity has been previously associated with defective purine salvage resulting from impaired synthesis of guanine nucleotides from adenine. We propose that xanthine dehydrogenase contributes to this purine interconversion.

Adenine↗
PubMed1999

Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) type IV promoter by interferon regulatory factors 1 and 2.

Class II transactivator (CIITA) activates the expression of major histocompatibility class II genes, which encode antigen-presenting molecules recognized by the T-cell receptor of CD4+ T cells. IFN-gamma induced CIITA transcription in many cell types is directed by the CIITA Type IV promoter. Here we report that the human CIITA Type IV promoter IRF-E binds IRF-1 and can be activated by exogenous expression of IRF-1. Surprisingly, the CIITA Type IV promoter IRF-E is also activated by IRF-2, another member of the IRF family that generally acts as a transcriptional repressor. In addition, we found that IRF-1 and IRF-2 synergistically activate the CIITA Type IV promoter. Electrophoretic mobility shift assays revealed that IRF-1 and IRF-2 can simultaneously occupy the IRF-E of the CIITA Type IV promoter, suggesting a novel mechanism for the role of these two proteins in promoter activation. Our results also indicate that IRF-1 and IRF-2 can cooperatively activate and co-occupy the IRF-E of the guanylate binding protein (GBP) promoter. Finally, CIITA induction by IFN-gamma does not occur in a pancreatic tumor cell line that expresses a mutated IRF-2, representing the first IRF-2 mutation identified in a human tumor cell line.

DNA-Binding Proteins↗
PubMed1999

Finite-volume lattice Boltzmann method.

We present a finite-volume formulation for the lattice Boltzmann method (FVLBM) based on standard bilinear quadrilateral elements in two dimensions. The accuracy of this scheme is demonstrated by comparing the velocity field with the analytical solution of the Navier-Stokes equations for time dependent rotating Couette flow and Taylor vortex flow. To demonstrate the flexibility of the scheme, we have also simulated a modified rotating Couette flow, where the inner cylinder has an elliptical shape. The results agree with those obtained from the traditional marker-and-cell method. The FVLBM scheme is applicable to arbitrarily shaped two-dimensional regions, and thus the range of applicability of the lattice Boltzmann method has been significantly extended.

Journal Article↗
PubMed1999

Finite-volume lattice Boltzmann schemes in two and three dimensions.

Simple and practical finite-volume schemes for the lattice Boltzmann equation are derived in two and three dimensions through the application of modern finite-volume methods. The schemes use a finite-volume vortex-type formulation based on quadrilateral elements in two dimensions and trilinear hexahedral elements in three dimensions. It is shown that the schemes are applicable to domains with irregular boundaries of arbitrary shape in two and three dimensions.

Journal Article↗
PubMed1997

[Treatment of lingual angiocavernoma by selective arteriocatheterization with urea injection].

Selective arteriocatheterization with urea injection was administered to 36 cases of lingual angiocavernoma. There were 20 males and 16 females, ranging in age from 6 to 18 years with an average of 12 years. Two to five mililiters of 40% urea were injected once a day for 10-15 days as a course of treatment, 29 cases (80.6%) were cured in one course of treatment. The other 7 cases (19.4%) were cured in the 2nd course of treatment. The results suggest that selective arteriocatheterization with urea injection is a safe, convenient and effective technique in the treatment of ingual angiocavernoma.

Adolescent↗
PubMed1992

Early afterdepolarizations and triggered activity induced by cocaine. A possible mechanism of cocaine arrhythmogenesis.

BACKGROUND: Cocaine may produce life-threatening cardiac arrhythmias, but it is not clear whether this is an indirect effect of coronary vasoconstriction and ischemia or a direct myocardial effect of the substance. Except for its effects on the Na+ current as a local anesthetic, little is known about the direct electrophysiological actions on cardiac cells. Therefore, we studied the effects of cocaine on action potentials and membrane currents in isolated feline ventricular myocytes to test the hypothesis that cocaine-induced arrhythmogenesis may be based on cellular and ionic mechanisms. METHODS AND RESULTS: Action potentials and membrane currents were recorded using the patch clamp technique. Single cells were isolated from feline left ventricles by enzymatic digestion. Exposure to cocaine (10 or 50 microM) depressed the plateau phase of the action potential and prolonged action potential duration. Action potential duration measured at 90% repolarization (APD90) was increased from 280 +/- 12 msec to 325 +/- 17 msec (p less than 0.01) by 5-minute exposure to 10 mumol cocaine, when the cells were stimulated at 1 Hz. During exposure to 50 mumol cocaine, APD90 was markedly increased from 298 +/- 13 msec to 437 +/- 35 msec (p less than 0.01) in seven of 16 cells, and early afterdepolarizations (EADs) developed in these cells. The take-off potential and the amplitude of EADs were -28.3 +/- 2.3 mV and 16.8 +/- 1.2 mV, respectively. Triggered activity arising from EADs was induced in four of the seven cells. Addition of 1 nmol isoproterenol augmented EADs and induced sustained triggered activity, whereas they were suppressed by exposure to 2 microM verapamil. Whole-cell voltage clamp experiments revealed that cocaine (50 microM) reduced the peak L-type Ca2+ current from 1.03 +/- 0.13 nA to 0.79 +/- 0.11 nA (23% reduction, p less than 0.05). Cocaine also reduced the peak delayed rectifier K+ current from 362 +/- 51 pA to 113 +/- 32 pA (69% reduction, p less than 0.01). However, cocaine did not affect activation and inactivation kinetics of these channels. Cocaine had no effect on the inward rectifier K+ current. CONCLUSIONS: We conclude that cocaine can prolong action potential duration and induce EADs and triggered activity by blocking the delayed rectifier K+ current, and that cocaine-induced abnormalities of repolarization, modulated by its inhibitory effects on catecholamine reuptake, may play a role in the potential of cocaine for induction of acute fatal arrhythmias.

Action Potentials↗
PubMed1992

Verapamil diminishes action potential changes during metabolic inhibition by blocking ATP-regulated potassium currents.

Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+ loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+ (KATP) current in action potential shortening and K+ loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATP current in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATP channel. Membrane potentials and currents were recorded using standard patch-clamp techniques. During 15-minute superfusion with 1 mM CN-, action potential duration measured at 90% repolarization was reduced from 259 +/- 12 to 98 +/- 15 msec (62% reduction) in the absence of verapamil and from 266 +/- 11 to 183 +/- 16 msec (31% reduction) in the presence of 2 microM verapamil (p less than 0.01). In inside-out membrane patches, the KATP current, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 microM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92 +/- 0.18 and 1.82 +/- 0.21 msec in the absence and presence of 2 microM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1 +/- 3.5 to 24.9 +/- 2.8 msec (p less than 0.01) and prolonged the closed time between bursts from 39.4 +/- 4.6 to 78.5 +/- 5.1 msec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗