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Biomedical subjects

Y Dong

Publications and source records attributed to Y Dong.

At least 145 records · Page 8Linked to original sources

IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes.

The transcriptional activation of class II MHC genes requires the class II transactivator (CIITA) protein, a regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The CIITA gene is controlled by multiple independent promoters; two promoters direct constitutive expression, while another, the type IV CIITA promoter, mediates IFN-gamma-induced expression. We investigated the molecular regulation of IFN-gamma-induced type IV CIITA promoter activity in astrocytes. IFN-gamma inducibility of the type IV CIITA promoter is dependent on three cis-acting elements contained within a 154-bp fragment of the promoter; the proximal IFN-gamma activation sequence (GAS) element, the E box, and the proximal IFN regulatory factor (IRF) element. Two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the proximal GAS and IRF elements, respectively. The E box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Furthermore, STAT-1alpha binding to the proximal GAS element is dependent on the binding of USF-1 to the adjacent E box. Functionally, the proximal IRF element is essential for IFN-gamma induction of type IV CIITA promoter activity, while the proximal GAS and E box elements contribute to the IFN-gamma inducibility of this promoter. In astrocytes, TNF-alpha enhances IFN-gamma-induced class II MHC transcription. Our results demonstrate that TNF-alpha does not enhance IFN-gamma-induced transcriptional activation of the type IV CIITA promoter, indicating that the enhancing effect of TNF-alpha is mediated downstream of CIITA transcription. These results define the molecular basis of IFN-gamma activation of the type IV CIITA promoter in astrocytes.

Animals↗

Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human.

LRP7 (the HGMW-approved gene symbol for LR3) is a novel member of the low-density lipoprotein receptor (LDLR) family. The unique modular features in both its extracellular and its intracellular regions and functional analysis suggest it to be a multifunctional protein with mitogenic activity and potential ligand-induced signal transduction capability. We describe here the cloning of Lrp7, the orthologue of the human LRP7 gene, from a mouse liver cDNA library and its expression profile in mouse tissues and developmental stages. Lrp7 is highly homologous to the human sequence, with 95% identity at the amino acid level and a perfect conservation of all the recognizable functional domains. A 6-kb mRNA transcript could be detected in all the tissues examined, with the highest expression levels in liver, heart, and lung and the lowest levels in brain and spleen. A similar expression level of a smaller transcript (4.5 kb) was seen at the four embryonic stages examined. We mapped the Lrp 7 gene to mouse chromosome 19B and the LRP7 gene to human chromosome 11q13.4. The LRP7 gene was also localized by radiation hybrid mapping between markers D11S24270 and D11S1975.

3T3 Cells↗

IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing transcription of the class II transactivator gene.

Class II MHC Ags are critical for the initiation of immune responses by presenting Ag to T lymphocytes, leading to their activation and differentiation. The transcriptional activation of class II MHC genes requires the induction of the class II transactivator (CIITA) protein, a master regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The cytokine IL-1beta has been shown to inhibit IFN-gamma-induced class II MHC expression in various cell types. We investigated the underlying mechanism of this inhibitory effect of IL-1beta using human astroglioma cell lines. Our findings demonstrate that IL-1beta prevents the expression of class II MHC mRNA and protein upon treatment with IFN-gamma. Furthermore, we demonstrate that IFN-gamma induction of CIITA mRNA expression is inhibited by treatment of cells with IL-1beta. IL-1beta suppressed IFN-gamma activation of the type IV CIITA promoter in astroglioma cells, indicating that the inhibitory influence of IL-1beta is mediated by inhibition of CIITA transcription. IL-1beta did not interfere with IFN-gamma receptor signal transduction, since tyrosine phosphorylation, nuclear translocation, and DNA binding of STAT-1alpha to an IFN-gamma activation sequence of the type IV CIITA promoter were not affected by IL-1beta. As well, IL-1beta treatment did not affect the ability of IFN-gamma-induced interferon-regulatory factor-1 (IRF-1) to bind the IRF-1 element within the type IV CIITA promoter. This study suggests that IL-1beta may play a role in regulating immunoreactivity by inhibiting transcription of the CIITA gene, thereby reducing subsequent class II MHC expression.

Astrocytoma↗

Treatment of hepatitis caused by cytomegalovirus with allitridin injection--an experimental study.

To demonstrate the anti-cytomegalovirus (CMV) activity of allitridin injection (AI), an active anti-infection component of garlic, the in vitro effects of AI on human CMV (HCMV) AD169 and 7 newly isolated strains from patients and its in vivo effect on mice of murine CMV (MCMV) hepatitis were assessed. It was found that plaque reduction rate reached 63.5% after infected cells were treated with cell maximal tolerable concentration (7.5 micrograms/ml) of AI. Meanwhile, flow cytometric analysis for effect of AI on expression of HCMV immediate-early antigen (IEA) showed that IEA inhibition rate of 7 isolated strains was in the range from 43.3% to 66.7%, with a mean of 58.4%, similar to that of AD169 strain (60.5%). On the other hand, in vivo anti-CMV activity of AI was evaluated in terms of liver pathological changes, liver function and viral replication. Six model mice with MCMV hepatitis received the treatment of AI for 2 weeks. The severity of liver damage, levels of sALT and MCMV IE genes expression in liver tissues in the treated mice were significantly lower than those of the corresponding untreated controls. Our results showed that AI had an obvious anti-CMV activity both in vitro and in vivo.

Allyl Compounds↗

Quinoline alkaloids from Acronychia laurifolia.

Bioassay-directed fractionation of a root extract of Acronychia laurifolia (Rutaceae) using the KB-V1+ human tumor cell line led to the isolation of six quinoline alkaloids. One of these alkaloids is novel, namely, 2,3-methylenedioxy-4,7-dimethoxyquinoline and the other five were identified as the known compounds, evolitrine, gamma-fagarine, skimmianine, kokusaginine and maculosidine. Two known bis-tetrahydrofuran lignans, sesamolin and yangambin, were also identified. The structure of the new alkaloid was determined by spectroscopic methods. All of the isolates were evaluated against a panel of human cancer cell lines; four of the alkaloids showed weak cytotoxic activity.

Alkaloids↗

Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss.

Individual variations in sensitivity to the ototoxic effects of aminoglycoside antibiotics are well documented. Our research demonstrates that there is an apparent difference in serum from patients who are resistant or susceptible to aminoglycoside ototoxicity. In the first study, the cytotoxicity of sera from patients with and without hearing loss after various time periods following the discontinuation of aminoglycoside treatment was assayed using the isolated outer hair cell toxicity assay. The results indicate that sera from patients with hearing loss were significantly more toxic than sera from patients with normal hearing or minimal hearing loss. This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therapy. In a second study, sera were obtained from patients who had received aminoglycoside therapy several years previously. None of these sera was toxic to isolated outer hair cells in vitro. Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixtures were tested for toxicity. The percentage of damaged outer hair cells was significantly higher when streptomycin had been treated with sera or a serum protein fraction from patients with hearing loss (58+/-10% and 68+/-9%, respectively) than with sera or a serum protein fraction from a control group (10+/-5% and 17+/-4%, respectively). In addition, several incubation mixtures were analyzed using high performance liquid chromatography. A new chromatographic peak was only found in the incubations of streptomycin with serum protein from patients with hearing loss. The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may metabolize these drugs to cytotoxins.

Adolescent↗

Cytotoxic hammerhead ribozymes.

Small catalytic RNA molecules of the hammerhead ribozyme type were found to have cytotoxic effects unrelated to their intended activity. An expression library of ribozyme sequence variants was constructed in a recA-deficient strain of Escherichia coli such that individual library members differed in regions designed to form base pairs with human immunodeficiency virus-1 (HIV-1) tat mRNA. The parental ribozyme and many variants exhibited a bacteriostatic effect. One variant studied in detail was also bactericidal. When its expression was induced, ribozyme-dependent inhibition of bacterial growth was not observed in recA+ or recA+ lexA3 (Ind-) cells, suggesting that the recombination function of the RecA protein, not the absence of the SOS response, is sufficient to alleviate the cytotoxic effect. These data document the need for careful testing for toxic effects during intracellular studies of ribozyme action.

Base Sequence↗

Spermicidal activity of oxovanadium(IV) complexes of 1, 10-phenanthroline, 2,2'-bipyridyl, 5'-bromo-2'-hydroxyacetophenone and derivatives in humans.

We have recently reported that tetrahedral metallocene complexes containing vanadium(IV) (vanadocene) have potent spermicidal activity against human sperm. The spermicidal activity was dependent on vanadium(IV) as the central metal ion within the bis-cyclopentadienyl (Cp2)-metal complex, but the variation of diacido groups and/or replacement with bidentate ligands coordinated to the Cp2-vanadium(IV) moiety also significantly modulated the spermicidal potency. To assess the structure-activity relationship between vanadocenes and other coordination complexes of vanadium(IV), a set of 11 oxovanadium(IV) complexes with different geometrical configurations were synthesized and evaluated for spermicidal activity by computer-assisted sperm analysis. These complexes included mono and bis ancillary ligands, 1,10-phenanthroline (phen): [VO(phen), VO(phen)2, VO(Me2-phen), VO(Me2-phen)2, VO(Cl-phen), and VO(Cl-phen)2]; 2,2'-bipyridyl (bipy): [VO(bipy), VO(bipy)2, VO(Me2-bipy), and VO(Me2-bipy)2], linked via nitrogen atoms; and 5'-bromo-2'-hydroxyacetophenone (acph): [VO(Br,OH-acph)2], linked via oxygen donor atoms. All 11 oxovanadium(IV) complexes elicited concentration-dependent spermicidal activity at micromolar concentrations (EC50 values: 5.5-118 microM). The bis-phenanthroline complex of oxovanadium(IV), VO(Cl-phen)2, was the most active, and the mono bipyridyl complex, VO(bipy), was the least active; the order of efficacy was VO(Cl-phen)2 > VO(phen)2 > VO(Br,OH-acph)2 > VO(Me2-phen) > VO(bipy)2 > VO(phen) > VO(Cl-phen) > VO(Me2-phen)2 > VO(Me2-bipy)2 > VO(Me2-bipy) > VO(bipy). The neutral complex, VO(Br, OH-acph)2, induced rapid sperm immobilization (T1/2 = 38 sec). The sperm-immobilizing activity of mono- and bis-ligated oxovanadium(IV) complexes was irreversible, since the treated sperm underwent apoptosis, as determined by the flow cytometric quantitation of mitochondrial membrane potential, surface Annexin V binding assay, and in situ DNA nick-end labeling of sperm nuclei. The percentages of apoptotic sperm quantitated by the flow cytometric assay correlated well with the spermicidal potency of oxovanadium(IV) complexes. These results provide unprecedented evidence that the spermicidal and apoptosis-inducing activities of vanadium(IV) complexes are determined by the oxidation state of vanadium as well as their geometry. Because of its rapid and potent sperm-immobilizing activity, the bromo-hydroxyacetophenone complex, [VO(Br,OH-acph)2], may be useful as a contraceptive agent.

2,2'-Dipyridyl↗

Effect of fluoroquinolone concentration on selection of resistant mutants of Mycobacterium bovis BCG and Staphylococcus aureus.

When Mycobacterium bovis BCG and Staphylococcus aureus were plated on agar containing increasing concentrations of fluoroquinolone, colony numbers exhibited a sharp drop, followed by a plateau and a second sharp drop. The plateau region correlated with the presence of first-step resistant mutants. Mutants were not recovered at concentrations above those required for the second sharp drop, thereby defining a mutant prevention concentration (MPC). A C-8-methoxy group lowered the MPC for an N-1-cyclopropyl fluoroquinolone.

Anti-Infective Agents↗

The murine homolog (Mph) of human herpesvirus entry protein B (HveB) mediates entry of pseudorabies virus but not herpes simplex virus types 1 and 2.

A mouse member of the immunoglobulin superfamily, originally designated the murine poliovirus receptor homolog (Mph), was found to be a receptor for the porcine alphaherpesvirus pseudorabies virus (PRV). This mouse protein, designated here murine herpesvirus entry protein B (mHveB), is most similar to one of three related human alphaherpesvirus receptors, the one designated HveB and also known as poliovirus receptor-related protein 2. Hamster cells resistant to PRV entry became susceptible upon expression of a cDNA encoding mHveB. Anti-mHveB antibody and a soluble protein composed of the mHveB ectodomain inhibited mHveB-dependent PRV entry. Expression of mHveB mRNA was detected in a variety of mouse cell lines, but anti-mHveB antibody inhibited PRV infection in only a subset of these cell lines, indicating that mHveB is the principal mediator of PRV entry into some mouse cell types but not others. Coexpression of mHveB with PRV gD, but not herpes simplex virus type 1 (HSV-1) gD, inhibited entry activity, suggesting that PRV gD may interact directly with mHveB as a ligand that can cause interference. By analogy with HSV-1, envelope-associated PRV gD probably also interacts directly with mHveB during viral entry.

3T3 Cells↗

Association between the C825T polymorphism of the G protein beta3-subunit gene and hypertension in blacks.

A polymorphism (C825T) of the G protein beta3-subunit gene has been associated with low renin hypertension in whites. The aim of this study was to examine the C825T polymorphism in relation to hypertension in a population-based study of black people of African origin who have high prevalence of low renin, salt-sensitive hypertension. A total of 428 men and women, aged 40 to 59 years (270 Caribbeans and 158 West Africans), who took part in a population-based survey were studied. All were blacks and first-generation immigrants. The C825T polymorphism was detected by polymerase chain reaction followed by restriction-enzyme digestion. The prevalence of hypertension (supine blood pressures >/=160 systolic and/or 95 mm Hg diastolic or on drug therapy) was 43%. The distribution of the genotypes (CC, CT, and TT) was in Hardy-Weinberg equilibrium with observed frequencies of 4.0% (n=17), 33.6% (n=144), and 62.4% (n=267), respectively. Allele frequencies were 20.8% for C and 79.2% for T. No difference was detected between Caribbeans and West Africans. A 3-fold higher risk of hypertension was found among the carriers of the T variant both as heterozygotes (odds ratio [OR], 3.43 [95% CI, 0.94 to 12.4]) and homozygotes (OR, 3.87 [95% CI, 1. 09 to 13.8]). The estimate of effect and the blood pressure values in the groups carrying the T variant suggested a dominant model for the T allele. This was confirmed by a significant association between the T allele and hypertension (OR, 3.71 [95% CI, 1.05 to 13. 1]), even when adjusted for age, sex, and body mass index (OR, 4.14 [95% CI, 1.11 to 15.4]). The study shows, for the first time, a high frequency of the 825T allele in black people, and it provides evidence that the T allele may be a susceptibility factor for the development of hypertension in blacks. Given the high frequency of the T allele, even a 2-fold increased risk of hypertension among the carriers of the T allele might account for 44% of the cases of hypertension in blacks.

Adult↗

In vivo antioxidant activity of genistein in a murine model of singlet oxygen-induced cerebral stroke.

We evaluated the in vivo antioxidant activity of genistein in a mouse model of singlet oxygen-induced cerebral stroke. Cerebral stroke was induced in male BALB/c mice through extensive microvessel damage caused by photoactivated rose bengal dye. The photoactivation of the intravenously administered rose bengal was achieved by transcranial illumination with green light. Genistein was more active than its analogs and other antioxidants that were used as control agents. At a dose of 16 mg/kg genistein administered every 6 h from 24 h prior to irradiation until 24 h after irradiation, the average size of the cerebral lesion of genistein-treated mice was significantly smaller than that in control mice treated with the carrier DMSO (8.1 +/- 1.0 mm(2) compared to 14.6 +/- 0.7 mm(2), P < 0.001). Our findings provide experimental evidence that genistein could be useful for the prevention of cerebral stroke and other pathological conditions caused by reactive oxygen species.

Animals↗

[Treating women with gestational impaired glucose tolerance reduces adverse outcome of pregnancy].

OBJECTIVE: To study the treatment of women with gestational impared glucose tolerance (GIGT) in relation to outcome of fetus and newborns. METHODS: 98 women with GIGT were randomized into untreated (37 mothers) and treated groups (61 mothers) that included diet control and insulin therapy. The perinatal outcomes were compared in the two groups. RESULTS: The incidence of macrosomia (P < 0.01) and fetal distress (P < 0.05) was found to be significantly higher in the untreated group when compared with the treated group. The prevalence of neonatal metabolic complications in the untreated group was higher than that of the treated group as well. CONCLUSION: Treatment of women with GIGT will reduce adverse outcome in pregnancy.

Adult↗

[Quantitive study of 6-keto-prostaglandin F1 alpha and thromboxane B2 in human pulp].

OBJECTIVE: To study the change of the levels of 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TXB2) in deep caries and pulpitis pulp. METHODS: The levels of 6-K-PGF1 alpha and TXB2 were determined by radioimmunoassay (RIA) in 44 pulp tissues from subjects with healthy pulp (H), deep caries (DC), chronic pulpitis (CP) and acute pulpitis(AP). The 6-K-PGF1 alpha/TXB2 ratio(K/T) was calculated. RESULTS: The lconcentrations of 6-K-PGF1 alpha in Group AP were highest and those in Group H were lowest. The levels of TXB2 in Group DC were lower than Group CP and those in Group H were lowest. Significant differences in K/T ratio were found among the groups except those between Group H and DC. The value of Group AP was highest and that of Group CP was lowest. CONCLUSION: The dysbolism and dysequilibrium of PGI2 and TXA2 may be closely related to the genesis of pulp diseases.

6-Ketoprostaglandin F1 alpha↗

[Study on the association between tumor necrosis factor alpha gene polymorphism and systemic lupus erythematosus].

OBJECTIVE: To examine whether polymorphism within the tumor necrosis factor alpha (TNFalpha) gene is associated with the susceptibility and clinic manifestations to systemic lupus erythematosus (SLE) in the patients of Han ethnic group collected from the Northern China. METHODS: TNF(1) and TNF(2) subtypes of TNFalpha gene were defined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in 89 Chinese patients with SLE and 70 ethnically matched controls from Peking Union Medical College Hospital. All SLE patients were diagnosed by the American Rheumatological Association SLE diagnostic criteria setup in 1982. Human leukocyte antigen (HLA)-DR(2) gene frequency was assigned by PCR with sequence-specific primers (SSP-PCR). RESULTS: The frequencies of TNF(2) and HLA-DR(2) were significantly increased in SLE patients respectively compared to that of the controls (0.23 vs 0.14, RR = 1.85, P < 0.05; 0.36 vs 0.22, RR = 2.02, P < 0.01). Both TNF(2) and HLA-DR(2) were associated with SLE independently (RR = 3.96, P < 0.05; RR = 3.07, P < 0.05), but there was no association between the two genes. In TNF(2) positive patients, the positive rate of anti-SSA antibody was apparently higher and the incidence of lupus nephritis was significantly increased. CONCLUSION: Both TNF(2) and HLA-DR(2) gene may play a role in SLE susceptibility. Anti-SSA antibody and lupus nephritis were strongly associated with TNF(2) gene.

Adolescent↗

[Central nervous system involvement in systemic lupus erythematosus].

OBJECTIVE: To investigate central nervous system (CNS) involvements in systemic lupus erythematosus (SLE) so as to enhance our knowledge in diagnosing and treating CNS involvement of SLE. METHODS: The clinical data of 171 in patients with CNS involvement of SLE in our hospital were retrospectively reviewed. RESULTS: The mean SLE disease duration at onset of CNS involvement was (2.21 +/- 1.87) years and in 163 (95.3%) it was associated with active disease. Cerebral spinal fluid abnormality was seen in 91.4% (138/151) of the patients with CNS involvement of SLE. Among them protein elevation was found in 113, pressure elevation in 69, white cell elevation in 51 and glucose reduction in 6. For the evaluation of CNS involvement of SLE, the sensitivity of cranial CT and MRI was 77.4% and 81.4% respectively (P > 0.50). The positive rate of antiribosomal P in patients with diffuse CNS involvement of SLE was significantly higher than that in patients without CNS involvement (P < 0.01). On the contrary, the positive rate of ACL in focal CNS involvement of SLE was significantly higher than that in diffuse type or in patients without CNS involvement (P < 0.01). The total mortality rate in 171 patients with CNS involvement of SLE was 18.7%. The Mortality rate in the period of 1993 to 1998 (4.0%, 3/75) was significantly lower than that of 1980 to 1992 (30.2%, 29/96), P < 0.01. 24 SLE patients with CNS involvement received intrathecal dexamethasone and methotrexate, 22 cases (91.7%) improved considerably. CONCLUSION: CNS involvement occurs in the early stage of SLE, most of the cases are associated with active disease. Cerebral spinal fluid analysis is the most essential test and cranial imaging serves as a supplementary approach, of which CT is preferred. ACL is associated with focal CNS involvement of SLE while antiribosomal P with diffuse CNS involvement of SLE, suggesting there might be different mechanisms in CNS involvement of SLE. Intrathecal therapy is an useful alternative for patients with CNS involvement of SLE refractory to conventional therapy.

Adolescent↗