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Wei Liu

Publications and source records attributed to Wei Liu.

At least 181 records · Page 10Linked to original sources
PubMed2005

Sp1 and Sp3 regulate the basal transcription of receptor activator of nuclear factor kappa B ligand gene in osteoblasts and bone marrow stromal cells.

Receptor activator of nuclear factor kappa B ligand (RANKL), a potent regulator of osteoclast formation and function, is expressed by osteoblasts and bone marrow stromal cells. However, the molecular mechanism underlying RANKL expression in osteoblast/stromal cells remains largely unclear. Here, we characterized the molecular mechanism controlling RANKL basal transcription in osteoblast/stromal cells. We cloned a 1,103-bp murine RANKL promoter (from -953 to +150, relative to the transcription start site). Using a series of deletion mutants of the 1,103-bp promoter, we identified a 100-bp region (-154 to -54) mediating RANKL basal transcription in both osteoblasts and bone marrow stromal cells. Electrophoretic mobility shift assay (EMSA) using five overlapping oligonucleotides (Probes 1-5) spanning the 100-bp region showed that Probes 1 and 2 specifically bound nuclear proteins with high affinity from both cell types. Computer analysis revealed that Probes 1 and 2 contain a putative Sp1-binding site. Supershift assays with Sp1 and Sp3 antibodies confirmed that the nuclear proteins binding to Probes 1 and 2 are Sp1 and Sp3. Functionally, the mutation of the Sp1/Sp3 site in Probe 1 profoundly reduced the basal promoter activity while the mutation of the one in Probe 2 resulted in moderate reduction in the basal promoter activity. Moreover, the mutation of both sites abrogated the RANKL basal promoter activity, indicating that Sp1 and Sp3 play a key role in the RANKL basal transcription in osteoblasts and bone marrow stromal cells.

Animals↗
PubMed2005

Receptor activator of NF-kappaB (RANK) cytoplasmic motif, 369PFQEP373, plays a predominant role in osteoclast survival in part by activating Akt/PKB and its downstream effector AFX/FOXO4.

Receptor activator of NF-kappaB ligand (RANKL) plays a crucial role in osteoclast differentiation, function, and survival. RANKL exerts its effect by activating its receptor RANK (receptor activator of NF-kappaB), which recruits various intracellular signaling molecules via specific motifs in its cytoplasmic tail. Previously, we identified three RANK cytoplasmic motifs (Motif 1, 369PFQEP373; Motif 2, 559PVQEET564; and Motif 3, 604PVQEQG609) mediating osteoclast formation and function. Here, we investigated RANK cytoplasmic motifs involved in osteoclast survival. Motif 1, in contrast to its minimal role in osteoclast formation and function, plays a predominant role in promoting osteoclast survival. Moreover, whereas Motif 2 and Motif 3 are highly potent in osteoclast formation and function, they exert a moderate effect on osteoclast survival. We also investigated the role of these motifs in activating Akt/protein kinase B (PKB), which has been implicated in RANKL-induced osteoclast survival. Motif 1, but not Motif 2 or Motif 3, is able to stimulate Akt/PKB activation. Because Akt/PKB has been shown to utilize distinct downstream effectors (glycogen synthase kinase-3beta, FKHR/FOXO1a, BAD, and AFX/FOXO4) to regulate cell survival, we next determined which downstream effector(s) is activated by Akt/PKB to promote osteoclast survival. Our data revealed that RANKL only stimulates AFX/FOXO4 phosphorylation, indicating that AFX/FOXO4 is a key downstream target activated by Akt/PKB to modulate osteoclast survival. Taken together, we conclude that Motif 1 plays a predominant role in mediating osteoclast survival in part by activating Akt/PKB and its downstream effector AFX/FOXO4.

Amino Acid Motifs↗
PubMed2005

[Relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation].

The apoptosis of cardiomyocytes plays a pivotal role in the pathogenesis of cardiac failure transformed from cardiac hypertrophy, so that suppression of cardiomyocytes apoptosis is an effective pharmacotherapeutic target to prevent cardiac failure. This study focused on the relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. Cardiomyocyte hypertrophy was induced by angiotensin II (0.1 mumol/L ) and norepinephrine (1 mumol/L), and the cells were cultured under the condition of hypoxia ( 95% N2 and 5% CO2, the O2 partial pressure was regulated at least lower than 5 mmHg ) for 8 h, then were recovered to normal culture environment. Apoptosis was detected with TUNEL. The activity of pyruvate dehydrogenase (PDH) and carnitine palmitoyltransferase 1 (CPT-1), the rate of glycose oxidation and glycolysis, and fatty acid metabolism were detected by liquid scintillation counting. The results are as follows: (1) The activity of active PDH (PDHa) was slightly higher in hypertrophic cardiomyocytes than that in normal cardiomyocytes, but the activity of CPT-1 was significantly lower in hypertrophic cardiomyoctes than that in normal cardiomyocytes.Compared with the hypertrophic cardiomyocytes cultured with normal oxygen concentration, the activities of PDHa and CPT-1 were decreased significantly after hypoxia for 8 h, and the activity of PDHa were decreased further after reoxygenation for 4 h, but the activity of CPT-1 recovered quickly after reoxygenation. (2) The rate of glucose oxidation in hypertrophic cardiomyocytes increased slightly when cultured under normal O2 partial pressure than that in normal cardiac cells. The rate of glucose oxidation reduced (16 +/- 0.9)% and (48 +/- 1.1)% in normal and hypertrophic cardiomyocytes, respectively, after hypoxia. It reduced further in hypertrophic cardiac cells at 4 h of reoxygenation, then recovered gradually. In normal cardiocytes, it recovered quickly after reoxygenation. (3) The rate of glycolysis of hypertrophic cardiocytes increased slightly than that of the normal cardiocytes when cultured in the general O(2) environment. Compared with the normal cardiomyocytes, the rate of glycolysis of hypertrophic cardiac cells was the same during hypoxia-reoxygenation culture, i.e., the rate of glycolysis decreased slightly after hypoxia for 8 h, but increased rapidly and significantly after reoxygenation. (4) The rate of fatty acid oxidation was slightly lower in hypertrophic cardiocytes than that in normal cardiomyocytes. After hypoxia for 8 h, the rate of fatty acid oxidation decreased significantly in normal and hypertrophic cardiomyocytes, there was no difference between normal and hypertrophic cardiomyocytes. But the alterations of fatty acid oxidation after reoxygenation were different between normal and hypertrophic cardiac cells, namely, the fatty acid oxidation of normal cardiomyocytes were activated slowly and slightly, while the rate of fatty acid oxidation of hypertrophic cardiomyocytes increased markedly at the early stage of reoxygenation, and increased further at 8 h of reoxygenation. (5) The rate of apoptosis in hypertrophic cardiocytes increased obviously after hypoxia for 8 h, and increased further and markedly at the early stage of reoxygenation, then gradually decreased to normal level. (6) Dicholoroacetate could inhibit apoptosis of hypertrophic cardiocytes through increasing glucose oxidation and inhibiting the activation of glycolysis and fatty acid oxidation of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. These data demonstrate that apoptosis in hypertrophic cardiomyocytes after hypoxia-reoxygenation is mainly due to the inhibition of glucose oxidation and the activation of glucolysis and fatty acid oxidation. Furthermore, increasing glucose oxidation may be a new pharmacotherapeutic target to inhibit apoptosis of hypertrophic cardiac cells.

Angiotensin II↗
PubMed2005

Effects of atorvastatin on the Th1/Th2 polarization of ongoing experimental autoimmune myocarditis in Lewis rats.

OBJECTIVE: Experimental autoimmune myocarditis (EAM) in rats is a T cell-mediated disorder and the involvement of Th1/Th2 unbalance has been demonstrated. This study was designed to test the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, affects T cell-mediated autoimmunity through modulating the balance of Th1/Th2 and reduces the severity of EAM. METHODS: Myocarditis was induced in 23 Lewis rats by injection of porcine cardiac myosin. High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) atorvastatin or vehicle was administered orally for 3 weeks to rats with EAM at the same time of immunization. Seven Lewis rats received neither immunization nor statins therapy were used as normal controls. On day 21 after immunization (the climax of inflammation), echocardiography was examined and the severity of myocarditis was evaluated by histopathological evaluation. The area ratio (affected/entire area percentage) of myocardial lesions was determined in histological sections. Heart weight/body weight ratio was determined and the serum lipid levels were measured. Levels of serum IFN-gamma, IL-2, IL-4 and IL-10 were measured by ELISA. RESULTS: Cardiac function was improved in the two atorvastatin-treated groups compared to the untreated group. Heart weight/body weight ratio and the degree of inflammation were significantly lower in the two dosage statin-treated groups than that in the untreated one. Furthermore, treatment with atorvastatin decreased the expression levels of Th1 cytokine (IFN-gamma and IL-2), and increased the expression levels of Th2 cytokine (IL-4 and IL-10). Atorvastatin attenuated the histopathological severity of myocarditis. Plasma lipid levels did not differ between the groups. CONCLUSIONS: Atorvastatin ameliorates EAM by inhibiting T cell responses and suppressing Th1-type and inflammatory cytokines production and this activity is independent of cholesterol reduction, whereas Th2-type cytokines production was promoted. Atorvastatin may have beneficial effects on myocarditis by modulating the Th1/Th2 balance. These results demonstrate an important role of Th1/Th2 polarization in the pathogenesis of EAM and suggest that HMG-CoA reductase blockade may be a promising new strategy for the treatment of organ specific autoimmune diseases.

Animals↗
PubMed2005

COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial cells.

Chlamydiae alter apoptosis of host target cells, which regulates their growth. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin E2 (PGE2) production, modulates epithelial cell survival. We addressed whether endogenous PGE2 alters chlamydial growth or apoptosis of epithelial cells infected with Chlamydia muridarum. PGE2 is secreted by infected host cells in the genital tract (GT). Using immunohistochemical techniques, we found that COX-2 enzyme was localized to epithelial cells in the GT in vivo. Pellets of the COX-2 enzyme inhibitor, NS-398, and placebo were implanted in mice subcutaneously and released a constant amount of these chemicals throughout the infection. NS-398-treated mice were found to exhibit 10-fold lower bacterial load than the placebo group on day 3 post infection, suggesting disruption of the chlamydial developmental cycle. To prove this, the human lung adenocarcinoma cell line A549 was then infected with different MOIs of C. muridarum in the presence of multiple concentrations of NS-398 in vitro. There was no difference in inclusion forming units (IFUs) between NS-389-treated and untreated cells. We also found no alterations in C. muridarum IFUs in A549 cells transfected with a 2.0 kb cDNA fragment of human COX-2 cloned in the sense (S) or anti-sense (AS) orientation. However, the inclusion size was reduced and the number of EB was significantly diminished during reinfection in AS-transfected cells. In addition, the absence of COX-2 did not significantly modify apoptosis in infected cells. In total, COX-2 deficiency reduces the infectious burden in vivo and may modulate transmission of the organism.

Animals↗
PubMed2005

Freeze-drying of proteins from a sucrose-glycine excipient system: effect of formulation composition on the initial recovery of protein activity.

The purpose of this study was to investigate the effect of sucrose-glycine excipient systems on the stability of selected model proteins during lyophilization. Recovery of protein activity after freeze-drying was examined for the model proteins lactate dehydrogenase and glucose 6-phosphate dehydrogenase in a sucrose-glycine-based excipient system in which the formulation composition was systematically varied. In a sucrose-only excipient system, activity recovery of both model proteins is about 80% and is independent of sucrose concentration over a range from 1 to 40 mg/mL. When both sucrose and glycine are used and the ratio of the 2 excipients is varied, however, activity recovery decreases in a pattern that is consistent with the inhibition of activity recovery by glycine crystals, despite the presence of an adequate amount of sucrose to afford protection. Annealing of sucrose-glycine formulations causes a small but significant decrease in activity recovery relative to unannealed controls, whereas no annealing effect is observed with sucrose-only formulations. Addition of 0.01% polysorbate 80 to the formulation resulted in complete recovery of activity, irrespective of the sucrose-glycine ratio or annealing. Addition of the same concentration of polysorbate 80 to the reconstitution medium caused an increase in activity recovery for each formulation, but the overall pattern remained unchanged. The data are consistent with an interfacial model for lyophilization-associated loss of protein activity involving denaturation at a solid/freeze-concentrate interface.

Animals↗
PubMed2005

Involvement of platelet-activating factor and leukotrienes in anaphylactic segmental venoconstriction in ovalbumin sensitized guinea pig livers.

The hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension, and is characterized by significant post-sinusoidal constriction and liver congestion in guinea pigs. We determined what chemical mediators are involved in anaphylaxis-induced segmental venoconstriction and liver congestion in perfused livers isolated from ovalbumin sensitized guinea pigs. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. An antigen injection increased both the portal vein pressure and Pdo, resulting in 4.1- and 2.3-fold increases in Rpre and Rpost, respectively. Hepatic congestion was observed as reflected by liver weight gain. Pretreatment with TCV-309 (10microM, platelet-activating factor (PAF) receptor antagonist) or ONO-1078 (100microM, human cysteinyl-leukotriene (Cys-LT) receptor 1 antagonist), but not indomethacin (10microM, cyclooxygenase inhibitor), ketanserin (10microM, serotonin receptor antagonist), or diphenhydramine (100microM, histamine H1 antagonist), significantly attenuated this anaphylactic hepatic venoconstriction. Anaphylaxis-induced increases in Rpre and Rpost were significantly inhibited by TCV-309 (by 48%) and ONO-1078 (by 36%), respectively. Combined TCV-309 and ONO-1078 pretreatment exerted additive inhibitory effects on anaphylactic hepatic venoconstriction. Anaphylactic hepatic weight gain was converted to weight loss when post-sinusoidal constriction was attenuated. It is concluded that anaphylaxis-induced pre-sinusoidal constriction is mainly caused by PAF and the post-sinusoidal constriction by Cys-LTs in guinea pig livers.

Animals↗
PubMed2005

Induction of tumor arrest and differentiation with prolonged survival by intermittent hypoxia in a mouse model of acute myeloid leukemia.

We showed previously that mild real hypoxia and hypoxia-mimetic agents induced in vitro cell differentiation of acute myeloid leukemia (AML). We here investigate the in vivo effects of intermittent hypoxia on syngenic grafts of leukemic blasts in a PML-RARalpha transgenic mouse model of AML. For intermittent hypoxia, leukemic mice were housed in a hypoxia chamber equivalent to an altitude of 6000 m for 18 hours every consecutive day. The results show that intermittent hypoxia significantly prolongs the survival of the leukemic mice that received transplants, although it fails to cure the disease. By histologic and cytologic analyses, intermittent hypoxia is shown to inhibit the infiltration of leukemic blasts in peripheral blood, bone marrow, spleen, and liver without apoptosis induction. More intriguingly, intermittent hypoxia also induces leukemic cells to undergo differentiation with progressive increase of hypoxia-inducible factor-1alpha protein, as evidenced by morphologic criteria of maturating myeloid cells and increased expression of mouse myeloid cell differentiation-related antigens Gr-1 and Mac-1. Taken together, this study represents the first attempt to characterize the in vivo effects of hypoxia on an AML mouse model. Additional investigations may uncover ways to mimic the differentiative effects of hypoxia in a manner that will benefit human patients with AML.

Animals↗
PubMed2005

Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members.

Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on the presence of the active site serine for Adiponutrin, Desnutrin/ATGL, and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like, but not Adiponutrin, decreases intracellular triglyceride levels. This is consistent with a function for Desnutrin/ATGL, GS2, and GS2-Like in lipolysis, but not for Adiponutrin. Consistent with previously reported data, Desnutrin/ATGL is upregulated by fasting in adipose tissue, whereas Adiponutrin is downregulated. Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL, are strongly induced in the liver of ob/ob mice. Our data support distinct functions for Adiponutrin and Desnutrin/ATGL and raise the possibility that GS2 may contribute significantly to lipolysis in human adipose tissue.

Adipocytes↗
PubMed2005

Loss of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in a wide range of human cancers.

Metastasis is a major contributing factor to poor prognosis in cancer. Reliable and sensitive biomarkers that indicate the development of metastasis of primary tumors would be of great clinical use. In this study, we show that the neuronal protein synuclein-gamma (SNCG) is abnormally expressed in a high percentage (67.5%) of tumor tissues of diversified cancer types, including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer, but rarely expressed in tumor-matched nonneoplastic adjacent tissues (0.6%). Expressions of SNCG protein in different cancer types all display stage-specific patterns of very low expression in stage I and high expression in stages II to IV. Importantly, we observe a strong association between SNCG protein expression in primary tumors with distant metastasis in patients regardless of the cancer type (60.6%, P < 0.001). By performing genomic sequencing and methylation-specific PCR assays, we identify an inclusive demethylation of CpG sites within the CpG island of SNCG gene in every tumor sample (100%) across all cancer types, illustrating a universal loss of the epigenetic control of SNCG gene expression in tumors and further demonstrating that the demethylation of SNCG CpG island is primarily responsible for the aberrant expression of SNCG protein in cancerous tissues. These new findings strongly suggest that reactivation of SNCG gene expression by DNA demethylation is a common critical contributing factor to malignant progression of many solid tumors and its expression in primary carcinomas is an effective molecular indicator of distant metastasis. Our studies also suggest that the methylation status of SNCG gene can be used as a sensitive molecular tool in early detections of tumorigenesis.

Aged↗
PubMed2005

Modifications of protein by polyunsaturated fatty acid ester peroxidation products.

The ability of unsaturated fatty acid methyl esters to modify bovine serum albumin (BSA) in the presence of a metal-catalyzed oxidation system [ascorbic acid/Fe (II)/O2] was investigated. The exposure of BSA to PUFA esters led to the generation of carbonyl groups and the formation of high-molecular-weight proteins, which were strongly dependent on the degree of fatty acid unsaturation. The high-molecular-weight proteins were detected by Western blot analysis and were not recognized by five antibodies. The observation that levels of conjugated dienes and malondialdehyde formed in the presence of BSA were substantially lower in the presence than in the absence of BSA indicated that radicals formed during the degradation of lipid hydroperoxides are likely involved in the formation of protein derivatives. These results may be important in understanding the specific roles of different polyunsaturated fatty acids in the pathophysiological effects associated with oxidative stress.

Electrophoresis, Polyacrylamide Gel↗
PubMed2005

[Cartilage-derived morphogenetic protein 1 initiates chondrogenic differentiation of human dermal fibroblasts in vitro].

OBJECTIVE: To explore the factors influencing the differentiation of fibroblasts into chondrocyte phenotype induced by a growth factor, cartilage-derived morphogenetic protein 1 (CDMP1). METHODS: Fibroblasts isolated from foreskin obtained during circumcision were cultured in the forms of micromass and monolayer culture. The culture fluid of the fibroblasts at the passage 2, 7, and 10 was added with CDMP1 of the concentrations at the concentrations of 10, 30, 100, and 300 ng/ml respectively and co-cultured for 7 days. RT-PCR was used to detect the expression of bone morphogenetic protein receptor (BMPR), activin receptor-like kinase (ALK) receptor, collagen types II, IV, and X before and after CDMP1 induction. Western blotting was used to detect the protein expression of collagen types II, a transcriptional factor Sox9, and aggrcan before and after the induction. Flow cytometry was used to detect the superficial markers CD29, CD105, CD106, and CD166, and the expression of collagen types I and II. RESULTS: Western blotting showed that the collagen type II positive cell rate in the passage 5 cells was 74.3% +/- 0.4%, not significantly different from that of the passage 2 cells (73.4% + 0.5%). When the concentrations of CDMP1 were 10 and 30 ng/ml no expression of aggrecan and collagen type II was detected, When the concentrations of CDMP1 was 100 and 300 ng/ml, the expression of aggrecan and collagen type II could be detected and without significant differences between these 2 concentrations. The expression of aggrcan and collagen type II mRNA disappeared in the monolayer cultured P2 and P5 fibroblasts induced by CDMP1 for 14 days, However, RT-PCR and Western blotting showed expression of collagen type II, aggrcan and SOX9 in the micromass cultured fibroblasts. RT-PCR showed that all fibroblasts cultured in vitro expressed ActR-I/ALK-2, BMPR-IA/ALK-3, and BMPR-IB/ALK-6 genes, and the expression of these genes significantly increased after CDMP1 for 7 days. CONCLUSION: CDMP1 stimulates the human dermal fibroblasts expanded in vitro to differentiate into chondrogenic phenotype in a dose dependent manner. Three-dimensional culture environments accelerate the chondrogenic differentiation. The expression of ALK receptors may involve the CDMP1 stimulated differentiation of fibroblasts.

Adolescent↗
PubMed2005

Distinct gene expression profiles and reduced JNK signaling in retinitis pigmentosa caused by RP1 mutations.

To understand the mechanisms underlying autosomal dominant progressive retinitis pigmentosa (RP) caused by the mutations of the RP1 gene and to identify molecules that play roles in the early disease process, we used Affymetrix U74Av2 microarrays to compare the gene expression profiles of retinas from Rp1-/- and Rp1+/+ mice at postnatal days (P) 7, 10, 14, 18 and 21. These profiles were independently verified by comparison with results of retinal serial analysis of gene expression, U74Av2 array studies of mouse retinas, real-time PCR and in situ hybridization. We found that the disruption of Rp1 significantly affected the expression of multiple clusters of genes whose products were involved in diverse biological pathways. The molecular responses to the disruption of Rp1 changed dramatically during development and were distinct from responses to the disruption of photoreceptor transcription factors (Crx-/- or Nrl-/-) and a phototransduction molecule (Pde6brd1). We found specific alterations of gene expression in the c-Jun N-terminal kinase (JNK) signaling cascades. Western analysis confirmed that the phosphorylation of key members in the JNK signaling cascades (i.e. JNK1, JNK2, MAP2, MKK4 and c-Jun) is reduced, whereas phospho-ERK and phospho-p38 are unchanged, in Rp1-/- retinas at P18-21. Immunostaining demonstrated that, like Rp1, phospho-JNKs and phospho-MAP2 are present in outer segments of photoreceptors. Our studies reveal unique molecular phenotypes in multiple biological pathways and the specific reduction of JNK signaling cascades in RP1 diseases, and suggest that RP1, a doublecortin-containing microtubule associated protein, and JNK signaling cascades play integral roles in photoreceptor development and maintenance. Our studies further suggest JNK-related therapeutic strategies for RP1 diseases.

Animals↗
PubMed2005

Cisplatin ototoxicity to the rat inner ear: a role for HMG1 and iNOS.

Cisplatin is a chemotherapeutic agent that causes toxic damage to the inner ear (ototoxicity). Although much attention has been directed at identifying ways to protect the inner ear against cisplatin ototoxicity, little is known about the mechanisms by which cisplatin causes damage to the inner ear. Binding of high-mobility group (HMG1) protein to cisplatin-modified DNA participates in mediating the antitumor effects of cisplatin. This study seeks to determine if HMG1 may also participate in the ototoxicity of cisplatin. To address this, patterns and levels of expression of HMG1 have been evaluated in the rat cochlea in response to cisplatin chemotherapy. Our findings demonstrate a marked upregulation of HMG1 protein in the spiral (auditory) ganglion cells of cisplatin-treated rats in comparison to levels of expression of HMG1 in the spiral ganglion cells of untreated control animals. Increased levels of HMG1 were observed in the cisplatin-treated kidney, a peripheral target tissue of cisplatin, but not in the heart, a tissue not typically affected by cisplatin chemotherapy, suggesting HMG1 specificity in cisplatin toxicity. Furthermore, levels of inducible nitric oxide synthase (iNOS), an HMG-regulated enzyme associated with cochlear pathology, are increased in the spiral ganglion cells of cisplatin-treated rats 1 day post the cisplatin-mediated upregulation in HMG1. This increase in HMG1 and iNOS can be prevented in the cochleae of cisplatin-treated rats by administration of l-methionine, an established method of protection against cisplatin ototoxicity. Our results support a role for HMG1 and iNOS in mechanisms of cisplatin ototoxicity in the rat inner ear.

Animals↗
PubMed2005

Patterns of HIV prevalence among injecting drug users in the cross-border area of Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China.

BACKGROUND: To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. METHODS: Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral ("snowball") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. RESULTS: Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. CONCLUSION: Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and "local cross border" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence.

Adult↗
PubMed2005

Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine during six years of follow-up.

A locally produced Vi polysaccharide vaccine against typhoid fever was licensed in China following two placebo-controlled, efficacy trials conducted in the early 1990s in Baoying, Jiangsu Province, and Quan-zhou, Guangxi Province. The two trials each enrolled over 80,000 participants and followed participants for 12 and 19 months post-vaccination, respectively. To define the long-term efficacy of this vaccine, we retrospectively assessed the occurrence of typhoid fever, diagnosed with clinical and serological criteria, in the two study populations for 6 years following vaccination. During the second year following vaccination, vaccine efficacy was 100% (95% CI: 17%, 100%) in Baoying and 85% (95% CI: 49%, 96%) in Quan-zhou. There was suggestive protection (51%; PE: -95%, 88%) during the third year in Baoying, nearly identical to the level observed in the third year of an earlier trial in South Africa. These results confirm that this vaccine protects for at least 2 years, and are consistent with the assertion that the vaccine protects for at least 3 years.

Antigens, Bacterial↗
PubMed2005

The effect of Helicobacter pylori infection on expression of macrophage migration inhibitory factor by T cells and macrophages in gastric mucosa.

BACKGROUND: Macrophage migration inhibitory factor (MIF) plays a pivotal role in inflammatory and immune-mediated diseases. However, its molecular function and role in gastrointestinal diseases has rarely been studied and thus warrants an in-depth investigation. This study was designed and conducted to determine MIF expression in Helicobacter pylori (H. pylori)-induced gastritis and the effect of H. pylori on MIF expression in monocytes in vitro. METHODS: Gastric specimens of 62 patients with chronic gastritis were obtained through endoscopic biopsies. Both gastric antrum and body were examined for histopathologic changes. Positive H. pylori was determined through rapid urease test and histopathological examination. A patient was classified as H. pylori positive if both tests showed positive results. The updated Sydney System was employed to assess the severity and activity of gastric inflammation. Double immunoassaying for MIF/T-cells (CD45RO) and MIF/macrophage (KP1), as well as in situ hybridization for the expression of MIF mRNA were used for the current analysis. THP-1, a monocyte cell line, was co-incubated with H. pylori strains (ATCC26695) and subsequently examined for the expression of MIF protein and mRNA by enzyme linked immunosorbent assay and retrospective transcription-polymerase chain reaction, respectively. RESULTS: Among 62 patients with chronic gastritis, significant increase in total T-cells, MIF+ T-cells, total macrophages, MIF+ macrophages and MIF mRNA+ cells was observed in 42 H. pylori positive patients compared to H. pylori negative patients. Moreover, the increase of the MIF mRNA+ cells was highly correlated with the severity of the disease (number of MIF mRNA+ cells/mm(2), mild: 2834 +/- 382, moderate: 3569 +/- 123, severe: 3881 +/- 118, P < 0.01). In vitro results showed that the expression of MIF protein and mRNA in monocytes was significantly increased after incubation with H. pylori strains. CONCLUSIONS: Overexpression of MIF is common in H. pylori-induced gastric inflammation, which suggests MIF may play an important role in the initiation and development of this disease.

Female↗