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Biomedical subjects

W Liu

Publications and source records attributed to W Liu.

At least 37 records · Page 2Linked to original sources

Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis.

AIMS: Macrophage migration inhibitory factor (MIF) is implicated in tumorigenesis. This study was conducted to determine whether MIF expression is associated with gastric pathology and whether MIF expression is increased in malignant gastric cells in vitro. MATERIALS AND METHODS: Patients with a normal gastric mucosa, Helicobacter pylori infected gastritis, intestinal metaplasia, and gastric adenocarcinoma were included. Immunohistochemistry and enzyme linked immunosorbent assay (ELISA) were used to determine MIF expression in gastric epithelial cells and MIF levels in serum, respectively. Five gastric cancer cell lines (AGS, MKN-45, MKN-28, MGC-803, and SGC-7901) and one non-malignant gastric cell line (GES-1) were cultured for 24 hours. MIF protein in the supernatant and MIF mRNA in cultured cells were measured by ELISA and reverse transcription-polymerase chain reaction, respectively. RESULTS: The percentage of MIF expressing epithelial cells was low in normal mucosa (12%) but substantially higher in gastritis (52%), intestinal metaplasia (66%), and gastric cancer (96%) (p<0.001, ANOVA). Serum MIF levels were low in patients with a normal mucosa (576 (82) pg/ml) but higher in patients with gastritis (2100 (349) pg/ml), intestinal metaplasia (4498 (253) pg/ml), and gastric cancer (9737 (1249) pg/ml) (p<0.001, ANOVA). There was a correlation between epithelial MIF expression and serum MIF levels (r = 0.776, p<0.001). In vitro, expression of MIF protein and mRNA was increased in malignant cells compared with non-malignant cells. CONCLUSIONS: Epithelial and serum MIF expression was progressively increased in H pylori induced gastritis, intestinal metaplasia, and gastric cancer, suggesting that MIF is involved in gastric carcinogenesis and may be a valuable biomarker for the early detection of gastric cancer.

Adenocarcinoma↗

Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability.

Mutation or epigenetic silencing of mismatch repair genes, such as MLH1 and MSH2, results in microsatellite instability (MSI) in the genome of a subset of colorectal carcinomas (CRCs). However, little is yet known of genes that directly contribute to tumor formation in such cancers. To characterize MSI-dependent changes in gene expression, we have now compared transcriptomes between fresh CRC specimens positive or negative for MSI (n=10 for each) with the use of high-density oligonucleotide microarrays harboring >44,000 probe sets. Correspondence analysis of the expression patterns of isolated MSI-associated genes revealed that the transcriptome of MSI+ CRCs is clearly distinct from that of MSI- CRCs. Such MSI-associated genes included that for AXIN2, an important component of the WNT signaling pathway. AXIN2 was silenced, apparently as a result of extensive methylation of its promoter region, specifically in MSI+ CRC specimens. Forced expression of AXIN2, either by treatment with 5'-azacytidine or by transfection with AXIN2 cDNA, resulted in rapid cell death in an MSI+ CRC cell line. These data indicate that epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in MSI+ CRCs.

Adaptor Proteins, Signal Transducing↗

Comparative analysis of whole saliva proteomes for the screening of biomarkers for oral lichen planus.

OBJECTIVE: To screen possible biomarkers in whole saliva from oral lichen planus (OLP) patients by proteomic techniques. METHODS: Two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were applied to whole saliva of OLP patients and controls, and the differential protein components were analyzed with peptide mass fingerprinting and database searching. RESULTS: A total of 31 protein spots representing 14 proteins with at least two-fold difference in abundance between OLP and controls were identified. Among these, the expression of urinary prokallikrein was increased while short palate, lung and nasal epithelium carcinoma associated protein (PLUNC) was decreased in all samples of OLP. CONCLUSIONS: Urinary prokallikrein and PLUNC may be the new biomarkers which play a role in inflammation and immune response of OLP.

Adult↗

[Glycogenesis Type II (M. Pompe). Selective failure of the respiratory musculature--a rare first symptom].

Late-onset Pompe's disease, a generalized lysosomal glycogen storage disease caused by acid maltase deficiency, usually presents as a slowly progressive muscular weakness of proximal muscles in lower limbs, followed by involvement of respiratory muscles. In the case presented here, however, respiratory failure was the first and selective symptom which caused the uncommon appearance of a patient entering our outpatient clinic on foot carrying his own artificial respirator. Intercostal muscle biopsy eventually led to the diagnosis.

Adult↗

Hypoxia-mimetic agents desferrioxamine and cobalt chloride induce leukemic cell apoptosis through different hypoxia-inducible factor-1alpha independent mechanisms.

Hypoxia presents pro-apoptotic and anti-apoptotic biphasic effects that appear to be dependent upon cell types and conditions around cells. The substantial reports demonstrated that commonly used hypoxia-mimetic agents cobalt chloride (CoCl(2)) and desferrioxamine (DFO) could also induce apoptosis in many different kinds of cells, but the mechanism was poorly understood. In this work, we compare the apoptosis-inducing effects of these two hypoxia-mimetic agents with acute myeloid leukemic cell lines NB4 and U937 as in vitro models. The results show that both of them induce these leukemic cells to undergo apoptosis with a loss of mitochondrial transmembrane potentials (DeltaPsi m), the activation of caspase-3/8 and the cleavage of anti-apoptotic protein Mcl-1, together with the accumulation of hypoxia-inducible factor-1 alpha (HIF-1alpha) protein, a critical regulator for the cellular response to hypoxia. Metavanadate and sodium nitroprusside significantly abrogate DFO rather than CoCl(2)-induced mitochondrial Delta Psi m collapse, caspase-3/8 activation, Mcl-1 cleavage and apoptosis, but they fail to influence DFO and CoCl(2)-induced HIF-1alpha protein accumulation. Moreover, inducible expression of HIF-1alpha gene dose not alter DFO and CoCl(2)-induced apoptosis in U937 cells. In conclusion, these results propose that although both DFO and CoCl(2)-induced leukemic cell apoptosis by mitochondrial pathway-dependent and HIF-1alpha-independent mechanisms, DFO and CoCl(2)-induced apoptosis involves different initiating signal pathways that remain to be investigated.

Base Sequence↗

Genome-wide approach to identify risk factors for therapy-related myeloid leukemia.

Using a target gene approach, only a few host genetic risk factors for treatment-related myeloid leukemia (t-ML) have been defined. Gene expression microarrays allow for a more genome-wide approach to assess possible genetic risk factors for t-ML. We assessed gene expression profiles (n=12 625 probe sets) in diagnostic acute lymphoblastic leukemic cells from 228 children treated on protocols that included leukemogenic agents such as etoposide, 13 of whom developed t-ML. Expression of 68 probes, corresponding to 63 genes, was significantly related to risk of t-ML. Hierarchical clustering of these probe sets clustered patients into three groups with 94, 122 and 12 patients, respectively; 12 of the 13 patients who went on to develop t-ML were overrepresented in the latter group (P<0.0001). A permutation test indicated a low likelihood that these probe sets and clusters were obtained by chance (P<0.001). Distinguishing genes included transcription-related oncogenes (v-Myb, Pax-5), cyclins (CCNG1, CCNG2 and CCND1) and histone HIST1H4C. Common transcription factor recognition elements among similarly up- or downregulated genes included several involved in hematopoietic differentiation or leukemogenesis (Maz, PU.1, ARNT). This approach has identified several genes whose expression distinguishes patients at risk of t-ML, and suggests targets for assessing germline predisposition to leukemogenesis.

Child↗

Effects of adenovirus-mediated gene transfer of ICOSIg and CTLA4Ig fusion protein on experimental autoimmune myocarditis.

OBJECTIVE: To explore the therapeutic alliance effects of adenovirus vector-mediated gene transfer of ICOSIg and CTLA4Ig fusion protein on experimental autoimmune myocarditis (EAM). METHODS: Expression vector pAdeno-CTLA4Ig and pAdeno-ICOSIg was constructed and transfected into HEK293 cells. Adenovirus expresses CTLA4Ig and ICOSIg was produced. Ad-CMV-GFP was used as controls. EAM was induced in Lewis rats by injection of procine cardiac myosin. All the immunized rats were divided into four groups. Group A (n = 15) received adenovirus containing CTLA4Ig and ICOSIg from day 14-28; group B (n = 15), group C (n = 15) and group D (n = 15) received adenovirus containing CTLA4Ig, ICOSIg and GFP, respectively. Group E (n = 10) was normal controls never received immunization. On day 28, all the rats were killed after echocardiography examination. Histopathological examination was used to observe inflammation in the myocardium. Western blot was used to detect CTLA4, ICOS, ICOSL and competitive RT-PCR for B7-1, B7-2 expression. T lymphocyte proliferation assay was performed and ELISPOT was used to detect the Th1 and Th2 production. RESULTS: Alliance application of CTLA4Ig and ICOSIg exerts therapeutic effects on EAM. After a treatment duration of 14 days, cardiac function and myocardial inflammation improved significantly compared to group D. Expression of CTLA-4, ICOS and ICOSL, B7-1 was statistically decreased in group A, B and C compared with group D. T-cell proliferation was inhibited by costimulatory blockade in a dose-dependent style. ICOSIg blockade significantly augments IL-4 and IL-10 production while diminished IFN-gamma production. CONCLUSIONS: Blockade of costimulatory pathway with alliance therapy of CTLA4Ig and ICOSIg alleviated autoimmune damage in EAM and improved cardiac function. The mechanisms may be downregulation of costimulatory molecules and anti-inflammation.

Abatacept↗

An open-label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis.

OBJECTIVE: To demonstrate the efficacy and safety of once-monthly (QM) darbepoetin alfa administration in maintaining haemoglobin (Hb) 11.0-13.0 g dL(-1) in subjects with chronic kidney disease (CKD) not receiving dialysis and previously treated with darbepoetin alfa every other week (Q2W). SUBJECTS: This open-label study enrolled subjects > or =18 years of age who had glomerular filtration rate > or =15 and < or =60 mL min(-1)/1.73 m(2), had Hb 11.0-13.0 g dL(-1), and were receiving Q2W darbepoetin alfa. DESIGN: Subjects were switched to QM darbepoetin alfa therapy for 28 weeks; the QM dose was titrated to maintain Hb levels. Primary end-point: proportion of subjects maintaining Hb > or =11.0 g dL(-1) during the final 8 weeks of the study (evaluation phase). Secondary end-points: Hb concentration during evaluation, darbepoetin alfa dose during the study, adverse events, laboratory parameters, and blood pressure. RESULTS: The study enrolled 152 subjects (female 52%, white 64%). Mean Hb > or =11.0 g dL(-1) during evaluation was achieved by 76% of the 150 subjects who received at least one dose of darbepoetin alfa [95% confidence interval (CI): 68%, 83%]. Mean (SD) Hb during evaluation was 11.71 (0.92) g dL(-1). Eighty-five per cent of 129 subjects who completed the study (95% CI: 78%, 91%) had Hb > or =11.0 g dL(-1) during evaluation. The dose of darbepoetin alfa over the study period was median (95% CI) 124.4 mug (106.2, 140.0). Darbepoetin alpha administered QM was well tolerated in study subjects. CONCLUSION: Darbepoetin alpha administered QM maintained Hb in study subjects with CKD not receiving dialysis.

Administration, Oral↗

Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population.

OBJECTIVE: This study used the population of the Central Valley of Costa Rica (CVCR) and phenotyping strategies alternative to DSMIV classifications to investigate the association of neuregulin 1 with schizophrenia. METHOD: Using 134 family trios with a history of psychosis, we genotyped six of the seven markers originally identified to be associated with schizophrenia in Iceland. RESULTS: The neuregulin Icelandic haplotype was not associated with schizophrenia in the CVCR population. However, a novel haplotype was found to be overrepresented in subjects with functional psychosis (global P-value > 0.05). Stratification of the sample by history of mania suggests that this haplotype may be preferentially over-transmitted to persons with a history of manic psychosis. CONCLUSION: These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.

Bipolar Disorder↗

Skin phototyping in a Chinese female population: analysis of four hundred and four cases from four major cities of China.

BACKGROUND/PURPOSE: The sun-reactive skin types in 404 Chinese females living in different cities were investigated in this study. METHODS: A questionnaire was designed according to the original concept of skin types proposed by Fitzpatrick and the investigation was conducted in two ways: self-administered reporting and then a personal interview. Minimal erythema dose (MED) and minimal persistent pigmentation dose (MPPD) were also measured in part of the volunteers with a standard solar simulator. RESULTS: The results show that in the way of personal interview, the predominant skin type of the investigated group is type III (71.4%), and then type II (14.7%) and type IV (14.2%), while in the self-reporting manner, the result is as follows: type III, 74.3%, type II, 25.6% and type IV, 1%. There are no skin type I, V or VI in the studied group. MED and MPPD from the same population show some relevance to the skin types, e.g. with the change of skin type from Type II to IV, the mean value of MED increases gradually and the MPPD decreases slightly. CONCLUSIONS: From the study we concluded that the skin types of the investigated Chinese females are principally type III (more than 70%), and then type II and type IV. The different ways of answering the questionnaire did not affect the results remarkably. The measurements of photobiology parameters confirmed that there is a certain correlation between skin types and MED or MPPD determined in this group of volunteers.

Age Distribution↗

A synergistic effect between PG490-88 and tacrolimus prolongs renal allograft survival in monkeys.

This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.

Animals↗

Prevalence and genetic diversity of coronaviruses in bats from China.

Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.

Animals↗

cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken.

We report sequence, tissue expression and map position data for the adiponectin gene (ADIPOQ) in chicken. This gene is involved in adipocyte differentiation in mammals and may play similar roles in chicken. The complete coding sequence of chicken ADIPOQ encodes a 244 amino acid protein. The coding region of the chicken ADIPOQ is organized in two exons and spans an approximately 2.1 kb genomic region. Domain/motif structures of the adiponectin protein among chicken and mammalian homologs are highly conserved. Reverse transcription-PCR revealed chicken ADIPOQ mRNA displayed high expression levels in fat tissue, heart, stomach and skin and weak expression in muscle. Analysis of a radiation hybrid panel indicated that ADIPOQ showed the most significant linkage to FOXL2 (LOD = 12.63, 12 cR) and ATSV (LOD = 7.53, 3 cR) both of which are located on chicken chromosome 9. Information provided in this study will be useful in further studies to determine the role the adiponectin gene plays in the regulation of glucose and lipid metabolism and body weight in chicken.

Adiponectin↗

Montelukast improves regional air-trapping due to small airways obstruction in asthma.

Quantitative image analysis of high-resolution computed tomography (HRCT) performed at residual volume, before and after methacholine, is a sensitive method of detecting small airways involvement in asthma and response to therapy targeted to the small airways. Since an oral anti-leukotriene reaches the small airways via the circulation, the present authors hypothesised that treatment with montelukast would lead to improved small airway patency. A double-blind crossover study compared the effect of montelukast versus placebo for 4 weeks in 16 mild-to-moderate steroid-naïve asthmatics. Small airways function was evaluated by HRCT at residual volume before and after methacholine to assess regional air-trapping and airways hyperresponsiveness, as well as by physiological studies of small airways. Montelukast treatment resulted in significantly less regional air-trapping on HRCT on the pre-methacholine images when compared with placebo, as well as improvement in total quality of life scores and symptom sub-scores. However, montelukast treatment had no effect on increases in regional air-trapping on HRCT in response to methacholine. No differences were noted in global measures of small airways physiology between placebo and montelukast. In conclusion, distal airways disease improves in asthmatic subjects treated with montelukast. This improvement can be detected with high-resolution computed tomography, but not with conventional physiological studies.

Acetates↗

Changes in serum cardiac troponins following a 21-km run in junior male runners.

AIM: This study was designed to examine the appearance and clearance characteristics of serum cardiac troponin T (cTnT) and I (cTnI) in junior runners after an exhaustive 21-km run. The dependence of the alternations of the cardiac troponins on the runners' training status reflected in training years, running ability and physiological profile at ventilatory threshold (Th(vent)) was also examined. METHODS: Ten trained male adolescents (16.2+/-0.6 years) performed 21-km run and graded treadmill exercise with maximum effort on two different days. cTnT and cTnI immediately before and 2, 4 and 24 hours after exercise were measured in the 21-km trial. The parameters at Thvent including the running speed (Th(vent)-Speed) and VO2 (Th(vent)-VO2) were identified in the graded exercise trial. RESULTS: Serum cTnT and cTnI in 6 of the 10 subjects measured 4 hours after the 21-km run were above the myocardial injury cutoffs of 0.03 and 0.09 ng x mL(-1), respectively, but returned towards pre-exercise levels within 24 hours that were not in the same manner observed in the clinical situation of myocardial infraction. The 6 subjects' training status was generally lower than that of the rest 4. Further, subjects' 4-h serum cTnT and cTnI were negatively related to their training years, Th(vent)-Speed and Th(vent)-VO2, and positively related to their personal best in half- and full-marathon races (r2 = or > 36%, n = 10). CONCLUSIONS: Such findings implied that clinicians based the diagnosis of long-distance run-induced myocardial infraction in novice junior runners upon the transient postexercise elevations of cardiac troponins alone should be with caution.

Adolescent↗

Sequence variations in the MBL gene and their relationship to pulmonary tuberculosis in the Chinese Han population.

SETTING: The mannan binding lectin (MBL) gene is thought to play a role in human innate immune response to tuberculosis (TB) infection. OBJECTIVE: To investigate the possible association between MBL sequence variants and TB infection in the Chinese Han population. DESIGN: A total of 152 male pulmonary tuberculosis (PTB) patients and 293 healthy male subjects were recruited. Six MBL single nucleotide polymorphisms (SNPs) (A/B, A/C, A/D, H/L, Y/X and P/Q) were genotyped and haplotyped using the combined analysis of polymerase chain reaction using sequence-specific primers (PCR-SSP) and the PCR-sequence specific oligonucleotide probe (PCR-SSOP) assay. The genotype and haplotype frequencies were compared between TB cases and controls using an unconditional logistic regression model. RESULTS: Neither the genotypes nor the haplotypes of the five loci were significantly associated with the disease when considered individually. After the haplotypes were regrouped, however, the XB haplotype group coding for diminished MBL levels was present at a significantly higher frequency in the patients compared with the YA group (OR 1.57, 95% CI 1.02-2.41, P < 0.05). CONCLUSION: No convincing evidence of association between MBL sequence variants and PTB was observed individually, although the low-producing XB haplotype group may serve as a minor risk factor for PTB infection in the male Chinese Han population.

Adolescent↗