Biomedical subjects

Hua Su

Publications and source records attributed to Hua Su.

36 records · Page 2Linked to original sources

PubMed2004

Extracting gene pathway relations using a hybrid grammar: the Arizona Relation Parser.

MOTIVATION: Text-mining research in the biomedical domain has been motivated by the rapid growth of new research findings. Improving the accessibility of findings has potential to speed hypothesis generation. RESULTS: We present the Arizona Relation Parser that differs from other parsers in its use of a broad coverage syntax-semantic hybrid grammar. While syntax grammars have generally been tested over more documents, semantic grammars have outperformed them in precision and recall. We combined access to syntax and semantic information from a single grammar. The parser was trained using 40 PubMed abstracts and then tested using 100 unseen abstracts, half for precision and half for recall. Expert evaluation showed that the parser extracted biologically relevant relations with 89% precision. Recall of expert identified relations with semantic filtering was 35 and 61% before semantic filtering. Such results approach the higher-performing semantic parsers. However, the AZ parser was tested over a greater variety of writing styles and semantic content. AVAILABILITY: Relations extracted from over 600 000 PubMed abstracts are available for retrieval and visualization at http://econport.arizona.edu:8080/NetVis/index.html.

Artificial Intelligence↗

PubMed2004

High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a high-risk Chinese population.

Because previous studies have shown that loss of heterozygosity (LOH) is common on chromosome arm 9p in esophageal squamous cell carcinoma (ESCC) and that genetic alterations in CDKN2A and CDKN2B on 9p are also common, we sought to determine whether LOH and these genetic alterations are related. We performed LOH studies on chromosome bands 9p21-p22 and searched for genetic alterations of CDKN2A and CDKN2B in 56 ESCCs from a high-risk Chinese population. Seventy-three percent of patients were found to have LOH at one or more loci on chromosome bands 9p21-p22, and LOH occurred more frequently in patients with a family history of upper gastrointestinal cancer than in those with a negative family history (P = 0.01, global permutation test). CDKN2A mutations (point mutations, deletions, insertions) were observed in 25% (14 of 56) of cases, and the LOH pattern was significantly different for individuals with and without a CDKN2A mutation (P = 0.01, global test). Three new single nucleotide polymorphisms (SNPs) and 2 previously reported SNPs were identified in this group of patients. Intragenic allelic loss at polymorphic sites in CDKN2A was detected in 32% (18 of 56) of patients. Seven of the 56 (13%) cases exhibited what is considered classic evidence (n = 4) or showed potential evidence (n = 3) of biallelic inactivation. Only one alteration was observed in CDKN2B, G171A in the 5' untranslated region. Both mutation and intragenic allelic loss in CDKN2A appear to play a role in the development of ESCC.

Alleles↗

PubMed2004

Identification of RARhoGAP, a novel putative RhoGAP gene expressed in male germ cells.

A gene encoding a novel RhoGAP of 1146 amino acids was isolated from rat testis RNA. Analysis of this protein identified two conserved domains, a RhoGAP domain and an RA domain. Thus the gene was named RARhoGAP. The RhoGAP domain contained conserved residues critical for RhoGAP activity, suggesting this domain is involved in the down-regulation of Rho GTPases. The presence of the RA domain suggests that RARhoGAP also functions as an effector for Ras- or Ral-like GTPases. RT-PCR analysis showed the transcript was ubiquitous in extragonadal tissues; however, Northern analysis indicated highest expression was in the testis. Homologues of rat RARhoGAP were found in mouse and human and were found expressed in testis by nested RT-PCR. In situ hybridization confirmed the specific expression of RARhoGAP in differentiating male germ cells. We postulate that RARhoGAP may be involved in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis.

Amino Acid Sequence↗

PubMed2004

[Study on the cost of expanded programme on immunization in areas with different economic levels].

OBJECTIVE: The expanded programme on immunization (EPI) is an important part of the social commonwealth projects providing health care service by the government, which benefits communities. Government has the responsibility for EPI's financing which should be covered by the national budget. It is essential that the cost of EPI service be scientifically estimated to provide propriety information for policy makers. METHODS: This study, using the cost accounting theory of health economics, to calculate EPI service cost at different levels. 3 provinces, 3 prefectures, 9 counties, 18 towns and 12 villages were selected from three provinces Guizhou, Heilongjiang and Zhejiang from the western, central and eastern regions of the country. RESULTS: The average costs for one EPI-targeted child in Guizhou, Heilongjiang and Zhejiang, were 15.68 Yuan, 29.00 Yuan and 31.09 Yuan, and the costs for one dose were 10.99 Yuan, 18.64 Yuan and 16.51 Yuan, respectively. The costs for complete immunization program for one child were 131.88 Yuan, 242.32 Yuan and 280.67 Yuan, respectively. The main factors affecting the cost would include the average personnel cost (salary and benefit cost) by different economic levels of areas, the number of EPI items developed, and the number of total doses for one child. CONCLUSION: (1) Obvious differences were found between different areas. (2) The proportion of the cost was not reasonably set because of the shortage of input. (3) Guideline for different areas to compensate the working item cost according to the number of the items should be formulated.

China↗

PubMed2003

Gene expression analysis of esophageal squamous cell carcinoma reveals consistent molecular profiles related to a family history of upper gastrointestinal cancer.

Tumor and matched normal tissue from 19 esophageal squamous cell carcinoma patients from a high-risk area of China were analyzed with 7680 gene cDNA microarrays. Forty-one genes were differentially expressed (P < 0.001; >/==" BORDER="0">2-fold change) between tumor and matched normal samples (13 overexpressed and 28 underexpressed). Hierarchical clustering showed consistent molecular profiles across patients. Multidimensional scaling plots visually distinguished cases by family history status, which was confirmed statistically using a global permutation test (P = 0.007); we then identified 152 genes of which the expression differed in tumors from family history positive versus negative cases (55 overexpressed and 97 underexpressed at P < 0.001). These data indicate that molecular profiles in esophageal squamous cell carcinoma are highly consistent and that expression patterns in familial cases differ from those in sporadic cases.

Aged↗

PubMed2003

Microsatellite alterations in esophageal dysplasia and squamous cell carcinoma from laser capture microdissected endoscopic biopsies.

Esophageal squamous cell carcinoma (ESCC), with a 5 year survival below 15%, is one of the most common fatal cancers worldwide. Significant reduction in mortality may be achieved by detecting and treating asymptomatic precursor lesions and curable early cancers. To explore this possibility and look for potential early detection markers, we examined alterations in 16 microsatellite markers in laser capture microdissected (LCM) endoscopic biopsies from the esophagus, including 15 dysplasias and 22 ESCCs, in patients from Shanxi Province, a region in north-central China. We found a significant increase in the total frequency of allelic loss with increasing disease severity. Allelic loss was seen in 2% of the markers in patients with low grade dysplasia (LGD), 15% of the markers in patients with high grade dysplasia (HGD), and 35% of the markers in patients with ESCC. Ten different markers (D3S4513, D5S2501, D8S1106, D9S118, D9S910, D13S1493, D13S894, D13S796, D15S655, and D17S1303) showed allelic loss in one or more of the premalignant lesions tested. The frequency of microsatellite instability (MSI) also increased with histological severity, from 22% in LGD to 33% in HGD and 59% in ESCC. These results indicate that the development of ESCC is associated with genetic instability, that this instability can be detected in endoscopic biopsies of recognized precursor lesions in patients without invasive cancer, and that these markers may be useful as predictive markers in the early detection of ESCC. Finally, we also report methodologic/technical modifications that enhance the use of LCM for screening endoscopic biopsies.

Adult↗

PubMed2003

Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma.

Previous studies have shown frequent allelic loss on chromosome 13 in esophageal squamous cell carcinoma (ESCC). We assessed the frequency of allelic loss on chromosome 13q14 and mutations of deleted in cancer 1 (DICE1) (also found on 13q14) in ESCC patients to determine if this candidate tumor suppressor gene has a role in the development of ESCC, and whether this gene was an inactivation target for allelic loss on chromosome 13q14. Initially, we examined allelic loss at five markers flanking DICE1 in 56 ESCC patients from Shanxi Province, China, and then examined the entire coding sequence of this gene for mutations using polymerase chain reaction-single-strand confirmation polymorphism (PCR-SSCP) analysis and DNA sequencing. Subsequently, we extended our evaluation to an additional 80 ESCC patients and 232 healthy individuals to confirm the germline variant found in the initial 56 ESCC patients. The frequencies of allelic loss were 71, 58, and 75% for D13S325, D13S757, and D13S887, respectively, in the initial 56 ESCC patients studied. Overall, 73% of informative patients had loss of heterozygosity (LOH) for at least one of these three markers. Somatic mutations were identified in three patients (3/56, 5%), and one novel polymorphism was identified in 3% of ESCC patients (4/136) and 3% of healthy individuals (6/232). We conclude that DICE1 mutations occur in ESCC but are infrequent. The candidate tumor suppressor gene corresponding to the frequent allelic loss on chromosome 13q14 in ESCC remains unknown.

Alleles↗

PubMed2003

Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China.

TP53 and BRCA2 are frequently mutated in cancer and polymorphisms of these genes may modify cancer risk. We used SSCP and DNA sequencing to assess and compare frequencies of R72P (TP53) and 5'UTR203G>A, N372H, and K1132K (BRCA2) polymorphisms in healthy Chinese subjects at varying risk for esophageal squamous cell carcinoma (ESCC) and in ESCC patients. Suggestive overall differences in the distributions of genotypes by risk groups were seen for all genotypes except K1132K. Differences in R72P and N372H were most likely a reflection of lack of Hardy-Weinberg equilibrium (HWE), however, the difference in 203G>A was due to low prevalence of GG in ESCC patients (0.22 versus 0.36 in high risk group (P=0.047), and 0.22 versus 0.40 in low risk group (P=0.010)), consistent with a disease association. These data suggest that the 203G>A polymorphism in BRCA2 may be associated with risk of ESCC.

Adult↗

PubMed2003

Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb.

Critical limb ischemia is an important clinical problem that often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote both collateral artery formation (arteriogenesis) and capillary angiogenesis in animal models of hindlimb ischemia. However, none of the previous studies has demonstrated an improvement in tissue hypoxia, the condition that drives the molecular response to ischemia. Furthermore, the optimal vector and route of gene delivery have not been determined. Recently, adeno-associated viral (AAV) vectors, which efficiently transduce skeletal muscle and produce sustained transgene expression, have been used as gene therapy vectors. We asked whether an intra-arterial injection of AAV-VEGF(165) normalizes muscle oxygen tension by increasing skeletal muscle oxygen tension, and promotes arteriogenesis and angiogenesis in a rat model of severe hindlimb ischemia. We found that AAV-VEGF treatment normalized muscle oxygen tension in the ischemic limb. In contrast, vehicle and AAV-lacZ-treated limbs remained ischemic. Collateral arteries were more numerous in AAV-VEGF-treated rats, but, surprisingly, capillaries were not. We conclude that intra-arterial AAV-mediated gene transfer of AAV-VEGF(165) normalizes muscle oxygen tension and leads to arteriogenesis in rats with severe hindlimb ischemia.

Animals↗

PubMed2003

Expression of the cation transporter McHKT1 in a halophyte.

From the ice plant, Mesembryanthemum crystallinum, McHKT1 was isolated encoding a protein 41-61% identical to other plant HKT1-like sequences previously described as potassium or sodium/potassium transporters. McHKT1 acts as a potassium transporter in yeast with specificity similar to that of wheat HKT1. In Xenopus oocytes it transports cations with a specificity Rb+ > Cs+ > [K+ = Na+ = Li+]. McHKT1 is exclusively localized to the plasma membrane. The isoform isolated is most highly expressed in leaves and is present in stems, flowers and seed pods but absent from the root where, according to immunological data, a second isoform exists which does not cross-hybridize with the leaf form in RNA blots at high stringency. McHKT1 transcript amounts increase during the first 6-10 h of stress and then decline to pre-stress levels with kinetics reminiscent of the initial influx of sodium into this halophyte. Immunocytological localization showed strong signals in the leaf vasculature and surrounding mesophyll cells but low-intensity signals are also detected in other cell types. In roots, McHKT is mainly confined to endodermis and stele. Possible functions of McHKT1 in ion homeostasis in the halophytic ice plant are discussed.

Amino Acid Sequence↗

PubMed2003

Enhanced immunogenicity to Mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85A.

The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against M. tuberculosis compared with the conventional vector.

Acyltransferases↗

PubMed2003

Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis.

The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

Acute Disease↗

PubMed2002

Identification of somatic mutations of the RNF6 gene in human esophageal squamous cell carcinoma.

We mapped a tumor suppressor gene locus to an 800-kb interval on human chromosome 13q12.11 for esophageal squamous cell carcinoma (ESCC). Two genes, ML-1 and RNF6, are located within this 800-kb interval. We analyzed both genes for the presence of mutations in 24 ESCC primary tumors and 16 tumor cell lines by directly sequencing the PCR products that were amplified from each exon. No mutation was detected in ML-1. In contrast, three somatic mutations in the RNF6 gene were detected in the ESCC primary tumors, and one mutation was also found in a tumor cell line. Identification of multiple somatic mutations in RNF6 suggests that RNF6 is a potential tumor suppressor gene involved in the pathogenesis of ESCC.

Carcinoma, Squamous Cell↗

PubMed2002

Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model.

Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors in vivo may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3' end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium.

3T3 Cells↗

PubMed2002

Characterization of a HKT-type transporter in rice as a general alkali cation transporter.

We report the characterization of rice OsHKT1 (Oryza sativa ssp. indica) homologous to the wheat K+/Na+-symporter HKT1. Expression of OsHKT1 in the yeast strain CY162 defective in K+-uptake restored growth at mM and micro M concentrations of K+ and mediated hypersensitivity to Na+. When expressed in Xenopus oocytes, rice OsHKT1 showed uptake characteristics of a Na+-transporter but mediated transport of other alkali cations as well. OsHKT1 expression was analysed in salt-tolerant rice Pokkali and salt-sensitive IR29 in response to external cation concentrations. OsHKT1 is expressed in roots and leaves. Exposure to Na+, Rb+, Li+, and Cs+ reduced OsHKT1 transcript amounts in both varieties and, in some cases, incompletely spliced transcripts were observed. By in situ hybridizations the expression of OsHKT1 was localized to the root epidermis and the vascular tissue inside the endodermis. In leaves, OsHKT1 showed strongest signals in cells surrounding the vasculature. The repression of OsHKT1 in the two rice varieties during salt stress was different in various cell types with main differences in the root vascular tissue. The data suggest control over HKT expression as a factor that may distinguish salt stress-sensitive and stress-tolerant lines. Differences in transcript expression in space and time in different lines of the same species appear to be a component of ion homeostasis correlated with salt sensitivity and tolerance.

Animals↗

PubMed2002

The expression of HAK-type K(+) transporters is regulated in response to salinity stress in common ice plant.

Four transcripts homologous to K(+) transporters of the HAK/KT/KUP family have been characterized from the common ice plant (Mesembryanthemum crystallinum). We report tissue-specific expression of McHAK1 and McHAK4 transcripts abundant in roots, leaves, and stems. McHAK2 was predominantly present in stems and McHAK3 in root tissues. By in situ hybridizations, the McHAKs showed signals in the leaf vascular bundles, mesophyll, and epidermal cells as well as in epidermal bladder cells. In mature roots, transcripts were mainly localized to the vasculature, and in differentiated root tips, the strongest signals were obtained from the epidermis. Expression of McHAK1, McHAK2, and McHAK4 complemented a yeast mutant defective in low- and high-affinity K(+) uptake. Growth of the yeast mutant was restored at low-millimolar K(+) concentrations and was inhibited by Rb(+) and Cs(+) but was not affected by Na(+). Transcript levels of McHAK1 and McHAK4 increased by K(+) starvation and by salt stress of 400 mM NaCl in leaves and roots. Expression of McHAK2 and McHAK3 was stimulated in leaves and was transiently induced in roots in response to high salinity with prestress transcript levels restored in salt-adapted plants. We discuss possible roles for such transporters in ion homeostasis at high salinity.

Amino Acid Sequence↗

PubMed2002

The link between psychosocial factors and functional dyspepsia: an epidemiological study.

OBJECTIVE: To investigate the prevalence of functional dyspepsia (FD) and the psychological disorders in Chinese population and their relation. METHODS: A total of 1016 apparently healthy people (study population) randomly selected from population were interviewed. A general questionnaire, Zung self-rating depression scales (SDS), and anxiety scales (SAS) were given to each subject. Seventy-two inpatients with confirmed diagnosis of FD, 84 with organic dyspepsia, and 197 with other organic diseases were also studied. RESULTS: Among the study population, 23.5% had FD and 9. 1% had disturbances of depression and/or anxiety. The prevalence of psychological disturbances in FD group (15.5%) differed significantly from that in non-FD group (7.1%, P < 0.01 ) . In the survey of inpatients, the rate of depression/anxiety in FD group (54.2%) was greater than that in organic dyspepsia group (19.0%) and other organic diseases group (28.9%), P < 0.05, and was also significantly higher than that of the FD cases in the study population (15.5%), P < 0.01. Further analysis showed that some psychosocial disturbances were risk factors of FD. CONCLUSION: Both FD and depression/anxiety disturbances are common in China, and there is a link between them.

Adolescent↗

PubMed2002

[Culture and identification of dendritic cells from the peripheral blood of patients with laryngeal squamous cell carcinoma in vitro].

OBJECTIVE: To culture dendritic cells (DC) from peripheral blood of patients with laryngeal carcinoma for therapeutic aid. METHODS: Adherent peripheral blood mononuclear cells from peripheral blood were cultured with 15 ng/ml rhGM-CSF and 7 ng/ml rhIL-4 for one or two weeks. The purity of DC was detected by immunocytochemistry method. The mixed leukocyte reactions stimulated by DC loaded with laryngeal carcinoma antigen were tested by measuring 3H-TdR uptake. RESULTS: A considerable number of suspended cells with spicular or dendritic appearance were observed after 1 week of culture, and their mitochondria were rich in cytoplasm. The positivity of DC was about 30%-60%. DC loaded with laryngeal antigen could induce proliferation of syngeneic T lymphocytes. CONCLUSION: A large number of DC with high purity can be cultured from peripheral blood of patients with laryngeal carcinoma in vitro. It may be used in further experimental studies for clinical applications.

Carcinoma, Squamous Cell↗