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Biomedical subjects

Jian Su

Publications and source records attributed to Jian Su.

At least 19 recordsLinked to original sources

ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth.

ASPP2 stimulates the apoptotic function of the p53 family in vivo. We show here that ASPP2-/- pups died before weaning. This postnatal lethality was significantly enhanced in p53+/- background and both deletions are synthetic lethal. ASPP2+/- mice developed spontaneous tumors. The tumor onset was accelerated by gamma-irradiation or in p53+/- background. Tumors derived from ASPP2+/- mice retained wild-type ASPP2 allele even though some of them lost p53. These provide the first genetic evidence that ASPP2 is a haploinsufficient tumor suppressor that shares overlapping function(s) with p53 in mouse development and tumor suppression.

Alleles↗

Quantitative analysis of type IV collagen subchains in the glomerular basement membrane of patients with Alport syndrome with confocal microscopy.

BACKGROUND: Alport syndrome (AS) is an inherited nephropathy characterized by glomerular basement membrane (GBM) abnormalities due to mutations in the type IV collagen genes. Through immunofluorescence analysis, the absence of alpha3(IV), alpha4(IV) and alpha5(IV) chains within the GBM has been shown in the majority of AS cases. In some atypical AS cases, however, staining of the GBM with antibodies against the alpha3(IV), alpha4(IV) and alpha5(IV) chains appeared normal. In this study, we studied these atypical AS cases by quantitative analysis of the expression of type IV collagen subchains in GBM. METHODS: Twelve patients diagnosed with AS, yet having normal staining for alpha3(IV) and alpha5(IV) chains in the GBM, were recruited. Quantitative analysis of type IV collagen subchains in the GBM was performed using confocal microscopy and immunofluorescence double label techniques. RESULTS: The absolute amounts of alpha3(IV), alpha4(IV) and alpha5(IV) were significantly lower in AS patients than that in normal subjects, associated with up-regulated expression of type IV collagen in GBM. It was found that eight cases had decreased ratios of alpha3(IV)/IV, alpha4(IV)/IV and alpha5(IV)/IV in the GBM simultaneously; one had reduced levels of alpha3(IV)/IV and alpha5(IV)/IV but had a normal level of alpha4(IV)/IV, and one had reduced alpha3(IV)/IV with normal alpha4(IV)/IV and alpha5(IV)/IV levels. The remaining two patients had normal ratios of alpha3(IV)/IV, alpha4(IV)/IV and alpha5(IV)/IV. CONCLUSIONS: Confocal analysis demonstrated for the first time that the ratios of alpha3(IV)/IV, alpha4(IV)/IV and alpha5(IV)/IV in the GBM decreased in patients with AS, even though routine immunofluorescence staining for alpha(IV) chains appeared normal. This result not only sheds light on the pathogenesis of AS, but also provides an alternative approach to diagnose atypical AS cases.

Adult↗

Experience with a step-down respiratory care center at a tertiary referral medical center in Taiwan.

OBJECTIVE: The aim of the study was to describe the outcome of patients after 1 year's implementation of an integrated delivery system for respiratory care mandated by the National Health Insurance Bureau in Taiwan. DESIGN: A retrospective observational study was conducted in a step-down respiratory care center (RCC). PATIENTS: Patients included adults receiving prolonged mechanical ventilation (> or =21 days). MEASUREMENTS AND MAIN RESULTS: A total of 224 cases were available for review; 108 (48.2%) patients were successfully weaned. Those who failed weaning had a longer stay in the intensive care unit and RCC (25.1 vs 20.9 and 31.4 vs 18.6 days, P < .05), but there were no differences in the patients' ages (74.3 vs 70.4 years, P = .17) or the Simplified Acute Physiology Score II (52 vs 46.9, P = .18) before admission to the RCC. After discharge from the RCC, only 4.9% of the patients still on a ventilator were weaned within 1 year. Patients who failed weaning in the RCC had a shorter overall survival (5.2 vs 10.4 months, P < .05) and a lower 1-year survival (23.6% vs 44.6%, P < .05). CONCLUSION: Patients admitted to the RCC were still critically ill. Patients who failed weaning in the RCC had had a longer intensive care unit and RCC stay and a worse outcome after leaving the RCC.

APACHE↗

[The association of von Willebrand factor and von Willebrand factor-cleaving protease in systemic lupus erythematosus].

OBJECTIVE: To evaluate the clinical significance of plasma von Willebrand factor (vWF) and von Willebrand factor-cleaving protease (vWF-CP) activity in systemic lupus erythematosus (SLE). METHODS: vWF antigen (vWF:Ag) and vWF-CP activity were respectively evaluated by using ELISA and residual-collagen binding assay (R-CBA) in 30 patients with SLE and 40 normal controls. RESULTS: The level of the vWF:Ag in SLE patients (114.6 +/- 16.3)% was significantly higher than that in the normal controls (71.3 +/- 49.5)% (P < 0.01), while the level of plasma vWF-CP activity in the SLE patients (57.7 +/- 16.3)% was significantly lower than that in the controls (86.6 +/- 1.8)% (P < 0.01). The level of vWF-CP activity was positively correlated with SLE disease activity index (SLEDAI). The alterations of these two indices were remarkable in lupus nephritis (LN) patients in comparison with those in non-LN patients. The level of vWF-CP activity in type IV LN was lowest among the four types of LN (II, III, IV, V). The level of the vWF:Ag in 30 SLE patients was reduced four weeks after therapy, on the other hand, the vWF-CP activity was significantly increased in those with SLEDAI below 9, but unchanged in whose with SLEDAI above 9. CONCLUSIONS: The injury of endothelial cells and to production autoantibodies against vWF-CP were the factors that resulted in lower vWF-CP activity in SLE patients and this lowered activity may influence the progression of SLE.

ADAM Proteins↗

[A study on the significance of plasma thrombospondin1 in thrombotic thrombocytopenic purpura and the relationship between thrombospondin1 and von Willebrand factor cleaving protease (ADAMTS13)].

OBJECTIVE: To measure plasma thrombospondin1 (TSP1) in thrombotic thrombocytopenic purpura (TTP) and other diseases such as idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), myocardial infarction, brain infarction, and malignant tumor et al. and 8 patients after bone marrow transplantation (BMT) were also investigated. Then to study on the relationship between TSP1 and von Willebrand factor cleaving protease (ADAMTS13); and to identify the significance of plasma TSP1 in TTP. METHODS: TSP1 was measured by a commercial kit and the activity of ADAMTS13 was evaluated by residue collagen binding assay. RESULTS: TSP1 in TTP plasma before plasma exchange or plasma infusion was 6.49 mg/L, and stepping up to 13.02 mg/L after therapy, but still significantly lower than 18.34 mg/L in normal control. While the decrease in different degree of ADAMTS13 activity was observed from 0%-52%, and there were 8 samples whose activity of ADAMTS13 were no more than 10%; the different extent of increase in those patients after therapy was demonstrated to be 2.9%-93.4%, only one patient's ADAMTS13 activity was below 10%. The activity of ADAMTS13 in some ITP and SLE patients were mildly decreased (63% +/- 16% and 70% +/- 14% respectively), TSP1 were also decreased (16 mg/L +/- 8 mg/L). TSP1 in patients of myocardial infarction and brain infarction were increased (24.0 mg/L +/- 2.9 mg/L), while ADAMTS13 activity had no significant change (72% +/- 16%). Same things happened in BMT patients. CONCLUSION: There was some concordance between the decrease of ADAMTS13 activity and TSP1 in plasma of TTP patients. And the change of TSP1 was restricted to TTP. TSP1 may contribute to the episode of TTP in a still unclear fashions.

ADAM Proteins↗

Recognition of protein/gene names from text using an ensemble of classifiers.

This paper proposes an ensemble of classifiers for biomedical name recognition in which three classifiers, one Support Vector Machine and two discriminative Hidden Markov Models, are combined effectively using a simple majority voting strategy. In addition, we incorporate three post-processing modules, including an abbreviation resolution module, a protein/gene name refinement module and a simple dictionary matching module, into the system to further improve the performance. Evaluation shows that our system achieves the best performance from among 10 systems with a balanced F-measure of 82.58 on the closed evaluation of the BioCreative protein/gene name recognition task (Task 1A).

Biomedical Research↗

[Expression of the metalloproteinase domain of von Willebrand factor-cleaving protease and preparation of its McAb].

The von Willebrand factor-cleaving protease (vWF-cp) is a newly identified plasma metalloproteinase and plays an important role in the pathogenesis of thrombotic microangiopathy. In the present study, the metalloproteinase domain of vWF-cp was expressed by IPTG-induced the recombinant engineered E.coli strain harbouring pET28a (+)-vWF-cp/MD and purified using chromatography on Ni-NTA column. Then the BALB/c mice were immunized with the recombinant protein to prepare the monoclonal antibodies (McAb) against vWF-cp and the obtained McAbs were characterized. Furthermore, the expression panels of vWF-cp in human normal tissues were investigated using immunohistochemistry. The results showed that high-level expression of the recombinant protein was achieved, which existed as inclusion body and amounted to 28% of total bacteria protein. Three monoclonal antibodies against the metalloproteinase domain of vWF-cp were obtained and two of them, SZ-112 and SZ-113, were further evaluated. Both of them belong to IgG(1). The concentration of them in ascites was 4 mg/ml, and their titers were as high as 1 x 10(-5). The data of ELISA showed that SZ-112 and SZ-113 recognized different epitopes of recombinant protein. The Western blot and immunoprecipitation data showed that the two monoclonal antibodies reacted not only with the recombinant protein, but also with a 200 kD protein in platelet lysate. Moreover, the vWF-cp was found to be present in the cytoplasm of many human tissues such as liver, prostate, ovary, etc. However, the protease could not be detected in brain tissue. In conclusion, the above-mentioned research work contributed not only to the further study of the structure and function of this protease, but also to the establishment of the method for quantifying the vWF-cp antigen in plasma.

ADAM Proteins↗

[A2 domain of human von Willebrand factor expressed in E. coli and its biological activity].

Von Willebrand factor (vWF) is the unique substrate for the metalloprotease, ADAMTS-13, and plays a pivotal role in the pathology of von Willebrand disease (vWD) and thrombotic thrombocytopenic purpure (TTP). To study the pathogenesis of TTP and to establish a method to diagnose TTP, the DNA fragment of vWF-A2 domain was amplified and inserted into expression vector with 6 x His tag (pQE-30), the recombinant expression vector was transformed into E. coli (strain M15) and induced by IPTG. The recombinant fragment comprising residues 718-905 of mature vWF was designated as rvWF-A2. It was purified by Ni-NTA resin column chromatography and refolded in Tris buffer containing GSH and GSSG. The results demonstrated that rvWF-A2 was expressed successfully in E. coli M15, amounting to 42% of total bacterial protein with the purity over 98%. It was identified that rvWF-A2 can be efficiently cleaved by the citrated normal plasma while no cleavage can be detected by the TTP plasma or plasma with EDTA. It is concluded that rvWF-A2 expressed efficiently in E. coli demonstrated excellent biological activity, which lays a solid foundation for establishment of method to measure quantatively the activity of ADAMTS-13.

ADAM Proteins↗

Recognizing names in biomedical texts: a machine learning approach.

MOTIVATION: With an overwhelming amount of textual information in molecular biology and biomedicine, there is a need for effective and efficient literature mining and knowledge discovery that can help biologists to gather and make use of the knowledge encoded in text documents. In order to make organized and structured information available, automatically recognizing biomedical entity names becomes critical and is important for information retrieval, information extraction and automated knowledge acquisition. RESULTS: In this paper, we present a named entity recognition system in the biomedical domain, called PowerBioNE. In order to deal with the special phenomena of naming conventions in the biomedical domain, we propose various evidential features: (1) word formation pattern; (2) morphological pattern, such as prefix and suffix; (3) part-of-speech; (4) head noun trigger; (5) special verb trigger and (6) name alias feature. All the features are integrated effectively and efficiently through a hidden Markov model (HMM) and a HMM-based named entity recognizer. In addition, a k-Nearest Neighbor (k-NN) algorithm is proposed to resolve the data sparseness problem in our system. Finally, we present a pattern-based post-processing to automatically extract rules from the training data to deal with the cascaded entity name phenomenon. From our best knowledge, PowerBioNE is the first system which deals with the cascaded entity name phenomenon. Evaluation shows that our system achieves the F-measure of 66.6 and 62.2 on the 23 classes of GENIA V3.0 and V1.1, respectively. In particular, our system achieves the F-measure of 75.8 on the "protein" class of GENIA V3.0. For comparison, our system outperforms the best published result by 7.8 on GENIA V1.1, without help of any dictionaries. It also shows that our HMM and the k-NN algorithm outperform other models, such as back-off HMM, linear interpolated HMM, support vector machines, C4.5, C4.5 rules and RIPPER, by effectively capturing the local context dependency and resolving the data sparseness problem. Moreover, evaluation on GENIA V3.0 shows that the post-processing for the cascaded entity name phenomenon improves the F-measure by 3.9. Finally, error analysis shows that about half of the errors are caused by the strict annotation scheme and the annotation inconsistency in the GENIA corpus. This suggests that our system achieves an acceptable F-measure of 83.6 on the 23 classes of GENIA V3.0 and in particular 86.2 on the "protein" class, without help of any dictionaries. We think that a F-measure of 90 on the 23 classes of GENIA V3.0 and in particular 92 on the "protein" class, can be achieved through refining of the annotation scheme in the GENIA corpus, such as flexible annotation scheme and annotation consistency, and inclusion of a reasonable biomedical dictionary. AVAILABILITY: A demo system is available at http://textmining.i2r.a-star.edu.sg/NLS/demo.htm. Technology license is available upon the bilateral agreement.

Abstracting and Indexing↗

Enhancing HMM-based biomedical named entity recognition by studying special phenomena.

The purpose of this research is to enhance an HMM-based named entity recognizer in the biomedical domain. First, we analyze the characteristics of biomedical named entities. Then, we propose a rich set of features, including orthographic, morphological, part-of-speech, and semantic trigger features. All these features are integrated via a Hidden Markov Model with back-off modeling. Furthermore, we propose a method for biomedical abbreviation recognition and two methods for cascaded named entity recognition. Evaluation on the GENIA V3.02 and V1.1 shows that our system achieves 66.5 and 62.5 F-measure, respectively, and outperforms the previous best published system by 8.1 F-measure on the same experimental setting. The major contribution of this paper lies in its rich feature set specially designed for biomedical domain and the effective methods for abbreviation and cascaded named entity recognition. To our best knowledge, our system is the first one that copes with the cascaded phenomena.

Abbreviations as Topic↗

Mental Status Expert: an expert system for scoring and reporting the mental status examination.

For neurology clerks and residents, the mental status examination is often the most difficult part of the neurological examination. We have developed the Mental Status Expert (MSE), a structured mental status examination designed for use by neurology student clerks and neurology residents. The MSE assesses seven areas of cognitive function: orientation and concentration, language, right parietal functions, left parietal functions, occipital lobe functions, frontal lobe functions, and memory. Norms for the test have been created based on administration to 281 subjects referred to the Neurology Clinic. The MSE uses production rules and other expert system features to assist in the scoring and reporting of test results.

Aged↗

Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP. METHODS: The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors. RESULTS: The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79 +/- 9.17)% (n = 30) and (79.47 +/- 10.78)% (n = 53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83 +/- 19.98)%, P < 0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P < 0.03 and P < 0.001, respectively), they were relatively high in comparison with that of TTP patients (P < 0.001). CONCLUSION: Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

ADAM Proteins↗

[Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor activity of chemotherapeutic drugs].

AIM: To investigate the inhibitory activity of salvianolic acid A (SAA) on nucleoside transport in cancer cells and its antitumor effect. METHODS: [3H] thymidine and [3H] uridine transport assays were used to determine the inhibitory activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to cultured cancer cells was examined with clonogenic assay. The antitumor effect in vivo was evaluated with transplantable tumor model in mice. RESULTS: SAA was shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with IC50 values of 18.1 and 17.1 micromol x L(-1), respectively. By clonogenic assay, the IC50 of SAA for KB cells was 44.7 micromol x L(-1). SAA markedly potentiated the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180 cells were transplanted sc in mice and tested drugs were administered ip. When administered separately, SAA at 200 mg x kg(-1) and 5-FU at 10 mg x kg(-1) inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs inhibited tumor growth by 63% (CDI = 0.86). CONCLUSION: SAA is active in blocking nucleoside transport in cancer cells and potentiates the cytotoxicity of chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo, SAA might be useful in combination cancer therapy.

Animals↗

[Residual collagen binding assay for von Willebrand factor-cleaving protease activity and its clinical application].

von Willebrand factor-cleaving protease (vWF-cp) is a newly identified metalloproteinase. The activity of vWF-cp would vary in different physiological or pathological states. To explore activity detectron of von Willebrand factor-cleaving protease and its clinical application, the vWF-cp activity was measured by a sensitive enzyme-linked immunoadsorbent assay to detect the residual collagen binding activity (R-CBA) of von Willebrand factor before and after digestion with vWF-cp. Moreover, its activity deficiency in patients with thrombotic thrombocytopenic purpura (TTP) and solid tumors was also investigated. The results showed that the residual collagen binding assay was sensitive enough to measure the serum or plasma vWF-cp activity in 87 health individuals, 79 patients suffering from TTP and solid tumors. The coefficient of variation within and between the batches was were 3.60% and 8.35%, respectively. The serum and plasma vWF-cp activity in health individuals was (79.47 +/- 10.78)% (n = 53) and (78.79 +/- 9.17)% (n = 30), respectively, whereas the vWF-cp activity in patients with TTP, benign and malignant tumors was significantly decreased (P values were less than 0.001, 0.03 and 0.001, respectively). It is concluded that the vWF-cp activity in plasma or serum of patients with TTP and solid tumors markedly decrease, especially in patients with TTP. Assay of the vWF-cp activity using R-CBA is a simple method.

ADAM Proteins↗