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Biomedical subjects

Hao Wu

Publications and source records attributed to Hao Wu.

At least 109 records · Page 6Linked to original sources

Mapping of antigenic sites on the nucleocapsid protein of the severe acute respiratory syndrome coronavirus.

Antigenic sites on the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) were mapped by Pepscan analysis with overlapping peptides that span the N protein sequence. Two major immunodominant epitopes located in the C-terminal region (amino acids [aa] 362 to 412) and middle region (aa 153 to 178) reacted with more than 75% of sera from SARS patients. Several minor immunodominant epitopes were reactive with about 50% of the SARS sera. Antisera from mice immunized with inactivated SARS-CoV recognized the two major immunodominant epitopes and one antigenic site located adjacent to the N-terminal region (aa 76 to 101), which did not react with the sera from SARS patients. Several monoclonal antibodies against SARS-CoV bound to the N- or C-terminal antigenic sites. These results suggest that the above antigenic sites on the N protein are important in eliciting humoral immune response against SARS-CoV in humans and animals and can be used as antigens for developing diagnostic tests.

Amino Acid Sequence↗

[Role of cyclin kinase inhibitor p27 in inhibition of emodin on mesangial cell proliferation induced by tumor necrosis factor-alpha].

OBJECTIVE: To investigate the role of p27 in the inhibition of emodin on the mesangial cell (MC) proliferation induced by tumor necrosis factor-alpha(TNF-alpha). METHODS: p27 protein of MC was detected with western blotting analysis. The degree of MC proliferation was estimated through [(3)H] thymidine ([(3)H] TdR) incorporation. Different dosage of emodin (50 mg/L,100 mg/L) was added into MC stimulated by TNF-alpha. RESULTS: TNF-alpha (200 kU/L) decreased p27 level of MC cultured in serum-free DMEM for 24 hours and increased[(3)H] TdR incorporation. Emodin increased p27 level of MC stimulated by TNF-alpha and decreased [(3)H] TdR incorporation. The more the emodin was added, the greater the above-mentioned effect of emodin. CONCLUSION: The increment of p27 level maybe play an important role in the inhibition of emodin on MC proliferation induced by TNF-alpha.

Animals↗

[Effect of integrated traditional Chinese and Western medicine therapy on progression of acute renal failure in patients with chronic renal insufficiency: a short-term clinical study].

OBJECTIVE: To evaluate the effect of integrated traditional Chinese and Western medicine therapy on the progression of acute renal failure in patients with chronic renal insufficiency. METHODS: Thirty-two patients with chronic renal insufficiency developed acute renal failure recently were treated with Chinese herbs and western drugs intravenously and clysterizing of Chinese herbs liquid for 30 minutes, and the treatment course was 14 days. Assessment of liver and renal function, blood routine, electrolytes and endogenous creatinine clearance rate (Ccr) was performed before and 2 weeks after the treatment. RESULTS: The levels of hemoglobin (HB), white blood cell count (WBC) and serum electrolytes showed no significant changes after the treatment. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) decreased, while the level of Ccr increased significantly (P<0.05) after the treatment. The total effective rate was 65.6%. CONCLUSION: The integrated traditional Chinese and Western medicine therapy can effectively delay the deterioration of renal function in patients with chronic renal insufficiency accompanied by acute renal failure.

Acute Kidney Injury↗

[A study on the differences of emotion and depression between patients as doctor/nurse and others occupation with severe acute respiratory syndrome].

OBJECTIVE: To study the emotional and depressive differences between severe acute respiratory syndrome (SARS) patients whose occupations were doctor/nurse and others. METHODS: During the three months when SARS was explosive in 2003, 524 questionnaires were collected from Xuanwu Hospital, You'an Hospital, Xiaotangshan Hospital, Renmin Hospital and Ditan Hospital in Beijing. There were 109 questionnaires finished by patients as doctors/nurses themselves. For a background matching, 109 questionnaires were also finished by the others. RESULTS: From 218 questionnaires, we found that the score on emotional condition (46.6204 +/- 8.4408 vs. 41.6789 +/- 8.612 95, P < 0.001) of SARS patients whose jobs were doctor/nurse was higher than the other groups on while the score of SARS patients whose jobs were doctor/nurse was lower than the other groups (37.7615 +/- 9.026 61 vs. 41.2844 +/- 9.655 25, P = 0.006) regarding depressive condition. The scores of emotional and depressive condition were all correlated with the factor as "I can not master my future". CONCLUSION: Doctors/nurses having SARS had less emotional and depressive conditions than the others, which might due to the difference in medical knowledge, working condition and the route of infection, suggesting that psychological intervention in the post-SARS period called for attention.

Case-Control Studies↗

[Partial remove of mastoid tip in open-ended tympanoplasty or mastoidetomy].

OBJECTIVE: To summarize the effect of partial remove of mastoid tip in open-ended tympanoplasty or simple redical mastoidectomy. METHOD: Ten cases of cholesteatoma otitis media were treated with simple redical mastoidectomy. Thirty-four cases were treated with open-ended tympanoplasty. The mastoid tip were partial removed in all cases. RESULT: The volume of mastoid cavity became small after operation. The follow up time was 3 months. The dry ear rate was 97.6% (43 cases). After 1 years follow up there wasn't recurrence of cholesteatoma. CONCLUSION: The technique of partial remove of mastoid tip effective in open-ended tympanoplasty or simple redical mastoidectomy. We believe that in order to destry death cavity, shorten dry ear time and decrease recurrence it is very necessary.

Adolescent↗

[Clinical diagnostic value for nasal bone fracture by three-dimensional reconstruction of spiral CT].

OBJECTIVE: To evaluate the value of three-dimensional reconstruction of spiral CT in diagnosing nasal bone fracture. METHOD: Forty-six patients with nasal bone fracture were scanned transverselly and reconstructed with three-dimensional software by GE Lightspeed Plus Multiple Slices Scaner. RESULT: Nine cases (19.6%) show false negative with X-ray examination. There were 35 cases (76%) of simple nasal bone fracture and 16 cases (34.8%) compound fracture. CONCLUSION: There is important significance for diagnosing nasal bone fracture by three-dimensional reconstruction at present of spiral CT.

Adolescent↗

[Enlarged translabyrinthine resection of recurrent acoustic neuroma after suboccipital resection].

OBJECTIVE: To evaluate the technique and the outcome of enlarged translabyrinthine removal of recurrent acoustic neuromas after a suboccipital resection. METHOD: Five patients were proved to have recurrent acoustic neuromas after previous suboccipital removal procedures. Revision surgery was accomplished in these patients using the enlarged translabyrinthine approach by sufficiently removing petrous temporal bone to enlarge exposed sight during the operation. RESULT: The sizes of the recurrent tumors ranged from 2.5 to 4.0 cm. Total removal was achieved in all patients, with no death and other major complications such as intracranial infection and cerebrospinal fluid leakage. The facial nerve function was the same as pre-operative condition. There was no residual tumor showed in CT scans and MRI examinations after operation. The cerebel and brainstem resumed to normal position in each patient. No second recurrences had occurred to date at follow-up of 6 months to 2 years and 7 months. All patients recuperated and came back to work. CONCLUSION: Acoustic neuroma recurs frequently after the suboccipital surgery because there is a residual tumor inside the internal acoustic canal (IAC). The enlarged translabyrinthine approach is the most direct access to acoustic neuroma and the brainstem by which recurrent tumor can be removed is avoided during the second operation. Moreover, it is praisable that there are several advantages such as slight invasion and convenience of facial nerve orientation so as to excellent outcome of facial nerve preservation in the enlarged translabyrinthine surgery.

Aged↗

[Study on optimizing the extraction process of total free organic acids in Pinellia ternate Breit].

OBJECTIVE: To optimize the extraction process of total free organic acids in Pinellia ternate Breit. METHOD: The optimum extraction was investigated by total free organic acids determined by direct potential titration. The concentration of ethanol, amount of ethanol, extraction time and extraction times were the four factors in the experiment. RESULTS: The optimum extraction process was adding 10 times amount of 75% ethanol, refluxing for 2 times, 1 h each time. CONCLUSION: This extraction process shows higher yield of total free organic acids in Pinellia ternate Breit and is available for industrial production.

Acids↗

Analysis of causes for liver function deterioration in patients with HIV/HCV co-infection.

BACKGROUND: Co-infection of hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) is common in hemophiliacs and drug abusers. To assess the interaction between HIV and HCV disease progression, we examined 82 HIV/HCV co-infection patients and 62 HCV infection patients. METHODS: Liver function, pathological changes, infection duration, immune function and qualitative HCV-RNA and HCV antibody were compared retrospectively between the two groups of patients. RESULTS: Fourty-eight patients (58.5%) in the HIV/HCV co-infection group and 53 patients (85.5%) in the HCV infection group showed abnormal liver function. No significant difference was observed in inflammation and fibrosis in the two groups (P=0.187, 0.954). However, liver abnormality in the patients with HIV/HCV co-infection appeared 8 years earlier than in those with HCV infection alone (P<0.001). As to immune function, the counts of CD+4 T and CD+8 T in the HIV/HCV group were (226.35+/-173.49)X10(6)/L and (914.40+/-448.28)X10(6)/L, whereas in the HCV group they were (752.31+/-251.69)X10(6)/L and (529.01+/-170.67)X10(6)/L respectively. The difference in the two groups was highly significant (P<0.001; P<0.001). The ratio of the number of people with both HCV-RNA and HCV antibody positive to the number of HCV-RNA positive and HCV antibody negative in the HIV/HCV group was 52:9, whereas in the HCV group it was 44:1 (P=0.043). CONCLUSION: HIV/HCV co-infection can accelerate deterioration of hepatitis C, which may be due to the effect of HIV on cellular immunity and humoral immunity of the body.

Adult↗

DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.

In conjunction with histone modifications, DNA methylation plays critical roles in gene silencing through chromatin remodeling. Changes in DNA methylation perturb neuronal function, and mutations in a methyl-CpG-binding protein, MeCP2, are associated with Rett syndrome. We report that increased synthesis of brain-derived neurotrophic factor (BDNF) in neurons after depolarization correlates with a decrease in CpG methylation within the regulatory region of the Bdnf gene. Moreover, increased Bdnf transcription involves dissociation of the MeCP2-histone deacetylase-mSin3A repression complex from its promoter. Our findings suggest that DNA methylation-related chromatin remodeling is important for activity-dependent gene regulation that may be critical for neural plasticity.

Animals↗

Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac.

The inhibitor of apoptosis proteins (IAP) are endogenous caspase inhibitors in the metazoan and characterized by the presence of baculoviral IAP repeats (BIR). X-linked IAP (XIAP) contains three BIR domains and directly inhibits effector caspases such as caspase-7 via a linker_BIR2 fragment and initiator caspases such as caspase-9 via the BIR3 domain. A mitochondrial protein Smac/DIABLO, which is released during apoptosis, antagonizes XIAP-mediated caspase inhibition by interacting directly with XIAP. Here, using glutathione S-transferase pulldown and caspase activity assay, we show that Smac is ineffective in relieving either caspase-7 or caspase-9 inhibition by XIAP domain fragments. In addition, Smac forms a ternary complex with caspase-7 and linker_BIR2, suggesting that Smac/linker_BIR2 interaction does not sterically exclude linker_BIR2/caspase-7 interaction. However, Smac is effective in removing caspase-7 and caspase-9 inhibition by XIAP fragments containing both the BIR2 and BIR3 domains. Surface plasmon resonance measurements show that Smac interacts with the BIR2 or BIR3 domain in micromolar dissociation constants. On the other hand, Smac interacts with an XIAP construct containing both BIR2 and BIR3 domains in a subnanomolar dissociation constant by the simultaneous interaction of the Smac dimer with the BIR2 and BIR3 domains of a single XIAP molecule. This 2:1 Smac/XIAP interaction not only possesses enhanced affinity but also sterically excludes XIAP/caspase-7 interaction, demonstrating the requirement of both BIR2 and BIR3 domains for Smac to relieve XIAP-mediated caspase inhibition.

Apoptosis Regulatory Proteins↗

Highly diastereoselective strecker reaction of enolizable aliphatic sulfinimines.

The reaction of chiral sulfinimines 1c-g derived from aliphatic aldehydes with TMSCN in the presence of CsF gave alpha-amino nitriles in high diastereoselectivity and yield. alpha,beta-Diamino acid derivatives were also obtained in high diastereoselectivity from the reaction of 2-aziridinesulfinimines 1h and 1i followed by ring-opening of the products with thiophenol. The presence of hydrogen at the alpha-position of the C=N double bond is crucial in this TMSCN addition reaction.

Journal Article↗

The mechanism of p21-activated kinase 2 autoactivation.

The p21-activated kinases (PAKs) play an important role in diverse cellular processes. PAK2 is activated by autophosphorylation upon binding of small G proteins such as Cdc42 and Rac in the GTP-bound state. However, the mechanism of PAK2 autophosphorylation in vitro is unclear. In the present study, the kinetic theory of the substrate reaction during modification of enzyme activity has been applied to a study of the autoactivation of PAK2. On the basis of the kinetic equation of the substrate reaction during the autophosphorylation of PAK2, the activation rate constants for the free enzyme and enzyme-substrate complex have been determined. The results indicate that 1) in the presence of Cdc42, PAK2 autophosphorylation is a bipartite mechanism, with the regulatory domain autophosphorylated at multiple residues, whereas activation coincides with autophosphorylation of the catalytic domain at Thr-402; 2) the autophosphorylation reactions in regulatory domain are either a nonlimiting step or not required for activation of enzyme; 3) the autophosphorylation at site Thr-402 on the catalytic domain occurs by an intermolecular mechanism and is required for phosphorylation of exogenous substrates examined; 4) binding of the exogenous protein/peptide substrates at the active site of PAK2 has little or no effect on the autoactivation of PAK2, suggesting that multiple regions of PAK2 are involved in the enzyme-substrate recognition. The present method also provides a novel approach for studying autophosphorylation reactions. Since the experimental conditions used resemble more closely the in vivo situation where the substrate is constantly being turned over while the enzyme is being modified, this new method would be particularly useful when the regulatory mechanisms of the reversible phosphorylation reaction toward certain enzymes are being assessed.

Catalysis↗

[Clinical manifestation, treatment, and outcome of severe acute respiratory syndrome: analysis of 108 cases in Beijing].

OBJECTIVE: To investigate the clinical manifestations, treatment, and outcome of severe acute respiratory syndrome (SARS). METHODS: The clinical data of 108 SARS in-patients were analyzed. RESULTS: Among the 108 cases, 35 males (32.4%) and 73 females (67.6%), aged 37 +/- 9 (range 13 approximately 83 years), most were white-collar workers, medical workers accounting for 28.7%. 87.0% had a definite contact history. 20.4% were complicated by other internal diseases. The main clinical manifestations included fever, cough, pectoralgia, chest distress, headache, etc. Involvement of multiple organs was often. The incubation period was 2 approximately 14 days. The course included early stage, progressive stage, climax, and convalescence. Mild type accounted for 4.6%, common type 39.8%, severe type 20.4%, and extremely severe type 35.2%. At the early stage, white blood cell count, lymphocyte count and ratio of lymphocyte, proalbumin, transferring, CD(3)(+), CD(4)(+), CD(8)(+) cell count were remarkably decreased, and C-reactive protein, alpha-acid glycoprotein, and alpha(2)-globulin were remarkably increased. X-ray chest film showed solitary or multiple local exudative changes, mostly in pulmonary lower field. During the progressive stage the hyaline or consolidation images were enlarged. High solution CT showed solitary or multiple cotton wadding like images and ground glass-like or consolidation images. Hypoxemia was common. At the progressive stage application of adrenocortical hormones and non-invasive mechanical ventilation helped stop the progress of disease. Ninety-four cases were discharged, 14 cases died. Traditional Chinese medicine (TCM) regards SARS as one of epidemic febrile diseases. Treatment by combination of TCM and Western medicine was effective. CONCLUSION: SARS mainly affects youth and people in their prime of life. It has its own characteristic clinical manifestations. The classification system of 5 types and 4 stages helps judge the condition. Treatment by combination of TCM and Western medicine is encouraged.

Adolescent↗

R/qtl: QTL mapping in experimental crosses.

SUMMARY: R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental populations derived from inbred lines. It is implemented as an add-on package for the freely-available statistical software, R, and includes functions for estimating genetic maps, identifying genotyping errors, and performing single-QTL and two-dimensional, two-QTL genome scans by multiple methods, with the possible inclusion of covariates. AVAILABILITY: The package is freely available at http://www.biostat.jhsph.edu/~kbroman/qtl.

Algorithms↗

Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells.

Overexpression of P-glycoprotein (P-gp), the MDR1 gene product, confers multidrug resistance (MDR) to cancer cells. Clinically, MDR is one of the major causes for chemotherapeutic treatment failure in cancer patients. To explore a new approach to circumventing MDR, we adopted RNA interference to target MDR1 gene expression. RNA interference is a conserved biological response to double-stranded RNA, which results in sequence-specific gene silencing [G. J. Hannon, Nature (Lond.), 418: 244-251, 2002]. We report that introduction of an MDR1-targeted small interfering RNA duplex into drug-resistant cancer cells markedly inhibited the expression of MDR1 mRNA and P-gp, as determined by reverse transcription-PCR and Western blot. Inhibition of P-gp expression by small interfering RNA enhanced the intracellular accumulation of and selectively restored sensitivity to drugs transported by P-gp. These studies indicate that RNA interference can modulate MDR in preclinical models.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluation of the catalytic mechanism of the p21-activated protein kinase PAK2.

The p21-activated kinases (PAKs) play important roles in diverse cellular processes. In the present study, we provide an in-depth kinetic analysis of one of the PAK family members, PAK2, in phosphorylation of a protein substrate, myelin basic protein (MBP), and a synthetic peptide substrate derived from LIM kinase, LIMKtide. Steady-state kinetic analysis of the initial reaction velocity of PAK2 phosphorylation of MBP is consistent with both randomly and compulsorily ordered mechanisms. Further kinetic studies carried out in various concentrations of sucrose revealed that solvent viscosities had no effect on k(cat)/K(m) for either ATP or MBP while k(cat) was highly sensitive to solvent viscosity, indicating that the enzymatic phosphorylation by PAK2 can be best interpreted by a rapid-equilibrium random bi-bi reaction model, and k(cat) is partially limited by both phosphoryl group transfer (31 s(-)(1)) and the product release (19 s(-)(1)). In the phosphorylation of LIMKtide, both k(cat) and k(cat)/K(m) were insensitive to solvent viscosity, and the product release (86 s(-)(1)) was much faster than the phosphoryl group transfer step (19 s(-)(1)). These studies suggest that the release of phospho-MBP product is likely partially rate determining for the PAK2-catalyzed reaction since the dissociation rate of products from the PAK2 active site for LIMKtide phosphorylation differs from that of MBP significantly. Such a mechanism is in contrast to the previously established kinetics for the phosphorylation of peptide substrates by cAMP-dependent kinase, in which this process is limited by the release of ADP but not the phospho-peptide product. These results complement previous structure-function studies of PAKs and provide important insight for mechanistic interpretation of the kinase functions.

Adenosine Triphosphate↗