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Biomedical subjects

Hao Wu

Publications and source records attributed to Hao Wu.

At least 91 records · Page 5Linked to original sources

Treatment ischemic necrosis of the femoral head with vascularized iliac graft in young patients with sickle-cell disease.

OBJECTIVE: To investigate the therapeutic effects of the vascularized iliac graft for ischemic necrosis of the femoral head in Niger young patients with sickle cell disease. METHODS: From November 1998 to Apirl 2001, 12 patients(5 males and 7 females, aging 11-22 years) with sickle cell disease suffered from ischemic necrosis of the femoral head in 14 hips. The lesion was on one hip in 10 patients and on bilateral hip in 2 patients. Necrosis was classified as Ficat Stage III-IV in all patients. Twelve hips in 12 patients were treated with vascularized iliac graft in Maradi Province Hospital of Niger. The effects were evaluated on the basis of the Harris hip score and radiological examination. RESULTS: The patients were followed up 24-30 months after operation(27.4 months on average). The clinical results were satisfactory though no radiological evidence of improvement was noted. The mean Harris hip score increased from 75 points to 90 points. Pain relief and hip function improvement were achieved in all patients. No patients needed revision during short-term follow-up of 24-30 months. CONCLUSION: The method is recommendation for treatment of ischemic necrosis of the femoral head in the Ficat Stages III-IV in young patients with sickle cell disease for pain relief and restoration of hip joint function. This procedure may prolong the timing and acting of total hip arthroplasty.

Adolescent↗

[Resection of child meningoencephaloceles by transnasal endoscopy].

OBJECTIVE: To discuss the diagnosis of child meningoencephaloceles in nasal cavity and its methods of transnasal endoscopic surgery. METHOD: Two cases of congenital meningoencephalocele which have manifested mass in nasal cavity or nasopharynx received total resection by transnasal endoscopic surgery. Their medical records, radiographic imagings, and surgical procedures were reviewed. RESULT: We identified 2 patients with endonasal meningoencephaloceles whose main symptoms were watery rhinorrhea,nasal obstruction and mass in nasal cavity. A high index of suspicion for this diagnosis must be maintained, especially in patients with reiterative high fever or meningitis. Imaging examination should be done in those patients. Endonasal meningoencephaloceles, wherever the bone defects were located on the ethmoid roof or skull base,can be remove by endoscopy. CONCLUSION: CT and MRI are significant in diagnosis of endonasal meningoencephaloceles, nasal endoscopic surgery could be considered to be the best surgical approach without any severe complications.

Child, Preschool↗

[Methylprednisolone pharmacokinetics in perilymph and plasma of guinea pig after topical administration and intracardial injection].

OBJECTIVE: To determine pharmacokinetics profiles of methylprednisolone (MTH) in perilymph and plasma of guinea pig after topical and systemic administration. METHOD: A granule gelfoam soaked with MTH (40 mg/ml) was placed in the niche of round window of guinea pig; otocyst was infused with MTH (40 mg/ml); 4 mg/kg of MTH was injected intracardially. Samples of blood and perilymph of the scala tympani were obtained 1-6 h after administration of two routes, respectively. High-performance liquid chromatography was used to assay MTH in the samples. RESULT: After intracardial injection of MTH, concentrations of drug in plasma were obviously higher than those of in perilymph in every hour while drug in perilymph could not be obtained in 4-6 h, and the results were significantly different. After niche was placed with granule gelfoam with drug or otocyst was infused with MTH,drug could not be obtained in plasma, concentrations of drug in perilymph were obviously higher than those of in plasma after intracardial injection,and the highest concentrations in perilymph were manifested in 1 h 20 min. The concentrations of drug in perilymph after otocyst was infused with MTH were higher than those of after niche was placed with granule gelfoam soaked with MTH in every hour, and there were significant differences in between except those in 4 and 6 h. The half-life time of MTH in perilymph after otocyst was infused was 1.51 h, and the one after niche was placed with granule gelfoam soaked with MTH was 1.55 h. CONCLUSION: MTH could penetrate effectively through membrane of round window into the cochlear fluid and reach a much higher concentration following topical administration as compared with systemic application. The concentrations of drug in perilymph after otocyst was infused with MTH were higher.

Administration, Topical↗

[Clinical analysis of 68 patients with obstructive sleep-disordered breathing in children].

OBJECTIVE: To explore the clinical features and the diagnosis and the treatment of pediatric obstructive sleep-disordered breathing. METHOD: Sixty- disordered breathing. METHOD: Sixty eight cases with obstructive sleep-disordered breathing were reviewed including clinical features and cephalometric analysis and endoscopic examination, 46 of all them were study of polysomnography. RESULT: Forty-six cases were examined with polysomnography in preoperative. AHI 0.1 approximately 24.0 times/hour. Follow-up 3 months to 1.5 year, 68 patients were performed with adenotonsillectomy, upper airway obstruction caused by adenotonsillar hypertrophy were enlarged remarkably. Fifty-six cases main symptoms (snoring, mouth breathing and apnea) disappeared completely, nine cases were relief, 3 cases were reappear. Eleven cases (16 ears) of secretory otitis media after insert plastic tube into tympanum and 9 cases chronic sinusitis were relief. CONCLUSION: Upper airway obstruction caused by adenotonsillar hypertrophy were major reasons to lead to pediatric obstructive sleep-disordered breathing. The diagnosis and treatment must be combined clinical features with all kinds of examinations (cephalometric, endoscopic, polysomnography). Tonsillectomy and/or adenoidectomy with soft-tissue shavers were safe and effective in treatment of OSAHS children.

Child↗

Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment.

In an evolutionarily conserved signaling pathway, 'soluble' adenylyl cyclases (sACs) synthesize the ubiquitous second messenger cyclic adenosine 3',5'-monophosphate (cAMP) in response to bicarbonate and calcium signals. Here, we present crystal structures of a cyanobacterial sAC enzyme in complex with ATP analogs, calcium and bicarbonate, which represent distinct catalytic states of the enzyme. The structures reveal that calcium occupies the first ion-binding site and directly mediates nucleotide binding. The single ion-occupied, nucleotide-bound state defines a novel, open adenylyl cyclase state. In contrast, bicarbonate increases the catalytic rate by inducing marked active site closure and recruiting a second, catalytic ion. The phosphates of the bound substrate analogs are rearranged, which would facilitate product formation and release. The mechanisms of calcium and bicarbonate sensing define a reaction pathway involving active site closure and metal recruitment that may be universal for class III cyclases.

Adenosine Triphosphate↗

[The methods of shorting of proximal femoral and total hip arthroplasty for old femoral neck fracture with severe hip joint dislocation].

OBJECTIVE: To discuss the effective method and outcome to old femoral neck fracture with severe hip joint dislocation. METHODS: From April 1996, 7 cases of old femoral neck fracture with severe hip joint dislocation were treated by the shorting of posterior femoral and total hip arthroplasty. RESULTS: The average age of 7 patients was 51 years old and the mean follow-up was 27.3 months. The mean Harris score was improved to 84.3 from 36.7 before operation in the latest follow-up. The prosthesis position of acetabular and femoral was excellent, there was no sinking or softening of artificial joint, nonunion of femoral osteotomy. CONCLUSION: The preliminary clinical results are quite satisfactory of the shorting of posterior femoral and total hip arthroplasty to old femoral neck fracture with severe hip joint dislocation, the follow-up is necessary for further long-term outcome.

Adult↗

Protein kinase CK2 is required for dorsal axis formation in Xenopus embryos.

Dorsal axis formation in Xenopus embryos is dependent upon asymmetrical localization of beta-catenin, a transducer of the canonical Wnt signaling pathway. Recent biochemical experiments have implicated protein kinase CK2 as a regulator of members of the Wnt pathway including beta-catenin. Here, we have examined the role of CK2 in dorsal axis formation. CK2 was present in the developing embryo at an appropriate time and place to participate in dorsal axis formation. Overexpression of mRNA encoding CK2 in ventral blastomeres was sufficient to induce a complete ectopic axis, mimicking Wnt signaling. A kinase-inactive mutant of CK2alpha was able to block ectopic axis formation induced by XWnt8 and beta-catenin and was capable of suppressing endogenous axis formation when overexpressed dorsally. Taken together, these studies demonstrate that CK2 is a bona fide member of the Wnt pathway and has a critical role in the establishment of the dorsal embryonic axis.

Animals↗

Crystal structure of human coactosin-like protein at 1.9 A resolution.

Human coactosin-like protein (CLP) shares high homology with coactosin, a filamentous (F)-actin binding protein, and interacts with 5LO and F-actin. As a tumor antigen, CLP is overexpressed in tumor tissue cells or cell lines, and the encoded epitopes can be recognized by cellular and humoral immune systems. To gain a better understanding of its various functions and interactions with related proteins, the crystal structure of CLP expressed in Escherichia coli has been determined to 1.9 A resolution. The structure features a central beta-sheet surrounded by helices, with two very tight hydrophobic cores on each side of the sheet. CLP belongs to the actin depolymerizing protein superfamily, and is similar to yeast cofilin and actophilin. Based on our structural analysis, we observed that CLP forms a polymer along the crystallographic b axis with the exact same repeat distance as F-actin. A model for the CLP polymer and F-actin binding has therefore been proposed.

Actins↗

Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines.

The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is not only responsible for receptor binding and virus fusion, but also a major Ag among the SARS-CoV proteins that induces protective Ab responses. In this study, we showed that the S protein of SARS-CoV is highly immunogenic during infection and immunizations, and contains five linear immunodominant sites (sites I to V) as determined by Pepscan analysis with a set of synthetic peptides overlapping the entire S protein sequence against the convalescent sera from SARS patients and antisera from small animals immunized with inactivated SARS-CoV. Site IV located in the middle region of the S protein (residues 528-635) is a major immunodominant epitope. The synthetic peptide S(603-634), which overlaps the site IV sequence reacted with all the convalescent sera from 42 SARS patient, but none of the 30 serum samples from healthy blood donors, suggesting its potential application as an Ag for developing SARS diagnostics. This study also provides information useful for designing SARS vaccines and understanding the SARS pathogenesis.

Amino Acid Sequence↗

Synthesis of OSW-1 analogs with modified side chains and their antitumor activities.

Four analogs of OSW-1 (1-4) with modified side chains on the steroidal skeleton were synthesized following modification of our previous route for the total synthesis of OSW-1. Testing of the analogs against growth of tumor cells demonstrated that the 22-one function and the full length of the side chain of OSW-1 were not required for the antitumor action of OSW-1.

Antineoplastic Agents↗

ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.

Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD). Here, we demonstrate that Abeta-binding alcohol dehydrogenase (ABAD) is a direct molecular link from Abeta to mitochondrial toxicity. Abeta interacts with ABAD in the mitochondria of AD patients and transgenic mice. The crystal structure of Abeta-bound ABAD shows substantial deformation of the active site that prevents nicotinamide adenine dinucleotide (NAD) binding. An ABAD peptide specifically inhibits ABAD-Abeta interaction and suppresses Abeta-induced apoptosis and free-radical generation in neurons. Transgenic mice overexpressing ABAD in an Abeta-rich environment manifest exaggerated neuronal oxidative stress and impaired memory. These data suggest that the ABAD-Abeta interaction may be a therapeutic target in AD.

3-Hydroxyacyl CoA Dehydrogenases↗

Crystal structure of the putative adapter protein MTH1859.

MTH1859 from Methanobacterium thermoautotrophicum is a 77 residue protein representing a conserved family of functionally uncharacterized proteins. We solved the crystal structure of MTH1859 by single wavelength anomalous diffraction phasing using selenomethionine labeled protein. MTH1859 adopts a mainly anti-parallel all-beta-fold. The beta-sheet is heavily bent to form a U-structure that is closed through a loop. The monomer structure possesses similarities to the photoreaction center (PRC) domain fold, but the protein employs a unique oligomerization scheme. Two monomers of MTH1859 occupy the asymmetric unit and dimerize in a head-to-head fashion. Crystal packing interactions identify a second protein-protein interaction interface at the MTH1859 tails which can simultaneously bind two partner molecules. These interactions lead to the formation of a honeycomb structure and suggest that the family of MTH1859-like proteins might function as adapters for protein complex assembly.

Adaptor Proteins, Signal Transducing↗

General co-expression vectors for the overexpression of heterodimeric protein complexes in Escherichia coli.

We have designed and constructed a novel pair of bacterial co-expression vectors to facilitate the production of substantial amounts of recombinant multiprotein complexes for biochemical, biophysical, and structural studies. pOKD4 (kanamycin-resistant) and pOKD5 (ampicillin-resistant) are derivatives of pACYC177 cloning and pET26b expression vectors. As a result, pOKD4 and pOKD5 are T7-based expression plasmids containing the p15A origin of replication. This feature permits either pOKD4 or pOKD5 to co-exist in the same bacterial cell with most Escherichia coli expression vectors including the popular pET expression vectors. The pOKD4 and pOKD5 vectors have been engineered to possess exactly the same multiple cloning sites as pET26b thus allowing for the relatively easy shuttling of genes to and fro. The efficacy and versatility of this novel pair of co-expression vectors was successfully applied to the production of significant amounts of active DFF40/DFF45 heterodimeric protein complex in E. coli for detailed biochemical and structural studies.

Bacterial Proteins↗

Assembly of post-receptor signaling complexes for the tumor necrosis factor receptor superfamily.

The tumor necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins that are structurally related in their extracellular domains and specifically activated by the corresponding superfamily of TNF-like ligands. Members of this receptor superfamily are widely distributed and play important roles in many crucial biological processes such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis. A remarkable dichotomy of the TNFR superfamily is the ability of these receptors to induce the opposing effects of gene transcription for cell survival, proliferation, and differentiation and of apoptotic cell death. The intracellular signaling proteins known as TNF receptor associated factors (TRAFs) are the major signal transducers for the cell survival effects, while the death-domain-containing proteins mediate cell death induction. This review summarizes recent structural, biochemical, and functional studies of these signal transducers and proposes the molecular mechanisms of the intracellular signal transduction.

Animals↗

Antagonizing XIAP-mediated caspase-3 inhibition. Achilles' heel of cancers?

In this issue of Cancer Cell, Schimmer et al. report the identification of small molecule antagonists of XIAP that overcome its inhibition of caspase-3. It was remarkable that the compounds directly induced cell death in tumor cells while having little toxicity on normal cells. This suggests that caspases are already activated in tumor cells, which is different from the caspase activation status in normal mammalian cells. In comparison with Smac peptides targeting XIAP-mediated caspase-9 inhibition, which do not directly induce cell death, it appears that liberating downstream caspases rather than upstream caspases may be a preferred strategy for cancer drug discovery.

Animals↗