Biomedical subjects

W Liao

Publications and source records attributed to W Liao.

At least 19 recordsLinked to original sources

PubMed2006

Discovery and preliminary structure-activity relationship studies of novel benzotriazine based compounds as Src inhibitors.

We report the discovery and preliminary SAR studies of a series of structurally novel benzotriazine core based small molecules as inhibitors of Src kinase. To the best of our knowledge, benzotriazine template based compounds have not been reported as kinase inhibitors. The 3-(2-(1-pyrrolidinyl)ethoxy)phenyl analogue (43) was identified as one of the most potent inhibitors of Src kinase.

Humans↗

PubMed2005

Studies into using manure in a biorefinery concept.

Animal manure is an underutilized biomass resource containing a large amount of organic carbon that is often wasted with the existing manure disposal practices. A research project funded by the US Department of Energy explored the feasibility of using manure via the sugar platform in a biorefinery, converting the carbon from fiber to biochemicals. The results showed that (1) fiber was the major component of manure dry material making up approx 50%, 40%, and 36% of the dry dairy, swine, and poultry manure material, respectively; within dairy manure, more than 56% of the dry matter was in particles larger than 1.680 mm; (2) in addition to being a carbon source, manure could provide a variety of nutrient for fungi T. reesei and A. phoenicis to produce cellulase; (3) the hemicellulose component in the manure fiber could be readily converted to sugar through acid hydrolysis; while concentrated acid decrystallization treatment was most effective in manure cellulose hydrolysis; (4) purification and separation was necessary for further chemical conversion of the manure hydrolysate to polyols through hydrogenation; and (5) the manure utilization strategy studied in this work is currently not profitable.

Agriculture↗

PubMed2003

PET investigation of post-traumatic cerebral blood volume and blood flow.

Hemodynamic changes following traumatic brain injury (TBI) may reflect cellular damage leading to secondary injury. The purpose of this study was to investigate the regional hemodynamic parameters acutely after TBI among regions in and around contusions. Sixteen patients (11 male, 5 female) showing evidence of contusion on CT and 18 normal volunteers (12 male, 6 female) underwent positron emission tomography (PET) with O-15 CO and O-15 H2O to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF), respectively. A flow to volume ratio (FVR = CBF/CBV) was also calculated as an index of vasodilatation. The hemodynamic parameters were compared among contusion, pericontusion, and remote areas. Globally, hemodynamic parameters did not differ between patients and normal volunteers, and did not correlate with intracranial pressure (ICP). Regionally, contusional and pericontusional areas showed significantly lower CBF and FVR compared with normal volunteers, while CBV did not differ significantly. The correlation between CBF and CBV was significant (r = 0.37, p < 0.01). Remote areas did not show a significant difference in any of the PET parameters. In conclusion, regional brain edema is likely to occur in contusion and pericontusion areas, while some of the contusional tissue may show vascular engorgement.

Adult↗

PubMed2001

Catalytic, asymmetric synthesis of siphonarienal.

This paper describes the synthesis of the marine natural product, siphonarienal. The key step of this synthesis is an aldol reaction that constructs most of the skeleton and sets all three stereocenters of the target in one step from commercially available starting materials. Deoxygenation and chain homologation steps complete the synthesis.

Alkanes↗

PubMed2001

[Construction of Cryptococcus neoformans cap70 transformation system].

OBJECTIVE: To construct a transformation system of Cryptococcus neoformans capsule-deficient strain cap70. METHODS: (1)Obtained ura5 mutants by screening the Cryptococcus neoformans cap70 using 5-fluoroorotic acid counter selection method, analyzed the obtaining strain by Southern blot and PCR; (2)Through the plasmid pCXJ18 and pCXJU which contained ura5 gene from Cryptococcus neoformans and ura3 from Kluyveromyces fragilils. as a selective marker, the ura5 strains were transformed by electrotransformation and chemical transformation. RESULTS: Obtained ura5 mutants, they were detected as lack of ura function. The chemical transformation method was first be used in Cryptococcus neoformans transformation. CONCLUSION: A transformation system of Cryptococcus neoformans cap70 has been established, which provides not only the basis for gene cloning from the species for studying gene function and gene expression.

Cryptococcus neoformans↗

PubMed2001

[Construction of attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori catalase and observation on its protective immunity].

OBJECTIVE: To investigated the effect of attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori (Hp) catalase (KatA) on protection against Hp infection. METHODS: Recombinant plasmid expressing KatA was constructed. Expression of KatA was induced with IPTG, and analyzed by SDS-PAGE and Western blot. The recombinant plasmid were introduced into attenuated Salmonella typhimurium SL3261 strain to construct live oral vaccine strain. C57BL/6 mice was orally immunized with this vaccine strain and then given orogastric challenge with live Hp Sydney strain. The stomach samples were submitted to a rapid urease test and quantitative culture. RESULTS: The SDS-PAGE showed a dominant additional protein with molecular weight of 79kDa which could specially react with antibody against GST and accounted for 19% of total bacteria proteins. Animal experiment indicated that this vaccine strain could protect mice against Hp infection. CONCLUSION: Attenuated Salmonella typhimurium vaccine strain expressing KatA could induce effective immune response in protection against Hp infection,which may play an important role in preventing and treating Hp infection and related diseases.

Administration, Oral↗

PubMed2001

One-pot, catalytic, asymmetric synthesis of polypropionates.

[reaction: see text] The opening of methylketene dimer, followed by aldol reactions of the resulting enolate, provides a convenient access to syn,syn-dipropionate aldol adducts of a variety of aldehydes. These aldol adducts are useful precursors in the synthesis of complex polypropionates.

Anti-Bacterial Agents↗

PubMed2001

Direct evidence for the size and conformational variability of the pyruvate dehydrogenase complex revealed by three-dimensional electron microscopy. The "breathing" core and its functional relationship to protein dynamics.

Structural studies by three-dimensional electron microscopy of the Saccharomyces cerevisiae truncated dihydrolipoamide acetyltransferase (tE(2)) component of the pyruvate dehydrogenase complex reveal an extraordinary example of protein dynamics. The tE(2) forms a 60-subunit core with the morphology of a pentagonal dodecahedron and consists of 20 cone-shaped trimers interconnected by 30 bridges. Frozen-hydrated and stained molecules of tE(2) in the same field vary in size approximately 20%. Analyses of the data show that the size distribution is bell-shaped, and there is an approximately 40-A difference in the diameter of the smallest and largest structures that corresponds to approximately 14 A of variation in the length of the bridge between interconnected trimers. Companion studies of mature E(2) show that the complex of the intact subunit exhibits a similar size variation. The x-ray structure of Bacillus stearothermophilus tE(2) shows that there is an approximately 10-A gap between adjacent trimers and that the trimers are interconnected by the potentially flexible C-terminal ends of two adjacent subunits. We propose that this springlike feature is involved in a thermally driven expansion and contraction of the core and, since it appears to be a common feature in the phylogeny of pyruvate dehydrogenase complexes, protein dynamics is an integral component of the function of these multienzyme complexes.

Acetyltransferases↗

PubMed2001

Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells.

Apolipoprotein (apo) B-100 is an essential component of atherogenic plasma lipoproteins. Previous studies have demonstrated that the production of apoB-100 is regulated largely by intracellular degradation at both the co-translational and post-translational levels and that proteasome-mediated and non-proteasome-mediated pathways are involved in this process. ApoB-100 is a glycoprotein. The present study was undertaken to address the question of whether the inhibition of N-linked glycosylation with tunicamycin would interfere with apoB-100 production. We demonstrated that the treatment of HepG2 cells with tunicamycin decreased the net production of apoB-100 by enhancing co-translational degradation of the protein. This effect of tunicamycin was partly prevented by lactacystin, a specific proteasome inhibitor. Because lactacystin only partly reversed the effects of tunicamycin on apoB biogenesis, tunicamycin seemed also to induce apoB co-translational degradation in HepG2 cells by one or more non-proteasomal pathways. Furthermore, tunicamycin increased apoB ubiquitination approx. 4-fold. The proportion of the newly synthesized apoB-100 that was secreted and incorporated into the nascent lipoprotein particles was unaffected by tunicamycin. Thus the tunicamycin-mediated inhibition of N-linked glycosylation interferes with the production of apoB-100 that is mediated by both proteasomal and non-proteasomal pathways.

Acetylcysteine↗

PubMed2001

The essential role of MEKK3 in TNF-induced NF-kappaB activation.

Activation of IkappaB kinase (IKK) is the key step in stimulation of the transcription factor NF-kappaB, which regulates many genes in the inflammatory response pathway. The molecular mechanism that underlies IKK activation in response to tumor necrosis factor (TNF) is still unknown. Using mitogen-activated protein kinase kinase kinase 3 (MEKK3)-deficient fibroblast cells, we found that MEKK3 plays a critical role in TNF-induced NF-kappaB activation. We have shown that MEKK3 is required for IKK activation and functions downstream of receptor-interacting protein (RIP) and TNF receptor- associated factor 2. We have also shown that MEKK3 interacts with RIP and directly phosphorylates IKK. The kinase activity of MEKK3 is pivotal to its function and, therefore, MEKK3 links RIP and IKK in TNF-induced NF-kappaB activation.

Animals↗

PubMed2001

Two-year results from the asthma self-management program: long-term impact on health care services, costs, functional status, and productivity.

Participants in a variety of health plans, clinics and employer groups were invited to participate in the Asthma Self-Management Program (ASMP), an education program designed to improve self-management skills and daily functioning in individuals with asthma. The ASMP is an 8-week classroom program that provides information on the respiratory system, trigger avoidance, use of monitoring techniques and asthma medications. After program completion, graduates were contacted at scheduled intervals to reinforce performance of behaviors that are important to asthma self-management and to collect outcomes data. This paper reports the results of 2 years of follow-up with these individuals.

Absenteeism↗

PubMed2001

Nucleotide sequence analysis of a transforming gene isolated from nasopharyngeal carcinoma cell line CNE2: an aberrant human immunoglobulin kappa light chain which lacks variable region.

A transforming gene, designated Tx, was isolated from a human nasopharyngeal carcinoma (NPC) cell line CNE2 by transfection and molecular cloning techniques. The Tx gene was analyzed using computer-based bioinformatics and compared with the known sequences in EMBL and GenBank databases. We found that Tx contains human immunoglobulin kappa light chain constant region, five intact joining regions J1-J5, five recombination signal sequences and an N-segment besides classic regulatory sequences such as TATA boxes, CAAT boxes, poly A signals, etc. Interestingly, Tx also contains several binding sites for nuclear transcription factors such as NF-kappaB, NF-IL6, TFIID, etc. In conclusion, there are only several base pairs mutations or deletions compared with normal Ig K JC gDNA fragment. In all, Tx is an aberrant human immunoglobulin kappa light chain that contains the constant region, five joining regions, which lacks the variable regions.

Genes, Immunoglobulin↗

PubMed2001

Epidemiological study of pathogenic fungi in China: 1986 and 1996.

OBJECTIVE: An annual decade epidemiological survey of pathogenic fungi of inpatients or outpatients includes more than 25 provinces in China has been done in 1986 and 1996. METHODS: In 1986, there were a total of 9096 strains of pathogenic fungi collected from more than 41 units of 25 provinces in China. 10 years late, 18,085 strains of pathogenic fungi from 41 units of 25 provinces were collected from January 1st to December 31st in 1996. RESULTS: The results showed that during this decade the prominent pathogenic fungus was Trichophyton rubrum, but its ratio gradually decreased. On the contrary, Candida albicans gradually increased in its ratio from 5th in 1986 to 2nd in 1996. CONCLUSION: The pathogenic fungi in China have changed greatly in the past decade from 1986 to 1996.

Candida albicans↗

PubMed2001

LMP1 activates NF-kappa B via degradation of I kappa B alpha in nasopharyngeal carcinoma cells.

OBJECTIVE: To elucidate the mechanisms by which Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappa B in nasopharyngeal carcinoma cells. METHODS: A tetracycline-regulated LMP1-expressing nasopharyngeal carcinoma cell line, Tet-on-LMP1-HNE2, was used as the cell model. The kinetics of the expression of proteins, including LMP1, I kappa B alpha and I kappa B beta, was analyzed by Western blotting. The subcellular localization of NF-kappa B (p65) was detected by indirect immunofluorescence assay. The NF-kappa B transactivity was studied by transient transfection and reporter gene assay. RESULTS: I kappa B alpha was phosphorylated and degraded after the inducible expression of LMP1, although the total protein levels remained stable. The steady-state level of total I kappa B beta protein may have resulted from the initiation of an autoregulation loop after the activation of NF-kappa B. No change in the I kappa B beta level was detected. NF-kappa B (p65) was translocated from the cytoplasm to the nucleus following degradation of I kappa B alpha. After the introduction of the dominant-negative mutant of I kappa B alpha (Del 71) into Tet-on-LMP1-HNE2 cells, both nuclear translocation and transactivation of NF-kappa B induced by LMP1 was significantly inhibited. CONCLUSIONS: The results indicated that in nasopharyngeal carcinoma cells, LMP1 activated NF-kappa B via phosphorylation and degradation of I kappa B alpha, but not I kappa B beta. The dominant-negative mutant of I kappa B alpha (Del 71) could completely inhibit both the nuclear translocation and transactivation of NF-kappa B induced by LMP1.

Biological Transport↗

PubMed2001

Increased expression of Hsp70 and co-localization with nuclear protein in cells infected with the Hantaan virus.

OBJECTIVE: To investigate the effect of Hantaan virus infection on the expression of stress genes. METHODS: Techniques of virus infection, Western blot, immunohistochemistry, dual-immunofluorecsence staining, laser scanning confocal microscopy, RNA dot blot and in situ hybridization were used. RESULTS: Expression of heat shock protein 70 (Hsp70) was observed in cells infected with HTV as well as the translocation of Hsp70 from cytoplasm to nucleoli following virus infection. The variable distribution of Hsp70 was related to the various time after infection. Double-label indirect immunofluorescence of nuclear protein (NP) and Hsp70 in infected cells demonstrated co-localization of these proteins in the cytoplasm. CONCLUSION: Overexpression of Hsp70 can be induced directly by Hantaan virus, which may be associated with virus protein assembly. The Hantaan virus proteins co-localize with, and possibly form a physical complex with cellular Hsp70 in infected cells.

Animals↗

PubMed2001

[EBV latent membrane protein 1 induces p53 expression via NF-kappa B in nasopharyngeal carcinoma].

OBJECTIVE: To ascertain if EBV-encoded latent membrane protein 1 (LMP1) induces p53 expression via NF-kappa B signaling. METHODS: A nasopharyngeal carcinoma cell line, Tet-on-LMP1 HNE2, transfected with LMP1, the expression of which was regulated by tetracycline, was used in this study. Functional activity of NF-kappa B was determined by luciferase reporter assay and expression of p53 and bcl-2 was detected by Western blot. RESULTS: LMP1 induced p53 expression via NF-kappa B signaling pathway. Induction of p53 expression could be blocked by phosphorothiate analogs of antisense oligonucleotides to NF-kappa B p65 and LMP1, but not by NF-kappa B p50. However, it seemed that LMP1 had no influence on bcl-2 expression in nasopharyngeal carcinoma. CONCLUSION: Induction expression of p53 by EBV-encoded LMP1 implies that p53 may act as a mediator in apoptosis triggered by LMP1, which brings about a complex balance in nasopharyngeal carcinogenesis.

Herpesvirus 4, Human↗

PubMed2001

[The development and application of computer-aided bone histomorphometry system].

The aim of this study is to develop a Computer-aided Bone Histomorphometry System. The method is based on the Micro-graphical Digital System composed of microscope, digital camera, computer and related programs. The methodology was developed to measure the basic data on each image of visual field of hard bone tissue with computer-assistance. Following this, the parameters of bone volume, bone structure and bone metabolism were calculated based on the standardization of bone histomorphometry. Such method has been used in the experimental and clinical studies of osteoporosis to predict the fracture risk and evaluate the drug effect.

Bone Density↗

PubMed2001

Effect of fetal spinal cord graft with different methods on axonal pathology after spinal cord contusion.

OBJECTIVE: To investigate the effect of fetal spinal cord (FSC) graft with different methods on axonal pathology and neurological function recovery after spinal cord injury (SCI). METHODS: Forty Wistar rats were divided into 4 groups. In Group A, the spinal cord was injured and hemisected. In Group B, fetal spinal cord (FSC) was transferred into the injured site. In Group C, after having done as Group B, the upper and lower spinal nerve roots were anastomosed. And in Group D, after having done as Group B, the pedicled omentum was transferred into the hemisection cavity. At 6 weeks after operation, light and electronic microscopes were used to examine the axonal pathology. The neurological function was assessed with inclined plane tests in the open field. The number of axons was quantitated by a computer image analysis system. RESULTS: A greater loss of axons was observed in Group A than that of other groups at 6 weeks. The sequence of the reduced rate of the axons was as following, Group A>Group B>Group C>Group D (P<0.05). The remaining axons were paralleled with the significant improvement in neurological function recovery of the rats. CONCLUSIONS: It indicates that FSC and pedicled omentum grafts after SCI can protect the axons and promote the neurological function recovery of the rats.

Animals↗