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Biomedical subjects

K Zhao

Publications and source records attributed to K Zhao.

At least 19 recordsLinked to original sources
PubMed2006

Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy.

Recently Simmons et al. reported a new mechanism for SARS virus entry into target cells, where MDL28170 was identified as an efficient inhibitor of CTSL-meditated substrate cleavage with IC(50) of 2.5 nmol/l. Based on the molecule fingerprint searching method, 11 natural molecules were found in the Traditional Chinese Medicines Database (TCMD). Molecular simulation indicates that the MOL376 (a compound derived from a Chinese medicine herb with the therapeutic efficacy on the human body such as relieving cough, removing the phlegm, and relieving asthma) has not only the highest binding energy with the receptor but also the good match in geometric conformation. It was observed through docking studies that the van der Waals interactions made substantial contributions to the affinity, and that the receptor active pocket was too large for MDL21870 but more suitable for MOL736. Accordingly, MOL736 might possibly become a promising lead compound for CTSL inhibition for SARS therapy.

Algorithms↗
PubMed2006

An electric bottle for colloids.

Particle concentration is a dominant control parameter for colloids and other soft matter systems. We demonstrate a simple technique, "dielectrophoretic equilibrium," implemented as an "electric bottle," a planar capacitor in a larger volume. The uniform field in the capacitor traps particles in this force-free region at a higher density than in the zero field regions outside. We show how the technique measures the equation of state and we initiate and grow colloidal crystals. "Dielectrophoretic equilibria" enable the study of a complete concentration-dependent phase diagram from a single microscopic sample, obviating the previous need for preparing a large number of samples.

Journal Article↗
PubMed2005

Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures.

The use of bone cement to treat vertebral compression fractures in a percutaneous manner requires placement of the cement under fluoroscopic image guidance. To enhance visualization of the flow during injection and to monitor and prevent leakage beyond the confines of the vertebral body, the orthopedic community has described increasing the amount of radiopacifier in the bone cement. In this study, static tensile and compressive testing, as well as fully reversed fatigue testing, was performed on three PMMA-based bone cements. Cements tested were SimplexP with 10% barium sulfate (Stryker Orthopedics, Mahwah, NJ) which served as a control; SimplexP with 36% barium sulfate prepared according to the clinical recommendation of Theodorou et al.; and KyphX HV-R with 30% barium sulfate (Kyphon Inc., Sunnyvale, CA). Static tensile and compressive testing was performed in accordance with ASTM F451-99a. Fatigue testing was conducted in accordance with ASTM F2118-01a under fully reversed, +/-10-, +/-15-, and +/-20-MPa stress ranges. Survival analysis was performed using three-parameter Weibull modeling techniques. KyphX HV-R was found to have comparable static mechanical properties and significantly greater fatigue life than either of the two control materials evaluated in the present study. The static tensile and compressive strengths for all three PMMA-based bone cements were found to be an order of magnitude greater than the expected stress levels within a treated vertebral body. The static and fatigue testing data collected in this study indicate that bone cement can be designed with barium sulfate levels sufficiently high to permit fluoroscopic visualization while retaining the overall mechanical profile of a conventional bone cement under typical in vivo loading conditions.

Barium Sulfate↗
PubMed2005

Molecular evolution and intragenic recombination of the merozoite surface protein MSP-3alpha from the malaria parasite Plasmodium vivax in Thailand.

The merozoite surface antigens of malaria parasites are prime anti-morbidity/mortality vaccine candidates. However, their highly polymorphic nature requires extensive surveys of parasite populations to validate vaccine designs. Previous studies have found 3 molecular types (A, B and C) of the Plasmodium vivax merozoite surface protein 3a (PvMSP-3alpha) among parasite field populations. Here we analysed complete PvMSP-3alpha sequences from 17 clinical P. vivax isolates from Thailand and found that the nucleotide diversity was as high as that from samples widely separated by time and space. The polymorphic sites were not randomly distributed but concentrated in the N-terminal Ala-rich domain (block 2A), which is partially deleted in type B and C sequences. The size variations among type A sequences were due to small indels occurring in block 2A, whereas type B and C sequences were uniform in length with each type having a different large deletion. Analysis of synonymous and non-synonymous substitutions suggested that different selection forces were operating on different regions of the molecule. The numerous recombination sites detected within the Ala-rich domain suggested that intragenic recombination was at least partially responsible for the observed genetic diversity of the PvMSP-3alpha gene. Phylogenetic analysis failed to link any alleles to a specific geographical origin, even when different domains of PvMSP-3alpha were used for analysis. The highly polymorphic nature and lack of geographical clustering of isolates suggest that more systematic investigations of the PvMSP-3alpha gene are needed to explore its evolution and vaccine potential.

Animals↗
PubMed2003

Hyperfine polarization and its normal gradient coefficient of (87)Rb atoms in the vicinity (approximately 10(-5) cm) of coated and uncoated Pyrex glass surfaces.

We have made regionally specific measurement of the hyperfine polarization of 87Rb atoms in the vicinity ( approximately 10(-5) cm) of coated and uncoated Pyrex glass surfaces. We find that the polarization near an uncoated surface decreases rapidly with decreasing distance from the surface whereas for a silicone-coated surface the polarization is independent of the distance from the surface. We have also determined the normal gradient coefficient micro (S.I) of the hyperfine polarization in uncoated cells. In a representative uncoated cell, at a Rb density 7.35 x 10(13) cm(-3) and a pump beam intensity 1.3 W/cm(2), we find micro(S.I)=24+/-7 microm(-1).

Journal Article↗
PubMed2003

Establishment of a highly efficient transformation system for pepper (Capsicum annuum L.).

Application of modern genetic manipulation has been limited in pepper ( Capsicum annuum L.) due to the lack of an efficient transformation system. Following the development of an efficient protocol for in vitro regeneration of pepper cotyledons, we investigated the key factors affecting transformation and established a highly efficient genetic transformation system using the pepper cotyledon as starting material. In this system, cotyledon explants are preconditioned for 2 days on kanamycin (km)-free DM1 medium [Murashige and Skoog (MS) salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l sucrose, 5,000 mg/l DJ nutrients and a hormone combination of 1.0 mg/l indoleacetic acid (IAA) and 5.0 mg/l 6-benzyladenine (BA) solidified with 0.7% agar, pH 5.8], followed by co-cultivation with Agrobacterium tumefaciens on DM1 for 2 days and delay selection on DM1 with 500 mg/l carbenicillin (carb) for 2 days. The explants are then placed on DM1 containing 10 mg/l AgNO(3), 50 mg/l km-sulfate and 500 mg/l carb. After 4-5 weeks, the explants with buds are transferred to EM1 medium (MS salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l sucrose, 5,000 mg/l DJ nutrients, 10 mg/l AgNO(3) and a hormone combination of 1.0 mg/l IAA, 3.0 mg/l BA and 2.0 mg/l gibberellic acid, solidified with 0.7% agar, pH 5.8) with 50 mg/l kanamycin and 500 mg/l carbenicillin for the elongation of buds. After 3-6 weeks, 1- to 2-cm-long elongated shoots are excised and planted on RM1 medium (MS basal medium supplemented with a hormone combination of 0.2 mg/l NAA and 0.1 mg/l IAA, solidified with 0.8% agar, pH 5.8) with 25 mg/l km and 200 mg/l carb for rooting. We tested four genotypes of pepper, and all presented a high differentiation efficiency (81.3% on average), elongation rate (61.5%) and rooting efficiency (89.5%). Polymerase chain reaction analysis results showed that 40.8% of the regenerated plantlets were transgenic plants.

Adenine↗
PubMed2003

Characterization of genotype II Rubella virus strains.

Two genotypes of Rubella virus have been described that differ by 8-9% at the nucleotide level in the E1 glycoprotein gene. Of these, genotype II (RGII) was only recently reported and in this study two RGII viruses, the BRDII vaccine strain and BR1 wild type strain, were characterized. Monoclonal antibodies against each of the virion proteins (capsid [C], glycoproteins E1 and E2) and polyclonal anti-rubella virus sera reacted similarly with purified virions from the RGII and reference RGI strains on Western gels, with the exception of one anti-E2 Mab, and thus the two genotypes are closely related antigenically. The genomic sequences of two genotype II (RGII) rubella virus strains were determined and compared with the six previously reported RGI sequences. The genomes of these viruses all contained 9762 nts and the lengths of the three untranslated regions (UTRs) and two open reading frames (ORF's) were identical. The overall difference between the RGI and RGII sequences at the nt level was approximately 8% and this difference was maintained across most of the genome. At the amino acid level, the RGI and RGII sequences differed overall by approximately 4%, however this difference was not uniform across the ORF's as the N-terminal third of P150 and the entirety of P90, both replicase proteins, were more conserved (<1% difference) while the C-terminal two thirds of P150 exhibited greater variation ( approximately 8% difference), including a hypervariable region between residues 771-801 within which divergence as great as 20-30% was detected. The parent wt virus of the BRDII vaccine was not available and its sequence was compared with the BR1 sequence to identify potential attenuating mutations. The BRDII and BR1 sequences varied at 252 residues (2.59%), including twelve in the UTRs and thirty coding differences in the ORF's. None of these differences in the BRDII sequence was vaccine-specific when compared with RGI wt and vaccine sequences and, therefore, there appeared to be no common pathway in the generation of live, attenuated rubella vaccines.

3' Untranslated Regions↗
PubMed2002

Effect of lipase treatment on the biocompatibility of microbial polyhydroxyalkanoates.

Films made from microbial polyesters polyhydroxybutyrate (PHB) and poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) were treated by lipases and NaOH solution. The change of the polyester biocompatibility was evaluated by inoculating mouse fibroblast cell line L929 on films of PHB, PHBHHx and their blends. Polylactic acid (PLA) was used as a control. It was found that untreated PHB and PLA films gave a poor support to the growth of L929 cells, viable cell density ranged from 0.1x10(4}) to 0.7x10(4) per ml only. While films of pure PHBHHx and PHB blended with PHBHHx showed improved biocompatibility, viable cell density observed increased from 9.6x10(2) to 6x10(4) on blended films of PHB/PHBHHx in ratios of 0.9/0.1 to 0/1, respectively. This result showed PHBHHx has a better biocompatibility compared with PHB. Films of PHB, PLA and the blends treated with lipases and 1 N NaOH, respectively, showed an improved ability to support cell growth. Biocompatibility of PHB was approximately the same as PLA after the treatment, while PHBHHx and its dominant blends showed improved biocompatibility compared with PLA. The sensitivity of the treatments was reduced when PHBHHx content increased in the PHB/PHBHHx blends. All three lipase treatments demonstrated more biocompatibility increase on all the films compared with the results of NaOH treatment. Scanning electron microscopy showed that PHB films changed its surface from multi-porous to rough non-porous after the lipase or NaOH treatment. While PHBHHx films showed little change after these treatments. The results showed that the polyester surface morphology played an important role in affecting cell attachment and growth on these materials.

Journal Article↗
PubMed2001

Rossby vortex simulation on a paraboloidal coordinate system using the lattice Boltzmann method.

In this paper, we apply our compressible lattice Boltzmann model to a rotating parabolic coordinate system to simulate Rossby vortices emerging in a layer of shallow water flowing zonally in a rotating paraboloidal vessel. By introducing a scaling factor, nonuniform curvilinear mesh can be mapped to a flat uniform mesh and then normal lattice Boltzmann method works. Since the mass per unit area on the two-dimensional (2D) surface varies with the thickness of the water layer, the 2D flow seems to be "compressible" and our compressible model is applied. Simulation solutions meet with the experimental observations qualitatively. Based on this research, quantitative solutions and many natural phenomena simulations in planetary atmospheres, oceans, and magnetized plasma, such as the famous Jovian Giant Red Spot, the Galactic Spiral-vortex, the Gulf Stream, and the Kuroshio Current, etc., can be expected.

Journal Article↗
PubMed2001

Regulation of CSF1 promoter by the SWI/SNF-like BAF complex.

The mammalian BAF complex regulates gene expression by modifying chromatin structure. In this report, we identify 80 genes activated and 2 genes repressed by the BAF complex in SW-13 cells. We find that prior binding of NFI/CTF to the NFI/CTF binding site in CSF1 promoter is required for the recruitment of the BAF complex and the BAF-dependent activation of the promoter. Furthermore, the activation of the CSF1 promoter requires Z-DNA-forming sequences that are converted to Z-DNA structure upon activation by the BAF complex. The BAF complex facilitates Z-DNA formation in a nucleosomal template in vitro. We propose a model in which the BAF complex promotes Z-DNA formation which, in turn, stabilizes the open chromatin structure at the CSF1 promoter.

Base Sequence↗
PubMed2001

Effect of menthone on the in vitro percutaneous absorption of tamoxifen and skin reversibility.

The effect of penetration enhancer (i.e., 1, 2, 3 and 5% menthone in combination with 50% ethanol (EtOH)) was investigated on the in vitro percutaneous absorption of tamoxifen, and post-recovery epidermal permeability after removal of the above enhancer. The flux of tamoxifen with menthone in combination with 50% EtOH was significantly greater (P<0.05) than the control (50% EtOH). The flux of tamoxifen increased with increasing concentrations of menthone. The post-recovery flux through enhancer exposed epidermis was significantly decreased (P<0.05) as compared to pre-recovery. However, post-recovery flux of tamoxifen through the enhancer-exposed epidermis did not completely recover to the baseline (i.e., post-recovery flux through phosphate buffered saline, pH 7.4 treated epidermis).

Administration, Topical↗
PubMed2001

MECP2 truncating mutations cause histone H4 hyperacetylation in Rett syndrome.

Rett syndrome (RTT) is a mostly sporadic disorder of developmental regression, with loss of speech and purposeful hand use, microcephaly and seizures. It affects 1 in 10 000-15 000 females. RTT is caused by mutations in the MECP2 gene, which is located in Xq28 and subject to X inactivation. MECP2 encodes a methyl-CpG-binding protein that binds to 5-methyl-cytosine in DNA through its methyl-binding domain. Recruitment of a transcriptional silencing complex through MeCP2's transcriptional repression domain results in histone deacetylation and chromatin condensation. To study the effects of two common truncating RTT mutations (R168X and 803delG), we examined mutant MeCP2 expression and global histone acetylation levels in clonal cell cultures from a female RTT patient with the mutant R168X allele on the active X chromosome, as well as in cells from a male hemizygous for the frameshift mutation 803delG (V288X). Both mutant alleles generated stable RNA transcripts, but no intact MeCP2 protein was detected with an antibody against the C-terminal region of MeCP2. Western blots with antibodies against acetylated histones H3 and H4 revealed that H4, but not H3, was hyperacetylated. By using antibodies against individual acetylated lysine residues, the observed H4 hyperacetylation was attributed to increased acetylation of lysine 16. Therefore, expression of endogenous truncating MECP2 alleles, in the absence of wild-type MeCP2 protein, is specifically associated with an increase in the mono-acetylated histone isoform H4K16. This observed effect may result in over-expression of MeCP2 target genes and, thus, play a role in the pathogenesis of RTT.

Acetylation↗
PubMed2001

Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution.

The p53 tumor suppressor is a sequence-specific DNA-binding protein that activates transcription in response to DNA damage to promote cell cycle arrest or apoptosis. The p53 protein functions in a tetrameric form in vivo and contains four domains including an N-terminal transcriptional activation domain, a C-terminal regulatory domain, a tetramerization domain, and a central core DNA-binding domain that is the site of the majority of tumor-derived mutations. Here we report the 2.7-A crystal structure of the mouse p53 core domain. Like the human p53 core domain in complex with DNA, the mouse p53 core domain adopts an immunoglobulin-like beta sandwich architecture with a series of loops and short helices at opposite ends of the beta sandwich. Comparison of the DNA-bound and DNA-free p53 core domains reveals that while the central beta sandwich architecture remains largely unchanged, a loop region important for DNA binding undergoes significant rearrangement. Although this loop region mediates major groove DNA contacts in the DNA-bound structure, it adopts a conformation that is incompatible with DNA binding in the DNA-free structure. Interestingly, crystals of the DNA-free core domain contain a noncrystallographic trimer with three nearly identical subunit-subunit (dimer) contacts. These dimer contacts align the p53 core domains in a way that is incompatible with simultaneous DNA binding by both protomers of the dimer. Surprisingly, similar dimer contacts are observed in crystals of the human p53 core domain with DNA in which only one of the three p53 protomers in the asymmetric unit cell is specifically bound to DNA. We propose that the p53 core domain dimer that is seen in the crystals described here represents a physiologically relevant inactive form of p53 that must undergo structural rearrangement for sequence-specific DNA binding.

Animals↗
PubMed2001

Update on the molecular genetics of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of retinal dystrophies characterized by photoreceptor cell degeneration. RP causes night blindness, a gradual loss of peripheral visual fields, and eventual loss of central vision. Advances in molecular genetics have provided new insights into the genes responsible and the pathogenic mechanisms of RP. The genetics of RP is complex, and the disease can be inherited in autosomal dominant, recessive, X-linked, or digenic modes. Twenty-six causative genes have been identified or cloned for RP, and an additional fourteen genes have been mapped, but not yet identified. Eight autosomal dominant forms are due to mutations in RHO on chromosome 3q21-24, RDS on 6p21.1-cen, RP1 on 8p11-21, RGR on 10q23, ROM1 on 11q13, NRL on 14q11.1-11.2, CRX on 19q13.3, and PRKCG on 19q13.4. Autosomal recessive genes include RPE65 on chromosome 1p31, ABCA4 on 1p21-13, CRB1 on 1q31-32.1, USH2A on 1q41, MERTK on 2q14.1, SAG on 2q37.1, RHO on 3q21-24, PDE6B on 4p16.3, CNGA1 on 4p14-q13, PDE6A on 5q31.2-34, TULP1 on 6p21.3, RGR on 10q, NR2E3 on 15q23, and RLBP1 on 15q26. For X-linked RP, two genes, RP2 and RP3 (RPGR), have been cloned. Moreover, heterozygous mutations in ROM1 on 11q13, in combination with heterozygous mutations in RDS on 6p21.1-cen, cause digenic RP (the two-locus mechanism). These exciting molecular discoveries have defined the genetic pathways underlying the pathogenesis of retinitis pigmentosa, and have raised the hope of genetic testing for RP and the development of new avenues for therapy.

Chromosome Mapping↗
PubMed2001

Novel rhodopsin mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

PURPOSE: To identify mutations in the rhodopsin (RHO) gene in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) and to measure the prevalence rate of RHO mutations in Chinese ADRP cases. METHODS: Thirteen Chinese families with ADRP were clinically characterized. The complete coding region and intron splice sites of RHO were analyzed for mutations with single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing. RESULTS: One of the 13 Chinese families with ADRP was found to have a new, previously unidentified RHO mutation, a change from GAG to TAG at codon 341. The mutation (E341X) results in an in-frame stop codon, leading to the truncation of the rhodopsin protein. Mutation E341X was not detected in 100 normal control individuals. Patients carrying mutation E341X reported night blindness and showed optic atrophy, vessel attenuation, and a few bone spicule-like pigments in peripheral retina at the age of 23-25 years. At the age of 30 years, visual acuity was severely impaired, peripheral visual field was greatly constricted, rod and cone ERG was not detectable, and only a slight left cone response remained. CONCLUSIONS: We have identified a novel rhodopsin mutation (E341X) in a Chinese family with ADRP. The location and character of the mutation expand the spectrum of RHO mutations causing RP. Identification of a RHO mutation in one of the 13 ADRP families studied suggests that only 7.7% of the ADRP cases in a Chinese population were caused by RHO mutations, a ratio significantly lower than that from North America or Europe.

Adult↗
PubMed2001

Novel deletion of the RPGR gene in a Chinese family with X-linked retinitis pigmentosa.

PURPOSE: To characterize a Chinese family with inherited retinitis pigmentosa (RP). METHODS: Linkage studies and haplotype analysis were used for gene mapping, and single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis were used for identifying the responsible mutation. RESULTS: Pedigree analysis suggests that RP in the Chinese family RP002 is inherited either as an autosomal recessive trait or as an X-linked trait. Linkage analysis of RP002 excluded all known autosomal recessive RP loci. Further analysis with 17 polymorphic markers covering the entire X chromosome localized the RP gene in RP002 between markers GATA175D03 and GATA144D04 on Xp11.4, a region where the RP3 gene (RPGR ) is found. Mutation analysis of the RPGR gene in RP002 revealed a novel 28-bp deletion in exon 7. This deletion resulted in an in-frame stop codon that eliminates the C-terminal two-thirds of the RPGR protein. The 28-bp deletion co-segregated with the disease in the family and was not present in 100 normal Chinese individuals. Female carriers of the deletion were affected with myopia and had ERG abnormalities and mild constriction of visual field. CONCLUSIONS: A novel 28-bp deletion in the RPGR gene identified in an X-linked Chinese RP family causes severe RP in male patients as well as myopia and ERG abnormalities in female carriers. The deletion represents the largest microdeletion identified in RPGR to date, and expands the spectrum of RPGR mutations causing XLRP.

Adolescent↗
PubMed2001

Development of an occupational illness and injury surveillance database for the electric energy sector.

Currently available occupational injury and illness data for electric energy companies provide only overall summary rates. Specific information about types of injury or illnesses, rates by occupational or work environments, and injury costs and severity are generally not readily available. Relevant data such as personnel and claims information are frequently not integrated into a comprehensive health and safety surveillance system suitable for epidemiologic and health and safety research purposes. Epidemiological methods are valuable for identifying key risk factors for work-related injuries and illnesses and assessing their magnitude, as well establishing priorities for health and safety research. Application of such methods can result in long-term reductions in injury and illness rates and their attendant costs. Aggregation of relevant health and safety data across companies improves statistical power for the assessment of rare (yet costly) injuries or illness or specific at-risk subgroups within the electric energy sector. A pilot occupational injury and illness database has been developed that can incorporate and standardize data across a spectrum of companies of differing sizes and configurations. In illustrative data analyses, injury trends were summarized by company size, occupation, and demographic factors, among others. Trends observed in these illustrative analyses were consistent with results previously reported in the epidemiological literature, however, results are considered preliminary pending development of the full database. This study shows that development of a standardized surveillance occupational injury and illness database across companies with different database configurations is feasible. This database will ultimately provide a stable and accurate occupational health and safety assessment tool not currently available for this sector.

Databases, Factual↗