PubMed Health⌕ Search

Biomedical subjects

K Zhao

Publications and source records attributed to K Zhao.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed2001

Food-derived heterocyclic amine mutagens: variable metabolism and significance to humans.

The cooking of meat has been found to generate compounds that possess extreme mutagenicity when examined in short term tests. This observation led to the isolation and identification of a family of mutagenic chemicals, all of which are heterocyclic amines. These amines are potent bacterial and eukaryotic cell mutagens, and all of those tested have been found to induce tumors in laboratory animals. Metabolic activation of the heterocyclic amines predominantly involves CYP1-mediated N-hydroxylation and then O-esterification by phase II enzymes. In contrast, carbon oxidation, glucuronidation, and sulfation reactions at sites other than the hydroxylamine yield detoxication metabolites. In humans, the activities of these pathways are known to vary between individuals and are likely to influence susceptibility to the genetic toxicity of the heterocyclic amines. Clearly, accurate determination of human exposure to the heterocyclic amines and identification of the key enzyme systems involved and their regulation will be required for rational assessment of the risk and will help devise strategies to reduce such risk.

Amines↗
PubMed2001

[Treatment of congenital jerky nystagmus with opposite bidirectional neutral zone].

OBJECTIVE: To explore a method for the treatment of congenital jerky nystagmus with opposite bidirectional neutral zones. METHOD: The relatively used side between the two neutral zone was found by neutralizing bilateral head torsion angle with prisms. The surgical intervention was indicated for those patients whose head position would not turn to another side. RESULT: There were 14 cases treated by this method, none of these cases whose head position turned to another side. Ten cases underwent once operation, 2 cases, twice operations and another 2 cases undertook once operation with additional prism correction. The compensatory head posture was corrected and the vision in the primary position of gaze was improved in all the cases. CONCLUSION: This therapy for congenital jerky nystagmus with opposite bidirectional neutral zone shows significant therapeutic effects and can be available for clinical application.

Adolescent↗
PubMed2000

CeReS-18, a cell regulatory sialoglycopeptide, inhibits proliferation and migration of rat vascular smooth muscle cells.

CeReS-18, a cell regulatory sialoglycopeptide, has been shown to inhibit proliferation of a wide array of target cells. In the present study, the effect of CeReS-18 on vascular smooth muscle cell (SMC) proliferation was characterized in cultured rat aorta SMCs (A7r5). More extensively, the effect of CeReS-18 on platelet-derived growth factor (PDGF)-induced SMC migration was examined using a modified Boyden's chamber assay. CeReS-18 inhibits both SMC proliferation and migration in a concentration-dependent, calcium-sensitive, and reversible manner. Furthermore, cells preincubated with the inhibitor had an increased sensitivity to CeReS-18-mediated inhibition of SMC migration. Immunoprecipitation and in vitro phosphorylation assays demonstrated that MAP kinase activity was inhibited in the CeReS-18-treated cells and pretreatment with CeReS-18 suppressed the activation of MAP kinase stimulated by PDGF. However, it is not likely that the suppression of the MAP kinase pathway was directly responsible for the ability of CeReS-18 to inhibit migration of the rat aorta smooth muscle cells since a MEK-specific inhibitor, PD98059, did not influence A7r5 cell migration.

Animals↗
PubMed2000

DNA damage induced by catechol derivatives.

We investigated the effect of catechol derivatives, including dopa, dopamine, adrenaline and noradrenaline, on DNA damage and the mechanisms of DNA strand breakage and formation of 8-hydroxyguanine (8HOG). The catechol derivatives caused strand breakage of plasmid DNA in the presence of ADP-Fe(3+). The DNA damage was prevented by catalase, mannitol and dimethylsulfoxide, suggesting hydroxyl radical (HO..)-like species are involved in the strand breakage of DNA. Iron chelators, such as desferrioxamine and bathophenanthroline, and reduced glutathione also inhibited the DNA damage. Deoxyribose, a molecule that is used to detect HO,, was not degraded by dopa in the presence of ADP-Fe(3+). By adding EDTA, however, dopa induced the marked deoxyribose degradation in the presence of ADP-Fe(3+), indicating that EDTA may extract iron from ADP-Fe(3+) to catalyze HO. formation by dopa. Thus, EDTA was a good catalyst for HO.-generation, whereas it did not promote the strand breakage of DNA. However, calf thymus DNA base damage, which was detected as 8-HOG formation, was caused by dopa in the presence of EDTA-Fe(3+), but not in the presence of ADP-Fe(3+). The 8HOG formation was also inhibited by catalase and HO. scavengers, indicating that HO&z.rad; was involved in the base damage. These results suggest that DNA strand breakage is due to ferryl species rather than HO., and that 8HOG formation is due to HO. rather than ferryl species.

Animals↗
PubMed2000

Epidemiologic study of pulmonary obstruction in workers occupationally exposed to ethyl and methyl cyanoacrylate.

The association between pulmonary obstruction (e.g., asthma) and occupational exposure to methyl cyanoacrylate (MCA) and ethyl cyanoacrylate (ECA) was examined in an occupational cohort of 450 persons at an adhesive production facility in Puerto Rico. Employee medical records containing information on physical examinations and pulmonary function tests (PFTs), as well as occupational histories, on each employee over a period of about 17 yr and industrial hygiene measurements were evaluated. The cohort analysis was based on a Cox proportional hazards model. Workers exposed to ECA or MCA were compared to workers unexposed to these chemicals with respect to their risk of becoming an "incident case." An "incident case" was defined as any person whose PFTs were normal at the time of employment, but later demonstrated an obstructive pattern, which was defined as a decline in the ratio of forced expiratory volume exhaled in 1 s to forced vital capacity (FEV1/FVC) below 70%. A separate case-control analysis was also conducted that compared "suspected cases," defined as all those whose PFTs ever demonstrated an obstructive pattern (e.g., asthma), to persons whose PFTs remained within normal limits throughout their employment with respect to their past peak and cumulative exposures to cyanoacrylates. All of these analyses showed no evidence that exposure to average short-term concentrations of ECA or MCA of less than 0.5 ppm and occasional daily peak exposures of at least 1.5 ppm (usually 10 min or less), with occasional higher concentrations during spills, were associated with an increased risk of pulmonary obstruction. However, the study suggested that persons occupationally exposed to cyanoacrylates were more likely to have some reversible eye or upper airway irritation than persons who were unexposed.

Adhesives↗
PubMed2000

Mechanism(s) of in vitro percutaneous absorption enhancement of tamoxifen by enhancers.

The effects of enhancers (5% terpenes; i.e., eugenol, limonene, and menthone) in combination with 50% propylene glycol in water (50% PG) on the in vitro percutaneous absorption of tamoxifen through the porcine epidermis, on biophysical changes in the stratum corneum (SC) lipids, on macroscopic barrier properties, and on binding of the drug to the SC were investigated. These enhancers in combination with 50% PG significantly increased (p<0.05) the permeability coefficient of tamoxifen in comparison with that of the control (50% PG in water). Fourier transform infrared spectroscopy (FT-IR) was employed to investigate the biophysical changes in the SC lipids. The FT-IR results showed that treatment of the SC with 5% terpenes/50% PG did not shift the asymmetric and symmetric C-H stretching absorbances peak positions to higher wavenumbers but resulted in a decrease in the peak heights and areas in comparison with the untreated SC. Treatment with menthone and limonene in combination with 50% PG significantly increased (p<0.05) the partition coefficient of tamoxifen in comparison with treatment with 50% PG alone. Also, exposure of the SC to 5% terpenes in combination with 50% PG significantly increased (p < 0.05) the in vitro transepidermal water loss (TEWL) in comparison with 50% PG alone. Thus, an enhancement by menthone, eugenol, and limonene in the permeability of the SC to tamoxifen is due to lipid extraction and macroscopic barrier perturbation. Moreover, the effective diffusion coefficient of tamoxifen through the epidermis was enhanced following the treatment with either 5% eugenol/50%PG or 5% limonene/50%PG compared with 50%PG alone.

Animals↗