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Biomedical subjects

Y Zhao

Publications and source records attributed to Y Zhao.

At least 73 records · Page 4Linked to original sources

Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort.

Among 367 subjects, the authors analyzed 167 patients with essential tremor, sporadic progressive cerebellar ataxia, multiple-system atrophy, and atypical parkinsonism and 200 healthy control subjects for FMR1 premutation alleles. None of the subjects carried alleles within the premutation range. These findings suggest that in the absence of other supportive clinical or imaging features, the cost-effectiveness of routine fragile X tremor/ataxia syndrome screening in this Asian cohort with movement disorders was low.

Adult↗

Predicted ATP-binding cassette systems in the phytopathogenic mollicute Spiroplasma kunkelii.

Spiroplasma kunkelii is a cell wall-free, helical, and motile mycoplasma-like organism that causes corn stunt disease in maize. The bacterium has a compact genome with a gene set approaching the minimal complement necessary for cellular life and pathogenesis. A set of 21 ATP-binding cassette (ABC) domains was identified during the annotation of a draft S. kunkelii genome sequence. These 21 ABC domains are present in 18 predicted proteins, and are components of 16 functional systems, which account for 5% of the protein coding capacity of the S. kunkelii genome. Of the 16 systems, 11 are membrane-bound transporters, and two are cytosolic systems involved in DNA repair and the oxidative stress response; the genes for the remaining three hypothetical systems harbor nonsense and/or frameshift mutations, so their functional status is doubtful. Assembly of the 11 multicomponent transporters, and comparisons with other known systems permitted functional predictions for the S. kunkelii ABC transporter systems. These transporters convey a wide variety of substrates, and are critical for nutrient uptake, multidrug resistance, and perhaps virulence. Our findings provide a framework for functional characterization of the ABC systems in S. kunkelii.

ATP-Binding Cassette Transporters↗

Alpha-synuclein haplotypes implicated in risk of Parkinson's disease.

The authors examined four- and six-loci haplotype constructs (from five single nucleotide polymorphisms and three microsatellite regions) of the alpha-synuclein gene in patients with Parkinson's disease (PD) and controls in an ethnic Chinese population. Logistic regression analysis demonstrated an association of NACP-Rep1 (p = 0.002) and L478 (p < 0.0001) with risk of PD after correction for the effects of age, sex, and the other polymorphic loci. Specific four-loci and six-loci haplotypes were significantly associated with an increased or decreased risk of PD.

Adult↗

Objective facial paralysis grading based on Pface and eigenflow.

To provide physicians with an objective and quantitative measurement of single-sided facial paralysis, the paper presents a computer-based approach that is different from the nine existing, subjective and hand-performed international scales, such as House-Brackman. For voluntary expressions of a patient, this approach used Pface, which stems from Dface, to measure the asymmetry between two sides of the face and used eigenflow to measure the expression variations between the patient and normal subjects. The results from Pface and eigenflow were then combined by the support vector machine produce to Pdegree. A study of 25 subjects revealed that Pdegree could differentiate paralysis states (Pdegree > or = 0) and normal states (Pdegree < 0), with the ability to grade facial paralysis automatically. Moreover, the Pface of specific facial areas can be used in the supervision of the rehabilitation process.

Adolescent↗

Inhibitory effects of budesonide, desloratadine and dexamethasone on cytokine release from human mast cell line (HMC-1).

OBJECTIVE: To determine the inhibitory potency of budesonide on interleukin (IL)-4, 6 and 8, GM-CSF and TNF-alpha release from the human mast cell line (HMC-1) in comparison with the systemic glucocorticosteroid, dexamethasone, and H(1) antagonist, desloratadine. METHODS: HMC-1 was stimulated with 25 ng/ml phorbol 12- myristate 13-acetate (PMA) and 2.5 x 10(-7) M ionomycin (A23187) for 6, 12 and 24 h in both the presence and absence of 10(-6)-10(-10) M concentrations of the test drugs. Culture supernatants were collected and assayed by ELISAs. RESULTS: HMC-1 produced substantial amounts of GM-CSF and IL-8 and smaller amounts of TNF-alpha, IL-4 and IL-6 after being stimulated with PMA together with A23187. Budesonide and dexamethasone had potent inhibitory effects and desloratadine had modest inhibitory effects on the release of these cytokines. Budesonide was more potent than dexamethasone at most concentrations and time points. IL-4 was the cytokine which was most susceptible to inhibition by the three tested drugs. The inhibitory effects, in some cases, were time- and concentration-dependent. CONCLUSION: Budesonide had a potent inhibitory effect on cytokine release from HMC-1. Its potency was greater than that of both dexamethasone and desloratadine.

Budesonide↗

Regulation of transgene expression in muscles by ultrasound-mediated hyperthermia.

Heat-sensitive transgene expression systems have been proposed recently for use in gene therapy to enable both spatial and temporal control of the gene activity. The transgene was put under the control of HSP-related promoters and could be turned on by external heat treatment. While the 'heat activation' phenomenon of the HSP-related promoters in vitro had been well documented, the detailed time response and temporal regulation profile in vivo were not fully understood. We reported here the regulation of transgene luciferase expression in vivo in muscles using a custom-built ultrasound-mediated hyperthermia instrument. The effects of different heating parameters and treatment regimens were evaluated. Optimal activation of gene expression was found at 39 degrees C. Significant tissue damage was observed at 41 degrees C and above, which directly correlated with the greatly reduced gene expression. The gene constructs remained stable and silent in muscle cells, and could be turned on at a later time without losing much activity. Repeated activation was also possible, but required heat treatment at a higher temperature to overcome thermotolerance.

Animals↗

Evaluation of Roche Diagnostics ONLINE DAT II, a new generation of assays for the detection of drugs of abuse.

A new generation of ONLINE assays has been developed that offers improved performance and enhanced ease of use. This family of assays is being applied to both the COBAS INTEGRA and Roche/Hitachi line of analyzers. The four ONLINE DAT II assays that were evaluated included cocaine (benzoylecgonine) (BE), methadone (MDN), opiates (OP), and tetrahydrocannabinol (THC). The BE assay has a dual cutoff (150/300 ng/mL) with a dynamic range from 0 to 5000 ng/mL. The MDN assay has a cutoff of 300 ng/mL with a dynamic range from 0 to 2000 ng/mL. The opiates assay has a 300 ng/mL cutoff with a 0 to 2000 ng/mL range and a 2000 ng/mL cutoff with a 0 to 8000 ng/mL range. The THC assay has 20, 50, and 100 ng/mL cutoffs with 0 to 100, 0 to 300, and 0 to 300 ng/mL dynamic ranges, respectively. The ranges of the intra-assay precision (coefficients of variation for n = 20) run in the semiquantitative mode are 2.3-7.5% for BE, 2.0-3.8% for MDN, 1.9-4.2% for OP, and 3.9-5.2% for THC. The intra-assay qualitative precision for all of the assays as calculated from absorbance values is generally higher than that of the intra-assay semiquantitative precision at the cutoff. The qualitative precision ranges between 0.4% and 3.1%. The standard curve stability defined for the COBAS INTEGRA systems for these reagents ranges from 35 to 68 days. The clinical sensitivity and specificity were compared to the OnLine generation I and CEDIA immunoassays, as well as gas chromatography-mass spectrometry (GC-MS). The results indicate that for each assay, the sensitivity and specificity were the same or greater when compared to the other two immunoassay technologies. The results of each assay also correlated very well (> 99%) when compared with GC-MS.

Automation↗

Evaluation of the role of platelet integrins in fibronectin-dependent spreading and adhesion.

BACKGROUND: Recent studies have shown that platelet adhesion and subsequent aggregation can occur in vivo in the absence of the two principal platelets adhesive ligands, von Willebrand factor and fibrinogen. These results highlight a possible role for fibronectin in supporting thrombus formation. OBJECTIVE AND METHODS: To evaluate the platelet integrins and subsequent activation pathways associated with fibronectin-dependent platelet adhesion utilizing both human and murine platelets. RESULTS: Platelets can adhere to fibronectin via the integrin alpha(IIb)beta(3), leading to formation of lamellipodia. This is mediated through an interaction with the tenth type III domain in fibronectin. Spreading on fibronectin promotes alpha(IIb)beta(3)-mediated Ca(2+) mobilization and tyrosine phosphorylation of focal adhesion kinase and phospholipase C gamma2. In contrast, studies with blocking antibodies and mice demonstrate that alpha(5)beta(1) and alpha(v)beta(3) support adhesion and promote formation of filopodia but not lamellipodia or tyrosine phosphorylation of these proteins. Further, neither alpha(5)beta(1) nor alpha(v)beta(3) is able to induce formation of lamellipodia in the presence of platelets agonists, such as collagen-related-peptide (CRP). CONCLUSIONS: These observations demonstrate that integrins alpha(5)beta(1) and alpha(v)beta(3) support platelet adhesion and the generation of filopodia but that, in contrast to the integrin alpha(IIb)beta(3), are unable to promote formation of lamellipodia.

Animals↗

Comparisons of protocols for decontamination of environmental ice samples for biological and molecular examinations.

Drilling and laboratory manipulations of glacial ice cores introduce contemporary microbes and biomolecules onto the cores. We report herein a systematic comparative study of several decontamination protocols. Only treatment with 5% sodium hypochlorite eliminated all external contaminating microbes and nucleic acids while maintaining the integrity of those within the cores.

Colony Count, Microbial↗

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

INTRODUCTION: Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE: We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS: 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS: We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

Adult↗

Complete nucleotide sequence and analysis of pPSR1 (72,601 bp), a pPT23A-family plasmid from Pseudomonas syringae pv. syringae A2.

Plasmid pPSR1 is a conjugative plasmid originally isolated from Pseudomonas syringae pv. syringae A2, and is a member of the recently described pPT23A plasmid family. We have determined the complete sequence of pPSR1 and found the plasmid to be 72,601 bp in length, encoding 55 ORFs. Putative functions were assigned to 49 ORFs; of these, 24 (49.0%) are involved in plasmid replication, maintenance or conjugation, 17 (34.7%) have roles in virulence or ecological fitness, and eight (16.3%) encode transposase functions as part of mobile elements. pPSR1 carries the effector gene orf34, the mutagenic DNA repair operon rulAB which confers tolerance to ultraviolet radiation, and two genes for methyl-accepting chemotaxis proteins, one of which was located within the novel transposon Tn 5395. The streptomycin resistance transposon Tn 5393a, which carries a strA-strB determinant, was found inserted immediately downstream of the pPSR1 repA gene. Functional analysis of the replication region of pPSR1 indicated that the repA gene and flanking upstream and downstream sequences are required for autonomous replication in P. syringae. Hybridization analyses of the distribution of 11 of the pPSR1 ORFs indicated that many of the ecologically important ORFs were confined to the pathovar P. syringae pv. syringae -either to strains from the local population from which pPSR1 was originally isolated, or strains from a worldwide collection. Conjugative transfer genes and a gene encoding a transcriptional regulator were more widely distributed among several P. syringae pathovars. The sequence analysis of pPSR1 suggests that pPT23A-family plasmids evolve by accumulating genes that are important for host-pathogen interactions or growth on plant hosts, which are incorporated onto a conserved backbone encoding conjugation and stability determinants.

Bacterial Proteins↗

Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family.

The clinical spectrum of spinocerebellar ataxia 3 (SCA 3) disease is wide and varied. We describe a Chinese patient with a mutation at the SCA 3 locus with clinical features of levodopa-responsive dystonia. The family history was suggestive of being autosomally dominant. Levodopa responsiveness though rare has been described in families with features of parkinsonism. Noteworthy is the relatively late onset of disease (>40 years) possibly explained by the low number of affected alleles at 59, the usual range being from 62 to 86, with the lowest recorded number at 56. This expands the wide and varied phenotypic manifestations of SCA 3, and highlights the observation that features suggestive of levodopa-responsive dystonia (DRD) such as focal dystonia, gait difficulty with diurnal fluctuation of symptoms, and a marked response to low doses of levodopa can be presenting features of SCA 3. SCA 3 should be considered a differential diagnosis in adult patients who present with DRD phenotype and with a positive family history.

Adult↗

Gene content and organization of an 85-kb DNA segment from the genome of the phytopathogenic mollicute Spiroplasma kunkelii.

Spiroplasma kunkelii, the causative agent of corn stunt disease in maize (Zea maysL.), is a helical, cell wall-less prokaryote assigned to the class Mollicutes. As part of a project to sequence the entire S. kunkelii genome, we analyzed an 85-kb DNA segment from the pathogenic strain CR2-3x. This genome segment contains 101 ORFs and two tRNA genes. The majority of the ORFs code for predicted proteins that can be assigned to respective clusters of orthologous groups (COGs). These COGs cover diverse functional categories including genetic information storage and processing, cellular processes, and metabolism. The most notable gene cluster in this genome segment is a super-operon capable of encoding 24 ribosomal proteins. The organization of genes in this operon reflects the unique evolutionary position of the spiroplasma. Gene duplications, domain rearrangements, and frameshift mutations in the segment are interpreted as indicators of phase variation in the spiroplasma. To our knowledge, this is the first analysis of a large genome segment from a plant pathogenic spiroplasma.

Base Sequence↗

Monoamine oxidase B polymorphism, cigarette smoking and risk of Parkinson's disease: a study in an Asian population.

Cigarette smoking is associated with reduced monoamine oxidase B (MAO B) activity. Polymorphisms of the MAO B gene may modify the relationship between smoking and Parkinson's Disease (PD). We examined the association of MAO B intron 13 G/A polymorphism and risk of PD, and the modulation of the polymorphism on smoking and PD in an Asian study population in Singapore. Two hundred and thirty PD patients (mean age 66.0 +/- 9.4 years, 63% men) and 241 age, gender, and race matched controls (mean age 64 +/- 9.2 years, 58.9% males) were studied. The frequency of G and A alleles in PD and controls was; 66/315 (21.0%) vs. 73/340 (21.5%) and 249/315 (79.0%) vs. 267/340 (78.5%). For women, the genotype frequency in PD and controls was; GG: 7/85 (8.2%) vs. 8/99 (8.1%); GA: 25/85 (29.4%) vs. 27/99 (27.3%); AA: 53/85 (62.4%) vs. 64/99 (64.6%). For men, allele frequency in PD and controls was; A: 118/145 (81.4%) vs. 112/142 (78.9%) and G: 27/145 (18.6%) vs. 30/142 (21.1%). The allele and genotype frequencies were not significantly different between young and late onset PD. The frequency of "ever" smokers in PD and controls was 31/230 (13.5%) vs. 52/241 (21.6%), P = 0.02. A stepwise logistic regression analysis did not reveal any interaction of smoking and the G allele and risk of PD. The MAO B G/A genotype frequency in our Asian population was quite different from Caucasians suggesting that ethnicity specific effects need to be considered in evaluating gene-environmental interaction.

Aged↗

Disability after clinical fracture in postmenopausal women with low bone density: the fracture intervention trial (FIT).

Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites. To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909 older (aged 55-81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ('bed days') and days of reduced usual activities because of the fracture ('limited activity days'). Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.

Activities of Daily Living↗