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Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 127 records · Page 7Linked to original sources

Snipping polymorphisms from large EST collections in barley (Hordeum vulgare L.).

The public EST (expressed sequence tag) databases represent an enormous but heterogeneous repository of sequences, including many from a broad selection of plant species and a wide range of distinct varieties. The significant redundancy within large EST collections makes them an attractive resource for rapid pre-selection of candidate sequence polymorphisms. Here we present a strategy that allows rapid identification of candidate SNPs in barley (Hordeum vulgare L.) using publicly available EST databases. Analysis of 271,630 EST sequences from different cDNA libraries, representing 23 different barley varieties, resulted in the generation of 56,302 tentative consensus sequences. In all, 8171 of these unigene sequences are members of clusters with six or more ESTs. By applying a novel SNP detection algorithm (SNiPpER) to these sequences, we identified 3069 candidate inter-varietal SNPs. In order to verify these candidate SNPs, we selected a small subset of 63 present in 36 ESTs. Of the 63 SNPs selected, we were able to validate 54 (86%) using a direct sequencing approach. For further verification, 28 ESTs were mapped to distinct loci within the barley genome. The polymorphism information content (PIC) and nucleotide diversity (pi) values of the SNPs identified by the SNiPpER algorithm are significantly higher than those that were obtained by random sequencing. This demonstrates the efficiency of our strategy for SNP identification and the cost-efficient development of EST-based SNP-markers.

Chromatography, High Pressure Liquid↗

Chilling stability of microtubules in root-tip cells of cucumber.

The chilling stability of microtubules was investigated in root-tip cells of cucumber (Cucumis sativus L.) using immunofluorescence labeling and a confocal laser scanning microscope. After low temperature (4 degrees C) treatment for 5 h, we found not only chilling-stable cortical microtubules under the plasma membrane of the root-tip cells, but also chilling-stable punctate microtubules in the cytoplasm, which might be the microtubules associated with organelles. 6-Dimethylaminopurine (6-DMAP), an inhibitor of protein kinase, reduced the chilling stability of the cortical microtubules in the cells. When the root-tip cells were restored to normal growth temperature (28 degrees C), the recovery of the microtubules seemed to be closely associated with the microtubules still remaining in these cells after chilling treatment.

Adenine↗

Oligodendrocyte progenitor migration in response to injury of glial monolayers requires the polysialic neural cell-adhesion molecule.

Injury to the nervous system results in reactive astrogliosis that is a critical determinant of neuronal regeneration. To analyze glial responses to mechanical injury and the role of the polysialic neural cell adhesion molecule (PSA-NCAM) in this process, we established primary glia cultures from newborn rat cerebral cortex. Scratching a confluent monolayer of primary glial cells resulted in two major events: rapid migration of oligodendrocyte progenitor-like (O-2A) cells into the wounded area and development of polarized morphology of type 1 astrocytes at the wound edge. Migrating O-2A progenitors had a bipolar morphology and exhibited A2B5 and O4 immunolabeling. Once these cells were established inside the wounded area, they lost A2B5 immunoreactivity and differentiated into glial fibrillary acidic protein-positive astrocytes. Migrating O-2A cells expressed PSA-NCAM, but type 1 astrocytes at the wound edge did not. Treatment of wounded cultures with Endo-N, which specifically removes PSA from the surface of cells, resulted in a significant decrease in O-2A cell migration into the wounded area and completely blocked the wound closure. Video time-lapse analysis showed that, in the presence of Endo-N, O-2A cells remained motile and migrated short distances but did not move away from the monolayer. These results demonstrate that O-2A progenitors contribute to reactive astrogliosis in culture and that PSA-NCAM is involved in this process by regulating cell migration.

Animals↗

Field-induced thermal metal-to-insulator transition in underdoped La(2-x)Sr(x)CuO(4+delta).

The transport of heat and charge in cuprates was measured in single crystals of La(2-x)Sr(x)CuO(4+delta) (LSCO) across the doping phase diagram at low temperatures. In underdoped LSCO, the thermal conductivity is found to decrease with increasing magnetic field in the T-->0 limit, in striking contrast to the increase observed in all superconductors, including cuprates at higher doping. In heavily underdoped LSCO, where superconductivity can be entirely suppressed with an applied magnetic field, we show that a novel thermal metal-to-insulator transition takes place upon going from the superconducting state to the field-induced normal state.

Journal Article↗

Familial invasive and in situ squamous cell carcinoma of the skin.

We used the updated nation-wide Swedish Family-Cancer Database to examine familial risks in data from 1961 to 1998 on 1252 invasive and 2474 in situ squamous cell carcinoma (SCC) of the skin among offspring, and over 10 times more among parents. In 259 families a parent and an offspring had skin SCC. The familial standardised incidence ratios (SIRs) were 2.72 for invasive and 2.40 for in situ skin cancers in offspring. Multiple skin cancers in parents were associated with increased SIRs for invasive SCC in offspring, being 2.55 for one and up to 14.93 for two invasive and two in situ cancers in parents; the corresponding in situ SCC risks were 2.28 and 7.49. The population attributable fraction for any familial skin SCC, invasive or in situ, was 4.1%. Melanoma was the only discordant tumour that was associated with invasive and in situ skin SCC. These results provide evidence that there is an underlying hereditary susceptibility for at least a part of the familial clustering for skin SCC.

Aged↗

Effect of different sample pretreatment methods on the concentrations of excitatory amino acids in cerebrospinal fluid determined by high-performance liquid chromatography.

Using high-performance liquid chromatography (HPLC), the effect of different sample pretreatment methods on the concentrations of excitatory amino acids (EAAs, glutamate and aspartate) measured in cerebrospinal fluid (CSF) was investigated. The results showed that the measured values of glutamate and aspartate were constant when the samples were stored at -80 degrees C and then methanol was used for CSF deproteinization before assay; the values of glutamate (Glu) increased when 0.3 M perchloric acid was used for CSF deproteinization with the CSF subsequently being stored at -20 degrees C; the values of Glu changed when the samples were stored at -20 degrees C over 8 weeks with methanol subsequently being used for CSF deproteinization before assay. This reference data suggested that the CSF sample would be better stored at -80 degrees C. If the sample is stored at -20 degrees C over 8 weeks, the Glu values change with the storage time. If strong acidic reagents are used for precipitation of protein in the CSF sample and then stored at -20 degrees C, Glu values are abnormally increased. From this study, an accurate and sensitive reversed-phase high-performance liquid chromatographic method has been developed for anti-excitotoxicity therapy and thorough study of EAAs in a clinical setting.

Aspartic Acid↗

Regulation of CD11b/CD18 (Mac-1) adhesion to fibrinogen by urokinase receptor (uPAR).

OBJECTIVE AND DESIGN: The goal of this study is to investigate the consequence of the interaction between Mac-1 and uPAR and determine the mechanisms by which uPAR regulates Mac-1 dependent adhesion to fibrinogen. MATERIAL: Human embryonic kidney 293 cells transfected with Mac-1 or uPAR or co-transfected with both Mac-1 and uPAR. METHODS: Cell adhesion and binding assays and Western Blotting for protein tyrosine phosphorylation analysis. RESULTS: The adhesion to fibrinogen was increased two-fold for Mac-1-uPAR co-transfected cells comparing to the Mac-1 transfected cells alone. The increased adhesion was inhibited when cells were treated with phosphatidylinositol-specific phospholipase C to remove uPAR. Occupancy of uPAR with urokinase-type plasminogen activator further enhanced the cell adhesion to fibrinogen. Phosphorylation of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) was increased in Mac-1-uPAR co-transfected cells but not in Mac-1 transfected cells. CONCLUSIONS: uPAR up-regulated the Mac-1 adhesion to fibrinogen and FAK and MAPK were involved in this regulation.

CD11b Antigen↗

A comparison study of the reference curves of bone mineral density at different skeletal sites in native Chinese, Japanese, and American Caucasian women.

To understand the differences among reference curves for bone mineral density (BMD) for Chinese, Japanese, and American Caucasian women, we measured the BMD at the anteroposterior (AP) lumbar spine (L1-L4), lateral lumbar spine (L2-L4), hip (including the femoral neck, trochanter, intertrochanter, Ward's triangle, and total hip), and ultradistal forearm by the dual-energy X-ray absorptiometry (DXA) in a total of 2728 healthy Chinese women, aged 5-96 years. Documented BMD data for Japanese women and device manufacturer's BMD new reference databases (including the NHANES III dataset) for American Caucasian women were also used in this study. The cubic regression model was found to fit best in analyzing the age-associated variations of BMD at various sites in Chinese women, i.e., the equations had the largest coefficient of determination (R2). At the AP/Lat spine, trochanter, intertrochanter, and Ward's triangle, BMD reference curves for Chinese women were lower than those for Japanese or Caucasian women, while at the femoral neck, total hip, and ultradistal forearm, the reference curves for Chinese women were higher than those for Japanese women, with overlaps and crossing of the curves for some age spans in comparing the Chinese and Caucasian women. There were significant differences in the peak BMD (PBMD) at various sites among the Chinese, Japanese, and Caucasian women (P = 0.000). The PBMDs for Chinese women at the lumbar spine and various sites of the hip were 5.7% +/- 2.1% (mean +/- SD, range, 2.7-7.9%) lower than those for Japanese women and 5.1% +/- 2.7% (range, 0.5-7.2%) lower than those for Caucasian women; however, the PBMDs for Chinese women were 26.2% higher than those for Japanese women and 10% higher than those for Caucasian women at the ultradistal forearm. After the PBMD, average T-scores of Chinese women for losses at the AP lumbar spine with increasing age were nearly identical to those for Japanese women, but both were greater than those for Caucasian women. The average T-scores for BMD loss at various sites in Chinese women were higher than those for both Japanese and Caucasian women except at the femoral neck, where the T-scores of Chinese women were exceeded by those of both Japanese and Caucasian women. Estimated from the T-score curve of BMD loss, the age of osteoporosis occurrence at the femoral neck in Chinese women was about 10 years later than that in Japanese or Caucasian women; at the AP spine, Chinese women were similar to Japanese women; at the other sites, the age for occurrence of osteoporosis in Chinese women was about 5-15 years earlier than that in either Japanese or Caucasian women. There are differences in prevalence or odds ratio (OR) of osteoporosis at the same skeletal region for Chinese, Japanese, and Caucasian women aged > or = 50 years or at different skeletal regions in women of the same race. The prevalences of osteoporosis at various regions of the hip in Chinese women are 10.1-19.8% and ORs are 22.0-32.3, of which prevalence at the femoral neck is the lowest (10.1%); the prevalences of osteoporosis in Japanese women are 11.6-16.8% and ORs are 21.1-26.3, of which prevalence at the femoral neck is the lowest (11.6%); and the prevalences of osteoporosis in Caucasian women are 13.0-20.0% and ORs are 19.4-48.9, of which prevalence at the femoral neck is the highest (20%). In conclusion, racial differences in BMD reference curves, prevalences, and risks of osteoporosis at various skeletal sites exist among native Chinese, Japanese, and American Caucasian women.

Absorptiometry, Photon↗

GM1 enhances dopaminergic markers in the brain of aged rats.

A number of presynaptic markers are compromised in the dopaminergic neurons of aged Sprague-Dawley rats (22 months old) compared with young rats (3 months old). Indeed, in the striatum of the aged rats there is a diminished capacity to transport dopamine (DA), to bind the dopamine transporter (DAT) marker mazindol, to bind the vesicular monoamine transporter 2 (VMAT2) marker dihydrotetrabenazine, and to release DA under basal conditions or after induction by K(+) or amphetamine. Furthermore, the expression of DAT and VMAT2 mRNA in the midbrain is suppressed. GM1 ganglioside, 30 mg/kg ip daily, administered for 30 days, restores the afore-mentioned markers to values approaching those for young rats. Taken together with our published observations that GM1 partially restores tyrosine hydroxylase activity and DA metabolism in aged nigrostriatal and mesoaccumbal neurons and improves their morphology, our work suggests that GM1 might act as a dopaminergic neurotrophic factor in the aged brain and be a useful adjuvant for treating age-associated dopaminergic deficits.

Age Factors↗

Anthropogenic metal enrichment of snow and soil in north-eastern European Russia.

Trace metal composition of winter snowpack, snow-melt filter residues and top-soil samples were determined along three transects through industrial towns in the Usa basin, North-East Russia: Inta, Usinsk and Vorkuta. Snow was analysed for Ag, Al, As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr and Zn using ICP-MS (Ca and K by F-AAS for Vorkuta only), pH and acidity/alkalinity. Filter residues were analysed for: Al, Ba, Ca, Cd, Cu, K, Mg, Mn, Ni, Pb, Sr and Zn using F-AAS and GF-AAS; top-soil samples were analysed for Ba, Cu, Mg, Mn, Na, Ni, Pb, Sr, Zn using F-AAS. Results indicate elevated concentrations of elements associated with alkaline combustion ash around the coal mining towns of Vorkuta and Inta. There is little evidence of deposition around the gas and oil town of Usinsk. Atmospheric deposition in the vicinity of Vorkuta, and to a lesser extent Inta, added significantly to the soil contaminant loading as a result of ash fallout. Acid deposition was associated with pristine areas whereas alkaline combustion ash near to emission sources more than compensated for the acidity caused by SO2.

Coal Mining↗

Comparison of newly isolated cuticular protein genes from six aphid species.

This paper reports on the first aphids' cuticular proteins. One gene (Mpcp1) was obtained by screening a cDNA library of Myzus persicae with antibodies to a lepidopteran cuticle protein. MpCP1 presents a putative signal peptide, a central extended R&R domain, flanked by N- and C-terminal repeats of alanine, tyrosine and proline. The mRNA of Mpcp1 could be detected in a larval and in adult stages. Primers based on Mpcp1 allowed isolating and comparing cuticle protein genes from five aphid species, but not from whitefly or thrips. Comparison revealed a high degree of similarity. Data from this paper suggest that this cuticle protein family is typical and predominant to aphids. The conformation of these cuticle proteins and the significance on particular properties of aphid cuticle is discussed.

Amino Acid Sequence↗

Profiling genes expressed in human fetal cartilage using 13,155 expressed sequence tags.

OBJECTIVE: To analyze the gene expression profile of human fetal cartilage by expressed sequence tags (ESTs). METHODS: A human fetal cartilage (8-12 weeks) cDNA library was constructed using the lambda ZAP Express vector. ESTs were obtained by partial sequencing of cDNA clones. The basic local alignment search tool algorithm was used to compare all generated ESTs to known sequences. RESULTS: A total of 13,155 ESTs were analyzed, of which 8696 ESTs (66.1%) matched known genes, 53 ESTs (0.4%) were putatively novel (with no match) and the rest matched other ESTs, genomic DNA and repetitive sequences. Importantly, we identified 2448 unique known genes through non-redundancy analysis of the known gene matches, which were then functionally categorized. The tissue specificity of this library was reflected by its EST profile of the extracellular matrix (ECM) proteins. Collagens were the major transcripts, representing 68.5% of the ECM proteins. Proteoglycans were the second most abundant, constituting 9.5%. Collagen type II was the most abundant gene of all. Glypican 3, decorin and aggrecan were the major transcripts of proteoglycans. Many genes involved in cartilage development were identified, such as insulin-like growth factor-II, its receptor and binding proteins, connective tissue growth factor and fibroblast growth factors. Proteases and their regulatory factors were also identified, including matrix metalloprotease 2 and tissue inhibitor of metalloproteinase 1. CONCLUSIONS: The EST approach is an effective way of characterizing the genes expressed in cartilage. These data represent the most extensive molecular information on human fetal cartilage to date. The availability of this information will serve as a basis for further research to identify genes that are essential in cartilage development.

Cartilage, Articular↗

Association between weight fluctuation and fasting insulin concentration in Japanese men.

OBJECTIVE: To investigate whether long-term weight fluctuation is associated with the fasting serum insulin concentration. DESIGN AND SUBJECTS: Weight histories of 1932 male Japanese workers aged 40-59 y were analyzed in relation to their current fasting serum insulin concentration. MEASUREMENTS: Individual weight fluctuation was calculated by root mean square error (RMSE) along the linear regression line of weight measured at five to six different ages. RESULTS: The mean RMSE and fasting insulin concentration were 1.22 kg and 4.5 microU/ml, respectively. The multivariate adjusted insulin level became higher with the increase in weight fluctuation. Subanalysis stratified by current body mass index (BMI) showed that the multivariate adjusted insulin level in individuals in the top quartile of fluctuation was 4.3 microU/ml, against 3.9 microU/ml in those in the bottom quartile (P=0.018, analysis of covariance (ANCOVA)) in the normal weight subgroup with current BMI below 25 kg/m(2). In the overweight subgroup with BMI 25 kg/m(2) or above, the level was 6.9 microU/ml in individuals in the top quartile and 6.2 microU/ml in those in the bottom quartile (P=0.054, ANCOVA). CONCLUSION: The results suggest that weight fluctuation increases the risk of developing hyperinsulinemia. Prospective observations together with measurement of changes in adiposity are needed for confirmation.

Adult↗

The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state.

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we examined the association of circulating CRP in healthy reference range (< or =1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS). DESIGN: Cross-sectional study of circulating CRP in adult men. SUBJECTS: A total of 3692 Japanese men aged 34-69 y. MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI). RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (> or =0.06 mg/dl) and moderately (> or =0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed. CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

Adult↗

Long-term body weight variability is associated with elevated C-reactive protein independent of current body mass index among Japanese men.

OBJECTIVE: To elucidate the effect of long-term weight variability on C-reactive protein (CRP) levels. DESIGN: Cross-sectional study of the circulating CRP. SUBJECTS: A total of 637 Japanese men aged 40-49 y in1997. MEASUREMENTS: Serum CRP levels, body mass index in 1997 (current BMI), the slope of weight on age (weight-slope) representing an individual's weight trend of direction and magnitude, and the root mean square error around the slope of weight on age (weight-RMSE) representing the weight fluctuation magnitude, as calculated by a simple linear regression model in which each value of the subject's five actual weights (aged 20, 25, 30 y, five years ago, and current) was a dependent variable and the subject's ages independent variables. RESULTS: After adjustment for age and confounders, including smoking and health status, the odds ratios of elevated CRP (> or =0.06 mg/dl) were 1.83 (95% CI: 1.25-2.69), 2.63 (1.69-4.11), and 10.31 (2.17-48.98) for upper normal-weight (BMI: 22-<25 kg/m(2)), overweight (25-<30), and obese (> or =30) persons, respectively, compared with lower normal-weight persons (18.5-<22). Adjusting for age, confounders, and current BMI, weight-slope was positively associated with CRP level especially among subjects with BMI> or =25 kg/m(2) (trend P<0.01), and weight-RMSE was positively associated with CRP level particularly among subjects with BMI <25 kg/m(2) (trend P<0.05). CONCLUSION: Our results suggest a state of low-grade systemic inflammation not only in overweight and obese persons, but also in normal-weight persons with large weight fluctuation, possibly explaining in part the positive association between weight fluctuation and CVD.

Adipose Tissue↗

Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain-containing receptor, KDR) antibody, IMC-1C11, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200 pM for IMC-1121 and IMC-2C6, respectively, as compared to 270 pM for IMC-1C11. Like IMC-1C11, both human antibodies block VEGF/KDR interaction with an IC(50) of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1C11. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities.

Animals↗