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Biomedical subjects

D Pan

Publications and source records attributed to D Pan.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of the 12C4 survivin monoclonal antibody and insight into the expression of survivin in human adult tissues.

AIMS: To elucidate the expression and regulation of survivin in normal tissues. METHODS AND RESULTS: A novel monoclonal antibody (12C4) to survivin was generated. Application of this antibody to determine survivin expression in human normal adult tissues revealed that most adult tissues do not express survivin and, where it is present, survivin is largely restricted to a small subset of epithelial cells and cells with proliferative potential such as thymus. Survivin expression among positive tissues showed individual variations, ranging from zero to < 5% positive cells in epithelial cell populations. Testis is the only human adult tissue highly expressing survivin, with 60-70% positivity in the nuclei of spermatogonia. Consistent with deregulated expression of survivin associated with oncogenesis, we found that certain ligands and transcription factors differentially modulate survivin promoter activity in cancer cells versus normal/untransformed cells. CONCLUSION: Deregulation of survivin transcription controls in individual epithelial cells may contribute to oncogenesis in various human adult tissues.

Adult↗
PubMed2005

A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals.

Numerous mouse models of prostate carcinogenesis have been developed, but hitherto there has been no model in which the prostate gland could be imaged in live animals. The transgenic model generated here targeted mouse prostate gland using a firefly luciferase enzyme under the control of a small but highly active and specific supra prostate-specific antigen (sPSA) promoter. We evaluated postnatal prostate development, involution and androgen-induced restoration of prostate growth in adult transgenic mice using bioluminescence imaging. Results of our study showed that: (i) the prostate gland of male offspring did not yield a significant bioluminescence signal until after sexual maturity. Luciferase was detected in the luminal epithelial cells of the ventral and dorsolateral lobes of the prostate gland and caput epididymis, with little or no activity in 18 other organs evaluated. (ii) While a constant high level of bioluminescence was detected in the mouse prostate from 5 to 35 weeks of age, a slight drop in bioluminescence was detected at 36 to 54 weeks. (iii) Upon castration, the luciferase activity signal associated with mouse prostate detected by a cooled charge-coupled device camera was dramatically reduced. This signal could be rapidly restored to pre-castration levels after androgen administration. Androgen-induced luciferase activity subsided to nearly basal levels 5 days following the last injection. These data demonstrate that a bioluminescent mouse model with luciferase activity restricted to the prostate gland under the control of a (sPSA) promoter can be used on a real-time basis in live animals to investigate the development and responsiveness of the prostate gland to exogenously administered androgen. This model can be extended to detect the responsiveness of the prostate gland to therapy and used as a founder strain to visualize tumors in hosts with different genetic backgrounds.

Androgens↗
PubMed2004

Activity of plasma sprayed yttria stabilized zirconia reinforced hydroxyapatite/Ti-6Al-4V composite coatings in simulated body fluid.

Hydroxyapatite (HA)/yttria stabilized zirconia/Ti-6Al-4V bio-composite coatings deposited onto Ti-6Al-4V substrate through a plasma spray technique were immersed in simulated body fluid (SBF) to investigate their behavior in vitro. Surface morphologies and structural changes in the coatings were analyzed by scanning electron microscopy, thin-film X-ray diffractometer, and X-ray photoelectron spectroscopy. The tensile bond strength of the coatings after immersion was also conducted through the ASTM C-633 standard for thermal sprayed coatings. Results showed that carbonate-containing hydroxyapatite (CHA) layer formed on the surface of composite coatings after 4 weeks immersion in SBF solution, indicating the composite coating possessed excellent bioactivity. The mechanical properties were found to decrease with immersion duration of maximum 56 days. However, minimal variation in mechanical properties was found subsequent to achieving supersaturation of the calcium ions, which was attained with the precipitation of the calcium phosphate layers. The mechanical properties of the composite coating were found to be significantly higher than those of pure HA coatings even after immersion in the SBF solution, indicating the enhanced mechanical properties of the composite coatings.

Alloys↗
PubMed2004

Microstructure and mechanical properties of plasma sprayed HA/YSZ/Ti-6Al-4V composite coatings.

Plasma sprayed hydroxyapatite (HA) coatings on titanium alloy substrate have been used extensively due to their excellent biocompatibility and osteoconductivity. However, the erratic bond strength between HA and Ti alloy has raised concern over the long-term reliability of the implant. In this paper, HA/yttria stabilized zirconia (YSZ)/Ti-6Al-4V composite coatings that possess superior mechanical properties to conventional plasma sprayed HA coatings were developed. Ti-6Al-4V powders coated with fine YSZ and HA particles were prepared through a unique ceramic slurry mixing method. The so-formed composite powder was employed as feedstock for plasma spraying of the HA/YSZ/Ti-6Al-4V coatings. The influence of net plasma energy, plasma spray standoff distance, and post-spray heat treatment on microstructure, phase composition and mechanical properties were investigated. Results showed that coatings prepared with the optimum plasma sprayed condition showed a well-defined splat structure. HA/YSZ/Ti-6Al-4V solid solution was formed during plasma spraying which was beneficial for the improvement of mechanical properties. There was no evidence of Ti oxidation from the successful processing of YSZ and HA coated Ti-6Al-4V composite powders. Small amount of CaO apart from HA, ZrO(2) and Ti was present in the composite coatings. The microhardness, Young's modulus, fracture toughness, and bond strength increased significantly with the addition of YSZ. Post-spray heat treatment at 600 degrees C and 700 degrees C for up to 12h was found to further improve the mechanical properties of coatings. After the post-spray heat treatment, 17.6% increment in Young's modulus (E) and 16.3% increment in Vicker's hardness were achieved. The strengthening mechanisms of HA/YSZ/Ti-6Al-4V composite coatings were related to the dispersion strengthening by homogeneous distribution of YSZ particles in the matrix, the good mechanical properties of Ti-6Al-4V and the formation of solid solution among HA, Ti alloy and YSZ components.

Aerosols↗
PubMed2003

HLA-DRB1, DQB1 and DPB1 polymorphism in the Naxi ethnic group of South-western China.

Polymorphism of HLA-DRB1, DQB1 and DPB1 was revealed with a sequencing-based typing (SBT) method in unrelated healthy volunteers from the Naxi ethnic group. Among the 43 DRB1 alleles detected, the most common allele was DRB1*12021 with a frequency of 17%, followed by DRB1*08032, DRB1*09012 and DRB1*1404 with frequencies of 8.5%, 7.4% and 7.4%, respectively. Among 23 DQB1 alleles detected, the most frequent DQB1 allele was DQB1*03011/0309 (21.9%), followed by DQB1*0502 (16.4%) and DQB1*05031 (9.6%). For the DPB1 locus, the most common alleles were DPB1*0501 (25.5%), DPB1*0402 (14.6%) and DPB1*02012 (12.0%). The most common DRB1-DQB1-DPB1 haplotype was DRB1*1404-DQB1*05031-DPB1*0402 with a frequency of 5.26%, followed by the DRB1*08032-DQB1*06011-DPB1*1301 (3.51%). The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese.

Alleles↗
PubMed2003

The relationship between body mass index, blood pressure and pulse rate among normotensive and hypertensive participants in the third National Health and Nutrition Examination Survey (NHANES).

Obesity is associated with high insulin and leptin levels. Studies also suggest that high levels of insulin and leptin increase sympathetic nervous system (SNS) activity and engender increased chronotropy, vasoconstriction and antinatriuresis that may contribute to the pathogenesis of obesity related hypertension. Sympathetic modulation of cardiovascular responses requires good baroreceptor sensitivity and optimal vascular compliance. The vascular changes associated with isolated systolic hypertension (ISH) have been shown to modify baroreceptor sensitivity and vascular compliance and may mitigate sympathetic modulation of cardiovascular responses and attenuate the hypertensive effect of obesity. The purpose of this study is to examine the differences in the relationship between body mass index, pulse rate (PR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) among participants with normal blood pressure and ISH using data from the third National Health and Nutrition Examination Survey. Data from 13,761 non-institutionalized adults 18 years and older not receiving antihypertensive therapy were analyzed. Results showed that PR, SBP and DBP increase with increasing BMI. The rise in PR, SBP and DBP with BMI is higher among participants with normal blood pressure than among those with ISH. We concluded that increasing level of obesity is associated with a rise in pulse rate and blood pressure but the effect of obesity on blood pressure and pulse rate might be weaker among participants with ISH.

Adolescent↗
PubMed2002

Novel ultrasonic fusion imaging method based on cyclic variation in myocardial backscatter.

Quantitative ultrasonic tissue characterisation of the myocardium based on integrated backscatter (IB) has the potential of becoming an effective method for detecting and evaluating myocardial ischaemia. To facilitate IB-based clinical applications, a new imaging method has been developed that combines the anatomical information of a B-mode image with the contractile performance of a selected myocardial region. To produce such a fusion image, a region of interest (ROI) in a B-mode cardiac image was first selected by the user. Algorithms for detection of the endocardium and epicardium were developed, and the resulting mean distance between the computer-detected curve and the manually traced curve was 0.83mm for the endocardium and 0.58mm for the epicardium. The cyclic variation of IB (CVIB) of each myocardial tissue element within the ROI was then calculated over one cardiac cycle. Finally, a grey-scale B-mode image at the end of diastole was displayed as a still image, and the pixels representing the myocardial tissue in the ROI colour-coded according to the corresponding CVIB over the past heart cycle. Both the B-mode image and the colour-coded region were refreshed (up-dated) at the next end-of-diastole. Preliminary results from normal (CVIB= 10-12dB) and ischaemic (CVIB = 5-7 dB) canine hearts are presented that demonstrate the utility of this new imaging method.

Diagnosis, Computer-Assisted↗
PubMed2002

HLA-DPB1 allelic frequency of the Pumi ethnic group in south-west China and evolutionary relationship of Pumi with other populations.

A sequencing-based typing of the HLA-DPB1 gene was carried out in 51 unrelated healthy individuals from the Yunnan Pumi ethnic minority. A total of 18 DPB1 alleles, in which DPB1*0501 (52.0%) and DPB1*0402 (15.7%) greatly predominated, were found, of which alleles DPB1*20011, 2201, 3601, 3701, 3801, 4901, 5001 and 8001 were recorded for the first time in the Chinese population. This may be because the typing methods used in previous genotyping of Chinese populations were of lower sensitivity than that used in our study. A dendrogram constructed by the maximum likelihood method showed that the Pumi ethnic minority belongs to the Asian/Australasian cluster and has the closest relationship to Trobriander, implying an unusual relationship between Australasian and South China populations. However, the Yi ethnic minority, which also comes from the ancient Qiang, did not show a very close relationship with the Pumi. This is probably because the Pumi were historically assimilated by local south-west China populations.

Asian People↗
PubMed2002

A novel DRB1*09 allelic sequence in the Jing ethnic minority of China.

A new DRB1 allele, DRB1*0902, has been identified in an individual of the Jing ethnic minority. Its sequence was confirmed by sequencing of PCR products and clones. This allele differed by three nucleotides from DRB1*09012 at positions 157, 161 and 166, and resulted in amino acid motif substitution from VAES to DAEY.

Amino Acid Motifs↗
PubMed2001

Chromophore structure in lumirhodopsin and metarhodopsin I by time-resolved resonance Raman microchip spectroscopy.

Time-resolved resonance Raman microchip flow experiments have been performed on the lumirhodopsin (Lumi) and metarhodopsin I (Meta I) photointermediates of rhodopsin at room temperature to elucidate the structure of the chromophore in each species as well as changes in protein-chromophore interactions. Transient Raman spectra of Lumi and Meta I with delay times of 16 micros and 1 ms, respectively, are obtained by using a microprobe system to focus displaced pump and probe laser beams in a microfabricated flow channel and to detect the scattering. The fingerprint modes of both species are very similar and characteristic of an all-trans chromophore. Lumi exhibits a relatively normal hydrogen-out-of-plane (HOOP) doublet at 951/959 cm(-1), while Meta I has a single HOOP band at 957 cm(-1). These results suggest that the transitions from bathorhodopsin to Lumi and Meta I involve a relaxation of the chromophore to a more planar all-trans conformation and the elimination of the structural perturbation that uncouples the 11H and 12H wags in bathorhodopsin. Surprisingly, the protonated Schiff base C=N stretching mode in Lumi (1638 cm(-1)) is unusually low compared to those in rhodopsin and bathorhodopsin, and the C=ND stretching mode shifts down by only 7 cm(-1) in D2O buffer. This indicates that the Schiff base hydrogen bonding is dramatically weakened in the bathorhodopsin to Lumi transition. However, the C=N stretching mode in Meta I is found at 1654 cm(-1) and exhibits a normal deuteration-induced downshift of 24 cm(-1), identical to that of the all-trans protonated Schiff base. The structural relaxation of the chromophore-protein complex in the bathorhodopsin to Lumi transition thus appears to drive the Schiff base group out of its hydrogen-bonded environment near Glu113, and the hydrogen bonding recovers to a normal solvated PSB value but presumably a different hydrogen bond acceptor with the formation of Meta I.

Animals↗
PubMed2001

TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.

Tuberous sclerosis is a human disease caused by mutations in the TSC1 or the TSC2 tumor suppressor gene. Previous studies of a Drosophila TSC2 homolog suggested a role for the TSC genes in maintaining DNA content, with loss of TSC2 leading to polyploidy and increased cell size. We have isolated mutations in the Drosophila homolog of the TSC1 gene. We show that TSC1 and TSC2 form a complex and function in a common pathway to control cellular growth. Unlike previous studies, our work shows that TSC1(-) or TSC2(-) cells are diploid. We find that, strikingly, the heterozygosity of TSC1 or TSC2 is sufficient to rescue the lethality of loss-of-function insulin receptor mutants. Further genetic analyses suggest that the TSC genes act in a parallel pathway that converges on the insulin pathway downstream from Akt. Taken together, our studies identified the TSC tumor suppressors as novel negative regulators of insulin signaling.

Animals↗
PubMed2001

Complete genome sequence of the shrimp white spot bacilliform virus.

We report the first complete genome sequence of a marine invertebrate virus. White spot bacilliform virus (WSBV; or white spot syndrome virus) is a major shrimp pathogen with a high mortality rate and a wide host range. Its double-stranded circular DNA genome of 305,107 bp contains 181 open reading frames (ORFs). Nine homologous regions containing 47 repeated minifragments that include direct repeats, atypical inverted repeat sequences, and imperfect palindromes were identified. This is the largest animal virus that has been completely sequenced. Although WSBV is morphologically similar to insect baculovirus, the two viruses are not detectably related at the amino acid level. Rather, some WSBV genes are more homologous to eukaryotic genes than viral genes. In fact, sequence analysis indicates that WSBV differs from all known viruses, although a few genes display a weak homology to herpesvirus genes. Most of the ORFs encode proteins that bear no homology to any known proteins, either suggesting that WSBV represents a novel class of viruses or perhaps implying a significant evolutionary distance between marine and terrestrial viruses. The most unique feature of WSBV is the presence of an intact collagen gene, a gene encoding an extracellular matrix protein of animal cells that has never been found in any viruses. Determination of the genome of WSBV will facilitate a better understanding of the molecular mechanism underlying the pathogenesis of the WSBV virus and will also provide useful information concerning the evolution and divergence of marine and terrestrial animal viruses at the molecular level.

Amino Acid Sequence↗
PubMed2001

Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes.

Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.3 +/- 0.1 and 5.0 +/- 0.1 kg/m2 in transgenic and non-transgenic mice, respectively). The blood glucose concentration of the control mice increased linearly with time and reached 17.0 +/- 1.3 mmol/l at the 30th week. In contrast, the blood glucose of GK transgenic mice rose to only 9.7 +/- 1.2 mmol/l at the 15th week, after which it returned to 7.6 +/- 1.0 mmol/l by the 30th week. The plasma insulin concentration was also lower in the GK transgenic animals (232 +/- 79 pmol/l) than in the controls (595 +/- 77 pmol/l), but there was no difference in plasma glucagon concentrations. Together, these data indicate that increased GK levels dramatically lessen the development of both hyperglycemia and hyperinsulinemia associated with the feeding of an HF diet.

Animals↗
PubMed2001

The effect of gender on age-related blood pressure changes and the prevalence of isolated systolic hypertension among older adults: data from NHANES III.

OBJECTIVE: To examine gender differences in age-related blood pressure changes and the prevalence of isolated systolic hypertension. DESIGN: Third National Health and Nutrition Examination Survey, 1988-1994. SETTING: 89 mobile examination centers and household questionnaire. PARTICIPANTS: 6635 men and 7189 women over the age of 18 years who were not under treatment for high blood pressure. MAIN OUTCOME MEASURES: Levels of systolic blood pressure, diastolic blood pressure, and pulse pressure by age and gender; prevalence of isolated systolic hypertension (ISH). RESULTS: Systolic blood pressures (SBP) and pulse pressures (PP) were higher in males than in females among adults less than 45 years old. After age 45, SBP and PP were higher in females. Diastolic blood pressures were lower among adult females across all age categories. The prevalence of stages 1 and 2/3 ISH were higher among females after age 44 years. The magnitude of the gender differences in the prevalence of ISH was also age-dependent. CONCLUSIONS: ISH was higher in elderly women than men. These age-related blood pressure changes may account in part for the higher cardiovascular mortality reported among elderly females compared with elderly males and should be considered an important target for cardiovascular preventive strategy, particularly in elderly females.

Adolescent↗
PubMed2001

[Association of human leukocyte antigen-DQA1 with endometriosis of women in southern China].

OBJECTIVE: To study the genetic susceptibility in patients with endometriosis by genotyping their human leukocyte antigen-DQA1 (HLA-DQA1) alleles. METHODS: The allelic types of HLA-DQA1 were detected by polymerase chain reaction single specific primers (PCR-SSP) technique in 51 patients with endometriosis proven by laparoscopy or histological examination, and 44 control women who had laparoscopic sterilization and without endometriosis. RESULTS: The frequency of HLA-DQA * 0401 allele (12%) in patients with endometriosis group was markedly higher than that in the control group (0%) (P = 0.019). Contrarily, the frequency of HLA-DQA1 * 0301 allele (39%) in control group was higher than that in endometriosis group (14%) (P = 0.005, odds ratio = 0.253). CONCLUSION: Our result indicated that HLA-DQA1 * 0401 may be a susceptible gene in correlation with endometriosis, whereas HLA-DQA1 * 0301 may be a protective gene against endometriosis.

Adult↗
PubMed2000

Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways.

The control of cell and organ growth is fundamental to the development of multicellular organisms. Here, we show that dPTEN, a Drosophila homolog of the mammalian PTEN tumor suppressor gene, plays an essential role in the control of cell size, cell number, and organ size. In mosaic animals, dPTEN(-) cells proliferate faster than their heterozygous siblings, show an autonomous increase in cell size, and form organs of increased size, whereas overexpression of dPTEN results in opposite phenotypes. The loss-of-function phenotypes of dPTEN are suppressed by mutations in the PI3K target Dakt1 and the translational initiation factor eif4A, suggesting that dPTEN acts through the PI3K signaling pathway to regulate translation. Although activation of PI3K and Akt has been reported to increase rates of cellular growth but not proliferation, loss of dPTEN stimulates both of these processes, suggesting that PTEN regulates overall growth through PI3K/Akt-dependent and -independent pathways. Furthermore, we show that dPTEN does not play a major role in cell survival during Drosophila development. Our results provide a potential explanation for the high frequency of PTEN mutation in human cancer.

Amino Acid Sequence↗
PubMed2000

"Supercharged Cells" for delivery of recombinant human iduronate-2-sulfatase.

Expression of iduronate-2-sulfatase (IDS) from three different promoters in four retroviral vectors was studied in peripheral blood lymphocytes from patients with Hunter syndrome (PBL(MPS)), i.e., the LTR in vectors L2SN and L2, avian beta-actin promoter in LB2, and the CMV early promoter in LNC2. PBL(MPS) were exposed to packaging cell supernatant resulting in transduction frequencies ranging 10-fold from 5 to 49%. Surprisingly, IDS activities were equally high in all transduced lymphocyte populations: 515 U/mg/h in PBL(MPS)-L2SN, 734 in PBL(MPS)-LB2, 352 in PBL(MPS)-L2, and 389 in PBL(MPS)-LNC2 compared to controls (<10 in PBL(MPS)-LXSN or PBL(MPS)). The half-life of endocytosed IDS in PBL(MPS) was 1.9 days. However, the level of lymphocyte IDS activity from proviral expression was found to be only a fraction of the total, a large portion being derived from reuptake of enzyme from murine packaging cells, i.e., a "second source" of enzyme. Therefore, measurement of transgene lysosomal enzyme soon after exposure of target cells to vector supernatant may yield a gross overestimate of long-term transgene expression by transduced cells. Nevertheless, patient fibroblasts cocultured with transduced PBL(MPS) had reduced (35)SO(4)-GAG accumulation, levels similar to those of normal fibroblasts. These studies revealed a broadly applicable phenomenon: cells can be charged with a lysosomal enzyme to levels much higher than those found in nature. By "supercharging" cells with a lysosomal protein (or other molecule bearing the mannose-6-phosphate ligand), such cells may be exploited as vehicles for systemic delivery of therapeutic or diagnostic agents.

Cells, Cultured↗