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Biomedical subjects

Z Zhang

Publications and source records attributed to Z Zhang.

At least 127 records · Page 7Linked to original sources

The Great Wall of China: a physical barrier to gene flow?

One population from each of six plant species along both sides of the Juyong-guan Great Wall, together with one population from each of five species along both sides of a path on a mountain top near Juyong-guan, were selected to study the effect of the Great Wall as a barrier on genetic differentiation between two subpopulations using RAPD markers. Significant genetic differentiation was found between the subpopulations on both sides of the Great Wall. A wind-pollinated woody species, Ulmus pumila, showed less genetic differentiation than four insect-pollinated species: Prunus armeniaca, Ziziphus jujuba, Vitex negundo, and Heteropappus hispidus. Cleistogenes caespitosa, a wind-pollinated perennial herb, displayed more genetic differentiation between subpopulations than the insect-pollinated species because of its propagation strategy. Although AMOVA analysis showed that subpopulations divided by a mountain path had diverged genetically, the variance component between the subpopulations on both sides of the Great Wall was significantly larger than that between the subpopulations at the control site. Therefore, it is reasonable to deduce that the Juyong-guan Great Wall has served as a physical barrier to gene flow between subpopulations separated for more than 600 years.

Biological Evolution↗

Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors.

One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of "controlled particle release and targeting" is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R approximately 1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.

Administration, Inhalation↗

T-bet expression is upregulated in active Behçet's disease.

AIM: To investigate T-bet mRNA and protein expression on peripheral blood mononuclear cells (PBMC) in patients with Behçet's disease with active uveitis. METHODS: Blood samples were taken from 24 patients with Behçet's disease who had active uveitis and 16 healthy individuals. PBMC were subjected to analysis of T-bet mRNA and protein expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The products from PCR were sequenced. In order to determine the influence of activation on T-bet expression, the phytohaemagglutinin (PHA) stimulated PBMC from each sample were also evaluated for expression of T-bet mRNA and protein. RESULTS: A significantly increased T-bet mRNA accumulation was detected in the samples from patients with active Behçet's disease compared with that in controls. A 62 kDa band was detectable in patients with active Behçet's disease, but not in controls. No difference was found between patients with Behçet's disease who had active uveitis and normal controls concerning the expression of either T-bet mRNA or its protein after stimulation with PHA for 72 hours. CONCLUSION: Behçet's disease is associated with an upregulation of T-bet expression, which supports a role for the Th1 subset of T cells in the pathogenesis of this disease.

Adult↗

Severe persistent orf in young goats.

Orf (contagious ecthyma) is a viral disease of small and wild ruminants, humans, and less frequently other species. In sheep and goats, the disease is characterized by the formation of vesiculo-proliferative lesions in the skin of lips and nostril. Here, a form of generalized orf in 16 goat kids from 2 different locations in west Texas is described. The disease was characterized by multifocal, severe, proliferative dermatitis that persisted from about 2 months of age until the goat kids were euthanized 3 months later. All affected goats were Boer or Boer crosses under 1 year of age. The mean immunoglobulin concentration in sera of affected goats was elevated compared with healthy control goats. Severe to moderate lymphadenomegaly of the nodes draining the areas of the skin affected with orf lesions was present in all 16 goat kids. Suppurative arthritis, chronic fibrinous pneumonia, and premature thymic involution were found in 3, 5, and 7 of the goat kids, respectively. The skin lesions of 3 goat kids were infested with larvae of the opportunistic black garbage fly (Ophira sp.). The orf virus was identified in skin lesions by isolation in Marbin-Darby ovine kidney cells, electron microscopy, and amplification of viral DNA by polymerase chain reaction. The orf virus was not detected in peripheral blood or lymph node mononuclear cells of any of the goats. Cross-neutralization experiments showed that an ovine orf virus antiserum raised in sheep was more effective in neutralizing a sheep orf virus isolate than a caprine orf virus isolate. The clinical and epidemiological characteristics of these orf cases may be the result of susceptibility factors within some individuals of the Boer breed of goats.

Animals↗

Adaptive hypersensitivity to estrogen: mechanism for superiority of aromatase inhibitors over selective estrogen receptor modulators for breast cancer treatment and prevention.

Clinical observations suggest that human breast tumors can adapt to endocrine therapy by developing hypersensitivity to estradiol (E(2)). To understand the mechanisms responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided in vitro and in vivo evidence that long-term E(2) deprivation (LTED) causes "adaptive hypersensitivity". The enhanced responses to E(2) do not involve mechanisms acting at the level of transcription of estrogen-regulated genes. We found no evidence of hypersensitivity when examining the effects of E(2) on regulation of c-myc, pS2, progesterone receptor, several estrogen receptor (ER) reporter genes, or c-myb in hypersensitive cells. Estrogen deprivation of breast cells long-term does up-regulate both the MAP kinase and phosphatidyl-inositol 3-kinase pathways. As a potential explanation for up-regulation of these signaling pathways, we found that ERalpha is 4- to 10-fold up-regulated and co-opts a classic growth factor pathway using Shc, Grb-2 and Sos. This induces rapid non-genomic effects which are enhanced in LTED cells. E(2) binds to cell membrane-associated ERalpha, physically associates with the adapter protein SHC, and induces its phosphorylation. In turn, Shc binds Grb-2 and Sos, which results in the rapid activation of MAP kinase. These non-genomic effects of E(2) produce biological effects as evidenced by Elk activation and by morphological changes in cell membranes. Further proof of the non-genomic effects of E(2) involved use of cells which selectively expressed ERalpha in the nucleus, cytosol and cell membrane. We created these COS-1 "designer cells" by transfecting ERalpha lacking a nuclear localization signal and containing a membrane localizing signal. The concept of "adaptive hypersensitivity" and the mechanisms responsible for this phenomenon have important clinical implications. Adaptive hypersensitivity would explain the superiority of aromatase inhibitors over the selective ER modulators (SERMs) for treatment of breast cancer. The development of highly potent third-generation aromatase inhibitors allows reduction of breast tissue E2 to very low levels and circumvents the enhanced sensitivity of these cells to the proliferative effects of E(2). Clinical trials in the adjuvant, neoadjuvant and advanced disease settings demonstrate the greater clinical efficacy of the aromatase inhibitors over the SERMs. More recent observations indicate that the aromatase inhibitors are superior for the prevention of breast cancer as well. These observations may be explained by the hypothesis that estrogens induce breast cancer both by stimulating cell proliferation and by their metabolism to genotoxic products. The SERMs block ER-mediated proliferation only, whereas the aromatase inhibitors exert dual effects on proliferation and genotoxic metabolite formation.

Adaptation, Physiological↗

Mechanical strength of microcapsules made of different wall materials.

The mechanical strength of microcapsules made of three different wall materials, including melamine-formaldehyde resin, urea-formaldehyde resin and gelatin-gum arabic coacervate, were measured by a micromanipulation technique. Single microcapsules were compressed to large deformations or rupture and the force being imposed on them were measured simultaneously. Melamine-formaldehyde and urea-formaldehyde microcapsules showed clear bursting under compression, and their bursting force, deformation at bursting and deformation at a pesudo yield point were determined. Gelatin microcapsules did not show clear bursting under compression, and their mechanical strength was characterized by the force required to cause their deformation to 50%. The mechanical strengths of these three types of microcapsules are compared in this paper.

Capsules↗

Chromatographic separation and characterization of hydrolyzed Cr(III) species.

Both macroscale and microscale methods to separate hydrolyzed Cr(III) species from acidic to near-neutral pH solutions have been developed. The macroscale approach is based on ion exchange, and involves separating monomeric, dimeric, trimeric, tetrameric, and higher order Cr(III) oligomers from such solutions using a gradient elution with increasing cationic charge. With this approach, the concentration of a given fraction can be maximized, and complete resolution between these species can be achieved. In addition, complete recovery of Cr(III) from the column is achievable. For the microscale approach, capillary electrophoresis with indirect detection is used to isolate and uniquely identify the same smaller oligomers and a fraction of larger Cr(III) species that are not uniquely identified. Capillary electrophoresis also provides indirect structural information for the Cr(III) trimer, suggesting that it exists in a triangular configuration rather than as a linear species. These methods are described in detail, and possible applications are discussed.

Journal Article↗

Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom.

In 2001, the United Kingdom experienced its worst epidemic of foot-and-mouth disease (FMD). To date approximately 3.9 million animals have been culled and direct and indirect revenue losses are probably in excess of pound 12 billion. This study was carried out to investigate the biological characteristics of the FMD virus strain O/UKG/2001 responsible for the epidemic. Animal transmission experiments indicated that this strain is not host restricted and will infect the three main susceptible livestock species (cattle, sheep and pigs). Immunisation with high potency emergency vaccine derived from O(1) Manisa strain of FMD virus protected all three species against clinical disease when challenged with FMD virus strain O/UKG/2001.

Animals↗

Evaluation of the portable Cepheid SmartCycler real-time PCR machine for the rapid diagnosis of foot-and-mouth disease.

The ability of the portable Cepheid SmartCycler real-time PCR machine to detect foot-and-mouth disease (FMD) virus sensitively and accurately was evaluated by comparing the results of the analyses of nasal swab and serum samples from experimentally infected animals with those obtained from the real-time PCR assay currently in use in the laboratory. The results indicated that the ability of the machine to detect viral RNA is greatly affected by the PCR reagents used for the assay. When it was used with PCR beads it was unable to detect weakly positive samples, but when TaqMan core reagents were used for the assay, its sensitivity was significantly increased. The machine could be used for the laboratory-based detection of FMD; however, as with all assays, significant optimisation of assay conditions as well as solid validation of the technique is required.

Animals↗

Single vs. dual vessel porcine extracorporeal liver perfusion.

BACKGROUND: The use of porcine extracorporeal liver perfusion (PECLP) to provide temporary hepatic support for patients in fulminant hepatic failure has been limited by the fact that individual perfusions can be sustained for only a few hours. Inadequate liver function and/or hemodynamic instability are the major contributing factors for early interruption of PECLP. Recent reports suggest that the choice of single (portal vein only) vs dual (portal vein and hepatic artery) vessel perfusion may influence the duration of perfusion. We hypothesize that PECLP with single vessel perfusion (SVP) is associated with worse liver function and greater hemodynamic instability than PECLP with dual vessel perfusion (DVP). MATERIALS AND METHODS: To eliminate the potentially confounding influences of liver failure and xenograft rejection, liver isografts procured from White-Landrace pig donors were perfused by either SVP or DVP via an extracorporeal circuit established with normal White-Landrace pig recipients. The function of perfused livers was evaluated by measuring production of bile and Factors V and VIII, clearance of ammonia and lactate, and extraction of O(2) at baseline and at 0, 1, 3, 6, 12, and 24 h after initiation of PECLP. The impact of PECLP on recipient hemodynamic status was assessed by monitoring BP, heart rate, urine output, O(2) saturation, etc. Among other parameters evaluated were serum albumin and total protein and hepatic release of IL-1beta and nitric oxide to assess their possible contributions to hemodynamic instability. RESULTS: DVP and SVP livers cleared ammonia and lactate similarly. Both approaches were associated with progressive hypoalbuminemia and hypoproteinemia. DVP livers produced more bile and Factor V and were associated with less recipient hypotension and IL-1beta and NO release than SVP livers. CONCLUSIONS: Livers with DVP function better than livers with SVP. The duration of PECLP can be limited by recipient hypotension, although this complication is less severe with DVP than with SVP.

Ammonia↗

Capsule-substrate contact deformation: determination of adhesion energy.

A study is reported of a cellular entity (liquid-filled microcapsule) adhered on a flat glass substrate in response to changes in osmotic pressure and temperature. High-resolution reflection interference contrast microscopy (HR-RICM) and phase-contrast microscopy were developed for probing the adhesion contact area, capsule-substrate separation profile and adhesion energy of the adhering microcapsule. The new technique increased the detection limit of the measured capsule wall-substrate separation in the cohesive zone from 1 to 4.5 microm and improved the spatial resolution of the heterogeneous contact zones. A theoretical model was applied to correlate quantitatively the adhesion energy to the area of the contact zone. The work demonstrated the possibility of ascertaining the quantitative interfacial adhesion energy of a liquid-filled microcapsule using the present technique and represents the first step in extending this novel approach to study more complicated systems, such as cell-substrate interactions, in the future.

Animals↗

Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal adhesion kinase in osteoclasts.

Calcitonin induces the association and tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and HEF1 in HEK-293 cells that overexpress the calcitonin receptor (C1a-HEK), but the hormone's effect on these adhesion-related proteins in osteoclasts is not known. We therefore studied the effect of calcitonin on the tyrosine phosphorylation and subcellular distribution of paxillin, HEF1, FAK, and Pyk2, a FAK-related tyrosine kinase, in osteoclasts. Osteoclasts expressed both Pyk2 and FAK, with Pyk2 much more highly expressed. The two tyrosine kinases and paxillin were prominently associated with small punctate structures that were most densely clustered in the region of the peripheral F-actin-rich ring. Some of the punctate structures stained either for Pyk2 alone or FAK alone. Treatment with calcitonin disrupted the actin ring and induced the loss of the peripheral staining of paxillin, Pyk2, and FAK. In calcitonin-treated osteoclast-like cells, the tyrosine phosphorylation of paxillin and FAK increased, whereas the tyrosine phosphorylation of Pyk2 decreased. Calcitonin also induced increased phosphorylation of Erk1 and Erk2 in osteoclasts, as it did in the C1a-HEK cells. The unexpected dephosphorylation of Pyk2 correlated with decreased phosphorylation of Tyr(402), the autophosphorylation site of Pyk2. The calcitonin-induced dephosphorylation of Pyk2 was not observed in C1a-HEK cells transfected with Pyk2, suggesting that the reduced phosphorylation seen in osteoclasts may be specific to these cells. Treatment of osteoclast-like cells with 12-phorbol 13-myristate acetate increased the tyrosine phosphorylation of both Pyk2 and FAK, and calphostin C, an inhibitor of protein kinase C, blocked calcitonin-stimulated FAK phosphorylation. Increasing intracellular calcium with ionomycin caused a decrease in the tyrosine phosphorylation of Pyk2 and the loss of the actin ring in a manner similar to the effect of calcitonin. Ionomycin had no effect on FAK tyrosine phosphorylation. Calcitonin (CT)-induced changes in Pyk2, FAK, and Erk1/2 phosphorylation were independent of c-Src.

Animals↗

Dissolved insecticides and polychlorinated biphenyls in the Pearl River Estuary and South China Sea.

Persistent organic pollutants (POPs) such as organochlorine (OCl) insecticides and polychlorinated biphenyls (PCB), together with the new generation of organophosphorus (OP) insecticides, are of global concern, due to their widespread occurrence, persistence, bioaccumulation and hormone disruption potential. This paper represents an attempt to study the source and transportation of such pollutants in estuarine and coastal environments as an integrated ecosystem, by determining the levels of 18 OCl insecticides, 21 PCB congeners, and 17 OP insecticides in the Pearl River Estuary and South China Sea. The total concentrations varied from 126-1198 ng l(-1) for OCl insecticides, 33.38-1064 ng l(-1) for PCB congeners, and 4.44-6356 ng l(-1) for OP insecticides in the Pearl River Estuary. In comparison, their levels in the South China Sea were significantly lower, varying from 57.09-202 ng l(-1) for OCl insecticides, 21.72-144 ng l(-1) for PCBs, and 1.27-122 ng l(-1) for OP insecticides, respectively. The predominance of beta-HCH in HCHs, and DDE in DDTs in all water samples was clearly observed, suggesting beta-HCH and DDE's resistance to further degradation. The PCBs were dominated by those with 3-6 chlorines. The distribution characteristic of OP insecticides shows that five compounds (methamidophos, dimethoate, malathion, dichlorvos and omethoate) accounted for 56% and 72% of the total OP insecticide concentration. The relationship between pollutant concentrations and salinity in the estuary showed that they were all removed during the mixing process, therefore behaving non-conservatively.

China↗

Granulocyte macrophage colony stimulating factor is elevated in alveolar macrophages from sheep naturally infected with maedi-visna virus and stimulates maedi-visna virus replication in macrophages in vitro.

Infection by maedi-visna virus, a lentivirus of sheep, leads to chronic inflammatory reactions of various tissues. In this report we have analysed the role of specific cytokines in the disease process. A significant increase in expression of interleukin-6, interleukin-10, granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-beta1 mRNA was observed in alveolar macrophages isolated from the lungs of naturally infected animals when compared with lungs of seronegative controls. Levels of GM-CSF mRNA expression in alveolar macrophages correlated with the presence of lung lesions, but there was no correlation of interleukin-10, interleukin-6, tumour necrosis factor-alpha and transforming growth factor-beta1 mRNA levels in alveolar macrophages from animals with pulmonary lesions. In vitro investigation showed that GM-CSF in the range 0.1-10 ng/ml induced a significant increase in viral p25 production after 7 days in acutely infected blood monocyte-derived macrophages. The production of p25 peaked between 7 and 14 days exposure to 10 ng/ml of GM-CSF. Quantitative polymerase chain reaction showed that the level of viral DNA in monocyte-derived macrophages was dose-dependent following GM-CSF treatment in the range 0.1-100 ng/ml after 7 days. Viral mRNA expression was also enhanced. These findings indicate a role for GM-CSF in the pathogenesis of lymphoid interstitial pneumonia in infected animals.

Animals↗

Energy dispersive spectroscopy analysis of aluminium segregation in silicon carbide grain boundaries.

The aluminium distribution in polycrystalline SiC hot-pressed with aluminium, boron and carbon additives was studied using X-ray energy-dispersive spectroscopy (EDS) and transmission electron microscopy (TEM). The Al excess in homophase SiC grain boundary films was determined, taking into account dissolved Al in the SiC lattice. In the spot-EDS analysis, an electron beam probe with a calibrated diameter was formed, and the total beam-specimen interaction volume was defined, taking the beam spreading through crystalline TEM foil into consideration. EDS spectra were collected from regions containing intergranular films and adjacent matrix grains, respectively. A theoretical treatment was presented and experimental errors were estimated, with a further discussion about the effects of foil thickness. Experimental examples are given, followed by statistical EDS analyses for grain boundary films in SiC samples hot-pressed with increased amounts of Al additions. The results demonstrated a substantial Al segregation in the nanometer-wide intergranular films in all samples. Al additions higher than 3 wt% saturated the Al concentrations in SiC grains and in grain boundary films. The effect of foil thickness, and the parameters for determining the optimum incident beam diameter in the EDS analysis are discussed.

Journal Article↗

Comparison of attractiveness in Japan and China of three synthetic pheromone blends based on geographic variations in the rice leaffolder, Cnaphalocrocis medinalis(Lepidoptera: Pyralidae).

Field bioassays using three different synthetic sex pheromone blends (Indian, Philippine and Japanese) based on geographic variations of Cnaphalocrocis medinalis Guenée were carried out at 11 sites in Japan and in Hangzhou, China. In all of the tests, only the Japanese pheromone blend attracted a significant number of male moths, while the Indian and Philippine pheromone blends showed no marked activity. The findings in Japan showed no evidence that moths of Philippine or Indian origin were able to migrate to Japan. The results from China also showed that most populations of C. medinalisin the Hangzhou region responded to the Japanese blend. This is consistent with the current hypothesis that most populations of C. medinalisin Japan are migrants from areas to the south of the Yangzhe Valley, including the region surrounding Hangzhou, China. Furthermore, populations in the Hangzhou region can not hibernate, but are considered migrants from the southernmost parts of China and southeast Asian countries such as Vietnam where they breed continuously. Consequently, at least some populations in these areas may respond to the Japanese pheromone blend.

Animals↗

Aerosol transport and deposition in a triple bifurcation bronchial airway model with local tumors.

Airflow characteristics and particle deposition have been numerically simulated in a triple bifurcation lung airway model (from generation 3-6 airways) with local tumors protruded from the sidewalls of generation 5 airways. The effects of tumors in terms of size and location on airflow, particle transport, and deposition patterns were analyzed for constant inspiratory flow rates with inlet Reynolds (Re(match) = 463 and 1882) and Stokes number (St(match) = 0.02-0.12) combinations that match different cyclic inhalation waveforms. The size of tumors was varied to induce an obstruction of airway lumen by 16-74%. Extreme conditions, 2 and 100% obstruction, were also examined. The results show that enhanced deposition occurs in the carina region at each bifurcation, and deposition increases with increasing Stokes and Reynolds number as expected from earlier studies. In addition, deposition increases at the tumor site until the tumor blocks about half of the airway lumen and then decreases with a further obstruction. In other words, there exists a maximum particle deposition fraction (DF) for a protruding tumor that occludes the lumen. The maximum DF at the tumor was 10.2% within the test conditions used. Deposition occurs mainly on the frontal surface of the tumors, but spreads out to the opposite wall, or upstream sections, or sister branches of the tumor at high flow rates and Stokes number. The present results (1) help in the understanding of the complex toxic or therapeutic aerosol dynamics in the lung with local airways obstruction, and (2) provide quantitative information on critical tumor size and particle deposition to health care specialists.

Administration, Inhalation↗