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Biomedical subjects

Z Zhang

Publications and source records attributed to Z Zhang.

At least 55 records · Page 3Linked to original sources

The role of biomaterials in stem cell differentiation: applications in the musculoskeletal system.

The capabilities of stem cells continue to be revealed, leading to excitement regarding potential new therapies. Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. Biomaterials play an important role in directing tissue growth and may provide another tool to manipulate and control stem cell behavior. Biomaterials are made from natural or synthetic polymers and can be processed into three-dimensional scaffolds designed to promote cell proliferation and/or differentiation that ultimately produces new tissue. Stem cells will have a significant impact on the fields of regenerative medicine and tissue engineering as a powerful cell source that will work, in conjunction with biomaterials, to treat tissue and organ loss. Herein, we survey our latest research on applying embryonic stem (ES) cells to hydrogel biomaterials for engineering musculoskeletal tissues, emphasizing the unique biomaterial requirements of ES cells for differentiation and tissue development.

Animals↗

Erythroid differentiation denucleation factors (EDDFs) function as intrinsic, post-erythropoietin regulators for mammalian erythroid terminal differentiation.

Regulatory factors other than erythropoietin (Epo) dependence, that control mammalian erythroid terminal differentiation, are currently uncertain. Here we report the existence of erythroid differentiation factors in erythroid cytoplasm. Purification of these factors from cultured Friend virus anaemia (FVA)-infected mouse splenic erythroblasts was carried out using isoelectrophoresis and high performance of liquid chromatography techniques. We have identified intracellular erythroid differentiation denucleation factors (EDDFs) that were able to mediate the events of post-Epo-dependent erythroblast terminal differentiation. Purified EDDF proteins bound specifically to the enhancer HS2 sequence of the globin gene activated the expression of haemoglobin in mouse erythroleukaemia and K562 erythroleukaemic cells and promoted them to differentiate into mature erythrocytes. EDDF proteins began to emerge at the pro-early erythroblast stages upon exposure to Epo in culture, and increased dramatically in early erythroblast stage. The dynamic of EDDF expression and its action on the key events of erythroblast differentiation and denucleation appeared to be closely consistent with its spatiotemporal distribution. These results suggest that EDDFs are the critical intracellular regulatory factors that may act as the successive regulators to Epo, responsible for the final stages of erythroid terminal differentiation.

Activins↗

Upregulation of frizzled 9 in astrocytomas.

Wnt/frizzled (FZD) cascades play important roles in controlling cell fate, proliferation, migration, tissue architecture and organogenesis during embryonic development and in adult organisms. The potential involvement of this pathway in tumorigenesis has been established in several types of cancers. Frizzled 9 (FZD9) is expressed in brain and its aberrant expression in gastric cancer was observed. However, its association with astrocytomas remains unknown therefore we studied FZD9 expression in astrocytomas of different malignancy. In the present study, FZD9 expression in 25 astrocytomas was investigated using immunohistochemistry with specific antibodies. Further FZD9 expression in native human brain tissue and glioblastoma cell line were analysed using real-time reverse transcription polymerase chain reaction (RT-PCR). In human astrocytomas, FZD9 immunoreactivity (IR) was observed in both microvessels and neoplastic cells. The percentage of FZD9+ microvessels in relation to FZD9+ vessels was significantly higher in malignant astrocytomas than in low-grade astrocytomas and positively correlated with the astrocytoma World Health Organization (WHO) grading (r = 1, P = 0.04). Furthermore, the FZD9 IR scores positively correlated with astrocytoma WHO grading (r = 1, P = 0.04) and proliferating activity (r = 0.77, P < 0.001). Real-time RT-PCR data showed that FZD9 expression in human glioblastoma was significant higher than in normal brain (P < 0.05) but FZD9 expression was only slightly induced in cobalt chloride-treated human glioblastoma T98G cells compared with untreated cells (P > 0.05). FZD9 is upregulated in astrocytomas, suggesting that FZD9 could be important in the tumorigenesis of human astrocytomas.

Adult↗

A comparative study of asthma, pollen, cat and dog allergy among pupils and allergen levels in schools in Taiyuan city, China, and Uppsala, Sweden.

We compared the school environment, asthma and allergy in 10 schools in Taiyuan, China, with eight schools in Uppsala, Sweden. In total 2193 pupils (mean age 13 years) participated. Chinese pupils had more respiratory symptoms, particularly daytime breathlessness after exercise (29.8% vs. 7.1%; P < 0.001), while cat allergy (1.2% vs. 6.6%; P < 0.001) and dog allergy (1.3% vs. 4.0%; P < 0.01) was less common. Cumulative incidence of asthma (1.8% vs. 9.5%; P < 0.001) and doctor's diagnosed asthma (1.2% vs. 9.0%; P < 0.001) were less common in China, indicating an under-diagnosis of asthma. Chinese classrooms were colder (mean 14.7 vs. 21.4 degrees C), more humid (mean 42% vs. 31% RH) and had higher CO2-levels (mean 2211 vs. 761 ppm). Levels of cat (Fel d1), dog (Can f1) allergens were low in settled dust from China (< 200 ng/g dust), but high in airborne dust on Petri-dishes (GM 16.8 ng/m2/day for Fel d1 and 17.7 for Can f1). The Swedish settled dust contained cat, dog and horse allergens in high levels (median 1300 ng/g, 1650 ng/g, 1250 U/g dust, respectively). In conclusion, there were large differences in the school environment, and in respiratory symptom and allergy. Allergen measurements in settled dust only may largely underestimate the classroom exposure. Practical Implications There is a need to improve the school environment, both in China and Sweden. The Swedish schools contained high levels of cat, dog and horse allergens and more amounts of open shelves and textiles that can accumulate dust and allergens. The air measurements indicated that Chinese schools may contain significant amounts of cat and dog allergen, and analysis of settled dust only may not reflect the true allergen exposure. Since the Chinese schools had no mechanical ventilation, they could not fulfill the ventilation standard in winter, and hence there is a need for improving the ventilation. The great discrepancy between respiratory symptoms and reports on asthma, and the high prevalence of attacks of breathlessness without wheeze, may have implication for future questionnaire studies on asthma in China.

Adolescent↗

Laminar airflow and nanoparticle or vapor deposition in a human nasal cavity model.

The transport and deposition of nanoparticles, i.e., dp = 1-2 nm, or equivalent vapors, in the human nasal cavities is of interest to engineers, scientists, air-pollution regulators, and healthcare officials alike. Tiny ultrafine particles, i.e., dp < or = 5 nm, are of special interest because they are most rapidly absorbed and hence have an elevated toxic or therapeutic impact when compared to larger particles. Assuming transient laminar 3-D incompressible flow in a representative human nasal cavity, the cyclic airflow pattern as well as local and overall nanoparticle depositions were computationally simulated and analyzed. The focus was on transient effects during inhalation/exhalation as compared to the steady-state assumption typically invoked. Then, an equation for a matching steady-state inhalation flow rate was developed that generates the same deposition results as cyclic inhalation. Of special interest is the olfactory region where the narrow channel surfaces receive only about one-half of a percent of the inhaled nanoparticles because the airflow bypasses these recesses located in the superior-most portions in the geometrically complex nasal cavities.

Absorption↗

Variables which might predict the response to salvage radiotherapy in chinese patients with biochemical failure after radical prostatectomy.

BACKGROUND/AIMS: To evaluate the relationship between the variables and the outcomes of salvage radiotherapy (sRT) to find some predictors of sRT. METHODS: The medical records of 56 patients receiving sRT for biochemical failure after radical prostatectomy (RP) were available for retrospective review. sRT was defined as external beam radiotherapy for patients with a continuous increase in the prostate-specific antigen (PSA) level of >or=0.2 ng/ml after RP. Response was defined as achievement of a PSA nadir of 6 months were all responders. The response rate in patients with seminal vesicle invasion was 42.9% (6/14) versus 76.2% (32/42) in patients without seminal vesicle invasion (OR=0.119, p=0.015). CONCLUSION: PSADT and the state of seminal vesicle invasion were good predictors of response to sRT. sRT was especially effective when the PSADT was >6 months and in patients without seminal vesicle invasion.

China↗

Detection and characterization of naturally acquired West Nile virus infection in a female wild turkey.

An adult female wild turkey exhibiting disorientation and failure to flee when approached was submitted to the Mississippi Veterinary Research and Diagnostic Laboratory. Gross pathologic examination revealed evidence of dehydration and the presence of modest numbers of adult nematodes in the small intestine. Histologic examination revealed extensive multifocal perivascular lymphocytic infiltration in brain, marked heterophilic hyperplasia in bone marrow, and multifocal interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and kidney tissues using cultured Vero cells. Higher copies of viral RNA were detected from brain, lung, and kidney than from heart, liver, or spleen by quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR) analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various tissues including neurons, kidney, respiratory tract epithelium, heart, and bone marrow. On the basis of the data from this investigation, it is concluded that WNV caused encephalitis along with many other pathologic changes in the affected wild turkey.

Animals↗

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer.

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P<0.0001), ER (P=0.02), and progesterone receptor (P=0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P=0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P=0.04), and longer survival after relapse (P=0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

Adult↗

Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice.

The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca(2+) transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca(2+) release upon electrical stimulus associated with a slowed intracellular Ca(2+) decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca(2+) hemostasis and ultrastructural derangement in ventricular myocytes.

Animals↗

Hydrogenation of single-walled carbon nanotubes.

Towards the development of a useful mechanism for hydrogen storage, we have studied the hydrogenation of single-walled carbon nanotubes with atomic hydrogen using core-level photoelectron spectroscopy and x-ray absorption spectroscopy. We find that atomic hydrogen creates C-H bonds with the carbon atoms in the nanotube walls, and such C-H bonds can be completely broken by heating to 600 degrees C. We demonstrate approximately 65 +/- 15 at % hydrogenation of carbon atoms in the single-walled carbon nanotubes, which is equivalent to 5.1 +/- 1.2 wt % hydrogen capacity. We also show that the hydrogenation is a reversible process.

Journal Article↗

Analysis of allele fidelity, polymorphic information content, and density of microsatellites in a genome-wide screening for hip dysplasia in a crossbreed pedigree.

Recent advances in genomics resources and tools are facilitating quantitative trait locus mapping. We developed a crossbreed pedigree for mapping quantitative trait loci for hip dysplasia in dogs by crossing dysplastic Labrador Retrievers and normal Greyhounds. We show that one advantage to using a crossbreed pedigree is the increased marker informativeness in the backcross/F2 population relative to the founder populations. We also discuss three factors that affect the detection power in the context of this crossbreed pedigree: being able to detect and correct genotyping errors, increasing marker density for chromosomes with a sparse coverage, and adding individuals to the mapping population as soon as they become available.

Alleles↗

Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on temporal differentiation: evidence for the involvement of 5-HT2A but not 5-HT3 receptors in interval timing behaviour.

RATIONALE: Temporal differentiation refers to animals' ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT(2A) receptors. There is evidence that 5-HT(3) receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT(3) receptor stimulation can influence temporal differentiation. OBJECTIVE: We examined the effects of a selective 5-HT(3) receptor agonist m-CPBG, a mixed 5-HT(2A/3) receptor agonist quipazine, and selective 5-HT(3) and 5-HT(2A) receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure. METHODS: Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M: , 50 microl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data [percent responding on B (%B) vs time from trial onset (t)], and quantitative indices of timing performance [T (50) (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S (50)] were derived. RESULTS: Quipazine (0.5, 1, and 2 mg kg(-1)) altered timing performance, dose-dependently reducing T (50) and S (50); m-CPBG (2.5, 5, and 10 mg kg(-1)) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg(-1)), but not by MDL-72222 (1 mg kg(-1)). CONCLUSIONS: The present results provide no evidence for the involvement of 5-HT(3) receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT(2A) receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT(2A) receptors in interval timing behaviour.

Animals↗

Comparison of the effects of clozapine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on progressive ratio schedule performance: evidence against the involvement of 5-HT1A receptors in the behavioural effects of clozapine.

RATIONALE: Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on the efficacy of reinforcers. A mathematical model (Killeen PR (1994) Mathematical principles of reinforcement. Behav Brain Sci 17:105-172) affords a basis for quantifying the effects of drugs on progressive ratio schedule performance. The model postulates a bitonic function relating response rate and ratio size. One parameter of the function, a, expresses the motivational effect of the reinforcer, whereas another parameter, delta, expresses the minimum time needed to execute a response, and is regarded as an index of 'motor capacity'. Previously we found that the atypical antipsychotic clozapine increased a, indicating an increase in reinforcer efficacy; a similar effect was observed with the 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). It has been suggested that some of clozapine's behavioural effects are mediated by agonistic action at 5-HT(1A) receptors. OBJECTIVE: This study was conducted to compare the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance. METHODS: Rats were trained under a time-constrained progressive ratio schedule (50-min sessions). In experiment 1, they received acute doses of clozapine (4 mg kg(-1)) and 8-OH-DPAT (100 microg kg(-1)), alone and in combination with the 5-HT(1A) receptor antagonist N-[2-(4-[2-methoxyphenyl]-1-piperazinyl)ethyl]-N-2-yridinylcyclohexanecarboxamide (WAY-100635; 30 microg kg(-1)). In experiment 2, the effects of clozapine (2, 4 and 8 mg kg(-1)) and 8-OH-DPAT (25, 50 and 100 microg kg(-1)) were compared between intact rats and rats whose 5-HTergic pathways had been ablated by 5,7-dihydroxytryptamine (5,7-DHT). RESULTS: In both experiments, clozapine and 8-OH-DPAT increased a and delta. In experiment 1, WAY-100635 abolished the effect of 8-OH-DPAT on a and delta, but did not alter clozapine's effects on these parameters. In experiment 2, the effects of clozapine and 8-OH-DPAT did not differ between sham-lesioned and 5,7-DHT-lesioned rats. CONCLUSIONS: The results confirm previous findings on the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance. 8-OH-DPAT's effects are probably mediated by post-synaptic 5-HT(1A) receptors; clozapine's effects are mediated by a different mechanism, which does not appear to involve 5-HT(1A) receptors and which does not depend upon an intact 5-HTergic pathway.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of a novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats.

RATIONALE AND OBJECTIVE: Recent work has shown that the novel compound N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) may selectively block nicotinic acetylcholine receptors involved in regulating dopamine release. The current experiments examined the acute effect of bPiDDB on nicotine self-administration, sucrose-maintained responding, and nicotine-induced changes in acute and sensitized locomotor activity. METHODS: Rats were first trained to respond for either nicotine (i.v.) or sucrose pellets using a standard two-lever operant conditioning procedure using a fixed ratio 5 schedule of reinforcement and were then pretreated with bPiDDB (0, 0.3, 1, or 3 mg kg(-1)) 15 min prior to the session. In separate experiments, rats were assessed for nicotine-induced changes in locomotor activity following pretreatment with bPiDDB (1 or 3 mg kg(-1)) or mecamylamine (1 mg kg(-1)); pretreatments were assessed with both acute and repeated nicotine (0.4 mg kg(-1)) treatment. RESULTS: Results showed that bPiDDB dose-dependently decreased nicotine self-administration, but not sucrose-maintained responding. In the locomotor experiments, bPiDDB attenuated the hyperactivity produced by acute and repeated nicotine; however, this effect was not robust compared to mecamylamine. In contrast to mecamylamine, bPiDDB did not block the initial hypoactivity produced by acute nicotine. CONCLUSION: Since bPiDDB decreased nicotine self-administration specifically, this novel nicotinic receptor antagonist may constitute a lead for the development of a clinically useful treatment for tobacco dependence.

Animals↗

Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits.

Increasing evidence suggests that abnormal iron handling may be involved in the pathogenesis of Parkinson's disease. The present study investigates the role of iron and the iron-storage protein ferritin in inflammation-induced degeneration of dopaminergic neurons of the substantia nigra pars compacta. Injection of lipopolysaccharide into the globus pallidus of young and middle-aged rats substantially decreased tyrosine hydroxylase immunostaining in substantia nigra pars compacta four weeks after injection. Loss of tyrosine hydroxylase expression was accompanied by increased iron and ferritin levels in glial cells of the substantia nigra pars reticulata. Despite greater increases in nigral iron levels, ferritin induction was less pronounced in older rats, suggesting the regulation of ferritin was compromised with age. Automated movement tracking analyses showed that young rats recovered from LPS-induced locomotor deficits within four weeks, yet older rats failed to improve on measures of speed and total distance moved. Intrapallidal lipopolysaccharide injection also increased expression of alpha-synuclein and ubiquitin in tyrosine hydroxylase-positive neurons of the substantia nigra pars compacta. These results suggest that pallidal inflammation significantly increases stress on dopamine-containing neurons in the substantia nigra pars compacta. Alterations in nigral iron levels and protein handing may increase the vulnerability of nigral neurons to degenerative processes.

Aging↗

Zn2+ and Sr2+ adsorption at the TiO2 (110)-electrolyte interface: influence of ionic strength, coverage, and anions.

The X-ray standing wave technique was used to probe the sensitivity of Zn2+ and Sr2+ ion adsorption to changes in both the adsorbed ion coverage and the background electrolyte species and concentrations at the rutile (alpha-TiO2) (110)-aqueous interface. Measurements were made with various background electrolytes (NaCl, NaTr, RbCl, NaBr) at concentrations as high as 1 m. The results demonstrate that Zn2+ and Sr2+ reside primarily in the condensed layer and that the ion heights above the Ti-O surface plane are insensitive to ionic strength and the choice of background electrolyte (with <0.1 A changes over the full compositional range). The lack of any specific anion coadsorption upon probing with Br-, coupled with the insensitivity of Zn2+ and Sr2+ cation heights to changes in the background electrolyte, implies that anions do not play a significant role in the adsorption of these divalent metal ions to the rutile (110) surface. Absolute ion coverage measurements for Zn2+ and Sr2+ show a maximum Stern-layer coverage of approximately 0.5 monolayer, with no significant variation in height as a function of Stern-layer coverage. These observations are discussed in the context of Gouy-Chapman-Stern models of the electrical double layer developed from macroscopic sorption and pH-titration studies of rutile powder suspensions. Direct comparison between these experimental observations and the MUltiSIte Complexation (MUSIC) model predictions of cation surface coverage as a function of ionic strength revealed good agreement between measured and predicted surface coverages with no adjustable parameters.

Journal Article↗

Characterization of the mechanical properties of polymeric chromatographic particles by micromanipulation.

Chromatographic particles should not possess only desirable surface chemical properties but also mechanical properties. The latter determine the deformation of the particles under hydrodynamic conditions of packed beds and further the pressure drop. Understanding the mechanical properties of chromatographic particles is essential to successful design and operation of such processing equipment. The mechanical properties of single chromatographic particles made of different formulations and with different surface modifications were characterized by a novel micromanipulation technique. The principle of this technique is to compress single particles between two parallel surfaces. The force being imposed on the particles and their deformation under compression are measured simultaneously. The particles range from 30 to 300 microm, depending on their formulation. 10-30 particles from each sample were compressed up to a particle deformation of 70% in order to get statistically representative data. Particles for hydrophobic interaction chromatography were proved more stable than resins for ion exchange or gel filtration. The difference is remarkable in dry state and is less in wet state. Water seems to "level out" the differences in mechanical stability of resins. The stability seems to be also dependent on the speed of water release out of the resins.

Algorithms↗