Biomedical subjects

M Yang

Publications and source records attributed to M Yang.

At least 109 records · Page 6Linked to original sources

PubMed2001

Elemental signals regulating eosinophil accumulation in the lung.

In this review we identify the elemental signals that regulate eosinophil accumulation in the allergic lung. We show that there are two interwoven mechanisms for the accumulation of eosinophils in pulmonary tissues and that these mechanisms are linked to the development of airways hyperreactivity (AHR). Interleukin-(IL)-5 plays a critical role in the expansion of eosinophil pools in both the bone marrow and blood in response to allergen provocation of the airways. Secondly, IL-4 and IL-13 operate within the allergic lung to control the transmigration of eosinophils across the vascular bed into pulmonary tissues. This process exclusively promotes tissue accumulation of eosinophils. IL-13 and IL-4 probably act by activating eosinophil-specific adhesion pathways and by regulating the production of IL-5 and eotaxin in the lung compartment. IL-5 and eotaxin co-operate locally in pulmonary tissues to selectively and synergistically promote eosinophilia. Thus, IL-5 acts systemically to induce eosinophilia and within tissues to promote local chemotactic signals. Regulation of IL-5 and eotaxin levels within the lung by IL-4 and IL-13 allows Th2 cells to elegantly co-ordinate tissue and peripheral eosinophilia. Whilst the inhibition of either the IL-4/IL-13 or IL-5/eotaxin pathways resulted in the abolition of tissue eosinophils and AHR, only depletion of IL-5 and eotaxin concurrently results in marked attenuation of pulmonary inflammation. These data highlight the importance of targeting both IL-5 and CCR3 signalling systems for the resolution of inflammation and AHR associated with asthma.

Animals↗

PubMed2001

PDGF-D, a new protease-activated growth factor.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer, fibrotic diseases and arteriosclerosis. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha, whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

3T3 Cells↗

PubMed2001

A photic visual cycle of rhodopsin regeneration is dependent on Rgr.

During visual excitation, rhodopsin undergoes photoactivation and bleaches to opsin and all-trans-retinal. To regenerate rhodopsin and maintain normal visual sensitivity, the all-trans isomer must be metabolized and reisomerized to produce the chromophore 11-cis-retinal in biochemical steps that constitute the visual cycle and involve the retinal pigment epithelium (RPE; refs. 3-8). A key step in the visual cycle is isomerization of an all-trans retinoid to 11-cis-retinol in the RPE (refs. 9-11). It could be that the retinochrome-like opsins, peropsin, or the retinal G protein-coupled receptor (RGR) opsin12-16 are isomerases in the RPE. In contrast to visual pigments, RGR is bound predominantly to endogenous all-trans-retinal, and irradiation of RGR in vitro results in stereospecific conversion of the bound all-trans isomer to 11-cis-retinal. Here we show that RGR is involved in the formation of 11-cis-retinal in mice and functions in a light-dependent pathway of the rod visual cycle. Mutations in the human gene encoding RGR are associated with retinitis pigmentosa.

Animals↗

PubMed2001

Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1.

Brachydactyly type A-1 (BDA-1; MIM 112500) is characterized by shortening or missing of the middle phalanges (Fig. 1a). It was first identified by Farabee in 1903 (ref. 2), is the first recorded example of a human anomaly with Mendelian autosomal-dominant inheritance and, as such, is cited in most genetic and biological textbooks. Here we show that mutations in IHH, which encodes Indian hedgehog, cause BDA-1. We have identified three heterozygous missense mutations in the region encoding the amino-terminal signaling domain in all affected members of three large, unrelated families. The three mutant amino acids, which are conserved across all vertebrates and invertebrates studied so far, are predicted to be adjacent on the surface of IHH.

Amino Acid Substitution↗

PubMed2001

Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood.

Infusion of ex vivo expanded megakaryocytic (MK) progenitor cells is a strategy for shortening the duration of thrombocytopenia after haematopoietic stem cell transplantation. The cell dose after expansion has emerged as a critical factor for achieving the desired clinical outcomes. This study aimed to establish efficient conditions for the expansion of the MK lineage from enriched CD34(+) cells of umbilical cord blood and to investigate the effect of platelet-derived growth factor (PDGF) in this system. Our results demonstrated that thrombopoietin (TPO) alone produced a high proportion of CD61(+)CD41(+) cells but a low total cell count and high cell death, resulting in an inferior expansion. The addition of interleukin-1 beta (IL-1 beta), Flt-3 ligand (Flt-3L) and to a lesser extent IL-3 improved the expansion outcome. The treatment groups with three to five cytokines produced efficient expansions of CFU-MK up to 400-fold with the highest yield observed in the presence of TPO, IL-1 beta, IL-3, IL-6 and Flt-3L. CD34(+) cells were expanded by five to 22-fold. PDGF improved the expansion of all cell types with CD61(+)CD41(+) cells, CFU-MK and CD34(+) cells increased by 101%, 134% and 70%, respectively. On day 14, the CD61(+) population consisted of diploid (86.5%), tetraploid (11.8%) and polyploid (8N--32N; 1.69%) cells. Their levels were not affected by PDGF. TPO, IL-1 beta, IL-3, IL-6, Flt-3L and PDGF represented an effective cytokine combination for expanding MK progenitors while maintaining a moderate increase of CD34(+) cells. This study showed, for the first time, that PDGF enhanced the ex vivo expansion of the MK lineage, without promoting their in vitro maturation. PDGF might be a suitable growth factor to improve the ex vivo expansion of MK progenitors for clinical applications.

Antigens, CD↗

PubMed2001

Differential-pulse voltammetric determination of trace formaldehyde using magnetic microspheres and magnetic electrode.

A new type of magnetic polymer microsphere containing acylhydrazine groups on the surface was synthesized. They can be reacted with formaldehyde to produce an electroactive adduct. Reduction of these derivatives following aggregation on a magnetic electrode is possible and is effective in the indirect determination of formaldehyde. The experimental conditions and electrode structure are discussed. Under the optimum conditions, it was found that the peak potential (Ep) of formaldehyde is -1.01 V (vs. Ag/AgCl). Formaldehyde in the range 1-1000 micrograms l-1 can be determined. The detection limit for formaldehyde is 0.3 microgram l-1 and the relative standard deviation for the determination of 100 micrograms l-1 formaldehyde was 2.26%. The method was applied to the determination of formaldehyde in environmental samples with satisfactory results.

Air Pollutants, Occupational↗

PubMed2001

Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src.

The protein tyrosine kinase Src is known to regulate NMDA receptors in native neurons. While NR2A, NR2B and NR2D are known to be phosphorylated on tyrosine residues, the exact sites have remained unidentified. Immunoprecipitation of NMDA receptor subunits followed by western blotting was used to analyze the state of tyrosine phosphorylation of recombinant NMDA receptor subunits expressed in HEK293 cells. Using antiphosphotyrosine antibody PY20, we find that on expression in HEK cells, v-Src and Fyn cause detectable tyrosine phosphorylation only of NR2A. Because a stronger signal was produced by the constitutively active v-Src, the general region of v-Src phosphorylation was delimited by expression of a series of truncation mutants of NR2A. Site-directed mutagenesis on candidate sites within the likely region allowed identification of three sites, Y1292, Y1325, and Y1387 that account for a significant fraction of the total PY20 signal. Two of these sites, Y1292 and Y1387, were suggested to control current modulation by Src in previous studies of HEK cells expressing NR1/NR2A. One of these sites, Y1325, has not yet been evaluated for effects on receptor current. A unique tyrosine site, Y1267, was shown not to be a site of detectable phosphorylation, in accordance with its Src-independent regulation of receptor currents.

Animals↗

PubMed2001

A molecular marker that is specific to medicinal rhubarb based on chloroplast trnL/trnF sequences.

"Da-Huang" (Radix et Rhizoma Rhei, medicinal rhubarb), a famous and important Traditional Chinese Medicine, has often been confused with the adulterant species in the same genus, Rheum. Through sequencing the trnL (UAA)/trnF (GAA) regions of chloroplast DNA of thirteen species of Rheum (three medicinal rhubarb species and ten adulterant ones), a molecular marker of the medicinal species was found. A pair of PCR primers based on the sequences, was thus designed, which amplified a highly specific DNA fragment in medicinal rhubarb exclusively, and absent in the adulterants at all under an optimized PCR condition.

Base Sequence↗

PubMed2001

Study on sludge expansion during treatment of salad oil manufacturing wastewater by yeast.

Five yeast strains, namely Rhodotorula rubra, Candida tropicalis, Candida utilis, Candida boidinii, Trichosporon cutaneum, were isolated from soil spots of a salad oil factory, and applied for continuous treatment of salad oil manufacturing wastewater. The oil and COD removal performance of the mixed cultures were comparable to the results other researchers obtained. Sludge expansion, accompanied with sludge morphology change from pseudomycelia to true mycelia, occurred during continuous treatment of wastewater. The true mycelia dominated sludge had a much higher water content and SVI value than that of the yeast pure cultures, although the two kinds of sludge had similar oil removal performance. A mold, Geotrichum candidum, was isolated from the expanded sludge, and was suspected to be a reason for sludge expansion. Addition of 0.3% sodium propionate into batch cultures degraded SVI value from around 100 to 60. In a continuous running, addition of 10 mg l-1 sodium hypochlorite decreased SVI value from over 200 to below 100. The yeast activity, however, was weakened to a large extent at the same time.

Industry↗

PubMed2001

Contribution from thoron on the response of passive radon detectors.

In order to evaluate the reliability of measured values of radon concentration, a thoron sensitivity test for passive radon detectors was carried out. To do this test, a thoron chamber system was first set up. The system consists of four parts: an exposure chamber, a gas generator, an environmental monitor, and a measuring device. Five types of radon detectors were examined using the chamber system. After connecting the exposure chamber with the gas generator through an external pump, thoron gas was circulated through the system. The detectors were exposed to thoron-rich air for several days. The mean ratio between thoron and radon concentrations throughout the exposure period was 10:1. Some of the detectors provided values different from the actual radon concentration. Although the presence of thoron can be negligible in most cases, it is necessary to check the thoron contribution to the detector response with the proposed or similar test before practical use.

Air Pollutants, Radioactive↗

PubMed2001

Effect of polymorphism in the human glutathione S-transferase A1 promoter on hepatic GSTA1 and GSTA2 expression.

The patterns of expression of glutathione S-transferases A1 and A2 in human liver (hGSTA1 and hGSTA2, respectively) are highly variable, notably in the ratio of hGSTA1/hGSTA2. We investigated if this variation had a genetic basis by sequencing the proximal promoters (-721 to -1 nucleotides) of hGSTA1 and hGSTA2, using 55 samples of human liver that exemplified the variability of hGSTA1 and hGSTA2 expression. Variants were found in the hGSTA1 gene: -631T or G, -567T, -69C, -52G, designated as hGSTA1*A; and -631G, -567G, -69T, -52A, designated as hGSTA1*B. Genotyping for the substitution -69C > T by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), showed that the polymorphism was widespread in Caucasians, African-Americans and Hispanics, and that it appeared to conform to allelic variation. Constructs consisting of the proximal promoters of hGSTA1*A, hGSTA1*B or hGSTA2, with luciferase as a reporter gene, showed differential expression when transfected into HepG2 cells: hGSTA1*A approximately hGSTA2 > hGSTA1*B. Similarly, mean levels of hGSTA1 protein expression in liver cytosols decreased significantly according to genotype: hGSTA1*A > hGSTA1-heterozygous > hGSTA1*B. Conversely, mean hGSTA2 expression increased according to the same order of hGSTA1 genotype. Consequently, the ratio of GSTA1/GSTA2 was highly hGSTA1 allele-specific. Because the polymorphism in hGSTA1 correlates with hGSTA1 and hGSTA2 expression in liver, and hGSTA1-1 and hGSTA2-2 exhibit differential catalysis of the detoxification of carcinogen metabolites and chemotherapeutics, the polymorphism is expected to be of significance for individual risk of cancer or individual response to chemotherapeutic agents.

Base Sequence↗

PubMed2001

Male meiotic spindle lengths in normal and mutant arabidopsis cells.

Spindle elongation is crucial to normal chromosome separation in eukaryotes; in particular, it is required for or associated with the extension of distance between spindle poles and the further moving apart of the already separated chromosomes. However, little is known about the relationship between spindle elongation and the status of chromosome separation, and it is unknown whether spindle elongation in different organisms shares any quantitative feature. The Arabidopsis ask1-1 mutant might be a unique material for addressing these questions because it appears to have functional spindles, but a severe defect in homolog separation at male anaphase I (M. Yang, Y. Hu, M. Lodhi, W.R. McCombie, H Ma [1999] Proc Natl Acad Sci USA 96: 11416-11421). We have characterized male meiotic spindle lengths in wild-type and the ask1-1 mutant plants. We observed that during meiosis I some ask1-1 cells had spindles that were similar in length to fully elongated normal spindles, but the chromosomes in these cells did not show appreciable movement from the equator. Furthermore, greater movement of chromosomes from the equator was usually found in the ask1-1 cells that had longer than normal spindles. These results suggest that additional elongation of ask1-1 spindles occurred; one possible reason for the extra-long spindles may be that it is a consequence of chromosome non-separation. We also found that normal and ask1-1 spindle lengths are clustered at discrete values, and their differences are of multiples of 0.7 microm. A search of the literature revealed that in each of several organisms, spindle lengths also differ by multiples of 0.7 microm. These findings strongly suggest that the spindle elongates in response to status of chromosome separation, and perhaps there are conserved mechanisms controlling the extent of spindle elongation.

Arabidopsis↗

PubMed2001

Interleukin-13 mediates airways hyperreactivity through the IL-4 receptor-alpha chain and STAT-6 independently of IL-5 and eotaxin.

Interleukin (IL)-13 is a central mediator of the processes underlying the induction of airways hyperreactivity (AHR) in the allergic lung. However, the mechanisms by which IL-13 induces AHR and the associated role of inflammatory infiltrates as effector cells has not been fully elucidated. In this investigation, we show that intratracheal administration of IL-13 induces AHR in the presence and absence of inflammation. The initial AHR response (peak, 6 to 24 h; preinflammatory phase [PIP]) was dissociated from inflammation (eosinophilia) and mucus hypersecretion but was critically regulated by signaling through the IL-4 receptor alpha chain (IL-4Ralpha) and signal transducers and activators of transcription (STAT)-6. The second response (> 24 h, inflammatory phase [IP]) was characterized by an amplified AHR, eosinophil accumulation, and mucus hypersecretion. These features of the IP were not observed in IL-4Ralpha- or STAT-6-deficient mice. To determine the role of eosinophils in the induction of IP AHR and mucus hypersecretion, we administered IL-13 to IL-5-, eotaxin-, and IL-5/eotaxin- deficient mice. IL-13-mediated eosinophil accumulation was significantly attenuated (but not ablated) in IL-5-, eotaxin-, or IL-5/eotaxin-deficient mice. However, IL-13-induced AHR and mucus secretion occurred independently of IL-5 and/or eotaxin. These findings demonstrate that IL-13 can induce AHR independently of these eosinophil regulatory cytokines and mucus hypersecretion. Furthermore, IL-13-induced AHR, eosinophilia, and mucus production are critically dependent on the IL-4Ralpha chain and STAT-6.

Animals↗

PubMed2001

Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function.

The androgen receptor (AR), a member of the steroid receptor superfamily of nuclear transcription factors, mediates androgen signaling in diverse target tissues. Here we report AR gene mutations identified in human prostate cancer and the autochthonous transgenic adenocarcinoma of the mouse prostate model that colocate to residues (668)QPIF(671) at the boundary of the hinge and ligand-binding domain, resulting in receptors that exhibit 2- to 4-fold increased activity compared with wild-type AR in response to dihydrotestosterone, estradiol, progesterone, adrenal androgens, and the AR antagonist, hydroxyflutamide, without an apparent effect on receptor levels, ligand binding kinetics, or DNA binding. The expression of these or similar variants could explain the emergence of hormone refractory disease in a subset of patients. Homology modeling indicates that amino acid residues (668)QPIF(671) form a ridge bordering a potential protein-protein interaction surface. The naturally occurring AR gene mutations reported in this study result in decreased hydrophobicity of this surface, suggesting that altered receptor-protein interaction mediates the precocious activity of the AR variants.

Adenocarcinoma↗

PubMed2001

Individual differences in urinary cotinine levels in Japanese smokers: relation to genetic polymorphism of drug-metabolizing enzymes.

Urinary cotinine, one of the main metabolites of nicotine, has been widely used as a biomarker for assessment of direct or passive exposure to cigarette smoke. However, there is wide variation of the cotinine level among smokers who smoke the same number of cigarettes. To use urinary cotinine as a proper exposure-biomarker for cigarette smoke, interindividual variations of cotinine formation must be considered. Therefore, we studied the effects of genetic polymorphisms in drug metabolic enzymes on urinary cotinine levels among 190 male Japanese smokers (ages 19-66 years; mean, 40.6 years). Genetic polymorphisms in cytochrome P-450s (CYP1A1, CYP2A6, CYP2E1), and aldehyde dehydrogenase 2 (ALDH2) were determined by analyzing DNA isolated from peripheral blood. Cotinine in morning spot urine was analyzed by high-performance liquid chromatography. Lifestyle, i.e., smoking, alcohol consumption, and intake of coffee or tea, was examined using a questionnaire. The number of cigarettes smoked and CYP2A6 polymorphism were significantly associated with the urinary cotinine level. Especially, the urinary cotinine levels was drastically lower in CYP2A6-deleted homozygous (CYP2A6*4/*4) subjects than in CYP2A6*1 allele-positive subjects. The polymorphism in the CYP2E1 5'-flanking region was related to the urinary cotinine level in intermediate smokers (who smoke 11-20 cigarettes/day; P < 0.01). Polymorphisms in CYP1A1 or ALDH2, and consumption of alcohol, coffee, or tea were not associated with the urinary cotinine level.

Adult↗

PubMed2001

Improved O3/H2O2 oxidation process for wastewater reclamation.

A continuous two step O3/H2O2 oxidation system, in which the waste gas from the former reactor was reused in the latter step with an ejector, was established for the purpose of wastewater reclamation in electronics industries. ORP monitor was combined into the system to obtain the optimum ratio of H2O2 to O3 by automatically adjusting the dosage of H2O2, and ion exchange resin was used for removing organic acids formed during oxidation. The effectiveness of the O3/H2O2 oxidation system for TOC removal was investigated under various conditions by using IPA, DMSO, and NMP as model substances. The optimum H2O2/O3 for oxidizing IPA was in a range above 0.15, and it increased with the increase of O3 dose. A sudden drop of ORP from ca. 800 mV to a little more than 200 mV was observed when H2O2/O3 was approaching the optimum point from the lower end. An ORP between 250 mV and 300 mV or 800 mV and 900 mV was proper for H2O2/O3 control. The treatability of the model substances was in an order of IPA << DMSO < NMP, being consistent with the magnitude of the energy of the highest occupied molecular orbital (epsilon HOMO). The two step treatment system developed in this study was found to be more efficient than the conventional single step system. With the help of H2O2 dosing control and two step treatment using waste O3, the system could save about 40% O3 in comparison with the conventional O3/H2O2 oxidation process.

Conservation of Natural Resources↗

PubMed2001

The Arabidopsis gene tardy asynchronous meiosis is required for the normal pace and synchrony of cell division during male meiosis.

Male meiosis in higher organisms features synchronous cell divisions in a large number of cells. It is not clear how this synchrony is achieved, nor is it known whether the synchrony is linked to the regulation of cell cycle progression. Here, we describe an Arabidopsis mutant, named tardy asynchronous meiosis (tam), that exhibits a phenotype of delayed and asynchronous cell divisions during male meiosis. In Arabidopsis, two nuclear divisions occur before simultaneous cytokinesis yields a tetrad of haploid cells. In tam, cell divisions are delayed, resulting in the formation of abnormal intermediates, most frequently dyad meiotic products, or in rare cases, dyad pollen (two gametophytes within one exine wall). Temperature-shift experiments showed that the percentage of the abnormal intermediates increased at 27 degrees C. Analysis of tam and the tam/quartet1 double mutant showed that most of these abnormal intermediates could continue through the normal rounds of cell divisions and form functional pollen, though at a slower than normal pace. The asynchrony of cell division started at the G2/M transition, with cells entering metaphase at different time points, during both meiosis I and II. In addition, chromosome condensation defects and mis-segregation were sometimes observed in tam. These observations suggest that the TAM protein positively regulates cell cycle progression, perhaps by promoting the G2/M transition. We speculate that there is a signal, perhaps TAM, that couples the normal pace of cell cycle progression with the synchrony of cell division during male meiosis.

Arabidopsis↗

PubMed2001

Antistress effect of oligosaccharides extracted from Morinda officinalis in mice and rats.

AIM: To explore the antistress effect of Morinda officinalis (Chinese medicine "Bajitian") oligosaccharides (MW-97) in mice. METHODS: Male mice and rats were subjected to a variety of unpredictable stressors on a daily basis over 15 d period and then the Vidiomex-V image pattern analytic system was used to observe the spontaneous motor activity. Meanwhile, regular method was used to prepare pathologic section of adrenal gland and blood cells analytic system was used to detect white blood cell (WBC) count (including relative WBC percentages) in peripheral blood. On the end, the serum level of stress hormone was detected using radioimmunoassay. RESULTS: Chronic stress resulted in diffuse hyperplasia of the adrenal cortex and atrophy of the adrenal medulla in mice, which suggested that stress-adaption failure of the adrenal gland occurred, while adrenal gland of the mice pretreated with MW-97 (100 mg/kg, ip) prior to each stressor for 15 d did not occur any pathologic changes. In addition, chronic stress also significantly reduced the WBC count and relative WBC percentages in the peripheral blood, including the percentage of lymphocytes, monocytes, neutrophils, however, MW-97 (25 and 100 mg/kg) reversed these changes and raised WBC count, along with relative WBC percentages significantly. Furthermore, the serum concentration of testosterone was decreased and corticosterone was increased significantly in chronically stressed animals. MW-97 also declined the serum level of corticosterone and raised level of testosterone. MW-97 had no effects on the spontaneous motor activity in the stressed mice. CONCLUSION: MW-97 had antistress effect against chronic stress, moreover, MW-97 had no excitatory or inhibitory effects on the CNS, which suggested that MW-97 might become a new kind of antistress agent.

Adrenal Glands↗