Search PubMed⌕ Search

Biomedical subjects

Y Jiang

Publications and source records attributed to Y Jiang.

At least 181 records · Page 10Linked to original sources
PubMed2001

[Recent developments of the atomization kinetics in electrothermal atomic absorption spectrometry].

Recent advances of the atomization kinetics in electrothermal atomic absorption spectrometry are critically reviewed with 31 references during 1994-2000. These include new methods for the determination of kinetic parameters, a two-parameters, a two-precursor model for the kinetics of analyte atomization, a kinetic model of atomization with redeposition, and the influences of matrices, chemical modifiers and atomizer surfaces on analyte atomization in an electrothermal atomizer.

Chemical Phenomena↗
PubMed2000

Equilibrium states and ground state of two-dimensional fluid foams.

We study the equilibrium energies of two-dimensional (2D) noncoarsening fluid foams, which consist of bubbles with fixed areas. The equilibrium states correspond to local minima of the total perimeter. We present a theoretical derivation of energy minima; experiments with ferrofluid foams, which can be either highly distorted, locally relaxed, or globally annealed; and Monte Carlo simulations using the extended large-Q Potts model. For a dry foam with small size variance we develop physical insight and an electrostatic analogy, which enables us to (i) find an approximate value of the global minimum perimeter, accounting for (small) area disorder, the topological distribution, and physical boundary conditions; (ii) conjecture the corresponding pattern and topology: small bubbles sort inward and large bubbles sort outward, topological charges of the same signs "repel" while charges of the opposite signs "attract;" (iii) define local and global markers to determine directly from an image how far a foam is from its ground state; (iv) conjecture that, in a local perimeter minimum at prescribed topology, the pressure distribution and thus the edge curvature are unique. Some results also apply to 3D foams.

Journal Article↗
PubMed2000

TGF-beta 2 attenuates the injury-induced death of mature motoneurons.

The distributions of transforming growth factor-betas (TGF-betas) and their receptors suggest that the TGF-betas regulate motoneuron survival. This hypothesis was tested by avulsing the hypoglossal nerve of adult rats and perfusing either TGF-beta 2 or vehicle adjacent to the hypoglossal nucleus. By 4 weeks, half of the avulsed motoneurons had died. Infusion of 6 ng of TGF-beta 2 adjacent to the avulsed motor nucleus caused a significant attenuation of this death. This dose of TGF-beta 2 is low compared to that used with GDNF or BDNF in previous studies of avulsed motoneurons, indicating that TGF-beta 2 may be one of the more potent survival factors for adult motoneurons. TGF-beta 2 was, however, unable to prevent or reduce the axotomy-induced down regulation of choline acetyltransferase. Other motoneuron survival factors also have a narrow-spectrum of actions, suggesting that the homeostasis of motoneurons is regulated by a cocktail of growth factors with distinct but partially overlapping actions.

Animals↗
PubMed2000

A domain with homology to neuronal calcium sensors is required for calcium-dependent activation of diacylglycerol kinase alpha.

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol produced during stimulus-induced phosphoinositide turnover and attenuate protein kinase C activation. Diacylglycerol kinase alpha is an 82-kDa DGK isoform that is activated in vitro by Ca(2+). The DGK alpha regulatory region includes tandem C1 protein kinase C homology domains and Ca(2+)-binding EF hand motifs. It also contains an N-terminal recoverin homology (RVH) domain that is related to the N termini of the recoverin family of neuronal calcium sensors. To probe the structural basis of Ca(2+) regulation, we expressed a series of DGK alpha deletions spanning its regulatory domain in COS-1 cells. Deletion of the RVH domain resulted in loss of Ca(2+)-dependent activation. Further deletion of the EF hands resulted in a constitutively active enzyme, suggesting that sequences in or near the EF hands are sufficient for autoinhibition. Binding of Ca(2+) to the EF hands protected sites within both the RVH domain and EF hands from trypsin cleavage and increased the phenyl-Sepharose binding of a recombinant DGK alpha fragment that included both the RVH domain and EF hands. These observations suggested that Ca(2+) elicits a concerted conformational change of these two domains. A cationic amphiphile, octadecyltrimethylammonium chloride, also activated DGK alpha. As with Ca(2+), this activation required the RVH domain. However, this agent did not protect the EF hands and RVH domain from trypsin cleavage. These findings indicate that the EF hands and RVH domain act as a functional unit during Ca(2+)-induced DGK alpha activation.

Amino Acid Sequence↗
PubMed2000

Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed its homologs.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies. Recently, two point mutations in alpha-synuclein were found to be associated with familial PD, but as of yet no mutations have been described in the homologous genes beta- and gamma-synuclein. alpha-Synuclein forms the major fibrillar component of Lewy bodies, but these do not stain for beta- or gamma-synuclein. This result is very surprising, given the extent of sequence conservation and the high similarity in expression and subcellular localization, in particular between alpha- and beta-synuclein. Here we compare in vitro fibrillogenesis of all three purified synucleins. We show that fresh solutions of alpha-, beta-, and gamma- synuclein show the same natively unfolded structure. While over time alpha-synuclein forms the previously described fibrils, no fibrils could be detected for beta- and gamma-synuclein under the same conditions. Most importantly, beta- and gamma-synuclein could not be cross-seeded with alpha-synuclein fibrils. However, under conditions that drastically accelerate aggregation, gamma-synuclein can form fibrils with a lag phase roughly three times longer than alpha-synuclein. These results indicate that beta- and gamma-synuclein are intrinsically less fibrillogenic than alpha-synuclein and cannot form mixed fibrils with alpha-synuclein, which may explain why they do not appear in the pathological hallmarks of PD, although they are closely related to alpha-synuclein and are also abundant in brain.

Amino Acid Sequence↗
PubMed2000

Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity.

beta(1)-integrin engagement on normal (NL) CD34(+) cells increases levels of the cyclin-dependent kinase inhibitor (cdki), p27(Kip), decreases cdk2 activity, and inhibits G(1)/S-phase progression. In contrast, beta(1)-integrin engagement on chronic myelogenous leukemia (CML) CD34(+) cells does not inhibit G(1)/S progression. We now show that, in CML, baseline p27(Kip) levels are significantly higher than in NL CD34(+) cells, but adhesion to fibronectin (FN) does not increase p27(Kip) levels. p27(Kip) mRNA levels are similar in CML and NL CD34(+) cells and remain unchanged after adhesion, suggesting posttranscriptional regulation. Despite the elevated p27(Kip) levels, cdk2 kinase activity is similar in CML and NL CD34(+) cells. In NL CD34(+) cells, >90% of p27(Kip) is located in the nucleus, where it binds to cdk2 after integrin engagement. In CML CD34(+) cells, however, >80% of p27(Kip) is located in the cytoplasm even in FN-adherent cells, and significantly less p27(Kip) is bound to cdk2. Thus, presence of BCR/ABL induces elevated levels of p27(Kip) and relocation of p27(Kip) to the cytoplasm, which contributes to the loss of integrin-mediated proliferation inhibition, characteristic of CML.

Antigens, CD34↗
PubMed2000

Determination of vitamin B12 in multivitamin tablets and fermentation medium by high-performance liquid chromatography with fluorescence detection.

A novel method for the determination of vitamin B12 by high-performance liquid chromatography with fluorescence detection is reported. The method was simple and highly sensitive with good precision. Vitamin B12 was analyzed by HPLC on a muBondapak C18 column (300x3.9 mm, 10 microm) with methanol-water (30:70) as mobile phase and fluorescence detection at 305 nm (with excitation at 275 nm). The calibration graph was linear from 1.000 to 100.0 ng ml(-1) for vitamin B12 with a correlation coefficient of 0.998 (n=6). The detection limit was 0.1 ng ml(-1). The method was successfully applied to the determination of vitamin B12 in vitamin B12 tablets, multivitamin tablets and fermentation medium. The recovery was from 94 to 102% and the relative standard deviation was in the range of 1.8 to 4.1%.

Chromatography, High Pressure Liquid↗
PubMed2000

Control of density fluctuations and electron transport in the reversed-field pinch

A recent study conducted on the Madison Symmetric Torus reversed-field pinch has shown that control of density fluctuations can be achieved through modification of the current density profile. Most of the power in the density fluctuations is directly associated with core-resonant resistive tearing modes. We report that, during auxiliary current drive experiments, these density fluctuations are reduced about an order of magnitude over the entire plasma cross section and the resulting electron confinement is increased eightfold.

Journal Article↗
PubMed2000

Comparative genomic hybridization analysis of 38 breast cancer cell lines: a basis for interpreting complementary DNA microarray data.

Breast cancer cell lines provide a useful starting point for the discovery and functional analysis of genes involved in breast cancer. Here, we studied 38 established breast cancer cell lines by comparative genomic hybridization (CGH) to determine recurrent genetic alterations and the extent to which these cell lines resemble uncultured tumors. The following chromosomal gains were observed: 8q (75%), 1q (61%), 20q (55%), 7p (44%), 3q (39%), 5p (39%), 7q (39%), 17q (33%), 1p (30%), and 20p (30%), and the most common losses were: 8p (58%), 18q (58%), 1p (42%), Xp (42%), Xq (42%), 4p (36%), 11q (36%), 18p (33%), 10q (30%), and 19p (28%). Furthermore, 35 recurrent high-level amplification sites were identified, most often involving 8q23 (37%), 20q13 (29%), 3q25-q26 (24%), 17q22-q23 (16%), 17q23-q24 (16%), 1p13 (11%), 1q32 (11%), 5p13 (11%), 5p14 (11%), 11q13 (11%), 17q12-q21 (11%), and 7q21-q22 (11%). A comparison of DNA copy number changes found in the cell lines with those reported in 17 published studies (698 tumors) of uncultured tumors revealed a substantial degree of overlap. CGH copy number profiles may facilitate identification of important new genes located at the hotspots of such chromosomal alterations. This was illustrated by analyzing expression levels of 1236 genes using cDNA microarrays in four of the cell lines. Several highly overexpressed genes (such as RCH1 at 17q23, TOPO II at 17q21-q22, as well as CAS and MYBL2 at 20q13) were involved in these recurrent DNA amplifications. In conclusion, DNA copy number profiles were generated by CGH for most of the publicly available breast cancer cell lines and were made available on a web site (http://www.nhgri.nih.gov/DIR/CGB/++ +CR2000). This should facilitate the correlative analysis of gene expression and copy number as illustrated here by the finding by cDNA microarrays of several overexpressed genes that were amplified.

Breast Neoplasms↗
PubMed2000

Endomorphin-1 and endomorphin-2 induce the expression of c-FOS immunoreactivity in the rat brain.

Using FOS immunoreactivity (FOSir) as an anatomical marker of neuronal activation, we examined the effects of intracerebroventricular (i.c.v.) injections of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in the rat brain to determine the sites of action of these two mu-opioid ligands. Radiant heat tail flick latency, as a measure of behavioral effects, was prolonged by either EM-1 or EM-2 administration. Dose-dependent EM-1- and EM-2-induced FOSir were observed in various nuclei throughout the rostral-caudal axis of the rat brain. While there was some overlap, EM-1-induced FOSir was more prevalent than EM-2. The pattern of EM-induced FOSir was similar to the distribution of EM immunoreactivity (EMir). However, some sites with little or no detectable EMir exhibited FOSir, while other nuclei with marked EMir showed only sparse FOSir. EM-induced FOSir was correlated with mu-opioid receptor location in most brain areas. However, EM-induced FOSir was absent in the caudate putamen and the accumbens nucleus, both areas of high mu-opioid receptor density.

Animals↗
PubMed2000

Molecular classification of cutaneous malignant melanoma by gene expression profiling.

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Adult↗
PubMed2000

Differential expression of a novel C-terminally truncated splice form of SMAD5 in hematopoietic stem cells and leukemia.

SMADs are evolutionarily conserved transducers of the differentiation and growth arrest signals from the transforming growth factor/BMP (TGF/BMP) family of ligands. Upon receptor activation, the ligand-restricted SMADs(1-35) are phosphorylated in the C-terminal MH2 domain and recruit the common subunit SMAD4/DPC-4 gene to the nucleus to mediate target gene expression. Frequent inactivating mutations of SMAD4, or less common somatic mutations of SMAD2 seen in solid tumors, suggest that these genes have a suppressor function. However, there have been no identified mutations of SMAD5, although the gene localizes to the critical region of loss in chromosome 5q31.1 (chromosome 5, long arm, region 3, band 1, subband 1) in myelodysplasia (MDS) and acute myelogenous leukemia (AML). A ubiquitously expressed novel isoform, SMAD5beta, encodes a 351 amino acid protein with a truncated MH2 domain and a unique C-terminal tail of 18 amino acids, which may be the functional equivalent of inactivating mutations. The levels of SMAD5beta transcripts are higher in the undifferentiated CD34(+) hematopoietic stem cells than in the terminally differentiated peripheral blood leukocytes, thereby implicating the beta form in stem cell homeostasis. Yeast 2-hybrid interaction assays reveal the lack of physical interactions between SMAD5beta and SMAD5 or SMAD4. The expression of SMAD5beta may represent a novel mechanism to protect pluripotent stem cells and malignant cells from the growth inhibitory and differentiation signals of BMPs. (Blood. 2000;95:3945-3950)

Alternative Splicing↗
PubMed2000

Selectivity of the diacylglycerol kinase inhibitor 3-[2-(4-[bis-(4-fluorophenyl)methylene]-1-piperidinyl)ethyl]-2, 3-dihydro-2-thioxo-4(1H)quinazolinone (R59949) among diacylglycerol kinase subtypes.

Diacylglycerol kinases (DGKs) attenuate diacylglycerol-induced protein kinase C activation during stimulated phosphatidylinositol turnover. This reaction also initiates phosphatidylinositol resynthesis. Two agents, 3-(2-(4-[bis-(4-fluorophenyl)methylene]-1-piperidinyl)ethyl)-2,3-dihydro -2-thioxo-4(1H)quinazolinone (R59949) and 6-(2-(4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl)ethyl)-7-m ethyl-5H-thiazolo(3,2-a)pyrimidin-5-one (R59022), inhibit diacylglycerol phosphorylation in several systems. To examine the mechanism of this effect, we developed a mixed micelle method suitable for in vitro study of DGK inhibition. Animal cells express multiple DGK isoforms. In a survey of DGK isotypes, these agents selectively inhibited Ca2+-activated DGKs. R59949 was the more selective of the two. To map the site of interaction with the enzyme, a series of DGKalpha deletion mutants were prepared and examined. Deletion of the Ca2+-binding EF hand motif, which is shared by Ca2+-activated DGKs, had no effect on inhibition. Consistent with this observation, inhibition kinetics were noncompetitive with Ca2+. A construct expressing only the catalytic domain was also inhibited by R59949. Studies of substrate kinetics demonstrated that MgATP potentiated R59949 inhibition, indicating synergy of inhibitor and MgATP binding. These results indicate that R59949 inhibits DGKalpha by binding to its catalytic domain.

3T3 Cells↗
PubMed2000

Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors.

We evaluated the effect of beta1-integrin receptor engagement on the expression and activity of cell cycle regulatory proteins in CD34(+) cells under conditions that mimic the steady-state marrow microenvironment and in the presence of supraphysiological concentrations of interleukin-3 (IL3) and stem cell factor (SCF). Adhesion of CD34(+) progenitors to fibronectin (FN) was similar whether IL3 or SCF was present or absent. Engagement of beta1-integrins blocked S-phase entry of CD34(+) cells in the absence of IL3 or SCF, whereas addition of 10 ng/mL IL3 or SCF prevented such a block in S-phase entry. In the absence of IL3 or SCF, cyclin-E levels were significantly lower and p27(KIP1) levels significantly higher in FN-adherent than in FN-nonadherent cells, or than in poly-L-lysine (PLL)-adherent or (PLL)-nonadherent cells. Cyclin-dependent-kinase (cdk)-2 activity was decreased and levels of cyclin-E-cdk2 complexes were lower in FN-adherent than in PLL-adherent cells. In contrast, cyclin-E and p27(KIP1) protein levels and cdk2 activity in cells adherent to FN in the presence of IL3 or SCF were similar to those in PLL-adherent and FN-nonadherent or PLL-nonadherent cells. In conclusion, under physiological cytokine conditions, integrin engagement prevents S-phase entrance of CD34(+) cells, which is associated with elevated levels of the contact-dependent cyclin kinase inhibitor p27(KIP1). Supraphysiological concentrations of IL3 or SCF prevent p27(KIP1) elevation and override the integrin-mediated inhibition of entry into S phase.

CDC2-CDC28 Kinases↗
PubMed2000

Complementary neural mechanisms for tracking items in human working memory.

Recognition of a specific visual target among equally familiar distracters requires neural mechanisms for tracking items in working memory. Event-related functional magnetic resonance imaging revealed evidence for two such mechanisms: (i) Enhanced neural responses, primarily in the frontal cortex, were associated with the target and were maintained across repetitions of the target. (ii) Reduced responses, primarily in the extrastriate visual cortex, were associated with stimulus repetition, regardless of whether the stimulus was a target or a distracter. These complementary neural mechanisms track the status of familiar items in working memory, allowing for the efficient recognition of a currently relevant object and rejection of irrelevant distracters.

Cerebral Cortex↗
PubMed2000

A multireflection cell for enhanced absorbance detection in microchip-based capillary electrophoresis devices.

The design, fabrication and testing of a photolithographically fabricated, glass-based multireflection absorbance cell for microfluidic devices, in particular microchip-based capillary electrophoresis (CE) systems is described. A multireflection cell was fabricated lithographically using a three-mask process to pattern aluminum mirrors above and below a flow channel in a chip, with 30 microm diameter optical entrance or exit apertures (one in each mirror) positioned 200 microm apart. Source and detector were positioned on opposite sides, and the metal mirrors were made 1 cm square, to reduce stray light effects. Calibration curves using bromothymol blue (BTB) with a 633 nm source (He:Ne laser) were linear to at least 0.5 absorbance units, with typical r2 values of 0.9997, relative standard deviations in the slopes of +/- 1.3%, and intercepts of zero within experimental error. Effective optical pathlengths of 50-272 microm were achieved, compared to single-pass pathlengths of 10-30 microm, corresponding to sensitivity enhancements (i.e., optical path length increase) of 5 to 10-fold over single-pass devices. Baseline absorbance noise varied within a factor of two in almost all devices, depending only weakly on path length. This device can give much higher absorbance sensitivity, and should be much easier to manufacture than planar, glass-based devices previously reported.

Electrophoresis, Capillary↗