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L Yang

Publications and source records attributed to L Yang.

At least 847 records · Page 47Linked to original sources
PubMedDate not supplied

Sequence diversity and haplotype structure at the human CYP3A cluster.

The four members of the human CYP3A subfamily play important roles in the clearance of xenobiotics, hormones, and environmental compounds. Many SNPs at the CYP3A locus have been characterized, with several showing large allele frequency differences across populations. In addition to the effects of CYP3A SNPs on drug metabolism, recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including hypertension and cancer. We previously showed that the CYP3A4 and CYP3A5 genes have a strong haplotype structure at varying frequencies across ethnic groups. Here, we extend our re-sequencing survey to the remaining CYP3A genes in the same cluster, CYP3A7 and CYP3A43. Our study identified a large number of SNPs in coding and conserved noncoding sequences, several of which are common. The combined data set allows us to investigate patterns of sequence variation and linkage disequilibrium at the entire CYP3A locus for use in future association studies.

Black or African American↗
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Comparative genomics analysis of human sequence variation in the UGT1A gene cluster.

Common polymorphisms within the human UGT1A gene locus are associated with irinotecan and tranilast toxicity. To uncover additional functional variation across this gene cluster, cross-species sequence comparisons were performed. Evolutionarily conserved segments (a total of 47.1 kb) were re-sequenced in 24 African-American, 24 European-American, and 24 Asian individuals, and 381 segregating sites (including 123 singletons) were identified. Highly conserved coding sites were less likely to be polymorphic than diverged sites (P<0.0001) but this pattern was not observed at non-coding sites (P=0.1025). Among coding variants, the distribution of those computationally predicted to affect function was skewed toward low frequencies. Some alleles occurred at similar frequencies in each population; others had wide disparities. Although strong linkage disequilibrium was detected among the hepatically expressed genes, the degree of linkage disequilibrium varied among populations. These results suggest that rare functional gene variants and inter-population variability must be considered in the interpretation of association studies between UGT1A and drug metabolism/toxicity phenotypes.

Animals↗
PubMedDate not supplied

Activation of latent transforming growth factor-beta1 is induced by mannose 6-phosphate/insulin-like growth factor-II receptor.

This study was conducted to further explore the mechanism of transforming growth factor beta1 (TGF-beta1) activation, which plays a critical role in many physiological and pathological conditions. We have previously shown that the large (270 kDa), but not small (40 kDa), mannose 6-phosphate receptors facilitate the cellular response to latent TGF-beta1 released from genetically modified cells. In this study, we explored the role of cell membrane associated transglutaminase and plasmin in mannose 6-phosphate receptor induced latent TGF-beta activation using MS and MS-9 cells bearing either no receptors or the 270 kDa mannose 6-phosphate/insulin-like growth factor II receptors, respectively. As a source of latent TGF-beta1, PA317 cells were transfected with either pLin-TGF-beta1 vector or pLin retroviral vector with no TGF-beta1 insert using calcium phosphate precipitation. The latency and bioactivity of TGF-beta1 in conditioned medium derived from transfected PA317 cells were evaluated by enzyme-linked immunosorbent assay and mink lung epithelial cell growth inhibition assay, respectively. The level of latent TGF-beta1 was 13-fold higher (20.1 +/- 0.4 vs. 1.5 +/- 0.03 ng/ml) in conditioned medium from pLin-TGF-beta1 transfected cells than that of control. The latency and bioactivity of TGF-beta1 released from pLin-TGF-beta1 transfected cells were confirmed by evaluation of 3H-thymidine incorporation in Mv1Lu epithelial cells treated with non- and heat-activated 10% conditioned medium. The results showed a significantly lower 3H-thymidine incorporation in Mv1Lu epithelial cells treated with heat-activated PA317 conditioned medium (4% of control) relative to those treated with either control or nonheated conditioned medium. This inhibition was abrogated by addition of 40 microg/ml of TGF-beta1 neutralizing antibody. The level of 3H-thymidine incorporation was then evaluated in MS-9 cells receiving Dulbecco's modified Eagle medium containing either 0% 10%, 30% or 50% volumes of nonactivated PA317 conditioned medium for 24 hours. The results showed a markedly lower proliferation in response to 30% and 50% conditioned medium used in MS-9 cells. Under similar experimental conditions, addition of only mannose 6-phosphate, but not fructose 6-phosphate or mannose 1-phosphate, at 1 mM concentration restored the MS-9 cell proliferative response to latent TGF-beta1. The inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation were restored by addition of either TGF-beta1 neutralizing antibody or cystamine, a transglutaminase inhibitor. In contrast, addition of aprotinin, a plasmin inhibitor, had a marginal influence on inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation. Interestingly, a mixture of latent TGF-beta1 + MS-9 cell membranes, but not MS cell membranes, also inhibited the mink lung epithelial cell proliferation (34% of control). These findings indicate that mannose 6-phosphate/insulin-like growth factor II receptors are involved in latent TGF-beta activation and that is at least partly dependent on cell membrane associated transglutaminase, but not on plasmin.

Animals↗
PubMedDate not supplied

Design and assembly of an 8 tesla whole-body MR scanner.

PURPOSE: The purpose of this report is to describe the design and construction of an 8 T/80 cm whole-body MRI system operating at 340 MHz. METHOD: The 8 T/80 cm magnet was constructed from 414 km of niobium titanium superconducting wire. The winding of this wire on four aluminum formers resulted in a total inductance of 4,155 H. Gradient subsystems included either a body gradient or a head gradient along with a removable shim insert. The magnet and gradient subsystems were interfaced to two spectrometers. These provided the control of the gradient amplifiers and the two sets of four RF power amplifiers. The latter provide in excess of 8 kW of RF power from 10 to 140 MHz and 10 kW of RF power from 245 to 345 MHz. A dedicated computer-controlled patient table was designed and assembled. The entire system is located in a clinical setting, facilitating patient-based studies. RESULTS: The 8 T/80 cm magnet was energized without complication and achieved persistent operation using 198.9 A of current, thereby storing 81.5 MJ of magnetic energy. Exceptional performance was observed for nearly all components both in isolation and when combined within the complete system. CONCLUSION: An 8 T/80 cm MRI system has been assembled. The magnet subsystem is extremely stable and is characterized by good homogeneity and acceptable boil-off rates.

Aluminum↗
PubMedDate not supplied

Dielectric resonance phenomena in ultra high field MRI.

PURPOSE: Dielectric resonances have previously been advanced as a significant cause of image degradation at higher fields. In this work, a study of dielectric resonances in ultra high field MRI is presented to explore the real importance of dielectric resonances in the human brain in this setting. METHOD: Gradient-recalled echo images were acquired using a transverse electromagnetic resonator at 1.5, 4.7, and 8 T. Images were obtained from the human head and from phantoms filled with pure water, saline, and mineral oil. In addition, an exact theoretical analysis of dielectric resonances is presented for a spherical phantom and for a model of the human head. RESULTS: Theoretical results demonstrate that distilled water can sustain dielectric resonances in head-sized spheres near 200 and 360 MHz, but the presence of significant conductivity suppresses these resonances. These findings are confirmed experimentally with proton images of water and saline (0.05 and 0.125 M NaCl). For lossy phantoms, coupling between the source and phantom overwhelms the dielectric resonance. Because of their low relative permittivity, mineral oil phantoms with 20 cm diameter do not exhibit dielectric resonances below approximately 900 MHz. Significant dielectric resonances were not observed in human head images obtained at 1.5, 4.7, and 8 T.

Algorithms↗
PubMedDate not supplied

Caffeine, mental stress, and risk for hypertension: a cross-cultural replication.

Separate and combined effects of caffeine and mental arithmetic stress on systolic blood pressure (SBP) and heart rate (HR) were assessed in a double-blind, placebo-controlled study. Thirty-six Chinese nationals, half with and half without a family history of hypertension, received either 0, 125, or 250 mg of caffeine in three separate experimental sessions, each preceded by a 12-hour abstention from caffeine consumption. Caffeine and mental stress elevated SBP, but caffeine did not potentiate the SBP response to mental stress. Caffeine did not affect HR. A positive family history of hypertension was associated with larger SBP elevations to the higher dose of caffeine. Family history of hypertension was associated with larger blood pressure elevations during mental stress, but only under conditions of high-level stimulation provided by the initial exposure to the stress. These results support previous findings of greater cardiovascular reactivity to laboratory stress in individuals at high risk for hypertension.

Adult↗
PubMedDate not supplied

Effects of all-trans-retinoic acid on human esophageal carcinoma cells and their nuclear matrices.

Esophageal cancer is a common cancer among ethnic Chinese. The reported incidence of esophageal cancer has increased many fold in the past decades and is apparently still rising. Nuclear matrix forms the scaffold of the nucleus and participates in various nuclear functions. Cancer specific nuclear matrix proteins have been identified in several tumor systems. 2-D gel analysis shows the presence of novel nuclear matrix proteins in ATRA treated tumor cells and these proteins are cell line specific. Our preliminary study also shows ATRA altered the nuclear matrix density of tumor cells. The significance of these nuclear matrix proteins is discussed.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of a cell differentiation inducer, ganglioside GM3, on the neutral glycosphingolipid composition and cell membrane fluidity of a human promyelocytic leukemia cell line HL-60.

In this paper the authors confirmed the finding reported by Nojiri et al that exogenous ganglioside GM3 could induce HL-60 cells to differentiate along the monocytic-macrophage route with significant inhibition of proliferation. It was found that after differentiation the neutral GSL content of CDH and CMH increased, while that of CXH, a polyhexosyl ceramide with a TLC mobility slower than CQH, decreased significantly. The membrane fluidity of HL-60 cells decreased after GM3 treatment.

Cell Differentiation↗
PubMedDate not supplied

An immuno-electron microscopic study on the relationship between nuclear matrix and DNA in rat spermatocytes.

The nucleus of the mammalian spermatid undergoes a series of changes in its chromatin and nucleoprotein composition during transport from testis to epididymis. The sperm DNA is very tightly packaged by protamines instead of histones in somatic cells. However, the nuclear matrix and its association with DNA have not yet been definitively scrutinized with the electron microscope. The present study reveals that the protamine-depleted sperm nuclear matrix appears as a network of thick and thin filaments with glodular structures attached the these fibers. Monoclonal antibody to single- and doublestranded DNA was used to localize remnant DNA after extraction. By immunofluorescence microscopy, monoclonal antibody against DNA was localized outside the nucleus as a halo. Immuno-electron microscopy showed that gold particles were mainly associated with nuclear matrix surrounding the sperm head. Our results suggest a specific structural organization of sperm DNA with its matrix.

Animals↗
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Ultrastructural study on the development of the rat [correction of mouse] spermatocyte nuclear matrix during epididymal maturation.

The rat sperm nucleus, after sequential extraction with detergents, nuclease and ammonium sulfate, consists of a skeletal structure that resembles the original nuclear shape. This chromatin-depleted skeleton is formed by thick and thin fibers as well as globular structures of different sizes. These fibers form anastomosis. The sperm nuclei obtained from testis and caput epididymis exhibits a loose fibrous network with thin fibers at the center. The entire nucleus of the sperm in the caudal epididymis is formed by a dense network of thick and thin fibers. These highly branched matrix fibers had diameters of 35 and 12 nm. It is concluded that the increase in density of the matrix fibers is related to the condensation of the chromatin in the maturation of the spermatozoa.

Animals↗
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Fine structural observation of a nucleolar-nuclear matrix-lamina-intermediate filament system in transformed cells.

The nuclear matrix is a nonchromatin structure of the nucleus normally concealed by a much larger mass of chromatin. Several methods have been developed to remove chromatin from nucleus while preserving the underlying matrix architecture to some degree. The present study showed that after extraction of PtK2 cells and cervical carcinoma cells (CC3) with Triton X-100, ammonium sulfate and DNase, the nucleolar-nuclear matrix-intermediate filament (Nu-Nm-L-IF) network remained. The nucleolus was oval in shape and appeared as a fibrillar mass with an accentric dense fibrillar centre. This nucleolar skeleton was in direct connection with the nuclear matrix which in turn is connected with cytoplasmic intermediate filaments by lamins. It is concluded from these observations that the Nu-NM-L-IF system forms a continuous system which plays an important role in the maintenance of the nucleolar, nuclear and cytoplasmic integrity and cellular function.

Animals↗
PubMedDate not supplied

Electron microscopic analysis of the relationship between nuclear matrix stability and cell differentiation.

Two cell lines, the less differentiated CC2/CUHK2 and the more differentiated CC3/CUHKE3, were used to study the difference in nuclear matrix stability against DNase 1 digestion. The nuclear matrix was almost totally extracted when the CC3/CUHK3 cells were digested with 100 micrograms/ml DNase 1, while that of the CC2/CUHK2 cells was still present even when 200 micrograms/ml DNase 1 was used. It is suggested that more differentiated cells have a less stable nuclear matrix while the less differentiated ones have a more stable nuclear matrix. The same phenomenon was also observed in normal human and rat cervical epithelia. The nuclear matrix of the poorly differentiated basal cells was more stable than that of the more differentiated superficial cells. This cell differentiation stage dependent stability of the nuclear matrix is probably related to the nuclear activity and gene expression.

Animals↗
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Adaptation of inner medullary collecting duct vacuolar H-adenosine triphosphatase to chronic acid or alkali loads in the rat.

Acidosis increases and alkalosis decreases proton secretion in the inner medullary collecting duct (IMCD). We examined the mechanism of this adaptation by studying the immunocytochemical distribution of the vacuolar H-adenosine triphosphatase (ATPase) in the IMCD from rats subjected to acid or alkali loads for a mean duration of 4 and 9 days. For immunocytochemical staining, a monoclonal antibody to the 31-kD subunit of the bovine kidney vacuolar H-ATPase was used. Intercalated cells were present only in the initial IMCD, and the principal cells and IMCD cells showed no appreciable H-ATPase staining under any experimental conditions. We found significant adaptive changes in the distribution of H-ATPase in the intercalated cells of the IMCD. H-ATPase staining in acid-loaded rats shifted from cytoplasmic vesicles to apical plasma membrane, whereas in alkali-loaded rats cytoplasmic vesicular staining was enhanced and staining of plasma membrane disappeared. These adaptive changes were most prominent on day 4 of acid-loaded and days 4 and 9 of alkali-loaded rats. Our results indicate that translocation of the H-ATPase pump between cytoplasmic vesicles and apical plasma membrane of the intercalated cells is an important mechanism is adaptation of the IMCD to chronic acid base perturbations.

Acidosis↗
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Stereo- and regioselective N- and S-oxidation of tertiary amines and sulfides in the presence of adult human liver microsomes.

Adult human liver microsomes supplemented with NADPH catalyzed the regioselective N-oxygenation of the aliphatic tertiary amine and S-oxidation of the phenothiazine sulfur atom of several 10-(N,N-dimethylaminoalkyl)phenothiazines. In addition, (+)- and (-)-4-bromophenyl-1,3-oxathiolane were converted to the corresponding S-oxides in the presence of NADPH and adult human liver microsomes. The (+) and (-) enantiomers of 4-bromophenyl-1,3-oxathiolane were converted to the S-oxides with low and high stereoselectivity, respectively. Studies on the biochemical mechanism for N-oxygenation of 10-(N,N-dimethylaminoalkyl)phenothiazines suggested that this reaction was catalyzed by the flavin-containing monooxygenase (form II), although cytochrome P-450 2D6 may also have contributed to N-oxide formation. S-Oxidation of chlorpromazine was catalyzed mainly by cytochrome P-450 3A. S-Oxidation of 10-(N,N-dimethylaminoalkyl)phenothiazines was catalyzed by a number of cytochromes P-450, including cytochromes P-450 2A6, 2C8, and 2D6. S-Oxygenation of (+)-4-bromophenyl-1,3-oxathiolane produced a mixture of the cis- and trans diastereomers in a process probably dependent on both hepatic monooxygenase systems. (-)-4-Bromophenyl-1,3-oxathiolane was converted almost exclusively to the trans-S-oxide in a process likely dependent on the adult human liver flavin-containing monooxygenase (form II). Development of regio- and stereochemical probes of adult human liver flavin-containing monooxygenase (form II) and cytochromes P-450 activity may be useful for eventual in vitro-in vivo correlations, but may require approaches quite distinct from that currently used for animal monooxygenases.

Adolescent↗
PubMedDate not supplied

Microwave fixation of nuclear matrix in tumor cells.

Microwave irradiation provides good fixation of human and animal tissues for light and electron microscopy. In this study, microwave irradiation was used for the fixation of cytoplasmic and nuclear matrix in tumor cells. The nuclear matrix appears well preserved and exhibits a network formed by thick and thin filaments. Hence microwave fixation can be used as a quick and effective method for the study of the morphology of nuclear matrix.

Animals↗
PubMedDate not supplied

Fine structural observations on the human sperm nuclear matrix.

The nucleus of the mammalian sperm is formed after a series of morphological and biochemical changes during spermatogenesis. The human sperm nucleus, after sequential extraction with detergents, nuclease and ammonium sulfate, consists of a fibroskeletal structure which maintains the original nuclear shape. The chromatin-depleted skeleton is formed by thick and thin fibers as well as electron-dense patches of different sizes. These highly branched matrix fibers had average diameters of 35 and 12 nm. Polarization of the fibroskeletal structure is apparent and can be used as a good model to study the function of nuclear matrix in nuclear compartmentation in germ cells.

Chromatin↗