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Biomedical subjects

C Yang

Publications and source records attributed to C Yang.

At least 55 records · Page 3Linked to original sources
PubMed2002

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis.

The aim of this study was to investigate whether systemic tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (p55, p75), interleukin 6 (IL-6), and soluble IL-6 receptor could be markers of biological activities of coal workers' pneumoconiosis (CWP). The study population was composed of 182 Chinese retired coal miners who had similar dust exposure histories. Among them, 71 were cases with CWP and 111 were controls. Chest radiographs were classified according to International Labour Organization Criteria (ILO, 1980). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Serum concentrations of TNF-alpha, TNF-alpha receptors (p55, p75), IL-6, and IL-6 receptor were measured by ELISA techniques. Mean serum levels of p55, p75 and IL-6 were significantly higher in cases than in controls (P < or = 0.01 for each comparison by crude analyses). Results from logistic regression models, adjusted for age, dust exposure variables, and smoking habits, found similar associations between soluble p55 and p75 levels and the presence of CWP. Linear regression analysis revealed that CWP radiographic stage (by ILO criteria) was significantly correlated with the individual serum concentrations of p55, p75 and IL-6. Serum concentrations of all measured cytokines were notcorrelated to age, dust exposure, or smoking, but there were correlations between soluble p75 and p55 levels, and between p75 and IL-6 levels. The results of this study suggest that serum levels of TNF receptors and IL-6 are associated with the fibrotic process of CWP and serum cytokine levels may be correlated with the severity of CWP.

Aged↗
PubMed2002

ProSeal versus the Classic laryngeal mask airway for positive pressure ventilation during laparoscopic cholecystectomy.

BACKGROUND: We tested the hypothesis that the ProSeal laryngeal mask airway (PLMA) is a more effective ventilatory device than the Classic laryngeal mask airway (LMA) for laparoscopic cholecystectomy. METHODS: Eighty anaesthetized, paralyzed patients (ASA 1-2, aged 18-80 yr) were randomly allocated for airway management with the PLMA or LMA. Ease of insertion and efficacy of seal were determined. Peak airway pressures were recorded immediately before and after carboperitoneum to 2.0 kPa. The inspired oxygen concentration and/or the ventilatory variable were adjusted according to a protocol to maintain SpO2 > or = 95% and E'CO2 < 6.0 kPa. Oxygenation was considered suboptimal if SpO2 fell to 94-90% and failed if SpO2 was < 90%. Ventilation was considered suboptimal if E'CO2 was > 6.0-7.3 kPa and failed if E'CO2 was > 7.3 kPa. RESULTS: First-time insertion success rates were higher for the LMA (40/40 vs 33/40; P = 0.02). Seven patients required two attempts with the PLMA. Oropharyngeal leak pressure was higher for the PLMA [29 (SD 6) vs 19 (4) cm H2O; P < 0.001]. There was a similar, significant increase in peak airway pressure after carboperitoneum for both devices (P < 0.001). Before carboperitoneum, oxygenation and ventilation were optimal in all patients in both groups. After carboperitoneum, oxygenation was optimal in all patients in both groups, but ventilation was suboptimal more frequently with the LMA (8 vs 0; P = 0.01). In three of these eight patients, ventilation failed but was subsequently optimal with the PLMA. CONCLUSION: The PLMA is a more effective ventilatory device for laparoscopic cholecystectomy than the LMA. We do not recommend the use of the LMA for laparoscopic cholecystectomy.

Adolescent↗
PubMed2001

Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution.

A coordinated growth arrest during mammary involution completes the dramatic changes in mammary cell proliferation seen during pregnancy and lactation. Signals regulating this arrest are poorly understood, despite their potential relevance to oncogenesis. Here we report that the arrest involves a unique pulse of p16(INK4A) expression in vivo, which accompanies decreased cyclin D1 expression and a shift to an active repressor E2F4 complex. We used INK4A/ARF-/- mice as well as cyclin D1 and p16(INK4A) transgenic strains to examine the physiological significance of these patterns. p16(INK4A) directly regulated the in vivo transition from E2F3 to E2F4 as the major E2F DNA binding activity, and its contribution to growth arrest was independent of cyclin D1. Transgenic cyclin D1 expression prevented normal terminal differentiation by ablating the p16(INK4A) pulse, abolishing the shift from E2F3 to E2F4, derepressing E2F target genes, and expanding a stem cell population. The effects of cyclin D1 were reversed by restoring p16(INK4A) but were not seen in INK4A/ARF-/- mice. Our results indicate that cyclin D1 may contribute to tumorigenesis by altering cell differentiation and demonstrate a significant function for p16(INK4A) in development in vivo. These regulatory mechanisms used during mammary involution offer a potential explanation for the protective effect of pregnancy against breast cancer.

3T3 Cells↗
PubMed2001

Thrombocytopenia caused by the development of antibodies to thrombopoietin.

Thrombocytopenia developed in some individuals treated with a recombinant thrombopoietin (TPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Three of the subjects who developed severe thrombocytopenia were analyzed in detail to determine the cause of their thrombocytopenia. Except for easy bruising and heavy menses, none of these subjects had major bleeding episodes; none responded to intravenous immunoglobulin or prednisone. Bone marrow examination revealed a marked reduction in megakaryocytes. All 3 thrombocytopenic subjects had antibody to PEG-rHuMGDF that cross-reacted with endogenous TPO and neutralized its biological activity. All anti-TPO antibodies were immunoglobulin G (IgG), with increased amounts of IgG4; no IgM antibodies to TPO were detected at any time. A quantitative assay for IgG antibody to TPO was developed and showed that the antibody concentration varied inversely with the platelet count. Anti-TPO antibody recognized epitopes located in the first 163 amino acids of TPO and prevented TPO from binding to its receptor. In 2 subjects, endogenous TPO levels were elevated, but the TPO circulated as a biologically inactive immune complex with anti-TPO IgG; the endogenous TPO in these complexes had an apparent molecular weight of 95 000, slightly larger than the full-length recombinant TPO. None of the subjects had atypical HLA or platelet antigens, and the TPO cDNA was normal in both that were sequenced. Treatment of one subject with cyclosporine eliminated the antibody and normalized the platelet count. These data demonstrate a new mechanism for thrombocytopenia in which antibody develops to TPO; because endogenous TPO is produced constitutively, thrombocytopenia ensues.

Adult↗
PubMed2001

The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum.

gp78, also known as the tumor autocrine motility factor receptor, is a transmembrane protein whose expression is correlated with tumor metastasis. We establish that gp78 is a RING finger-dependent ubiquitin protein ligase (E3) of the endoplasmic reticulum (ER). Consistent with this, gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate. In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD3-delta. gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis.

Animals↗
PubMed2001

Bidirectional regulation of mitochondrial gene expression during developmental neuroplasticity of visual cortex.

The first several months of life are a critical period for neuronal plasticity in the visual cortex, during which anatomical and physiological development depends upon visual experience. Rearing in darkness slows the time course of this critical period, such that at 5 weeks normal cats are more plastic than dark-reared cats, while at 20 weeks dark-reared cats are more plastic. This study reports the identification of a subset of mitochondrial genes that are regulated in this manner. Opponent patterns of bidirectional expression were found: several genes (ATPase 6, cytochrome b, NADH dehydrogenase subunits 4 and 2) showed elevation in normal cats at 5 weeks and in dark-reared cats at 20 weeks ("plasticity" genes); others (NADH dehydrogenase subunits 3 and 5) showed the opposite ("anti-plasticity" genes). These findings add a new dimension to the growing evidence that changes in mitochondrial gene expression are involved in the neuroplastic response.

Adenosine Triphosphatases↗
PubMed2001

Mpl ligand prevents lethal myelosuppression by inhibiting p53-dependent apoptosis.

A single dose of Mpl ligand (Mpl-L) given immediately after lethal DNA-damaging regimens prevents the death of mice. However, the mechanism of this myeloprotection is unknown. The induction of p53-dependent apoptosis in response to DNA damage signals suggests that immediate administration of Mpl-L may inhibit p53-dependent apoptosis. This hypothesis was tested by administering a single injection of pegylated murine Megakaryocyte Growth and Development Factor (PEG-rmMGDF, a truncated recombinant Mpl-L) to p53(-/-) and wild-type mice immediately after carboplatin (80 mg/kg) and 7.5 Gy total body gamma-irradiation. PEG-rmMGDF was required to prevent the death of wild-type mice, whereas p53(-/-) mice survived with or without the exogenous cytokine. The degree of platelet depression and subsequent recovery was comparable in p53(-/-) mice to wild-type animals given PEG-rmMGDF. Hence, either Mpl-L administration or p53-deficiency protected multipotent hematopoietic progenitors and committed megakaryocyte precursors. The myelosuppressive regimen induced expression of p53 and the p53 target, p21(Cipl) in wild-type bone marrow, indicating that Mpl-L acts downstream of p53 to prevent apoptosis. Constitutive expression of the proapoptotic protein Bax, was not further increased. Bax(-/-) mice survived the lethal regimen only when given PEG-rmMGDF; however, these Bax(-/-) mice showed more rapid hematopoietic recovery than did identically-treated wild-type mice. Therefore, administration of Mpl-L immediately after myelosuppressive chemotherapy or preparatory regimens for autologous bone marrow transplantation should prevent p53-dependent apoptosis, decrease myelosuppression, and reduce the need for platelet transfusions.

Animals↗
PubMed2001

The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response.

We have previously shown that specific RNA-binding proteins (RBP) are activated by genotoxic stress. The role and function of these stress-activated RBP are, however, poorly understood. The data presented here indicate that the RBP A18 heterogeneous ribonucleoprotein (hnRNP) is induced and translocated from the nuclei to the cytoplasm after exposure to UV radiation. Using a new in vitro system we identified potential cellular targets for A18 hnRNP. Forty-six mRNA transcripts were identified, most of which are stress- or UV-responsive genes. Two important stress-responsive transcripts, the replication protein A (RPA2) and thioredoxin, were studied in more detail. Northwestern analyses indicate that A18 hnRNP binds specifically to the 3'-untranslated region of RPA2 transcript independently of its poly(A) tail, whereas the poly(A) tail of thioredoxin mRNA reinforces binding. Overexpression of A18 hnRNP increases the mRNAs stability and consequently enhances translation in a dose-dependent manner. Moreover, cell lines expressing reduced levels of A18 hnRNP are more sensitive to UV radiation. These data suggest that A18 hnRNP plays a protective role against genotoxic stresses by translocating to the cytosol and stabilizing specific transcripts involved in cell survival.

3' Untranslated Regions↗
PubMed2001

Applications of anomalous scattering from S atoms for improved phasing of protein diffraction data collected at Cu Kalpha wavelength.

The anomalous signal of S atoms is easily detected at the Cu Kalpha wavelength of a non-synchrotron source with current data-collection methods. The position of sulfur and other anomalous scatterers can be located through an anomalous difference Fourier map (F+ - F-, phi(calc) - 90 degrees). It has been discovered experimentally that even low-quality preliminary phases are often sufficient to find anomalous scatterers. Their anomalous signal in the native crystal can contribute to significant improvement in phase refinement. This technique has been applied to solve the crystal structures of orthorhombic lysozyme and thaumatin. Furthermore, the structure of trypsin was solved using only the diffraction data set from a native crystal collected at a single wavelength (Cu Kalpha) from a rotating-anode X-ray generator. The anomalous scattering of sulfur was essential to solve the structure of trypsin which was initially phased from a single intrinsic Ca2+ atom. The positions of the S atoms of lysozyme and thaumatin were found using the initial SIRAS phases and used in phase refinement. The overall figures of merit and those in each resolution shell were consistently improved. This resulted in much improved electron-density maps even when the diffraction data were limited to 2.5 A resolution or worse. Furthermore, peaks from S atoms and other anomalous scatterers in anomalous difference Fourier maps can confirm the tracing of the peptide chain and also provide independent unbiased confirmation of molecular-replacement results. Thus, the anomalous signal of S atoms can contribute to many aspects of solving protein structures and should be used routinely.

Fourier Analysis↗
PubMed2001

Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells.

The topoisomerase II inhibitors teniposide (VM-26), doxorubicin, and amsacrine (m-AMSA), as well as ionizing radiation, induce a transient suppression of c-myc mRNA, which correlates with growth inhibition of MCF-7 breast tumor cells. To further assess the involvement of c-mvc in the DNA damage-induced signal transduction pathways of the breast tumor cell, we determined the influence of sustained DNA damage on c-myc expression, c-Myc protein levels and c-Myc function. Continuous exposure of MCF-7 breast tumor cells to VM-26 induced DNA strand breaks that were sustained for at least 9 hr. DNA strand breakage was accompanied by a decline in c-myc transcripts and c-Myc protein levels by >90% after VM-26 exposure for 24 hr. The activity of a transcriptional target of the c-Myc protein, ornithine decarboxylase, was reduced by approximately 75% within 9 hr of DNA damage, in parallel to the declines in c-myc mRNA and protein levels. Extended exposure to VM-26 resulted in an initial loss of approximately 35% of the cell population followed by the death of additional cells such that by 72 hr only 50% of the cells were viable. Although apoptosis was evident 72 hr after initiating drug exposure [based on cell cycle analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and an assessment of cell morphology], the primary phase of cell killing, which occurred during the first 24 hr was non-apoptotic. These studies indicate that non-apoptotic pathways can also mediate cell death in the breast tumor cell and support the role of c-myc expression, c-Myc protein, and c-Myc function as elements of the DNA damage response pathway in the breast tumor cell.

Antineoplastic Agents↗
PubMed2001

Segregation of human neural stem cells in the developing primate forebrain.

Many central nervous system regions at all stages of life contain neural stem cells (NSCs). We explored how these disparate NSC pools might emerge. A traceable clone of human NSCs was implanted intraventricularly to allow its integration into cerebral germinal zones of Old World monkey fetuses. The NSCs distributed into two subpopulations: One contributed to corticogenesis by migrating along radial glia to temporally appropriate layers of the cortical plate and differentiating into lamina-appropriate neurons or glia; the other remained undifferentiated and contributed to a secondary germinal zone (the subventricular zone) with occasional members interspersed throughout brain parenchyma. An early neurogenetic program allocates the progeny of NSCs either immediately for organogenesis or to undifferentiated pools for later use in the "postdevelopmental" brain.

Animals↗
PubMed2001

Antibodies in haystacks: how selection strategy influences the outcome of selection from molecular diversity libraries.

Antibodies against most antigens can be isolated from high quality phage antibody libraries. However, not all antibodies binding a particular antigen are necessarily found when standard selections are performed. Here we investigate the effect of two different selection strategies on the isolation of antibodies against a number of different antigens, and find that these different strategies tend to select different antibodies, with little overlap between them. This indicates that the full diversity of these libraries is not tapped by a single selection strategy and that each selection strategy imposes different selective criteria in addition to that of antigen binding. To fully exploit such libraries, therefore, many different selection strategies should probably be employed for each antigen. The use of alternative strategies should be considered when selection apparently fails, or when the number of different antibodies recognizing an antigen needs to be maximised. Furthermore, the microtitre selection strategy developed is likely to prove useful in the application of phage antibody libraries to the human genome project, allowing the high throughput selection of antibodies against multiple antigens simultaneously.

Antibodies↗
PubMed2001

Highly efficient Heck reactions of aryl bromides with n-butyl acrylate mediated by a palladium/phosphine-imidazolium salt system.

[reaction: see text] A new phosphine-imidazolium salt, L.HBr (1, L = (1-ethylenediphenylphosphino-3-(mesityl))imidazol-2-ylidene), has been prepared. A combination of 0.5 mol % of Pd(dba)(2) and 0.5 mol % of L.HBr in the presence of 2 equiv of Cs(2)CO(3) as base has proven to be highly efficient in the Heck coupling reactions of aryl bromides (from electron-deficient to electron-rich aryl bromides) with n-butyl acrylate.

Journal Article↗
PubMed2001

Molecular basis for the constitutive activity of estrogen-related receptor alpha-1.

Some orphan nuclear receptors, including estrogen-related receptor alpha-1 (ERRalpha-1), can activate gene transcription in a constitutive manner. Little is known about the molecular basis of the constitutive activity of these receptors. Our results from site-directed mutagenesis experiments have revealed that Phe-329 (analogous to Ala-350 in estrogen receptor alpha (ERalpha)) is responsible for the constitutive activity of ERRalpha-1. The ERRalpha-1 mutant F329A lost the transactivation activity and acted as a dominant negative mutant. The mammalian cell transfection experiments revealed that the ERRalpha-1 mutant F329A, like wild-type ERalpha, recognized toxaphene (an organochlorine pesticide) as an agonist. This compound was previously shown to be an antagonist of wild-type ERRalpha-1. On the other hand, like wild-type ERRalpha-1, the ERalpha mutant A350F was found to be constitutively active (as demonstrated by mammalian cell transfection and yeast two-hybrid assays). These results indicate that Phe-329 in ERRalpha-1 and Ala-350 in ERalpha play important roles in both ligand binding and transactivation function.

Alanine↗
PubMed2001

Dechlorination of polychlorobiphenyls using NaBH(4) and NaBH(4)/LiCl at 120-310 degrees C in glyme solvents.

High temperature PCB dechlorination (Aroclor 1016) occurred using NaBH(4) alone in tetraglyme at 290-310 degrees C within 2h in a sealed tube. Aroclor 1016 dechlorination was also quantitatively achieved using NaBH(4)/LiCl/glyme solvents (di-, tri-, or tetraglyme) at 125-135 degrees C. The best results were obtained by prestirring NaBH(4), LiCl and the glyme solvent at room temperature before heating at 125-135 degrees C. At equivalent conditions, PCB dechlorination rates were found to depend on solvent in the order: tetraglyme>triglyme>diglyme. At 130 degrees C, Aroclor 1016 can be dechlorinated in NaBH(4)/LiCl/tetraglyme in 4h. 2-Chlorobiphenyl and 2,2'-dichlorobiphenyl were the least reactive congeners in dechlorinations with NaBH(4)/LiCl in diglyme. Competitive dechlorinations with NaBH(4)/LiCl in diglyme showed 3-chloro- and 4-chlorobiphenyl reacted faster than 2-chlorobiphenyl at 130 degrees C. The reactions were clean with no solvent decomposition in the range of 120-162 degrees C.

Borohydrides↗