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1.
Sci Rep ; 7(1): 14635, 2017 11 07.
Article in English | MEDLINE | ID: mdl-29116130

ABSTRACT

Silicon Carbide (SiC) is a promising cladding material for accident-tolerant fuel in light water reactors due to its excellent resistance to chemical attacks at high temperatures, which can prevent severe accident-induced environmental disasters. Although it has been known for decades that radiation-induced swelling at low temperatures is driven by the formation of black spot defects with sizes smaller than 2 nm in irradiated SiC, the structure of these defect clusters and the mechanism of lattice expansion have not been clarified and remain as one of the most important scientific issues in nuclear materials research. Here we report the atomic configuration of defect clusters using Cs-corrected transmission electron microscopy and molecular dynamics to determine the mechanism of these defects to radiation swelling. This study also provides compelling evidence that irradiation-induced point defect clusters are vacancy-rich clusters and lattice expansion results from the homogenous distribution of unrecovered interstitials in the material.

2.
Vox Sang ; 110(3): 236-43, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26528880

ABSTRACT

BACKGROUND: New CD36 mutations are constantly being identified, although no study has specifically targeted a Taiwanese population. CD36 deficiency can result in dyslipid state and slow clearance of chylomicron. This could be linked to more frequent lipemic donations. STUDY DESIGN AND METHODS: We used flow cytometric methods to study the CD36 deficiency in 640 regular volunteer platelet apheresis donors from Taipei blood centre. The coding exons of CD36 gene were sequenced in CD36-deficient individuals, and the allele frequencies of CD36 variants were determined in the larger population by mutation-specific PCR and oligonucleotide hybridization. Visual inspection of lipemic plasma was routinely performed on samples taken before commencement of apheresis. Individuals found to have lipemic plasma are deferred until next donation. We investigated the link between positive lipemic deferral record and low platelet CD36 expression status. RESULTS: We found four donors (0·6%) with type I CD36 deficiency (both platelets and monocytes CD36(null) ) and six (1·0%) with type II CD36 deficiency (PLT: CD36(null) , monocyte: CD36(low) ). Six CD36 genetic variants were identified, two of them were novel, all but one are found exclusively in CD36(null) and CD36(low) expressors. Subjects with CD36 genetic variants also displayed deficient or reduced CD36 on monocytes. Donors with null or low PLT CD36 expression were more likely to have a lipemic deferral record than control subjects with normal PLT CD36 expression (X(2) = 27·36, odds ratio = 2·6, 95% conference interval: 1·8-3·8, P < 0·0001). CONCLUSION: Through this study, we established a donor registry to supply CD36-negative platelets for patients in need.


Subject(s)
Asian People/genetics , Blood Platelet Disorders/pathology , Blood Platelets/metabolism , CD36 Antigens/genetics , Genetic Diseases, Inborn/pathology , Lipids/blood , Blood Donors , Blood Platelet Disorders/blood , Blood Platelet Disorders/epidemiology , CD36 Antigens/metabolism , Exons , Female , Flow Cytometry , Gene Frequency , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/epidemiology , Humans , Male , Monocytes/metabolism , Plateletpheresis , Polymerase Chain Reaction , Polymorphism, Genetic , Risk Factors , Taiwan/epidemiology
3.
Opt Express ; 20 Suppl 2: A213-8, 2012 Mar 12.
Article in English | MEDLINE | ID: mdl-22418670

ABSTRACT

We show that it is possible to produce an efficient solution-processable phosphorescent poly(dendrimer) OLED with a 32 lm/W power efficiency at 100 cd/m2 without using a charge transporting host or any improvements in light extraction. This is achieved by using the dendrimer architecture to control inter-chromophore interactions. The effects of using 4,4',4″-tris(N-carbazolyl)triphenylamine (TCTA) as a charge transporting host and using a double dendron structure to further reduce inter-chromophore interactions are also reported.

4.
Inorg Chem ; 51(5): 2821-31, 2012 Mar 05.
Article in English | MEDLINE | ID: mdl-22339288

ABSTRACT

We use a combination of low temperature, high field magnetic circular dichroism, absorption, and emission spectroscopy with relativistic time-dependent density functional calculations to reveal a subtle interplay between the effects of chemical substitution and spin-orbit coupling (SOC) in a family of iridium(III) complexes. Fluorination at the ortho and para positions of the phenyl group of fac-tris(1-methyl-5-phenyl-3-n-propyl-[1,2,4]triazolyl)iridium(III) cause changes that are independent of whether the other position is fluorinated or protonated. This is demonstrated by a simple linear relationship found for a range of measured and calculated properties of these complexes. Further, we show that the phosphorescent radiative rate, k(r), is determined by the degree to which SOC is able to hybridize T(1) to S(3) and that k(r) is proportional to the inverse fourth power of the energy gap between these excitations. We show that fluorination in the para position leads to a much larger increase of the energy gap than fluorination at the ortho position. Theory is used to trace this back to the fact that fluorination at the para position increases the difference in electron density between the phenyl and triazolyl groups, which distorts the complex further from octahedral symmetry, and increases the energy separation between the highest occupied molecular orbital (HOMO) and the HOMO-1. This provides a new design criterion for phosphorescent iridium(III) complexes for organic optoelectronic applications. In contrast, the nonradiative rate is greatly enhanced by fluorination at the ortho position. This may be connected to a significant redistribution of spectral weight. We also show that the lowest energy excitation, 1A, has almost no oscillator strength; therefore, the second lowest excitation, 2E, is the dominant emissive state at room temperature. Nevertheless the mirror image rule between absorption and emission is obeyed, as 2E is responsible for both absorption and emission at all but very low (<10 K) temperatures.

5.
Neuroscience ; 190: 301-6, 2011 Sep 08.
Article in English | MEDLINE | ID: mdl-21712070

ABSTRACT

Apoptosis, or programmed cell death, resulting from cerebral ischemia may be related to decreased levels of anti-apoptotic factors, such as serine/threonine kinase (Akt), phosphorylated Akt (pAkt), pBAD, and Bcl-2, and increased levels of pro-apoptotic factors, such as BAD, caspase 9, and caspase 3 activities. In this study, we investigated the effects of low-energy laser (660 nm) irradiation (LLI) on the levels and activity of various anti- and pro-apoptotic factors following ischemia. Transient cerebral ischemia was induced in Sprague-Dawley rats by unilateral occlusion of the middle cerebral artery for 1 h, followed by reperfusion. LLI was then directed on the cerebrum for varying lengths of duration (1, 5, or 10 min at an energy density of 2.64 J/cm², 13.2 J/cm², and 24.6 J/cm², respectively). The expression levels of Akt, pAkt, BAD, pBAD, Bcl-2, caspase 9, and caspase 3 activities were measured 4 days after injury. The levels of Akt, pAkt, Bcl-2, and pBAD were significantly increased following laser irradiation. In addition, LLI significantly decreased caspase 9 and caspase 3 activities caused by ischemia-reperfusion. LLI may protect the brain by upregulating Akt, pAkt, pBAD, and Bcl-2 expression and downregulating caspase 9 and caspase 3 expression following transient cerebral ischemia. This modality is a promising protective therapeutic intervention after strokes or other ischemic events.


Subject(s)
Apoptosis/radiation effects , Ischemic Attack, Transient/radiotherapy , Low-Level Light Therapy , Animals , Caspase 3/metabolism , Ischemic Attack, Transient/metabolism , Ischemic Attack, Transient/pathology , Male , Phosphorylation/radiation effects , Pilot Projects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , bcl-Associated Death Protein/metabolism
6.
Chemosphere ; 82(7): 1038-43, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21075414

ABSTRACT

To study the influence of mariculture on mercury (Hg) speciation and distribution in sediments and cultured fish around Hong Kong and adjacent mainland China waters, sediment samples were collected from six mariculture sites and the corresponding reference sites, 200-300 m away from the mariculture sites. Mariculture activities increased total mercury, organic matter, carbon, nitrogen and sulfur concentrations in the surface sediments underneath mariculture sites, possibly due to the accumulation of unconsumed fish feed and fish excretion. However, methylmercury (MeHg) concentrations and the ratio of MeHg to THg (% MeHg) in sediments underneath mariculture sites were lower than the corresponding reference sites. The % MeHg in sediments was negatively correlated (r = -0.579, p < 0.05) with organic matter (OM) content among all sites, indicating that OM may have inhibited Hg methylation in surface sediments. Three mariculture fish species were collected from each mariculture site, including red snapper (Lutjanus campechanus), orange-spotted grouper (Epinephelus coioides) and snubnose pompano (Trachinotus blochii). The average MeHg concentration in fish muscle was 75 µg kg⁻¹ (wet weight), and the dietary intake of MeHg through fish consumption for Hong Kong residents was 0.37 µg kg⁻¹ week⁻¹, which was lower than the corresponding WHO limits (500 µg kg⁻¹ and 1.6 µg kg⁻¹ week⁻¹).


Subject(s)
Aquaculture , Geologic Sediments/chemistry , Mercury/analysis , Perciformes/metabolism , Water Pollutants, Chemical/analysis , Animals , Carbon/analysis , China , Diet/statistics & numerical data , Environmental Exposure/analysis , Environmental Exposure/statistics & numerical data , Environmental Monitoring , Female , Humans , Mercury/metabolism , Muscles/metabolism , Nitrogen/analysis , Oceans and Seas , Risk Assessment , Seafood/analysis , Seafood/statistics & numerical data , Sulfur/analysis , Water Pollutants, Chemical/metabolism
7.
Langmuir ; 25(21): 12800-5, 2009 Nov 03.
Article in English | MEDLINE | ID: mdl-19610640

ABSTRACT

Determining how analytes are sequestered into thin films is important for solid-state sensors that detect the presence of the analyte by oxidative luminescence quenching. We show that thin (230 +/- 30 A) and thick (750 +/- 50 A) films of a first-generation dendrimer comprised of 2-ethylhexyloxy surface groups, biphenyl-based dendrons, and a 9,9,9',9'-tetra-n-propyl-2,2'-bifluorene core, can rapidly and reversibly detect p-nitrotoluene by oxidative luminescence quenching. For both the thin and thick films the photoluminescence (PL) is quenched by p-nitrotoluene by approximately 90% in 4 s, which is much faster than that reported for luminescent polymer films. Combined PL and neutron reflectometry measurements on pristine and analyte-saturated films gave important insight into the analyte adsorption process. It was found that during the adsorption process the films swelled, being on average 4% thicker for both the thin and thick dendrimer films. At the same time the PL was completely quenched. On removal of the analyte the films returned to their original thickness and scattering length density, and the PL was restored, showing that the sensing process was fully reversible.

8.
Inflammopharmacology ; 16(4): 188-94, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18759077

ABSTRACT

The lipid extract of Perna canaliculus (Lyprinol) has known anti-inflammatory effects. However, the only information on mechanisms is regulation of cytokine secretion. Therefore, we conducted a proteomic study exploring the effects of Lyprinol on protein expression in splenocytes collected from AIA rats. Splenocytes from AIA rats fed with Lyprinol had increased protein expression of malate dehydrogenase (MDH). Lyprinol also decreased the expressions of 5 other proteins: protein-o-mannosyl- transferase 2 (PMT-2), Tdrd 7, telethonin, dynactin 2 and protein disulfide isomerase (PDI or glucose-regulated protein (GRP)). Besides MDH, PMT- 2, titin-cap protein and protein disulfide isomerase (PDI) are known to be related to metabolism. However, it is currently unknown if Lyprinol administration decreases metabolic glucose in the body and alleviates symptoms of inflammation and arthritis. Further experiments are required to correlate levels of citric acid intermediates and glucose to the severity of inflammation and pain in AIA rats fed Lyprinol.


Subject(s)
Arthritis, Experimental/metabolism , Gene Expression Regulation/drug effects , Lipids/pharmacology , Perna/chemistry , Animals , Lipids/isolation & purification , Malate Dehydrogenase/drug effects , Malate Dehydrogenase/metabolism , Male , Proteins/drug effects , Proteins/metabolism , Proteomics , Rats , Rats, Sprague-Dawley , Spleen/cytology , Spleen/drug effects
9.
Eur Ann Allergy Clin Immunol ; 40(4): 148-53, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19227651

ABSTRACT

As published initially in this same journal in 2000, the lipid extract of Perna canaliculus (New Zealand green-lipped mussel; Lyprinol) is known for its anti-inflammatory effects in animal models and in human controlled studies (arthritis; asthma). As a follow-up of its effects on pain in a rat model of adjuvant-induced arthritis (ALA), we studied its effects on the production of cytokines known to be associated with inflammation (IL-6, IL-1alpha TNF-alpha, IFN-gamma). Feeding with Lyprinol was associated with significantly decreased expression levels of TNF-alpha and IFN-gamma when compared to Naproxen (positive control) and, even more when compared with sham and extra-virgin olive oil (negative control). When compared to Naproxen, sham and extra-virgin olive oil, the levels of IL-6 and IL-1alpha were also marginally decreased in rats fed with Lyprinol. This study demonstrates that AIA rats fed with Lyprinol had decreased production ofcytokines associated with inflammation.


Subject(s)
Arthritis, Experimental/drug therapy , Leukotriene Antagonists/administration & dosage , Lipids/administration & dosage , Lymphocyte Activation/drug effects , Perna/immunology , Spleen/metabolism , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Arthritis, Experimental/immunology , Cell Extracts , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-1alpha/genetics , Interleukin-1alpha/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Male , Naproxen/administration & dosage , Rats , Rats, Sprague-Dawley , Spleen/drug effects , Spleen/immunology , Spleen/pathology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
11.
Mol Cell Endocrinol ; 243(1-2): 27-34, 2005 Nov 24.
Article in English | MEDLINE | ID: mdl-16198475

ABSTRACT

Repression of cancer-protective phase II enzymes may help explain why estrogen exposure leads to the development of cancer. In an earlier report we described the ability of 17beta-estradiol (E(2)) to repress phase II enzyme activity in vivo. Phase II enzymes are coordinately regulated via the presence of the antioxidant response element (ARE) in their promoter. We wanted to determine if estrogen receptors (ER) repress ARE-dependent gene expression through a mechanism that requires interaction with Nrf2, the transcription factor that regulates ARE-mediated gene transcription. E(2)-bound ERalpha, but not ERbeta, represses ARE-regulated gene expression in the presence of exogenously expressed Nrf2 as well as when the transactivation domain of Nrf2 was fused to a heterologous DNA-binding domain. Deletion of the activation function-2 (AF-2) and the ligand-binding domain of ERalpha result in a constitutive repression of Nrf2-mediated transcription. Finally, E(2)-bound ERalpha co-immunoprecipitates with Nrf2. Repression of Nrf2-mediated transcription by E(2)-bound ERalpha expands our knowledge of E(2)-regulated genes and provides a potential drug-screening target for the development of selective estrogen receptor modulators with a lower risk of causing cancer.


Subject(s)
Antioxidants/physiology , Estradiol/pharmacology , Estrogen Receptor alpha/metabolism , Gene Expression Regulation , NF-E2-Related Factor 2/metabolism , Response Elements , Animals , Cell Line , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/metabolism , Female , Gene Silencing , Genes, Reporter , Humans , Ligands , NF-E2-Related Factor 2/genetics , Nuclear Proteins/metabolism
12.
Vox Sang ; 83(2): 162-4, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12201846

ABSTRACT

BACKGROUND AND OBJECTIVES: The red blood cell Mi III phenotype is prevalent in Asia, and its corresponding alloantibody, anti-Mi(a), has been reported to cause haemolytic transfusion reactions and haemolytic disease of the newborn. However, a complete picture of the immunological characteristics of anti-Mi(a) is still lacking. We therefore conducted a systematic study to evaluate the potential clinical significance of this antibody. MATERIALS AND METHODS: From April 1999 to March 2000, we identified 60 sera containing anti-Mi(a) among pretransfusion samples at a teaching hospital in Taiwan. These antibodies were tested for immunoglobulin class, thermal range and activity in a monocyte monolayer assay. RESULTS: Thirty-four (57%) of the antibodies were immunoglobulin M (IgM), and 15 retained their activity at 37 degrees C. Of those that were immunoglobulin G (IgG), 96% were of subclasses IgG1 and/or IgG3. Monocyte monolayer assay studies showed that 69% (18/26) of the IgG anti-Mi(a) sera were reactive. CONCLUSIONS: Our study justifies the implementation of anti-Mi(a) screening in Taiwan.


Subject(s)
Isoantibodies/immunology , MNSs Blood-Group System/immunology , Erythrocytes/immunology , Humans , Immunoglobulins/blood , Immunoglobulins/classification , Isoantibodies/blood , Mass Screening , Phenotype , Taiwan/epidemiology
13.
Nitric Oxide ; 6(2): 205-13, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11890745

ABSTRACT

Nitric oxide (NO) has recently been identified as an important signaling molecule in plant immune response. The present study aims to investigate the signaling pathway that leads to NO production. Using the NO specific fluorescent dye DAF-2DA, we observed rapid production of NO in mung bean leaves after the addition of 10 mM hydrogen peroxide (H(2)O(2)). NO was probably produced by a NOS-like enzyme in plants, as the NO production was inhibited by l-NAME, a NOS inhibitor. The NOS-like activity in the total leaf protein preparation of mung bean (Phaseolus aureus) was elevated 8.3-fold after 10 mM H(2)O(2) treatment, as demonstrated using the chemiluminescence NOS assay. The NOS-like activity was BH(4) dependent: omitting BH(4) in the reaction mixture of NOS assay reduced the NOS activity by 76%. We also found that the H(2)O(2) induced NO production was mediated via calcium ion flux, as it was blocked in the presence of a calcium ion channel blocker, verapamil. Results from the present study identified H(2)O(2) as an upstream signal that leads to NO production in plants. H(2)O(2) and NO, besides acting as two independent signaling molecules in plant immune response, may interrelate to form an oxidative cell death (OCD) cycle.


Subject(s)
Calcium/metabolism , Hydrogen Peroxide/pharmacology , Nitric Oxide/biosynthesis , Phaseolus/drug effects , Plant Leaves/drug effects , Calcium Channel Blockers/pharmacology , Drug Interactions , Fluorescein/analysis , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Phaseolus/metabolism , Plant Leaves/enzymology , Plant Leaves/metabolism , Verapamil/pharmacology
14.
J Recept Signal Transduct Res ; 21(1): 71-84, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11693174

ABSTRACT

Chloramphenicol acetyltransferase (CAT) is widely used as a reporter to determine the transcriptional specificity of promoters and for the quantification of transcriptional activity of transcription factors such as nuclear receptors. However, large-scale quantification of CAT activity in transfected mammalian cells is still heavily labor-intensive, time-consuming and expensive. Here, we describe a simplified method that combined using multiwell tissue culture plates in transfection and sample preparation and a modified single step method for quantitatively assaying CAT activity. By using multiwell plates, the tedious sample preparation procedure was dramatically simplified. The CAT assay is performed by mixing cell lysate, chloramphenicol, 3H-acetyl co-enzyme A and non-aqueous scintillation fluid in scintillation vials, followed by automatically continuously counting samples two or three cycles at fixed time intervals. The catalytic reaction and determination of CAT activity are carried out in the vials simultaneously. This simplified protocol is faster, less expensive and more accurate than other CAT assay procedures and the results can be normalized easily. The utility of the assay is demonstrated by the analysis of the transcriptional activity of the glucocorticoid and androgen receptors cotransfected into cells with a CAT reporter.


Subject(s)
Chloramphenicol O-Acetyltransferase/analysis , Chloramphenicol O-Acetyltransferase/genetics , Receptors, Androgen/genetics , Receptors, Glucocorticoid/genetics , Transcription, Genetic , Animals , CHO Cells , COS Cells , Cell Line , Cricetinae , Dexamethasone/pharmacology , Genes, Reporter , Mice , Mutation , Progesterone/pharmacology , Scintillation Counting/methods , Transfection
15.
Exp Biol Med (Maywood) ; 226(8): 753-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11520941

ABSTRACT

Patients with acquired immune deficiency syndrome (AIDS) often develop Kaposi's sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been disputed. Telomerase activity that maintains telomere length and ensures chromosomal stability, a frequently appearing marker in human malignancies, has been proposed to play a critical role in supporting continued cell growth, hence formation of tumors. We examined telomerase activity in tissue extracts from 22 KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) using the telomeric repeat amplification protocol (TRAP). All of the tumor tissues were previously cryopreserved at -80 degrees C. In this study, all tumor samples tested were positive for telomerase activity. Consistent with the presence of the enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the tissue extracts of some samples needed to be diluted or extracted by phenol before the enzyme activity was detected in the TRAP assay. All KS as well as two other skin carcinoma samples revealed positive telomerase activity. Our finding supports telomerase's role in tumor cell immortality and suggests the true neoplastic nature of KS.


Subject(s)
Carcinoma, Basal Cell/enzymology , Carcinoma, Squamous Cell/enzymology , Sarcoma, Kaposi/enzymology , Skin Neoplasms/enzymology , Telomerase/biosynthesis , Adult , Humans , Middle Aged , Repetitive Sequences, Nucleic Acid , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
16.
Curr Microbiol ; 43(3): 163-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11400064

ABSTRACT

Many individuals are chronically infected or parasitically colonized with mycoplasmas in their respiratory or urogenital tracts without apparent clinical significance. However, prolonged close interaction between prokaryotic agents and eukaryotic host cells may gradually and significantly alter normal biological or physiological properties of infected hosts. Steroid hormones are associated with rates of cancer formation in human. The purpose of this study is to establish a sensitive reporting system to examine whether mycoplasmal infections affect biological responses to steroid hormones in mammalian cells. We established pMTV-CAT stably transfected cell lines to test the effect of mycoplasmal lipid-associated membrane proteins (LAMPs). Results showed that LAMPs (1 microg/ml) from seven different species of human mycoplasmas-M. penetrans, M. fermentans, M. genitalium, M. salivarium, M. pneumoniae, M. orale, and M. hominis-had an inhibitory effect on androgen receptor (AR) response to 5alpha-dihydrotestosterone (DHT) in the E82 transfectants. The inhibitory effect of mycoplasmal LAMPs appeared to be dose dependent. LAMPs from M. penetrans, M. genitalium, M. salivarium, M. pneumoniae, and M. orale also had an inhibitory effect on glucocorticoid receptor (GR) response to hormone dexamethasone (Dex) in TSU transfectants. In contrast, LAMPs from M. fermentans and M. hominis showed a stimulatory effect on the GR response to Dex in these TSU cells. The results suggest that colonization or chronic infection by mycoplasmas may significantly affect the responses of mammalian host cells to various steroid hormones, potentially affecting rates of cancer formation.


Subject(s)
Bacterial Proteins/pharmacology , Membrane Proteins/pharmacology , Mycoplasma , Receptors, Androgen/drug effects , Receptors, Glucocorticoid/drug effects , Steroids/pharmacology , Animals , Cell Line , Dexamethasone/pharmacology , Dihydrotestosterone/pharmacology , Dose-Response Relationship, Drug , Humans , Receptors, Androgen/metabolism , Receptors, Glucocorticoid/metabolism , Transcription, Genetic/drug effects , Transfection , Tumor Cells, Cultured
17.
IEEE Trans Med Imaging ; 20(4): 289-301, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11370896

ABSTRACT

This paper presents a statistical model supported approach for enhanced segmentation and extraction of suspicious mass areas from mammographic images. With an appropriate statistical description of various discriminate characteristics of both true and false candidates from the localized areas, an improved mass detection may be achieved in computer-assisted diagnosis (CAD). In this study, one type of morphological operation is derived to enhance disease patterns of suspected masses by cleaning up unrelated background clutters, and a model-based image segmentation is performed to localize the suspected mass areas using stochastic relaxation labeling scheme. We discuss the importance of model selection when a finite generalized Gaussian mixture is employed, and use the information theoretic criteria to determine the optimal model structure and parameters. Examples are presented to show the effectiveness of the proposed methods on mass lesion enhancement and segmentation when applied to mammographical images. Experimental results demonstrate that the proposed method achieves a very satisfactory performance as a preprocessing procedure for mass detection in CAD.


Subject(s)
Breast Neoplasms/diagnostic imaging , Diagnosis, Computer-Assisted , Image Processing, Computer-Assisted/methods , Mammography , Female , Humans , Models, Statistical
18.
IEEE Trans Med Imaging ; 20(4): 302-13, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11370897

ABSTRACT

Based on the enhanced segmentation of suspicious mass areas, further development of computer-assisted mass detection may be decomposed into three distinctive machine learning tasks: 1) construction of the featured knowledge database; 2) mapping of the classified and/or unclassified data points in the database; and 3) development of an intelligent user interface. A decision support system may then be constructed as a complementary machine observer that should enhance the radiologists performance in mass detection. We adopt a mathematical feature extraction procedure to construct the featured knowledge database from all the suspicious mass sites localized by the enhanced segmentation. The optimal mapping of the data points is then obtained by learning the generalized normal mixtures and decision boundaries, where a is developed to carry out both soft and hard clustering. A visual explanation of the decision making is further invented as a decision support, based on an interactive visualization hierarchy through the probabilistic principal component projections of the knowledge database and the localized optimal displays of the retrieved raw data. A prototype system is developed and pilot tested to demonstrate the applicability of this framework to mammographic mass detection.


Subject(s)
Artificial Intelligence , Breast Neoplasms/diagnostic imaging , Decision Support Techniques , Diagnosis, Computer-Assisted , Mammography , Databases as Topic , Female , Humans , Models, Statistical , Neural Networks, Computer
19.
Biochem J ; 355(Pt 2): 459-64, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11284734

ABSTRACT

Telomerase, a specialized ribonucleoprotein reverse transcriptase that directs the synthesis of telomeric DNA, is repressed in normal human somatic cells, but is activated in most cancers. Little is known concerning how telomerase activity is activated and maintained in cancer cells. We have shown previously that inhibition of protein kinase C (PKC) decreases the telomerase activity of human nasopharyngeal carcinoma (NPC) cells. Here, we provide evidence that the decrease of telomerase activity by PKC inhibition is not mediated by transcriptional down-regulation of hTERT, the catalytic protein of human telomerase. In vitro phosphorylation studies revealed that exogenous addition of PKC-alpha, -betaI, -delta or -zeta led to restoration of telomerase activity in the crude extracts of PKC-inhibited NPC cells. However, depletion of PKC-alpha and -betaI in vivo had no detectable effect on the telomerase activity of NPC cells. Using antisense oligonucleotides against individual PKC isotypes, we observed that telomerase activity was inhibited only by the antisense oligonucleotide against PKC-zeta but not by those against PKC-alpha, -betaI or -delta. Taken together, these data demonstrate that PKC participates in the regulation of telomerase activity by direct or indirect phosphorylation of telomerase proteins, and that PKC-zeta is the PKC isotype that functions in vivo in the NPC cells.


Subject(s)
Nasopharyngeal Neoplasms/enzymology , Protein Kinase C/metabolism , Telomerase/metabolism , Base Sequence , DNA Primers , Humans , Nasopharyngeal Neoplasms/pathology , Phosphorylation , Protein Kinase C/antagonists & inhibitors , Tumor Cells, Cultured
20.
J Natl Cancer Inst ; 93(1): 51-6, 2001 Jan 03.
Article in English | MEDLINE | ID: mdl-11136842

ABSTRACT

BACKGROUND: High mammographic density is associated with increased breast cancer risk. Previous studies have shown that estrogens increase breast density on mammograms, but the effect on mammographic density of selective estrogen receptor modulators, such as raloxifene, is unknown. We assessed changes in mammographic density among women receiving placebo, raloxifene, or conjugated equine estrogens in an osteoporosis prevention trial. METHODS: In a 5-year multicenter, double-blind, randomized, placebo-controlled osteoporosis prevention trial, healthy postmenopausal women who had undergone hysterectomy less than 15 years before the study and had no history of breast cancer received placebo, raloxifene (at one of two doses), or conjugated estrogens (ERT). Women from English-speaking investigative sites who had baseline and 2-year craniocaudal mammograms with comparable positioning (n = 168) were eligible for this analysis. Changes in mammographic density were determined by digital scanning and computer-assisted segmentation of mammograms and were analyzed with the use of analysis of variance. All statistical tests were two-sided. RESULTS: Among the four treatment groups after 2 years on study, the mean breast density (craniocaudal view) was statistically significantly greater in the ERT group than it was in the other three groups (P<0.01 for all three comparisons). Within treatment groups, the mean breast density from baseline to 2 years decreased statistically significantly in women receiving the placebo or either the higher or lower raloxifene dose (P = 0.003, P = 0.002, and P<0.001, respectively) and showed a nonstatistically significant increase in women receiving ERT. CONCLUSIONS: In an osteoporosis prevention trial, raloxifene did not increase breast density after 2 years of treatment. Raloxifene administration should not interfere with, and could even enhance, mammographic detection of new breast cancers.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/prevention & control , Breast/drug effects , Breast/pathology , Estrogens, Conjugated (USP)/pharmacology , Mammography , Raloxifene Hydrochloride/pharmacology , Selective Estrogen Receptor Modulators/pharmacology , Double-Blind Method , Estrogen Replacement Therapy , Female , Humans , Image Interpretation, Computer-Assisted , Mammography/methods , Middle Aged , Osteoporosis, Postmenopausal/prevention & control
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