Biomedical subjects

Liying Chen

Publications and source records attributed to Liying Chen.

12 recordsLinked to original sources

PubMed2006

New bis-N9-(methylphenylmethyl)purine derivatives: synthesis and antitumor activity.

A series of ortho-, meta- and para-bis-N9-(methylphenylmethyl)purine derivatives 4-15 were obtained by two-step synthesis from various substituted chloropurines with alpha,alpha'-dichloroxylenes. These bis-N9-(methylphenylmethyl)purines 4-15 were evaluated for the primary cytotoxic activity against a panel of NCI-H460 (lung), MCF-7 (breast) and SF-268 (CNS) cancer cell lines. The 'active' compounds which reduced growth of cancer cells to ca. 32% or less, have been evaluated in a full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute, Bethesda, MD. In this series, the most activity is correlated to the compounds derived from the 2,6-dichloropurines such as bis-9-[o-(methylphenylmethyl)]2,6-dichloropurine (5), bis-9-[m-(methylphenylmethyl)]2,6-dichloropurine (8), and bis-9-[p-(methylphenylmethyl)]2,6-dichloropurine (11). In particular compound 8 exhibited high sensitivity in leukemia cell lines and compounds 5, 8 and 11 exhibited consistent high sensitivity in many breast cancer cell lines. Compound 11 was the most potent in this series and exhibited GI(50)<0.01 microM sensitivity against non-small lung cancer EKVX, colon cancer HT-29, melanoma SK-MEL-28, renal cancer RXF 393, prostate cancer DU-145 and several breast cancer HS 578T and BT-549 cell lines.

Alkylation↗

PubMed2006

Interference with O-glycosylation in RMA lymphoma cells leads to a reduced in vivo growth of the tumor.

Carbohydrate processing in cancer cells can influence the growth, metastatic potential, vascularization and immune recognition of such cells. Interference with N-glycosylation has been shown both to reduce the membrane expression of MHC class I and to increase the in vitro sensitivity of tumor cells to NK cell killing. We investigated the effect of O-glycosylation inhibition on the in vivo growth, phenotype and NK sensitivity of RMA lymphoma cells using benzyl N-acetyl-alpha-D-galactosamide (BAG). BAG-treated cells were found to have a strongly reduced local growth potential in vivo. However, inhibition of O-glycosylation caused this effect without any significant downregulation of MHC-I and increase in sensitivity to NK killing as seen after inhibition of N-glycosylation using Castanospermine. BAG treatment of RMA cells resulted in the removal of larger O-linked glycans and a high expression of the T-antigen (GalGalNAc), a target for natural antibodies (NAs) induced by the gastrointestinal bacterial flora. Whether the loss of larger O-linked glycans, and associated functions, or of biological effects of NA contributed to the antitumor effect remains to be established. The results support the idea that inhibitors of O- as well as N-linked glycosylation may be useful for the treatment of cancer, given that they can be specifically targeted to the tumor tissue.

Acetylgalactosamine↗

PubMed2005

Maladaptive role of IL-6 in ischemic acute renal failure.

The role of IL-6 was investigated in murine ischemic acute renal failure. The renal pedicles were clamped for 17 min, and the mice were studied at various times after reperfusion. We found that serum IL-6 increased after murine ischemic renal injury. This increase was associated with increased IL-6 mRNA in the ischemic kidney but not in the contralateral kidney or the liver. Maximal IL-6 production occurred at 4 to 8 h and decreased to baseline by 24 h. Reperfusion of the kidney was required for IL-6 production. In situ hybridization and immunohistochemistry showed that macrophages infiltrated areas adjacent to the vascular bundles in the outer medulla within hours of reperfusion and showed that these macrophages produced IL-6 mRNA. For understanding how macrophages were stimulated to produce IL-6, an in vitro model in which S3 proximal tubular cells were injured by reactive oxygen species was set up. These injured cells released molecules that activated macrophages to produce IL-6 in vitro. IL-6 that was produced in response to renal ischemia was maladaptive because transgenic knockout of IL-6 ameliorated renal injury as measured by serum creatinine and histology. IL-6 transgenic knockout mice were lethally irradiated, and their bone marrow was reconstituted with wild-type IL-6 cells. Such bone marrow transfers abolished the protective effects of transgenic IL-6 knockout. It is concluded that macrophages infiltrate the area of the vascular bundles of the outer medulla, these macrophages produce IL-6, and this IL-6 exacerbates ischemic murine acute renal failure.

Acute Kidney Injury↗

PubMed2005

Isolation and characterisation of antimicrobial peptides from deer neutrophils.

The New Zealand deer industry is the largest and most advanced in the world. Antimicrobial peptides have been isolated from a wide range of organisms, but as yet there have been no reports on any from deer. This work investigates the antimicrobial activity and characterisation of peptides isolated from Cervus elaphus blood. It was found that deer blood contains proline/arginine-rich cathelicidins, similar to Bac5 peptides isolated from cattle, sheep and goats. A beta-defensin was also isolated that had a conserved amino acid sequence and mass similar to bovine neutrophil beta-defensins. The cathelicidin displayed strong activity against Gram-negative bacteria, but lesser activity against Gram-positive bacteria and yeast, whilst the beta-defensin showed good activity against all three test organisms.

Animals↗

PubMed2005

Task-based lens design with application to digital mammography.

Recent advances in model observers that predict human perceptual performance now make it possible to optimize medical imaging systems for human task performance. We illustrate the procedure by considering the design of a lens for use in an optically coupled digital mammography system. The channelized Hotelling observer is used to model human performance, and the channels chosen are differences of Gaussians. The task performed by the model observer is detection of a lesion at a random but known location in a clustered lumpy background mimicking breast tissue. The entire system is simulated with a Monte Carlo application according to physics principles, and the main system component under study is the imaging lens that couples a fluorescent screen to a CCD detector. The signal-to-noise ratio (SNR) of the channelized Hotelling observer is used to quantify this detectability of the simulated lesion (signal) on the simulated mammographic background. Plots of channelized Hotelling SNR versus signal location for various lens apertures, various working distances, and various focusing places are presented. These plots thus illustrate the trade-off between coupling efficiency and blur in a task-based manner. In this way, the channelized Hotelling SNR is used as a merit function for lens design.

Algorithms↗

PubMed2004

Loading of the antigen-presenting protein CD1d with synthetic glycolipids.

CD1 proteins present mammalian and microbial lipid and glycolipid antigens to different subsets of T cells. Few such antigens have been identified and the binding of these to CD1 molecules has mainly been studied by using responding T cells in cellular assays or recombinant solid-phase CD1 proteins. In the present study we use four different glycolipids, some of which contain tumor-associated carbohydrate antigens, to develop a procedure to easily detect binding of glycolipids to CD1 proteins on viable cells. Two of these glycolipids are novel glycoconjugates containing alpha-D-N-acetylgalactosamine (alpha-GalNAc) that were prepared by a combined solution and solid-phase approach. The key step, a Fischer glycosylation of 9-fluorenylmethoxycarbonylaminoethanol with GalNAc, furnished the alpha-glycoside 4 in 34% yield. Cells were incubated with glycolipids and stained with monoclonal antibodies specific for the carbohydrate part. The level of glycolipid bound to cells was then determined by flow cytometry with a secondary antibody labeled with fluorescein isothiocyanate. All four glycolipids were found to bind to CD1d but with different selectivity. The loading was dose dependent and could be inhibited by an established CD1d ligand, alpha-galactosylceramide. Through use of this procedure, glycolipids were selectively loaded onto CD1d expressed on professional antigen-presenting cells for future use as cellular vaccines. Moreover, the glycolipids described in this study represent novel CD1d-binding ligands that will be useful derivatives in the study of CD1d-dependent immune responses, for example, against tumors.

Animals↗

PubMed2004

Alternative processing for MHC class I presentation by immature and CpG-activated dendritic cells.

Exogenous proteins can be processed by antigen-presenting cells for the generation of MHC class I-restricted T cell responses. Where this occurs is not clear, although both transfer of internalized antigen into the cytosol and alternative processing in endolysosomes and phagosomes have been reported. Here we have studied the capacity of bone marrow-derived mouse myeloid dendritic cells (DC) to process the OVA protein for peptide presentation by H2-K(b). We have found that immature DC (iDC), both wild-type and transporter associated with antigen processing (TAP)-deficient cells, can transiently process OVA in a pathway which is resistant to inhibitors of the classical MHC class I pathway including the Golgi inhibitor Brefeldin A (BFA) and the proteasome inhibitor lactacystin. This alternative pathway is not found in subcultured DC with an intermediate maturity (imDC) or in resting, IL-3 expanded macrophages but can be re-expressed in imDC if these are activated by an immunostimulatory CpG oligonucleotide. Both iDC and CpG-activated DC were found to process OVA by regurgitation. In addition, we found that iDC secrete proteolytic enzymes into the supernatant, which can process OVA in the extracellular phase. These results suggest that multiple pathways exist for the processing of exogenous protein antigens into MHC class I-binding peptides.

Acetylcysteine↗

PubMed2003

Hypoxia-ischemic encephalopathy in full-term neonate: correlation proton MR spectroscopy with MR imaging.

INTRODUCTION: To evaluate 1H Magnetic Resonance Spectroscopy (1HMRS) in the diagnosis of hypoxia-ischemic encephalopathy (HIE) of full-term neonates correlated with Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: Thirty-eight cases of full-term neonates diagnosed as HIE clinically were selected to perform MRI and 1HMRS examination. The ages ranged from 7 to 17 days, with median age of 8.2 days. In which, 26 cases were followed up and/or MRI reexamined at 6 months of age or later. Eight healthy neonates, with no evidence of birth asphyxia, also underwent 1HMRS for comparison. SE sequences were used for routine MR examination; point resolved spectroscopy sequence was required for 1HMRS. The metabolites in the spectra includes: N-acetylaspartate (NAA), choline compounds (CHO), creatine compounds (CR), myo-inositol (MI), lactate (LAC), glutamate and glutamine (Glu-Gln). RESULTS: The peaks of NAA were fall in two cases; the peaks of LAC, which were elevated, appeared as typical double-peaks appearance in 26 cases; the peaks of Glu-Gln, which were also elevated, appeared as zigzag appearance in nine cases. The peaks of CR were decreased in 11 cases, while those of MI were increased in seven cases. Mild type of lesions was present on MRI in 12 cases whose LAC/CR ratio lower than 0.5; mild and moderate types of lesions were present in 15 cases whose LAC/CR ratio between 0.5 and 1.5. Whereas, nine cases of severe lesions and two cases of moderate lesions were present on MRI in 11 cases whose LAC/CR ratio greater than 1.5. Twenty-six of 38 cases were followed up and/or MRI reexamined after 6 months, in which, sequelae were present in 12 cases. Among them, eight cases of sequelae in nine cases whose LAC/CR ratio greater than 1.5 were present (account for 88.89%). CONCLUSION: 1HMRS plays an important role to diagnose and predict outcome of HIE.

Apgar Score↗

PubMed2003

Experimental determination of object statistics from noisy images.

Modern imaging systems rely on complicated hardware and sophisticated image-processing methods to produce images. Owing to this complexity in the imaging chain, there are numerous variables in both the hardware and the software that need to be determined. We advocate a task-based approach to measuring and optimizing image quality in which one analyzes the ability of an observer to perform a task. Ideally, a task-based measure of image quality would account for all sources of variation in the imaging system, including object variability. Often, researchers ignore object variability even though it is known to have a large effect on task performance. The more accurate the statistical description of the objects, the more believable the task-based results will be. We have developed methods to fit statistical models of objects, using only noisy image data and a well-characterized imaging system. The results of these techniques could eventually be used to optimize both the hardware and the software components of imaging systems.

Artifacts↗

PubMed2003

Effects of different therapies on coronary artery disease.

OBJECTIVE: To analyse the effects of different therapies on coronary artery disease (CAD). METHODS: A total of 1055 patients who suffered from CAD diagnosed by coronary angiography were divided into three groups, namely pure drug therapy, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) groups. Follow up was carried out from March to May in 2001, and the major adverse cardiac events (MACEs) including death, no-lethal myocardial infarction (MI) and revascularization were observed. In long-term observation, angina reoccurred, and their improvement was evaluated. The short-term period was defined as the duration of 30 days after discharge, and the long term period was defined as the duration from 30 days after discharge. RESULTS: In the long-term period, the recurrences of angina both in PCI group and CABG group were lower than pure drug group (P 0.018, 0.002 respectively). No differences about long-term endpoint events were observed among these three groups (P > 0.05). Forty-two patients suffering from left main coronary disease were intervened by the three therapies, and there was no death or MI both in PCI and CABG groups, three patients died and suffered from AMI in pure drug therapy group (P = 0.015). In the short-term period, mortality in CABG group (5.77%) was higher than those in the other two groups (1.91% for PCI, and 1.40% for medical therapy, P = 0.002), and no obvious difference observed in the latter two groups. No significance was concluded about the recent MI among this three groups (P = 0.357). There were no differences on revascularization in these three groups. CONCLUSIONS: Percutaneous coronary interventions can not only reduce the attack of angina but also improve the life quality of patients, however it can not improve the long-term existence but left main CAD.

Adult↗

PubMed2003

Evaluation of transisthmus conduction interval in predicting bidirectional block after ablation of typical atrial flutter.

OBJECTIVE: To determine whether the extent of prolongation of the transisthmus interval after ablation predicts complete bidirectional block. METHODS: Since 1996 to 2002, 30 consecutive patients underwent ablation procedures for isthmus-dependent atrial flutter. There were 23 males and 7 females [mean age (47.85 +/- 9.35) years]. With the use of fluoroscopic view of anatomy, radiofrequency ablation was performed during coronary sinus pacing at a cycle length of 600 ms. RESULTS: Bidirectional block was achieved with ablation in 29 (97%) of 30 patients. The transisthmus intervals before ablation and after complete transisthmus block were (73.82 +/- 13.01) ms and (140.47 +/- 20.48) ms, respectively, in the clockwise direction (P < 0.0001), and (77.63 +/- 8.36) ms and (138.17 +/- 15.55) ms, respectively, in the counterclockwise direction (P < 0.0001). A period of incomplete isthmus block was observed during 17 (58%) of the 29 ablation procedures. The clockwise transisthmus intervals during incomplete block [(107.65 +/- 21.33) ms] were (45.5 +/- 8.7)% longer than the baseline transisthmus intervals. An increase in the transisthmus interval by > or = 50% in both directions after ablation predicted complete bidirectional block with 100.0% sensitivity and 83.3% specificity. The positive and negative predictive values were 90.6% and 100.0%, respectively. The diagnostic accuracy of a > or = 50% prolongation in the transisthmus interval was 83.3%. CONCLUSION: The analysis of transisthmus interval is a valuable method for determining complete bidirectional isthmus block.

Atrial Flutter↗

PubMed2000

Analysis of urgent reconstruction of electrical injuries.

OBJECTIVE: To summarize the reconstruction exp erience of the electrical injuries in emergency. METHODS: All 309 wounds in 105 patients who suffered from elect rical injuries were reviewed during a 10 year period from Jan. 1st 1986 to Dec. 31st, 1996. Treatment method, patient data and results wer e compared and analyzed. A comprehensive urgent reconstruction alternative used in all cases included the followings, 1) debriding the wound in emergency, 2) preserving the vital tissues as much as possible, even devitalized tissues or loca l necrosis, 3) transplanting these vital tissues during the first surgery if the functional reconstruction required, 4) nourishing the wound bed by tissue flaps covering with rich blood supply, 5) improving flap survival by continuous irrig ation for 24-720 hours beneath the flaps with a compound medicine after surgery. RESULTS: Satisfactory results were obtained with the extremity loss ratio of less than 7% in this group compared with 42.5% which was 10 ye ars before 1984 in the same hospital. CONCLUSIONS: This urgent comprehensive reconstruction alternati ve is an effective and workable method for reducing extremity loss of electrical injuries.

Journal Article↗