Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 631 records · Page 35Linked to original sources

PubMed2000

alpha-Tocopherol and protein kinase C inhibition enhance platelet-derived nitric oxide release.

Platelet activation is tightly regulated by products of the endothelium and platelets including nitric oxide (NO). Excess vascular oxidative stress has been associated with impaired NO release, and antioxidant status has been shown to alter endothelium-derived NO bioactivity. Although physiological levels of a-tocopherol are known to inhibit platelet function, the effect of a-tocopherol on platelet NO release is unknown. Loading platelets with physiologic levels of a-tocopherol increased platelet NO production approximately 1.5-fold (Pa-tocopherol, platelet NO release increased 50% (Pa-Tocopherol-loaded platelets also produced 74% less superoxide as compared with control (Pa-tocopherol inhibited PKC-dependent eNOS phosphorylation as determined by immunoprecipitation. Lastly, platelets isolated from NOS3-deficient mice released 80% less superoxide as compared with control animals (P=0.011), and incubation of NOS III-deficient platelets with 500 mM a-tocopherol only caused a modest additional decrease in platelet superoxide release (NS). Thus, a-tocopherol appears to enhance platelet NO release both in vitro and in vivo through antioxidant- and PKC-dependent mechanisms.

Alkaloids↗

PubMed2000

Field evaluation of the Computer Science and Applications, Inc. physical activity monitor.

PURPOSE: The purpose of this study was to evaluate the Computer Science and Applications, Inc. (CSA) activity monitor to quantify physical activity in free living subjects using an activity diary as the criterion measure. METHODS: Subjects also completed a 7-d physical activity recall at the end of the monitoring period. Nine male and 10 female subjects (mean, SD) (25.0, 3.6 yr) wore the CSA monitor for 7 consecutive days. On 3 of those days, subjects completed an activity diary (2 weekdays and 1 weekend day). Total kcal per day (Dkcal(tot)) was calculated from the self-reported diary classifications of the subject's activities. For the 3 days that coincided with the diary, total number of counts accumulated per day (cnt(tot)) was obtained from the monitor. RESULTS: The amount of activity per day recorded by the CSA monitor followed the same pattern of change as the activity diary. The cnt(tot) and Dkcal(tot) were significantly (P < or = 0.05) correlated on day 1 (r = 0.65), day 2 (r = 0.49), day 3 (r = 0.55), and for the 3 days pooled (r = 0.51). Subjects were classified as low, moderate, or highly active based on tertiles of kcal from the diary and counts from the CSA monitor. The percentage agreement between the CSA and the activity diary was 68.4% (Kappa = 0.53, P < 0.01). The number of minutes spent in the various activity categories were compared between instruments using an ANOVA model. The results of these analyses suggest that the CSA overestimated light activity and underestimated vigorous activity compared with the diary. CONCLUSION: In conclusion, the CSA monitor may be useful in a field situation where total physical activity and patterns of physical activity are the desired outcomes.

Adult↗

PubMed2000

Structure and function of apolipoprotein A-I and high-density lipoprotein.

Structural biology and molecular modeling have provided intriguing insights into the atomic details of the lipid-associated structure of the major protein component of HDL, apo A-I. For the first time, an atomic resolution map is available for future studies of the molecular interactions of HDL in such biological processes as ABC1-regulated HDL assembly, LCAT activation, receptor binding, reverse lipid transport and HDL heterogeneity. Within the context of this paradigm, the current review summarizes the state of HDL research.

Animals↗

PubMed2000

Isolation and complete nucleotide sequence of a Chinese Sindbis-like virus.

Infection with alphaviruses is common in the Chinese population. Here we report the isolation of a Sindbis-like virus from a pool of Anopheles mosquitoes collected in Xinjiang, China during an arbovirus survey. This virus, designated XJ-160, rapidly produced cytopathic effects on mosquito and hamster cells. In addition, it was lethal to neonatal mice if inoculated intracerebrally. Serologically, XJ-160 reacted with and was neutralized by an anti-Sindbis antibody. Anti-XJ-160 antibodies were found in several cohorts of Chinese subjects. The complete 11626-base nucleotide sequence of XJ-160 was determined. XJ-160 has diverged significantly from the prototype Sindbis virus, with an 18% difference in nucleotide sequence and an 8.6% difference in amino acids; there are 11 deletions and 2 insertions, involving 99 nucleotides in total. XJ-160 is most closely linked to Kyzylagach virus isolated in Azerbaijan. Both belong to the African/European genetic lineage of Sindbis virus, albeit more distantly related to other members.

Alphavirus Infections↗

PubMed2000

Cytochrome P450-dependent metabolism of oxylipins in tomato. Cloning and expression of allene oxide synthase and fatty acid hydroperoxide lyase.

Allene oxide synthase (AOS) and fatty acid hydroperoxide lyase (HPL) are plant-specific cytochrome P450s that commit fatty acid hydroperoxides to different branches of oxylipin metabolism. Here we report the cloning and characterization of AOS (LeAOS) and HPL (LeHPL) cDNAs from tomato (Lycopersicon esculentum). Functional expression of the cDNAs in Escherichia coli showed that LeAOS and LeHPL encode enzymes that metabolize 13- but not 9-hydroperoxide derivatives of C(18) fatty acids. LeAOS was active against both 13S-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid (13-HPOT) and 13S-hydroperoxy-9(Z),11(E)-octadecadienoic acid, whereas LeHPL showed a strong preference for 13-HPOT. These results suggest a role for LeAOS and LeHPL in the metabolism of 13-HPOT to jasmonic acid and hexenal/traumatin, respectively. LeAOS expression was detected in all organs of the plant. In contrast, LeHPL expression was predominant in leaves and flowers. Damage inflicted to leaves by chewing insect larvae led to an increase in the local and systemic expression of both genes, with LeAOS showing the strongest induction. Wound-induced expression of LeAOS also occurred in the def-1 mutant that is deficient in octadecanoid-based signaling of defensive proteinase inhibitor genes. These results demonstrate that tomato uses genetically distinct signaling pathways for the regulation of different classes of wound responsive genes.

Aldehyde-Lyases↗

PubMed2000

A novel approach to extract colon lumen from CT images for virtual colonoscopy.

An automatic method has been developed for segmentation of abdominal computed tomography (CT) images for virtual colonoscopy obtained after a bowel preparation of a low-residue diet with ingested contrast solutions to enhance the image intensities of residual colonic materials. Removal of the enhanced materials was performed electronically by a computer algorithm. The method is a multistage approach that employs a modified self-adaptive on-line vector quantization technique for a low-level image classification and utilizes a region-growing strategy for a high-level feature extraction. The low-level classification labels each voxel based on statistical analysis of its three-dimensional intensity vectors consisting of nearby voxels. The high-level processing extracts the labeled stool, fluid and air voxels within the colon, and eliminates bone and lung voxels which have similar image intensities as the enhanced materials and air, but are physically separated from the colon. This method was evaluated by volunteer studies based on both objective and subjective criteria. The validation demonstrated that the method has a high reproducibility and repeatability and a small error due to partial volume effect. As a result of this electronic colon cleansing, routine physical bowel cleansing prior to virtual colonoscopy may not be necessary.

Adult↗

PubMed2000

Searching for one versus two identical targets: when visual search has a memory.

A recent study has suggested that observers' visual explorations of the external world can proceed unimpaired when the visual environment precludes the operation of memory processes (as, for instance, when the display elements change locations every 100 ms). One theoretical limitation of this study was that distractors were the only elements that had the potential to be tagged during visual search. The present study sought to clarify the amnesic-search hypothesis by investigating whether memory processes can guide search in other contexts in which targets also have the potential to be tagged. Accordingly, the experimental conditions of the previous study were repeated using a different search task in which observers had to decide whether one target or two were present among a variable number of similar distractors. Under these search conditions, the present findings provided strong evidence that memory processes can guide visual search.

Adult↗

PubMed2000

Interrelationships between cellular nucleotide excision repair, cisplatin cytotoxicity, HER-2/neu gene expression, and epidermal growth factor receptor level in non-small cell lung cancer cells.

Nucleotide excision repair (NER) is a major repair mechanism for DNA lesions induced by cisplatin. Overexpressions of epidermal growth factor receptor (EGFR) and HER-2/neu have been reported to affect the sensitivity of certain human cancer cells to cisplatin, presumably by modification of DNA repair activity through interference with NER. Using an in vitro repair assay, we investigated NER activity of cisplatin-induced DNA lesions in a panel of 16 non-small cell lung cancer (NSCLC) cell lines. The interrelationships between NER activity, cisplatin sensitivity, HER-2/neu expression and EGFR level, were also analyzed. The results showed that high NER activity was closely correlated with cisplatin resistance and high levels of HER-2/neu expression (P<0.05). Analysis of the relationships between EGFR level and each of the other three parameters revealed no statistically significant correlations (all P values were >0.05 by Spearman rank correlation), but a trend of association (all the values of proportion of accordance were > or =62.5% by using a 2x2 contingency table). These results suggest that NER activity may play an important role in the cisplatin resistance of NSCLC cells and there may be an association between enhanced NER activity and high levels of p185neu and probably EGFR in NSCLC cells. The finding that high levels of EGFR showed very little influence on the relationship between p185neu and cisplatin resistance suggests that EGFR may be a less crucial factor in modulating the chemoresistance of NSCLC cells when compared with HER-2/neu.

Antineoplastic Agents↗

PubMed2000

Injury hospitalisation rates in Victoria, 1987-97: trends, age and gender patterns.

OBJECTIVE: To estimate the injury hospitalisation trends and the age and gender patterns in Victoria between 1987/88 and 1996/97. METHOD: The Victorian Injury Surveillance System maintains a collection of injury hospitalisation records in Victoria. We used loglinear models for rates to estimate the temporal trends and patterns by age group and gender of all-injury and cause-specific injury hospitalisation rates. RESULTS: The all-injury hospitalisation rate appeared stable until 1992/93, after which it increased substantially (1993/94 was 1.13 times that of 1987/88). While motor vehicle crash and fire/burn/scald injury hospitalisation rates decreased substantially, suicide attempt and self-inflicted injury hospitalisation rates more than doubled. The all-injury hospitalisation rate was highest for persons 75 years of age and older. Females had a lower all-injury hospitalisation rate than males up to 60-64 years of age and a higher rate thereafter. The cause-specific injury hospitalisation rates showed various age and gender patterns. CONCLUSION: Substantial increases in the all-injury hospitalisation rate were observed after the introduction of the casemix funding policy to public hospitals. There were remarkable variations in temporal trend and age and gender patterns of injury hospitalisation rates by cause of injury. IMPLICATIONS: Hospitalised injuries generally are serious and incur high cost. Certain injury causes and age and gender groups should receive particular attention for prevention efforts. The use of injury surveillance based on hospitalisation records should be improved and further expanded.

Adolescent↗

PubMed2000

Eicosanoid regulation of angiogenesis in human prostate carcinoma and its therapeutic implications.

Cancer of the prostate is the most commonly diagnosed cancer in America. There are several lines of evidence implicating the involvement of arachidonate 12-lipoxygenase, an enzyme metabolizing arachidonic acid to form 12(S)-hydroxyeicosatetraenoic acid (HETE), in prostate cancer progression. First, as prostate cancer reaches a more advanced stage, the level of 12-lipoxygenase expression is increased. Second, overexpression of 12-lipoxygenase in human prostate cancer cells stimulates angiogenesis and tumor growth. Third, an inhibitor of 12-lipoxygenase has been found effective against metastatic prostate tumor growth, and the inhibition of 12-lipoxygenase is related with the reduction of tumor angiogenesis. Collectively, these studies suggest that 12-lipoxygenase regulates tumor angiogenesis in prostate cancer and that inhibition of 12-lipoxygenase is a novel therapeutic approach for the treatment of prostate cancers.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2000

How strongly is muscle activity associated with joint moments?

In this commentary we question whether the relationship between muscle activity and joint moments is the same for natural motor tasks as for controlled experimental situations. An important consideration in this regard is the identification of the correct electromechanical delay (EMD) for comparing EMG and joint moment data. Data from recent cycling studies are used to illustrate the importance of EMD, and how changing task constraints can alter the relation between muscle activity and joint moment balance for bi-articular antagonist pairs.

Electromyography↗

PubMed2000

Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione.

One member of the OATP family of transporters, rat Oatp1, functions as an anion exchanger that is driven in part by the glutathione (GSH) electrochemical gradient, indicating that other OATP-related transporters may also be energized by this mechanism. The present study examined whether rat Oatp2 is also an anion exchanger, and, if so, whether it is energized by the GSH electrochemical gradient. As with Oatp1, uptake of 10 microM [(3)H]taurocholate in Oatp2-expressing Xenopus laevis oocytes was trans-stimulated by intracellular 0.2 mM unlabeled taurocholate, indicating bidirectional transport. Interestingly, [(3)H]taurocholate uptake in Oatp2-expressing oocytes was also trans-stimulated when oocytes were preloaded with GSH, S-methylglutathione, S-sulfobromophthalein-glutathione, S-dinitrophenyl glutathione, or ophthalmic acid (a GSH analog) but not by glutarate or N-acetylcysteine, suggesting that GSH derivatives and conjugates may function as intracellular substrates for Oatp2. Support for this hypothesis was provided by the demonstration of enhanced [(3)H]GSH and [(3)H]S-(2,4-dinitrophenyl)-glutathione efflux in Oatp2-expressing oocytes. However, in contrast to Oatp1, extracellular GSH failed to cis-inhibit uptake of [(3)H]taurocholate or [(3)H]digoxin in Oatp2-expressing oocytes, indicating that the stimulatory effect of high intracellular GSH concentrations is not due to a coupled exchange mechanism. Taken together, the results indicate that Oatp2 mediates bidirectional transport of organic anions by a GSH-sensitive facilitative diffusion mechanism and suggest that this transporter may play a role in cellular export of specific organic molecules.

Animals↗

PubMed2000

Metabolism and mode of inhibition of varicella-zoster virus by L-beta-5-bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil is dependent on viral thymidine kinase.

A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or mitochondrial DNA synthesis was observed at concentrations up to 200 microM. L-BVOddU was phosphorylated by viral thymidine kinase but not by human cytosolic thymidine kinase, and the antiviral activity of this compound is dependent on the viral thymidine kinase. Unlike other D-configuration bromovinyl deoxyuridine analogs, such as E-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-arabinofuranosyl-E-5-(2-bromovinyl)uracil, this compound was metabolized only to its monophosphate metabolite. The di- or triphosphate metabolites were not detected. This suggested that the inhibitory mechanism may be unique and different from other anti-herpesvirus nucleoside analogs.

Acyclovir↗

PubMed2000

Global gene expression profiles of Bacillus subtilis grown under anaerobic conditions.

Bacillus subtilis can grow under anaerobic conditions, either with nitrate or nitrite as the electron acceptor or by fermentation. A DNA microarray containing 4,020 genes from this organism was constructed to explore anaerobic gene expression patterns on a genomic scale. When mRNA levels of aerobic and anaerobic cultures during exponential growth were compared, several hundred genes were observed to be induced or repressed under anaerobic conditions. These genes are involved in a variety of cell functions, including carbon metabolism, electron transport, iron uptake, antibiotic production, and stress response. Among the highly induced genes are not only those responsible for nitrate respiration and fermentation but also those of unknown function. Certain groups of genes were specifically regulated during anaerobic growth on nitrite, while others were primarily affected during fermentative growth, indicating a complex regulatory circuitry of anaerobic metabolism.

Aerobiosis↗

PubMed2000

Characterization of a baculovirus alkaline nuclease.

All baculovirus genomes sequenced to date encode a homolog of an alkaline nuclease that has been characterized in the Herpesviridae. In this report we describe the characterization of the alkaline nuclease (AN) homolog of the Autographa californica multinucleocapsid nucleopolyhedrovirus (AcMNPV) (open reading frame 133). His-tagged AN constructs were expressed in recombinant baculoviruses and affinity purified, and then their enzymatic activity was characterized. AN was found to degrade linear DNA at alkaline pH, preferred Mg(2+) over Mn(2+), had optimal activity at 35 degrees C, and did not appear to have a salt requirement. To rule out contamination by the endogenous baculovirus gene product or a cellular enzyme, point mutations were introduced into a highly conserved domain of the gene. These mutations were found to markedly reduce or eliminate most of the activity of the affinity-purified enzyme. An antibody generated against the protein was used to analyze its expression by Western blot analysis. AN was found to be expressed at low levels by 12 h postinfection, with maximal expression at 24 h postinfection. Attempts to generate a virus with this gene inactivated were unsuccessful, suggesting that AN may be encoded by an essential gene.

Amino Acid Sequence↗

PubMed2000

Retroviral cDNA integration: stimulation by HMG I family proteins.

To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes.

DNA, Complementary↗

PubMed2000

Containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment.

To better understand the viral and host factors involved in the establishment of persistent productive infection by primate lentiviruses, we varied the time of initiation and duration of postinoculation antiretroviral treatment with tenofovir (9-[2-(R)-(phosphonomethoxy)propyl]adenine) while performing intensive virologic and immunologic monitoring in rhesus macaques, inoculated intravenously with simian immunodeficiency virus SIVsmE660. Postinoculation treatment did not block the initial infection, but we identified treatment regimens that prevented the establishment of persistent productive infection, as judged by the absence of measurable plasma viremia following drug discontinuation. While immune responses were heterogeneous, animals in which treatment resulted in prevention of persistent productive infection showed a higher frequency and higher levels of SIV-specific lymphocyte proliferative responses during the treatment period compared to control animals, despite the absence of either detectable plasma viremia or seroconversion. Animals protected from the initial establishment of persistent productive infection were also relatively or completely protected from subsequent homologous rechallenge. Even postinoculation treatment regimens that did not prevent establishment of persistent infection resulted in downmodulation of the level of plasma viremia following treatment cessation, compared to the viremia seen in untreated control animals, animals treated with regimens known to be ineffective, or the cumulative experience with the natural history of plasma viremia following infection with SIVsmE660. The results suggest that the host may be able to effectively control SIV infection if the initial exposure occurs under favorable conditions of low viral burden and in the absence of ongoing high level cytopathic infection of responding cells. These findings may be particularly important in relation to prospects for control of primate lentiviruses in the settings of both prophylactic and therapeutic vaccination for prevention of AIDS.

Adenine↗

PubMed2000

Role of K(+) channel expression in polyamine-dependent intestinal epithelial cell migration.

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K(+) channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) by governing the driving force for Ca(2+) influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K(+) channel gene expression, E(m), and [Ca(2+)](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, alpha-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca(2+) channels, the depolarized E(m) in DFMO-treated cells decreased [Ca(2+)](cyt) as a result of reduced driving force for Ca(2+) influx through capacitative Ca(2+) entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca(2+)](cyt) but also restored cell migration to normal. Removal of extracellular Ca(2+) or blockade of Kv channels (by 4-aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca(2+)](cyt) by increasing the driving force (the electrochemical gradient) for Ca(2+) influx and thus stimulates cell migration.

Animals↗