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Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 109 records · Page 6Linked to original sources

Three-dimensional representation of curved nanowires.

Nanostructures, such as nanowires, nanotubes and nanocoils, can be described in many cases as quasi one-dimensional curved objects projecting in three-dimensional space. A parallax method to construct the correct three-dimensional geometry of such one-dimensional nanostructures is presented. A series of scanning electron microscope images was acquired at different view angles, thus providing a set of image pairs that were used to generate three-dimensional representations using a matlab program. An error analysis as a function of the view angle between the two images is presented and discussed. As an example application, the importance of knowing the true three-dimensional shape of boron nanowires is demonstrated; without the nanowire's correct length and diameter, mechanical resonance data cannot provide an accurate estimate of Young's modulus.

Journal Article↗

Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity.

Interleukin-18 (IL-18) has been demonstrated to synergize with BCG for induction of a T-helper-type 1 (Th1) immune response. Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a recombinant (r) BCG strain that functionally secretes mouse (m) IL-18. This rBCG-mIL-18 strain significantly increased production of the major Th1 cytokine IFN-gamma in splenocyte cultures, at levels comparable to that elicited by control BCG plus exogenous rIL-18. IFN-gamma production by splenocytes was eliminated by addition of neutralizing anti-IL-18 antibody. Endogenous IL-12 played a favourable role whereas IL-10 played an adverse role in rBCG-mIL-18-induced IFN-gamma production. Enhanced host antimycobacterial immunity was observed in mice infected with rBCG-mIL-18 which showed less splenic enlargement and reduced bacterial load compared to control mice infected with BCG. Further, splenocytes from rBCG-mIL-18-infected mice, in response to BCG antigen, displayed increased production of IFN-gamma and GMCSF, decreased production of IL-10, elevated cellular proliferation and higher differentiation of IFN-gamma-secreting cells. rBCG-mIL-18 also enhanced BCG-induced macrophage cytotoxicity against bladder cancer MBT-2 cells in a dose-dependent manner. Neutralizing all endogenous macrophage-derived cytokines tested (IL-12, IL-18 and TNF-alpha) as well as IFN-gamma severely diminished the rBCG-mIL-18-induced macrophage cytolytic activity, indicating a critical role for these cytokines in this process. Cytokine analysis for supernatants of macrophage-BCG mixture cultures manifested higher levels of IFN-gamma and TNF-alpha in rBCG-mIL-18 cultures than in control BCG cultures. Taken together, this rBCG-mIL-18 strain augments BCG's immunostimulatory property and may serve as a better agent for bladder cancer immunotherapy and antimycobacterial immunization.

Animals↗

Novel murine model of pneumococcal pneumonia: use of temperature as a measure of disease severity to compare the efficacies of moxifloxacin and levofloxacin.

Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30 degrees C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < or = 30 degrees C were not significantly different from those seen in the lungs of mice allowed to die without intervention. These data support temperature change as a more subtle indicator of outcome than death and demonstrate that this could be used as a reliable end point for euthanasia. To test the utility of our model in a drug trial, we examined the efficacies of moxifloxacin and levofloxacin by using temperature as a measure of disease severity prior to and during treatment. Regardless of the antibiotic used, mice assessed as moderately ill (temperature > or = 32 degrees C) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32 degrees C). However, moxifloxacin offered better protection and greater bacterial clearance than did levofloxacin in all infected mice independent of disease severity. This model not only allows a more subtle evaluation of drug efficacy but also ensures a better degree of standardization and a more humane approach to drug efficacy studies involving animals.

Animals↗

Cloning and characterization of the mouse Arht2 gene which encodes a putative atypical GTPase.

ARHT is a new subgroup of the Rho family identified recently, which consists of two Rho-like genes, Arht1 and Arht2. ARHT may be involved in mitochondrial homeostasis and apoptosis. Constitutively active mutants of ARHT1 induced an aggregation of the mitochondrial network and resulted in an increased apoptotic rate of the cells. Here we report the molecular cloning and characterization of a novel mouse cDNA encoding a putative atypical GTPase protein, Arht2. Mouse Arht2 consists of 19 exons and has been mapped to mouse chromosome 17A3.3. Both human and mouse Arht2 genes are ubiquitously expressed in adult tissues. The results of RT-PCR experiments indicated that the Arht2 gene is expressed in all stages of mouse testis and reached the adult level of transcription at postnatal day 30. In situ hybridization revealed strong hybridization signals of Arht2 in residual bodies. In the mouse testis, Arht2 may be involved in the differentiation of testis and spermiogenesis. The molecular characterization of the mouse Arht2 gene may provide a clue for functional studies of the human ARHT genes.

Amino Acid Sequence↗

Clinical and radiological features of odontogenic ghost cell carcinoma: review of the literature and report of four new cases.

OBJECTIVES: To analyse systematically the clinical and radiological features of odontogenic ghost cell carcinoma (OGCC). METHODS: Clinical and radiological features of 22 OGCCs (4 new and 18 from the literature) were analysed. RESULTS: There were 17 (77%) males and 5 (23%) females (male-to-female ratio of 3.4:1). Ages ranged from 13 years to 72 years (mean 36.7) with a peak in the fourth (40.9%) and fifth (27.3%) decades. The maxilla was involved in 68% and the mandible in 32%. Our study confirmed that OGCC is more prevalent in Asians (12/18) than in other racial groups. The mixed radiolucent and radiopaque lesion pattern was the most frequent (14/19) compared with radiolucent lesions (5/19). 89% (17/19) showed poorly defined borders and 11% (2/19) showed well defined borders. Root resorption was reported in 31% (6/19) of patients and tooth displacements in 21%. CONCLUSIONS: OGCC demonstrates clinical and radiographic features of a malignant tumour with high recurrence.

Adult↗

Leukotriene A4 hydrolase as a target for cancer prevention and therapy.

Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc enzyme with the activities of epoxide hydrolase and aminopeptidase. As an epoxide hydrolase, LTA4H catalyzes the hydrolysis of the epoxide LTA4 to the diol, leukotriene B4 (LTB4), which mainly functions as a chemoattractant and an activator of inflammatory cells. As an aminopeptidase, LTA4H may process peptides related to inflammation and host defense. In a chronic inflammation-associated animal model of esophageal adenocarcinoma, we have shown that LTA4H was overexpressed in tumor as compared to normal tissues. Bestatin, an LTA4H inhibitor, suppresses tumorigenesis in this animal model. Since LTA4H has long been regarded as an anti-inflammatory target, we propose LTA4H as a target for prevention and therapy of cancers, especially those associated with chronic inflammation. Here we review the gene structure, expression, regulation and functions of LTA4H, as well as its involvement in carcinogenesis. We believe LTA4H/LTB4 may play an important role in chronic inflammation associated carcinogenesis by at least two mechanisms: a) the inflammation-augmenting effect on inflammatory cells through positive feedback mediated by its receptors and downstream signaling molecules; and b) the autocrine growth-stimulatory effect of LTB4 produced by epithelial cells, and the paracrine growth-stimulatory effect of LTB4 produced by inflammatory cells, on precancerous and cancer cells. Based on our present knowledge, inhibitors of LTA4H or antagonists of LTB4 receptors may be used alone or in combination with other agents (e.g., cyclooxygenase 2 inhibitors) in cancer prevention and treatment trials to test their effectiveness.

Animals↗

Effect of exercise on the bone strength, bone mineral density, and metal content in rat femurs.

We have investigated the effect of exercise on the bone strength, bone mineral density (BMD), and metal content in rat femurs. Five Wister rats acting as an exercised group (E group) were exercised at intervals on a treadmill every day for four weeks. Another five rats were fed in a cage, acting as a control group (C group), without any exercise. After four weeks, the bend strength, Young's modulus, BMD value, and metal content of the femurs were measured using a three-point bend test, Dual-Energy X-ray Absorptiometry (DEXA), and chemical analysis. The bend strength of the E group was 101+/-5 MPa, and that of the C group was 86+/-7 MPa. The Young's modulus was 1.16+/-0.03 GPa for the E group, and 0.98+/-0.06 GPa for the C group. The BMD values were 0.179+/-0.002 g/cm(2) for the E group, and 0.166+/-0.002 g/cm(2) for the C group. The Ca concentration was 230600 +/- 1500 microg/g for the E group, and 223000 +/- 2700 microg/g for the C group. The Zn concentration was 160 +/- 7 microg/g for the E group, and 188 +/- 8 microg/g for the C group.

Adaptation, Physiological↗

Field performance of VAQTA (inactivated, purified hepatitis a vaccine) in Chinese children in Jiangsu.

In Jiangsu, 30% of children between the ages of 5 and 8 years test seropositive for hepatitis A. The safety, tolerability, and immunogenicity of a 2-dose regimen (0, 6 months) of VAQTA (0.5 ml of 25U) administered IM in 50 healthy children aged 5 to 8 years without prior serological screening was evaluated. Blood samples were collected prior to the first dose and after each additional dose of VAQTA to determine the initial anti-HAV serostatus and response rates to the vaccine. Twelve children (24%) were initially seropositive and 38 (76%) were initially seronegative. Four weeks after the primary dose of VAQTA, 34 of the 38 subjects (89.5%, 95% CI 75 to 97) were anti-HAV seropositive. The geometric mean titer was 33.1 mIU/ml (95% CI 22.4 to 49.0). After the booster dose at 6 months, all the subjects were seropositive (37/37), giving a seroconversion of 100% (95% CI: 90, 100). The geometric mean titer was 7585.8 mIU/ml (95% CI: 5623.4 to 10,471.3). Adverse experiences were generally mild and transient. Results of this study are consistent with results from a previous double-blind randomized trial of this vaccine and confirm that VAQTA is highly immunogenic, and generally well-tolerated.

Child↗

Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours.

This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

Adult↗

Microbial fed-batch production of 1,3-propanediol by Klebsiella pneumoniae under micro-aerobic conditions.

The microbial production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under micro-aerobic conditions was investigated in this study. The experimental results of batch fermentation showed that the final concentration and yield of 1,3-PD on glycerol under micro-aerobic conditions approached values achieved under anaerobic conditions. However, less ethanol was produced under microaerobic than anaerobic conditions at the end of fermentation. The batch micro-aerobic fermentation time was markedly shorter than that of anaerobic fermentation. This led to an increment of productivity of 1,3-PD. For instance, the concentration, molar yield, and productivity of 1,3-PD of batch micro-aerobic fermentation by K. pneumoniae DSM 2026 were 17.65 g/l, 56.13%, and 2.94 g l(-1) h(-1), respectively, with a fermentation time of 6 h and an initial glycerol concentration of 40 g/l. Compared with DSM 2026, the microbial growth of K. pneumoniae AS 1.1736 was slow and the concentration of 1,3-PD was low under the same conditions. Furthermore, the microbial growth in fed-batch fermentation by K. pneumoniae DSM 2026 was faster under micro-aerobic than anaerobic conditions. The concentration, molar yield, and productivity of 1,3-PD in fed-batch fermentation under micro-aerobic conditions were 59.50 g/l, 51.75%, and 1.57 g l(-1) h(-1), respectively. The volumetric productivity of 1,3-PD under microaerobic conditions was almost twice that of anaerobic fed-batch fermentation, at 1.57 and 0.80 g l(-1) h(-1), respectively.

Aerobiosis↗

SVM-Prot: Web-based support vector machine software for functional classification of a protein from its primary sequence.

Prediction of protein function is of significance in studying biological processes. One approach for function prediction is to classify a protein into functional family. Support vector machine (SVM) is a useful method for such classification, which may involve proteins with diverse sequence distribution. We have developed a web-based software, SVMProt, for SVM classification of a protein into functional family from its primary sequence. SVMProt classification system is trained from representative proteins of a number of functional families and seed proteins of Pfam curated protein families. It currently covers 54 functional families and additional families will be added in the near future. The computed accuracy for protein family classification is found to be in the range of 69.1-99.6%. SVMProt shows a certain degree of capability for the classification of distantly related proteins and homologous proteins of different function and thus may be used as a protein function prediction tool that complements sequence alignment methods. SVMProt can be accessed at http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi.

Amino Acid Sequence↗

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein.

Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma-specific band of serum gamma-glutamyl transferase (GGTII), and alpha-fetoprotein (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC) and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HCC patients was higher than that in cirrhotic patients. A total of 53.3% of patients (64 out of 120) with HCC had PIVKAII levels above 40 mAU ml(-1). However, only 13 patients with cirrhosis had higher PIVKA II levels. Of 32 small HCC patients, 13 (40.6%) had PIVKAII values above 40 mAU ml(-1). An increased concentration of AFP (i.e. 20 ng ml(-1)) was observed in 70 out of 120 (58.3%) patients with HCC and in 33 out of 90 (36.7%) patients with cirrhosis. Positive GGTII was found in 74.0% (89 out of 120) cases of HCC (sensitivity), in 16 of 90 cases of cirrhosis, and 14 of 32 (43.8%) small HCC patients had GGTII positive. No significant correlation was found between serum levels of AFP and PIVKAII. Combining the information from PIVKAII, AFP, and GGTII significantly increases the sensitivity over AFP alone. PIVKAII and GGTII are useful tumour markers complementary to AFP for diagnosis of HCC.

Adult↗

KDBI: Kinetic Data of Bio-molecular Interactions database.

Understanding of cellular processes and underlying molecular events requires knowledge about different aspects of molecular interactions, networks of molecules and pathways in addition to the sequence, structure and function of individual molecules involved. Databases of interacting molecules, pathways and related chemical reaction equations have been developed. The kinetic data for these interactions, which is important for mechanistic investigation, quantitative study and simulation of cellular processes and events, is not provided in the existing databases. We introduce a new database of Kinetic Data of Bio-molecular Interactions (KDBI) aimed at providing experimentally determined kinetic data of protein-protein, protein-RNA, protein-DNA, protein-ligand, RNA-ligand, DNA-ligand binding or reaction events described in the literature. KDBI contains information about binding or reaction event, participating molecules (name, synonyms, molecular formula, classification, SWISS-PROT AC or CAS number), binding or reaction equation, kinetic data and related references. The kinetic data is in terms of one or a combination of the following quantities as given in the literature of a particular event: association/dissociation or on/off rate constant, first/second/third/. order rate constant, equilibrium rate constant, catalytic rate constant, equilibrium association/dissociation constant, inhibition constant and binding affinity constant. Each entry can be retrieved through protein or nucleic acid or ligand name, SWISS-PROT AC number, ligand CAS number and full-text search of a binding or reaction event. KDBI currently contains 8273 entries of biomolecular binding or reaction events involving 1380 proteins, 143 nucleic acids and 1395 small molecules. Hyperlinks are provided for accessing references in Medline and available 3D structures in PDB and NDB. This database can be accessed at http://xin.cz3.nus.edu.sg/group/kdbi/kdbi.asp.

DNA↗

Foreign body injury in children in the twentieth century: a modern comparison to the Jackson collection.

OBJECTIVE: To compare two databases of foreign body (FBs) objects causing injury in children (>20 years of age) and record differences in size, shape and material for children at risk over a 70-year period of time. STUDY DESIGN: Retrospective analysis of the Jackson collection (JC) of FBs (1920-1932) and a 12-year modern study (MS) of data taken from 25 children's hospitals in North America over the period 1988-2000. Digital images were obtained of the JC collection. METHODS: Identify age, sex, and type of products, size, shape, and consistency of material from the injury-producing FBs. Statistical Processing for Social Sciences was used for analysis of JC versus MS. RESULTS: 5528 children were evaluated from the MS, and compared with 1238 from the JC. Boys remain at greater risk than young girls (53% versus 47%) over the 70-year period of study. Coins have replaced safety pins (31% versus 15%) as the most common offending FBs. Although 99% of FBs causing injury are less than 1.25 in. in greatest diameter in both the JC and MS, 100% of FBs are eliminated when the test size is greater than 1.75 in. CONCLUSIONS: Boys remain at greater risk of injury over the last 60 years. However, coins have now emerged as the leading cause of injury in children. Children achieve greater protection from risk by modification of the Small Parts Test Fixture (SPTF) from 1.25 to 1.75 in. diameter.

Adolescent↗

The South African experience with ingestion injury in children.

INTRODUCTION: The Red Cross Children's Hospital is the only children's hospital in South Africa. It has a dedicated trauma unit for all children under the age of 13 and serves a population of approximately 2 million inhabitants. As part of the Child Accident Prevention Foundation program we have kept a database of all children treated for trauma in our hospital since 1991. Presently, we have over 88,000 entries in our database. AIM: To study our experience with ingested foreign bodies in children. MATERIALS AND METHODS: A retrospective study was performed using the CAPFSA database of a total of 3677 patients presenting with foreign bodies. The hospital folders were searched using a standardised data extraction form. Only foreign bodies aspirated or ingested were included. RESULTS: To date, 241 folders have been analysed. DEMOGRAPHICS: Both sexes were equally affected (boys 49%). Age ranged between 0 and 12 years, although there was only one child under the age of 1. At the age of 3 years there was a peak in incidence (24% of all cases). Nature of ingested object: Although the objects were from a range of materials, most were metal (40%) or plastic (23%). The most commonly ingested object was a coin (28%), a ball (20%) or bone (8%). The size ranged from 0.1 to 3 cm (as measured by virtual ring), the most common size of an ingested foreign body was 0.5 cm. Anatomical site: The most common anatomical site of impaction was the nose (41%), followed by the oesophagus (20%), the stomach (14%) and bowel (11%). Other anatomical sites included hypopharynx, nasopharynx, bronchus, larynx and oral cavity. Severity of symptoms: Only 0.4% of our cases were assessed as being severe, 14% as moderate, and 44% as mild. Forty-two percent (42%) had no symptoms. Removal: Fifty-seven percent (57%) of ingested foreign bodies were removed surgically, 19% were left in situ, 14% spontaneously dislodged and only 1% was removed by Foley catheter manipulation. CONCLUSION: A presentation with a foreign body is quite common in our patient population, representing approximately 4.2% of all our cases. The majority of ingested foreign bodies produced mild or no symptoms, needed surgical removal and had no complications.

Bronchi↗

Application of data for prevention of foreign body injury in children.

BACKGROUND: To develop design criteria for consumer products, based on foreign body injury and fatality data, to prevent airway obstruction injuries to children. METHOD: Beginning in 1988, RAM Consulting has created a worldwide database of foreign body injuries. This ongoing project now includes approximately 7000 data points from 51 children's hospitals in 15 countries located on five continents. Statistical analysis of these data, especially in terms of size, shape and consistency of the object and obstruction location and severity of injury for the patient has allowed the creation of an injury prevention criterion. RESULTS: Analysis of these data reveals that adoption of an injury prevention criteria based on the use of a 1.50 in. (38.10 mm) diameter gauge for non-spherical objects and a 1.75 in. (44.50 mm) diameter gauge for spherical objects would greatly reduce airway obstruction injuries to children. Furthermore, the data show that this criterion is independent of country and culture. However, the data suggest that a child's exposure to the "mix" of objects that may cause airway obstruction varies with the country and culture of the child. For example, coins are well represented in the database, however, some countries make more coins than other countries and the exposure level may have made the difference in the occurrence of incidents. CONCLUSIONS: Airway obstruction injuries from consumer products could be greatly decreased by the adoption of the presented injury prevention criteria that is founded in a statistical analysis of known objects that have caused injury. This criteria is dependent on object characteristics and is independent of the country or culture of the child.

Adolescent↗

Altered temporal pattern of mechanically evoked C-fiber activity in a model of diabetic neuropathy in the rat.

While enhanced nociceptor activity has been demonstrated in models of painful peripheral neuropathy, analyses of activity pattern, which could play a role in the symptoms experienced as well as help elucidate underlying mechanism, are still limited. We evaluated the pattern of C-fiber activity, in response to mechanical and chemical stimuli, in a rat model of diabetes induced by a pancreatic beta-cell toxin, streptozotocin (STZ). In diabetic rats the number of action potentials produced by threshold and suprathreshold (10 g) sustained (60 s) mechanical stimuli was elevated in approximately half of C-fibers. These high-firing C-fibers demonstrated a disproportionate increase in interspike intervals (ISIs) between 100 and 199 ms, compared with low-firing diabetic and control C-fibers. The co-efficient of variability (CV2), a frequency independent measure of ISI variability, was also greater in high-firing fibers, compared with control fibers. Unexpectedly, instantaneous frequency of the initial burst of activity during the first second was lower in high-firing fibers, even though the average frequency over the last 59 s was significantly higher. The number of action potentials evoked by a noxious chemical stimulus, 300 and 600 mM KCl, injected adjacent to the mechanical receptive field was also significantly increased in C-fibers from diabetic rats and mechanically high-firing fibers had more action potentials in response to KCl than control fibers and a disproportionate increase in ISIs between 100 and 199 ms for responses to chemical stimuli appeared only in mechanically high-firing C-fibers, compared with the mechanically low-firing diabetic or control C-fibers. There was, however, no corresponding change in CV2 or instantaneous frequency plots for the response to chemical stimulation in mechanically high-firing fibers, as there was in the response to mechanical stimulation. Our data demonstrate specific changes in firing pattern of high-firing C-fibers in the rat model of painful neuropathy produced by STZ-diabetes that might contribute to the symptoms experienced by patients.

Action Potentials↗