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Biomedical subjects

L C Chen

Publications and source records attributed to L C Chen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effects of concentrated ambient particles in rats and hamsters: an exploratory study.

Considerable controversy surrounds the biological plausibility of adverse effects from exposure to ambient particulate matter (PM)*, chiefly because these adverse effects have been observed at particle mass concentrations below those that have been shown to produce effects in healthy animals and human volunteers in the laboratory. To address this research gap, we examined the potential for concentrated ambient PM to produce pulmonary and cardiovascular changes in compromise rodent models. Normal healthy and monocrotaline-treated rats received single or multiple exposures to concentrated ambient PM, and their responses were tested using functional, cellular, biochemical, and histological endpoints. Analyses determined that no changes in pulmonary function or structure occurred after exposure to concentrated ambient PM. Cardiac arrhythmias did not increase after PM exposure in normal or monocrotaline-treated rats. Increased atrial conduction time, accompanied by a decrease in the duration of the T wave portion of the electrocardiogram (ECG) waveform, was observed in PM-exposed monocrotaline-treated rats in one experiment. In addition, on several but not all exposure days, small yet statistically significant increases in heart rate and peripheral blood cell differential counts were observed in normal and monocrotaline-treated rats within 6 hours after exposure to concentrated ambient PM. The observed changes in cardiovascular parameters in rats returned to control values by 24 hours after exposure. In a hamster cardiomyopathy model, no adverse cardiac or pulmonary changes were detected after exposure to concentrated ambient PM. Thus, these studies found that cardiopulmonary effects could be produced in rats, but not in hamsters with cardiomyopathy, exposed to concentrated ambient PM. None of the changes occurred on every exposure day and none appeared to be life threatening. Thus, the cardiac changes may reflect changes in homeostasis that could affect individuals who are critically ill, and these findings do not resolve the biological plausibility of adverse health effects associated with ambient PM in epidemiologic studies.

Age Factors↗
PubMed2000

Association of diarrhoea and upper respiratory infections with weight and height gains in Bangladeshi children aged 5 to 11 years.

INTRODUCTION: The association between infection and growth delay is not well documented in school-age children in developing countries. We conducted a prospective cohort study to examine the association between infectious disease and weight and height gains among Bangladeshi children. METHODS: A one-year follow-up study was performed to elucidate the determinants and consequences of physical growth of children under five years of age. The study included 135 households randomly selected from four villages in the Matlab area. RESULTS: The most frequent infections were upper respiratory infections (mean = 4 episodes or 27 days per year) followed by non-dysenteric diarrhoea (mean = 2.3 episodes or 15 days per year) and dysentery (mean = 0.2 episodes or 2 days per year). The number of episodes and their duration decreased significantly with age. Over a 12-month period the mean weight gain was 1.3 kg and the mean increase in height was 2.9 cm. The total number of days when diarrhoea occurred was negatively associated with annual weight gain (regression coefficient beta = -7 g per day, P = 0.02), with adjustment for age, sex, energy and protein intake, and household land ownership. The incidence of diarrhoeal disease was significantly associated with weight gain in intermediate models but only marginally associated with it in the final multivariate model (P = 0.08). Neither the incidence nor the duration of upper respiratory infections was associated with weight gain. Height gain was not significantly associated with the duration or incidence of either category of illness. Diarrhoea was a significant correlate of retarded weight gain among children above preschool age, whereas upper respiratory infections were not. DISCUSSION: Diarrhoeal morbidity slowed growth in children well beyond the weaning age, suggesting that increased attention should be given to the study of the continuous impact of diarrhoea in children aged over 5 years. An understanding of the determinants of growth in school-age children in developing countries would maximize the health and developmental outcomes that are the target of international child survival strategies at younger ages.

Bangladesh↗
PubMed1999

Efficient discovery of inhibitory ligands for diverse targets from a small combinatorial chemical library of chimeric molecules.

Living systems are mainly composed and regulated by compounds in four biochemical classes and their polymers-nucleotides, carbohydrates, lipids, and amino acids. Early combinatorial chemistry libraries consisted of peptides. The present report describes the general bioactivity and biophysical properties of a combinatorial chemical library that used glyco, nucleotidyl, and lipid building blocks. The resulting chimeric combinatorial library of 361 compounds had a confirmed cumulative hit rate of 0.16%, which is 8-fold higher than a commonly claimed industrial benchmark of 0. 02%. It produced 7 structurally confirmed hits for a third of 12 proprietary drug discovery projects, and these comprised a variety of molecular targets. Diversity analyses demonstrated that despite the small number of compounds, a wider range of diversity space was covered by this library of biochemical chimeras than by a branched tripeptide library of the same size and similar generic formula.

Binding Sites↗
PubMed1999

Pharmacokinetic study of paeoniflorin in mice after oral administration of Paeoniae radix extract.

Quantification of paeoniflorin, the principal bioactive component of Paeoniae radix, in mice plasma following oral administration of Paeoniae radix extract was achieved by using a simple and rapid high-performance liquid chromatographic method. The calibration curve for paeoniflorin was linear (r2 = 0.998) over the concentration range 10-200 ng/ml. The coefficients of variation of intra- and inter-day assays were 15.04, 7.31, 6.14, 6.55, 6.63% and 12.71, 6.07, 3.61, 5.51, 4.52% at concentrations of 10, 60, 100, 160, 200 ng/ml, respectively. The recoveries of paeoniflorin from mice plasma were found to be 74.49, 76.83, 80.38 and 80.56% for concentrations of 30, 80, 120 and 160 ng/ml, respectively. The plasma concentration-time curves were fitted with mean terminal half-lives (t(1/2)) of 94.16 min.

Animals↗
PubMed1999

Astroglial differentiation of cortical precursor cells triggered by activation of the cAMP-dependent signaling pathway.

In the developing brain, differentiation of neural precursors into neurons or glial cells occurs in response to neurotrophic factors acting on the cell surface. Intracellular signaling mechanisms that relay information to initiate differentiative responses of neural precursor cells are poorly understood. To investigate whether stimulation of the cAMP-dependent signaling pathway participates in differentiative responses of cells in the developing CNS, we performed experiments using both conditionally immortalized neural precursor cells (RC2.E10 cells) and primary cultures of cells from developing rat cortex. Initially, we determined that RC2.E10 cells retain phenotypic features of neural precursors after inactivation of the immortalizing oncogene, a temperature-sensitive mutant of the simian virus 40 large-T antigen (SV40T). We found that, once SV40T is inactivated, RC2.E10 cells cease to divide and die. However, RC2. E10 cells can proliferate in the presence of basic fibroblast growth factor. In addition, they express nestin, a marker of neural precursor cells. Both RC2.E10 cells and primary cortical precursor cells undergo astroglial differentiation in response to cAMP stimulation by treatment with 8-bromo-cAMP. In both cases, cAMP-induced astrocyte differentiation is characterized by morphological changes, stimulation of glial fibrillary acidic protein expression, downregulation of nestin expression, and decreased proliferation. No increases in the expression of neuronal or oligodendrocytic markers were observed. Our results support the notion that the developing CNS contains neural precursor cells with the capacity of undergoing astrocyte differentiation in response to increased intracellular cAMP concentrations.

Animals↗
PubMed1999

Salicylate-enhanced activation of transcription factors induced by interferon-gamma.

Salicylate enhanced the interferon-gamma-dependent activation of two transcription factors in a murine macrophage cell line: signal transducer and activator of transcription (STAT)1 and interferon-gamma-responsive factor 1. Salicylate alone did not activate these transcription factors. This enhancement was reflected by increased DNA-binding activities and was the consequence of prolonged tyrosine phosphorylation of these transcription factors following interferon-gamma treatment. However, salicylate did not directly inhibit protein-tyrosine phosphatase activity in nuclear extracts of interferon-gamma-treated cells. The enhanced activation of STAT1 resulted in increased induction of mRNA encoding interferon regulatory factor-1. These results not only demonstrate that aspirin and its metabolite salicylate may have pro-inflammatory as well as anti-inflammatory effects but also raise the possibility that new cellular targets may be identified for modulating the Janus kinase-STAT signalling pathway.

Animals↗
PubMed1999

Induction of 12-lipoxygenase expression by transforming growth factor-alpha in human epidermoid carcinoma A431 cells.

Transforming growth factor-alpha (TGF-alpha) increased the expression of 12-lipoxygenase activity in a time-dependent manner in human epidermoid carcinoma A431 cells. The increase of 12-lipoxygenase activity was accompanied by an increase in 12-lipoxygenase mRNA. The effect of TGF-alpha on the promoter activation of 12-lipoxygenase gene was analyzed by using the luciferase fusion vectors. A dose-dependent effect of TGF-alpha on the reporter activity was observed, which paralleled with its effect on enzyme activity. Transient transfection with a series of 5'-deleted constructs showed that the 5'-flanking region spanning from -224 to -100 bp from translation starting site played an important role for TGF-alpha response. Site-directed mutagenesis and gel mobility shift assay indicated that two Sp1 binding sequences residing at -158 to -150 bp and 123 to -114 bp were responsible for the TGF-alpha in activation of human 12-lipoxygenase gene transcription. Expression of Sp1, but not Sp3, stimulated the promoter activity of 12-lipoxygenase in SL2 cells, indicating that the binding of Sp1 with Sp1 binding sequences played a significant role in the regulation of 12-lipoxygenase gene.

Arachidonate 12-Lipoxygenase↗
PubMed1999

Labeling of proteins with [35S]methionine and/or [35S]cysteine in the absence of cells.

Incubation of [35S]methionine and [35S]cysteine with bovine albumin, globulin, catalase, hemoglobin, or human globulin resulted in incorporation of the 35S label into each of these proteins. Trichloroacetic acid (TCA) precipitation revealed that the percentage of label incorporated ranged from 1 to 15%. The 35S labeling was resistant to dissociation by reducing SDS-PAGE, prolonged dialysis against 4 M urea, heating, TCA precipitation, and dilution by gel filtration. The labeling effect was more efficient with [35S]cysteine than [35S]methionine. Incubation of 35S label with proteins differing in methionine and cysteine content revealed no requirement for sulfur-containing amino acids in the target protein. Protein carboxymethylation reduced but did not prevent 35S label incorporation. Amino acid analysis of labeled proteins revealed that the radioactive label was not consistently associated with an individual amino acid. Differences in the ability of various proteins to spontaneously label with these amino acids suggest caution in the interpretation of metabolic labeling experiments and the necessity for inclusion of additional controls. Alternatively, our experience indicates a potentially useful method for labeling proteins in the absence of cells.

Amino Acid Substitution↗
PubMed1999

PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis).

This paper aims to remind paediatric clinicians to suspect and confirm 'PFAPA' syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome). We report two cases of PFAPA syndrome: a 3-year-old healthy boy with atopic rhinitis and a boy aged 8 years 5 months who simultaneously had lymphocytic vasculitis syndrome treated with immunosuppressive drugs. Both met Marshall's criteria. The literature regarding PFAPA syndrome was complied using a Medline search for articles published between 1963 and 1998 and we then reviewed the reference lists of the articles. The Medline search revealed 28 cases with available clinical manifestations, management and prognosis. Our study describes two additional cases. We divided the cases into typical (28 cases) and atypical (two cases) PFAPA syndrome. In typical PFAPA, the age of onset was less than 5 years in most cases and the patients presented 4.9 +/- 1.4 days of fever (100%), pharyngitis (89.3%), cervical adenitis (72.1%), stomatitis (71.4%), malaise (64.3%), headache (60.7%), abdominal pain (53.6%) and nausea/vomiting (17.9%). Afebrile intervals were 3.2 +/- 2.4 months and increased with age. The time from initial onset to final episode was 3 years 7 months +/- 3 years 6 months. The total number of episodes was 8.3 +/- 2.5 (range 6-14). Effective treatment included steroids, tonsillectomy/adenoidectomy and cimetidine. The general outcome was good. In atypical PFAPF, the clinical manifestations were similar to those of typical PFAPA except that the age of onset was more than 5 years, and life-threatening intestinal perforation happened once in a patient with underlying Fanconi's anaemia. It was concluded that typical PFAPA syndrome is benign and can be diagnosed by detailed history-taking and from physical findings during repeated febrile episodes with tests to rule out other periodic fever syndromes. A review of the literatures since the first report in 1987 has shown that typical PFAPA syndrome is not associated with significant long-term sequelae and has a good response to steroids. One patient with atypical PFAPA, who received low-dose steroids for over 1 year, developed intestinal perforation after an increment of the 7-day steroid dose. If an underlying problem requires long-term immunosuppressive medication, it is wiser to choose cimetidine rather than increasing the steroid dosage to resolve atypical PFAPA.

Azathioprine↗
PubMed1999

A centrifugal particle concentrator for use in inhalation toxicology.

Epidemiologic studies have provided strong evidence that episodic exposure to ambient particulate matter is associated with increases in morbidity and mortality. These adverse effects have been demonstrated at concentrations far below the National Ambient Air Quality Standard (NAAQS), and thus, the biological plausibility of these effects has been questioned. For the purpose of exposing test animals to relevant and reproducible exposure concentrations of ambient particulate matter (PM), we have developed a simple and inexpensive concentrator system that can concentrate ambient particles 10-fold. A high-volume blower is used to deliver ambient air to the inlet manifold of a centrifugal concentrator and the entrained particles travel along a concentric annulus formed by a stationary solid outer cylinder and a porous inner cylinder rotating at high speed (up to 12,500 rpm). Suction applied at one end of the porous shaft causes the dispersion medium (air) to pass through the porous cylinder and into the shaft. Since the rotational velocity of airborne particles is comparable to that of the rotating cylinder near its surface, the particles move radially outward due to the centrifugal force, in addition to their motion laterally along the cylinder and inward due to the suction of air into the rotating porous cylinder. The particles reach their highest concentration near the outlet manifold, where they enter the exposure chamber under positive pressure ( approximately 0.4 cm H2O). Except for coarse particle loss due to impaction and diffusional loss of ultrafine particles in the concentrator, the increase in particle concentration is the ratio of the flow rates for the inlet air and the air delivered to the exposure chamber. We have used the centrifugal concentrator to deliver concentrated ambient urban PM to a nose-only exposure chamber and examined the concentrating effect across ambient particle sizes.

Air↗
PubMed1999

Antibody response to Cryptococcus neoformans proteins in rodents and humans.

The prevalence and specificity of serum antibodies to Cryptococcus neoformans proteins was studied in mice and rats with experimental infection, in individuals with or without a history of potential laboratory exposure to C. neoformans, human immunodeficiency virus (HIV)-positive individuals who developed cryptococcosis, in matched samples from HIV-positive individuals who did not develop cryptococcosis, and in HIV-negative individuals. Rodents had little or no serum antibody reactive with C. neoformans proteins prior to infection. The intensity and specificity of the rodent antibody response were dependent on the species, the mouse strain, and the viability of the inoculum. All humans had serum antibodies reactive with C. neoformans proteins regardless of the potential exposure, the HIV infection status, or the subsequent development of cryptococcosis. Our results indicate (i) a high prevalence of antibodies reactive with C. neoformans proteins in the sera of rodents after cryptococcal infection and in humans with or without HIV infection; (ii) qualitative and quantitative differences in the antibody profiles of HIV-positive individuals; and (iii) similarities and differences between humans, mice, and rats with respect to the specificity of the antibodies reactive with C. neoformans proteins. The results are consistent with the view that C. neoformans infections are common in human populations, and the results have implications for the development of vaccination strategies against cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Use of standard radiography to diagnose paranasal sinus disease of asthmatic children in Taiwan: comparison with computed tomography.

Paranasal sinus disease and bronchial asthma are frequently associated. Computed tomography imaging is currently the most reliable method for confirming the diagnosis of sinusitis. Due to the cost and amount of radiation during computed tomography, our aim was to analyze whether standard radiography, under computed tomography-control, had a reasonable degree of confidence in the diagnosis of sinusitis. Fifty-three asthmatic patients (42 males and 11 females) with a mean age of 9 years (range 4-14) were enrolled. We evaluated the maxillary sinuses, ethmoidal sinuses, frontal sinuses, and sphenoidal sinuses using standard radiography (Waters' view, Caldwell view, and lateral view) and compared with computed tomography (coronal views), the latter served as a standard. Computed tomography (CT) showed paranasal sinusitis in 58% (31/53) of the asthmatic children. Compared with the results of computed tomography, standard radiography revealed a sensitivity of 81.1% and a specificity of 72.7% for maxillary sinusitis. The sensitivity and specificity for ethmoidal, frontal, and sphenoidal sinusitis were 51.8%, 84.8%; 47.3%, 87.2%; and 40.8%, 93.3%, respectively. In 21 (40%) of the 53 patients, discrepancies were seen between the interpretations of standard radiography c and those of CT scans. In patients with maxillary sinusitis, the correlation between standard radiography and CT was good. However, ethmoidal, frontal, and sphenoidal sinusitis were poorly demonstrated using radiography. Standard radiography can be recommended as a screening method for maxillary sinusitis, but it is not recommended for the diagnosis of other paranasal sinusitis.

Adolescent↗
PubMed1999

[Coding theories and analyzing methods of information contained in neuronal spike trains].

Information transmission in the central nervous system relies on neurons working in relays. At chemical synapses information transmission is by means of neurotransmitters, whereas long-distance transmission is carried out by action potentials conducting along nerve fibers. Hence how to pick up and analyze information contained in the spike trains are important topics of several branches of sciences such as neuroscience, bioinformatics, etc. So far there is lack of ideal ways and means. This review briefly introduces the advantages and limitations of the principal coding theories and analyzing methods of information contained in spike trains, and the progress in this field.

Action Potentials↗
PubMed1998

The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers.

Amplification is a key mechanism whereby a cancer cell increases the message level of genes that confer a selective advantage when they are overexpressed. In breast cancer, there are many chromosome regions present in multiple copies relative to overall DNA copy number (amplicons), and their target genes are unknown. Using differential display, we have cloned and sequenced the full coding region of a candidate amplicon target gene located on chromosome 13. This candidate is the human homologue of the Caenorhabditis elegans cul-4 gene, cul-4A, a member of the novel cullin gene family, which is involved in cell cycle control of C. elegans. cul-4A was amplified and overexpressed in 3 of 14 breast cancer cell lines analyzed, and it was overexpressed in 8 additional cell lines in which it was not amplified. The latter observation, indicating that its overexpression can occur by mechanisms other than gene amplification, suggests that cul-4A plays a key role in carcinogenesis. Moreover, cul-4A was found to be amplified in 17 of 105 (16%) cases of untreated primary breast cancers, and 14 of 30 cases analyzed (47%) were shown by RNA in situ hybridization to overexpress cul-4A. These results suggest that up-regulation of cul-4A may play an important role in tumor progression.

Amino Acid Sequence↗
PubMed1998

Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system.

The improvement in solubility of indomethacin due to the presence of menthol in various cosolvent systems consisting of water, alcohol and propylene glycol was examined by a mixture design in this study. A proper model to quantitatively describe the effect of menthol at different concentrations on the solubility of indomethacin was compared based on the statistical parameters provided by DESIGN-EXPERT. Then three cosolvent systems with the addition of menthol to solubilize indomethacin to extents of 1.0, 1.5 or 2.0% w/v were selected. The penetration of indomethacin through nude mouse skin from these three cosolvent systems with the addition of 0-12% menthol was investigated and followed by a discussion on the penetration mechanism. The results showed that menthol was able to improve drug solubility to different extents for different cosolvent systems. Optimally, a cosolvent system with an equal ratio of the three solvents, water, alcohol and propylene glycol, showed the highest extent of improvement in the solubility at all concentrations of menthol. The enhancement factors for indomethacin penetration due to menthol in different cosolvent systems were compared, based either on the permeation coefficient (Kp) or the separate overall effects on the skin (Flux). Both comparisons gave similar results. The influence of menthol was more significant compared to that of the cosolvent systems and the extent of this influence increased with an increase in the amount added, reaching a maximum at a specific amount of menthol for each different cosolvent system.

Animals↗
PubMed1998

Induction of interleukin-8 by ozone is mediated by tyrosine kinase and protein kinase A, but not by protein kinase C.

Ozone is one of the most common air pollutants humans routinely inhale. We have previously shown that in vitro ozone exposure induces the DNA-binding activities of NF-kappaB and NF-IL6 as well as the expression of interleukin 8 in respiratory epithelial cells. In this study, we investigated intracellular signaling steps mediating ozone-induced inflammatory mediator release. A549 cells, a type II like alveolar epithelial cell line, were exposed in vitro to air or 0.1 ppm of ozone in the presence of several kinase inhibitors. Exposure to ozone increased interleukin 8 expression and transcription factor activities in a protein tyrosine kinase (PTK)-dependent and protein kinase A (PKA)-dependent, yet protein kinase C (PKC)-independent, manner. Furthermore, ozone-induced PTK and PKA activities but failed to induce PKC activity. In addition, our results suggest that ozone-induced PTK and PKA activities were reactive oxygen intermediate dependent and occurred in parallel, because specific inhibitors for PTK and PKA failed to block the other kinase's activity. These results indicate that PTK and PKA activities are early events in the signal transduction cascade mediating the ozone-induced activation of NF-kappaB and NF-IL6 as well as the release of interleukin 8.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes.

Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumors in rats (Wistar strain) but not in mice (NMRI strain). The protein metallothionein (MT) plays an important role in Cd detoxification, and it has been suggested that differential inducibility of pulmonary MT may lead to interspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been examined in rats or mice. We compared pulmonary MT expression in Wistar Furth (WF) rats with that in DBA and C57 mice, following a single 3-h exposure to CdO fumes containing 1 mg Cd/m3. Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/argon furnace gases. We observed differential intra- and interspecies inducibility of the MT gene in the lung following Cd inhalation. DBA mice exhibited greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein content, and number of MT positive cells relative to C57 mice. WF rats showed lower transcription and translation responses of the MT gene upon Cd stimuli than C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, predict greater susceptibility of C57 to the carcinogenic effects of inhaled Cd. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of this rat strain to develop malignant lung tumors after chronic exposure to Cd via inhalation. Parallel to our findings in mice, differences in the responsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rats or mice to lung carcinogenesis induced by inhalation of Cd compounds.

Administration, Inhalation↗