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Biomedical subjects

S J Chen

Publications and source records attributed to S J Chen.

At least 37 records · Page 2Linked to original sources

Validation of pulmonary venous obstruction by electron beam computed tomography in children with congenital heart disease.

The purpose of this study was to explore the useful imaging findings of electron beam computed tomography (EBCT) for diagnosing pulmonary venous obstruction (PVO) in children with congenital heart disease. From July 1995 to March 1998, 17 children (9 girls and 8 boys, aged 7 days to 14 years and 9 months [median 3 months]) with the diagnosis of PVO were enrolled in this study. All images were obtained by EBCT at the end-diastolic phase of the cardiac cycle after administration of intravenous iodinated contrast medium. The findings of 25 EBCT studies were retrospectively analyzed by 2 radiologists and were correlated with echocardiography, angiocardiography, and surgical findings. Main findings on EBCT for PVO were (1) structural narrowing, (2) thickened interlobular septa, (3) peribronchovascular cuffing, and (4) ground-glass opacity of the alveoli. Structural narrowing along the course of the pulmonary venous drainage was the most important finding in all examinations (25 of 25). Lung parenchymal changes secondary to PVO included thickened interlobular septa (17 of 25), peribronchovascular cuffing (15 of 25), and ground-glass opacity of the alveoli (8 of 25). Thus, the combination of these findings provides very useful data for the definitive diagnosis of PVO. Characteristic electron beam computed tomographic findings can validate suspected PVO noninvasively.

Adolescent↗

Oxidation of human lens recombinant alphaA-crystallin and cysteine-deficient mutants.

Disulfide cross-linking, one of the results of oxidative stress, has been thought to play an important role in cataractogenesis. High molecular mass (HMM) protein aggregation also contributes to cataract development, and a prevailing speculation is that disulfide cross-linking induces HMM aggregation. However, there is no direct evidence to support this speculation. Dimerization is an effect of disulfide cross-linking but cannot explain the size of HMM aggregates observed in the lens. alphaA-crystallin has two cysteine residues (Cys131 and Cys142) and we have prepared three Cys-deficient mutants, two single mutants (C131I and C142I) and one double mutant (C131I/C142I). They were subjected to H202 oxidation in an ascorbate-FeCl(3)-EDTA-H202 system. The effects of oxidation on the mutants, including changes in aggregate size and conformation, were compared with those of the wild-type alphaA-crystallin by FPLC gel filtration, absorption, fluorescence, and circular dichroism measurements. The results indicated that other amino acid residues besides Cys, such as Trp and Tyr, were also oxidized by H202. Disulfide dimerization alone seems to play a less important role in HMM aggregation than does the secondary conformational change resulting from the combined effect of the oxidation of Trp and Tyr as well as Cys.

Amino Acid Substitution↗

Selective repopulation of normal mouse liver by hepatocytes transduced in vivo with recombinant adeno-associated virus.

The use of recombinant adeno-associated virus (rAAV) as gene therapy vector for treating liver metabolic diseases is limited by its low transduction efficiency. We describe a strategy for achieving stable and efficient genetic reconstitution in liver after direct administration of rAAV and selective expansion of transduced cells. We have exploited the biology of apoptosis to develop a generic approach for selectively repopulating liver with vector-transduced hepatocytes. Low-level, stable transduction of hepatocytes was achieved by direct injection of rAAV into mouse liver. Expansion of these vector-transduced cells was achieved by incorporating into the construct a minigene expressing Bcl-2 followed by induction of apoptosis in non-vector-containing hepatocytes by systemic administration of a Fas antibody (Ab). Western and Southern blot analysis demonstrated amplification of bcl-2 gene product and viral copy number, respectively, in vector-treated mouse liver when placed under selection. In addition, the percentage of vector transduced cells increased from 2 to 20% after three administrations of Fas Ab, based on immunohistochemical studies.

Animals↗

Serum levels of eosinophil cationic protein and eosinophils in asthmatic children during a course of prednisolone therapy.

Eosinophils play an important role in the inflammatory events of allergic asthma. Serum eosinophil cationic protein (ECP) is a marker of disease activity and of treatment efficacy in bronchial asthma. To understand the role of ECP concentrations in disease activity of acute asthma, we determined changes in serum concentrations of ECP elaborated by activated eosinophil before and after prednisolone therapy. Circulating levels of ECP in 15 normal control subjects, and in sera of 20 asthmatic children who were allergic to house dust mites, were measured during an acute exacerbation and when the children were in stable condition, using commercially available assay kits. The mean concentrations of serum ECP were significantly higher during an acute asthma exacerbation than when the children were stable (26.41 +/- 21.66 microg/L vs 15.74 +/- 11.36 microg/L P < 0.01) or when compared to control subjects (7.50 +/- 1.42 microg/L; P < 0.001). The mean eosinophil counts (EC) during acute asthma attacks (575 +/- 286/mm3) and when stable (467 +/- 204/mm3) were higher than in the control group (181 +/- 164/mm3). The differences were statistically significant among the three groups (P < 0.05). A significant correlation was found between serum levels of ECP and EC (r = 0.788, P = 0.001) in asthmatic children; there were also significant correlations between ECP and EC in nonallergic normal control subjects (r = 0.662; P = 0.007). In conclusion, this study provides further evidence that changes in serum ECP may serve as an objective indicator for clinical activity and results of treatment in allergic asthmatics.

Adolescent↗

Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors.

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion of vector leads to a systemic cytokine syndrome which may be triggered by the viral capsid proteins.

Adenoviridae↗

High-resolution cranial ultrasound in the shaken-baby syndrome.

With limited near-field resolution and accessible acoustic windows, sonography has not been advocated for assessing central nervous system injuries in the shaken-baby syndrome. Our purpose was to correlate high-resolution ultrasonographic characteristics of central nervous system injuries in whiplash injuries and the shaken-baby-syndrome with MRI and CT. Ultrasonographic images of 13 infants, aged 2-12 months, with whiplash or shaking cranial trauma were reviewed and compared with MRI in 10 and CT in 10. Five patients had serial ultrasonography and MRI or CT follow-up from 1 to 4 months after the initial injury. With ultrasonography we identified 20 subdural haematomas. MRI and CT in 15 of these showed that four were hyperechoic in the acute stage, three were mildly echogenic in the subacute stage, and that one subacute and seven chronic lesions were echo-free. Five patients had acute focal or diffuse echogenic cortical oedema which evolved into subacute subcortical hyperechoic haemorrhage in four, and well-defined chronic sonolucent cystic or noncystic encephalomalacia was seen at follow-up in two. Using ultrasonography we were unable to detect two posterior cranial fossa subdural haematomas or subarachnoid haemorrhage in the basal cisterns in three cases, but did show blood in the interhemispheric cistern and convexity sulci in two. U1-trasonography has limitations in demonstrating abnormalities remote from the high cerebral convexities but may be a useful adjunct to CT and MRI in monitoring the progression of central nervous system injuries in infants receiving intensive care.

Battered Child Syndrome↗

Interleukin-1beta and tumor necrosis factor-alpha in cerebrospinal fluid of children with bacterial meningitis.

Certain cytokines may contribute to the sequence of events that lead to meningeal inflammation in bacterial meningitis. The purpose of this study was to determine the levels of cytokines in the cerebrospinal fluid (CSF) of children with bacterial meningitis and aseptic meningitis of different etiologies. We determined the concentrations of interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha) in the CSF of 171 specimens of 144 patients whose cases were classified as follow: bacterial meningitis (n=23), aseptic meningitis (n=26) and non-meningitis (n=95). The detectable IL-1beta concentration (> or =20 pg/ml) in the bacterial meningitis, aseptic meningitis and non-meningitis groups were observed with 78.3%, 3.8%, and 8.4%, respectively. Significantly higher serum IL-1beta concentrations were detected in those with bacterial meningitis than those with aseptic meningitis (538.93+/-605.32 pg/ml vs 2.52+/-11.57 pg/ml; P<0.001) or among non-meningitis subjects (2.90+/-11.91 pg/ml; P<0.001). The mean TNF-alpha concentration was 148.74+/-338.77 pg/ml. There was significantly more TNF-alpha than aseptic meningitis (6.85+/-17.93 pg/ml; P<0.001) or non-meningitis (7.67+/-16.07 pg/ml; P<0.001). With regard to diagnosis, measurement of IL-1beta and TNF-alpha levels showed sensitivities of 78% and 74%, respectively; specificities of 96% and 81%, respectively. It is suggested that the levels of these cytokines, especially IL-1beta and TNF-alpha, are useful markers for distinguishing bacterial meningitis from aseptic meningitis.

Adolescent↗

A comparative MR and pathological study on fetal CNS disorders.

OBJECT: We used MR after sonography to help us in prenatal counseling in 58 complicated pregnancies from 1998 to 2000. METHODS: All fetal MR examinations were undertaken with a 1.5-T magnet using a body-phased-array coil and an ultrafast imaging technique, half-Fourier single-shot turbo spin-echo (HASTE). Twelve fetuses were found to have major anomalies, and in each of these cases either delivery was induced or the pregnancy was terminated. In 6 of the fetuses, with anomalies of the central nervous system, postmortem examinations were then performed after they failed to survive, and these constitute the patient sample investigated in the current study. The fetal gestational ages in these 6 cases ranged from 24 to 32 weeks. MR imaging demonstrated morphological details of the anomalies. They were: alobar holoprosencephaly in 2, middle interhemispheric fusion in 1, alobar holoprosencephaly with Dandy-Walker malformations in 1, a Dandy-Walker variant in 1 and twin-twin transfusion syndrome with hypoxic-ischemic injury to the brain in 1. CONCLUSIONS: Postmortem examinations confirmed the MR diagnoses, and these observations support us in improving our understanding of the pathogenesis of fetal CNS anomalies.

Abnormalities, Multiple↗

Environment, genome and cancer.

Cancer is one of the most serious diseases that threaten human being today. To some degree, it is a genetic disease but environmental and other nongenetic factors clearly play a role in many stages of neoplastic process. Genetic factors by themselves are thought to explain only about 5% of all cancer. The remainder can be attributed to external, 'environment' factors that act in conjunction with both genetic and acquired susceptibility. Of note, part of the susceptibility is owing to the variety of human genome. So, environment, human genome and cancer have much to do with each other. Combining all of the information from epidemiology and from research works in laboratory with policy-making and clinical works, purifying the environment, giving special protection to the high risk population, the mortality of cancer may decrease gradually in the future.

Carcinogens, Environmental↗

Visual acuity and contrast sensitivity in different types of posterior capsule opacification.

PURPOSE: To compare the visual acuity (VA) and contrast sensitivity in 2 types of posterior capsule opacification (PCO) in pseudophakic eyes before and after neodymium:YAG (Nd:YAG) capsulotomy and to evaluate vision test results after Nd:YAG capsulotomy. SETTING: Department of Ophthalmology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. METHODS: Fourteen eyes with fibrosis-type PCO and 15 eyes with Elschnig-pearl-type PCO were enrolled prospectively. Before and 1 week after Nd:YAG capsulotomy, VA and contrast sensitivity were assessed using the illiterate E version of the Bailey-Lovie chart and the Vistech VCTS 6000 chart, respectively. RESULTS: Before capsulotomy, the mean logMAR acuity in the group with Elschnig-pearl-type PCO was 0.47 +/- 0.32 (SD) and in the group with fibrosis-type PCO, 0.17 +/- 0.07. The difference between the 2 groups was significant (P =.002). After capsulotomy, there was no significant between-group difference (P >.05). Before capsulotomy, the contrast sensitivity was significantly worse (P <.01) at all spatial frequencies in the group with pearl-type PCO, especially at 6 cycles per degree. After capsulotomy, there was no significant between-group difference (P >.05) at any spatial frequency. CONCLUSIONS: After cataract surgery, patients with pearl-type PCO had lower VA and contrast sensitivity than those with fibrosis-type PCO. An Nd:YAG capsulotomy improved the VA and contrast sensitivity in patients with both types of PCO.

Aged↗

A new aspect of view in synthesizing new type beta-adrenoceptor blockers with ancillary antioxidant activities.

A series of vanilloid-type beta-adrenoceptor blockers derived from antioxidant traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant beta-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vivo tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent beta-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional alpha-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. The antioxidant activity may be due to their alpha and beta unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine.

Adrenergic beta-Antagonists↗

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.

Adolescent↗

Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage.

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As2O3). As2O3 was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As2O3 with the peak values of 1.535-3.424 micromol/l. After infusion, the plasma concentration was around 0.1-0.5 micromol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55+/-15.79% and 49.11+/-15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As2O3 had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.

Adolescent↗

Molecular cytogenetic characterization and clinical relevance of additional, complex and/or variant chromosome abnormalities in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by typical morphological manifestation, t(15;17) translocation and active response to all-trans retinoic acid (ATRA) in the great majority of patients. However, a subset of APL cases may present atypical phenotypic, cytogenetic or molecular features at different stages of the disease. The biological and clinical significance of these features sometimes remains obscure. In this study, 284 APL patients were cytogenetically analyzed and precise diagnosis was performed according to the molecular cytogenetic results. Twenty-six APL patients were identified as having additional, complex and/or variant chromosomal abnormalities at diagnosis or at relapse, 16 of them being further analyzed using fluorescence in situ hybridization (FISH) or chromosome painting (CP). Interestingly, some of these chromosomal aberrations were found to be associated with atypical morphology and/or drug response, indicating a genotype-phenotype correlation. Analysis of the complex karyotype may also allow a better understanding of the levels of cellular origin of the leukemogenesis. Examination of the remission induction and survival data showed that the presence of the additional/complex chromosome abnormalities was related to the prognosis in both primarily diagnosed and relapsed patients in this series.

Adolescent↗

Feasibility and clinical significance of real-time quantitative RT-PCR assay of PML-RARalpha fusion transcript in patients with acute promyelocytic leukemia.

INTRODUCTION: To study the relationship between the expression level of the PML-RARalpha fusion transcripts and the clinical status and efficiency of the therapy in acute promyelocytic leukemia (APL) patients, we applied a very sensitive and specific real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) system to quantify the dose of PML-RARalpha fusion transcripts in a series of APL patients at distinct disease stages. MATERIALS AND METHODS: A total of 31 APL patients (19 males and 12 females; aged from 8 to 74 years) from eight hospitals in Shanghai were analysed. Real-time Quantitative RT-PCR was used to measure the normalized dose (DoseN) of PML-RARalpha fusion transcripts. RESULTS: A wide range of PML-RARalpha DoseN above 1 x 10(3) was noted in 25 newly diagnosed patients. PML-RARalpha DoseN was significantly decreased after remission induction with ATRA, ATRA/chemotherapy or As2O3 and further reduced after consolidation. The fact that all patients with long disease free survival had a constantly low PML-RARalpha DoseN below 2 x 10(2) and a higher level predicted impending relapse suggests that this value could serve as a 'threshold' for molecular remission. PML-RARalpha DoseN was also of prognostic value in a group of relapsed patients, since good response to As2O3 reinduction was accompanied by a remarkable reduction of fusion transcript level, whereas patients with high PML-RARalpha Dose(N) after the second CR tended to relapse again rapidly. CONCLUSION: These results confirm that real-time RT-PCR assay for PML-RARalpha transcripts in APL patients is useful in reflecting leukemic burden, assessing response to treatment and indicating the ultimate clinical outcome or curability of disease.

Adolescent↗

Treatment of acute promyelocytic leukemia with arsenic compounds: in vitro and in vivo studies.

Arsenic compounds, Including arsenic trioxide (As2O3) and arsenic sulfide (As4S4), have recently been shown to be effective in the treatment of acute promyelocytic leukemia (APL). In vitro, As2O3 exerts a dose-dependent dual effect: it triggers apoptosis at relatively high concentrations (0.5 to 2.0 micromol/L) and induces partial differentiation at low concentrations (0.1 to 0.5 micromol/L). The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the retinoic acid signaling is required for APL cell differentiation. As2O3 over a wide range of concentrations (0.1 to 2.0 micromol/L) Induces degradation of PML-RARalpha as well as the wild-type PML and enhances the acetylation of histone, a process important for the transcriptional activation of genes. In vivo, As2O3 induces a high complete remission (CR) rate in patients with both primary and relapsed APL (around 85% to 90%). Side effects, such as skin reaction, gastrointestinal symptoms, electrocardiographic (EKG) changes, neuropathy, and liver dysfunction, are mild to moderate in relapsed patients, and severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As2O3 as postremission therapy has yielded better survival than treatment with As2O3 alone. This is in line with the observation that remission induction with As2O3 is not sufficient in most cases to obtain a molecular remission as Judged by reverse-transcriptase polymerase chain reaction for PML-RARalpha fusion transcripts. The in vivo effect of As2O3 seems to be related to the expression of APL-specific PML-RARalpha oncoprotein, and a synergistic effect between As2O3 and ATRA has been shown in the APL mouse model. Besides As2O3, other arsenic compounds such as As4S4 also show a therapeutic effect in APL. Because the toxic effects of arsenic treatment in primary APL need to be investigated further, we propose use of ATRA as a first-line drug for remission induction in primary APL, whereas As2O3 can be incorporated into multidrug postremission therapy or used as rescue for relapsed APL patients.

Animals↗

Comparison of pulmonary arterial flow phenomena in spiral and Lecompte models by computational fluid dynamics.

OBJECTIVES: The transposed great arteries are simply reversed by means of a conventional arterial switch operation with the Lecompte maneuver without resumption of their spiral relationship. We seek to clarify the functional implications of the spiral relationship of the great arteries by means of mathematic modeling. METHODS: Computational fluid dynamics is used to compare flow phenomena of the spiral and Lecompte (nonspiral) models under various body surface areas. RESULTS: The velocity profile and wall-shear stress distribution are more uniform for the spiral than for the Lecompte model. The pressure drop and power loss ratio are smaller for the spiral than the Lecompte model for all the body surface areas investigated. The power loss ratio increases abruptly starting from 0.43 m2 of body surface area for the Lecompte model. At that specific stage, after arterial switch operation with the Lecompte maneuver, suprapulmonary stenoses occur most frequently. CONCLUSIONS: Reconstructing the great arteries in spiral fashion might be recommended because the blood flow patterns are more streamlined than those of the Lecompte maneuver. Initiation of stenosis might be minimized to some extent.

Angiography↗

Visual impairment in a Taiwanese population: prevalence, causes, and socioeconomic factors.

PURPOSE: We sought to estimate the prevalence of visual impairment among an elderly population in urban Taiwan, determine the causes of visual impairment, and gain information about certain socioeconomic factors associated with visual impairment. METHODS: A population-based survey of ocular diseases in residents aged 50 years or older was conducted in Peitou Precinct, Taipei, Taiwan. All participants underwent a comprehensive ophthalmic examination, including visual acuity measurement, using standardized protocols. Demographic data, marital status, employment status, and educational level were gathered through an interview. RESULTS: A total of 2034 participants completed the visual acuity measurements. The prevalence of visual impairment (defined as best-corrected visual acuity in the better eye <6/18) among this population was 2.75% (95% confidence intervals: 2.04%-3.46%). Three major causes of visual impairment were cataract (30.4%), high myopic macular degeneration (25.0%), and age-related macular degeneration (14.3%). In multivariate analysis, age was positively correlated with visual impairment (P < 0.001), and higher education level was associated with a significant decrease in the odds of being visually impaired (P < 0.001). No relation was found between visual impairment and sex, or marital and employment status. CONCLUSIONS This study provides the first information about the prevalence and causes of visual impairment in Taiwan, and identifies age and educational level as the most important factors related to visual impairment. Additional educational programs should be developed to improve individual awareness of age-related ocular diseases and the availability of current ophthalmic intervention.

Age Distribution↗