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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 451 records · Page 25Linked to original sources

SOM integrated with CCA for the feature map and classification of complex chemical patterns.

Considering that the two-dimensional (2D) feature map of the high-dimensional chemical patterns can more concisely and efficiently represent the pattern characteristic, a new procedure integrating self-organizing map (SOM) networks with correlative component analysis (CCA) is proposed. Firstly, CCA was used to identify the most important classification characteristics (CCs) from the original high-dimensional chemical pattern information. Then, the SOM maps the first several CCs, which include the most useful information for pattern classification, onto a 2D plane, on which the pattern classification feature is concisely represented. To improve the learning efficiency of SOM networks, two new algorithms for dynamically adjusting the learning rate and the range of neighborhood around the winning unit were further worked out. Besides, a convenient method for detecting the topologic nature of SOM results was proposed. Finally, a typical example of mapping two classes natural spearmint essence was employed to verify the effectiveness of the new approach. The feature-topology-preserving (FTP) map obtained can well represent the classification of original patterns and is much better than what obtained by SOM alone.

Journal Article↗

Effect of bisoprolol on QT dispersion in patients with congestive heart failure--the etiology-dependent response.

AIMS: To evaluate the effect of beta1-selective blocker bisoprolol on the QT and QTc dispersion in patients with chronic heart failure and to compare the responses to bisoprolol in patients with different etiologies. METHODS AND RESULTS: Eighty-one patients with heart failure secondary to ischemic heart disease (n=47) or idiopathic dilated cardiomyopathy (n=34) were stratified by etiology and then randomly assigned to the bisoprolol and control group (no tablet) on top of the conventional treatment. QT dispersion was calculated by subtracting the shortest QT from the longest QT, in absolute value (Qtmax-Qtmin). It was also corrected with Bazett's formula (QTc dispersion). After 6 weeks of treatment, QT and QTc dispersion were significantly decreased in the bisoprolol group (QT dispersion: 66.5+/-13.4 ms vs. 49.1+/-16.8 ms for ischemic heart disease (P<0.01); 67.5+/-12.4 ms vs. 59.4+/-14.4 ms for dilated cardiomyopathy (P<0.05); QTc dispersion: 78.3+/-15.2 ms vs. 53.3+/-18.1 ms for ischemic heart disease (P<0.01); 79.1+/-14.2 ms vs. 69.0+/-17.9 ms for dilated cardiomyopathy (P<0.05)), but there was no significant decrease of QT and QTc dispersion in the control group. Linear regression analysis showed that patients with ischemic heart disease tend to have lower 6-week QT dispersion than patients with dilated cardiomyopathy (coefficient beta=-0.283, P=0.009) after controlling for their baseline values in the bisoprolol group. CONCLUSION: These findings suggested that bisoprolol reduces QT and QTc dispersion in patients with chronic heart failure, but the etiology of heart failure affects the response of patients to bisoprolol.

Adrenergic beta-Antagonists↗

Mitochondrial DNA variation in an aboriginal Australian population: evidence for genetic isolation and regional differentiation.

The mitochondrial DNA (mt-DNA) variation of in the Walbiri tribe of the Northern Territories, Australia, was characterized by high resolution restriction fragment length polymorphism (HR-RFLP) analysis and control region sequencing. Surveying each mt-DNA for RFLPs with 14 different restriction enzymes detected 24 distinct haplotypes, whereas direct sequencing of the control region hypervariable segment I (HVS-I) of these mt-DNAs revealed 34 distinct sequences. Phylogenetic analysis of the RFLP haplotype and HVS-I sequence data depicted that the Walbiri have ten distinct haplotype groups (haplogroups), or mt-DNA lineages. The majority of the Walbiri RFLP haplotypes lacked polymorphisms common to Asian populations. In fact, most of the Walbiri haplogroups were unique to this population, although a few appeared to be subbranches of larger clusters of mt-DNAs that included other Aboriginal Australian and/or Papua New Guinea haplotypes. The similarity of these haplotypes suggested that Aboriginal Australian and Papua New Guinea populations may have once shared an ancient ancestral population(s), and then rapidly diverged from each other once geographically separated. Overall, the mt-DNA data corroborate the genetic uniqueness of Aboriginal Australian populations.

DNA, Mitochondrial↗

Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro.

Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. These cultures were continuously treated with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat (1-72) protein, a non-neurotoxic HIV-1 Tat deletion mutant (TatDelta31-61) protein, or immunoneutralized HIV-1 Tat (1-72) protein. Neuronal and astrocyte viability was examined by ethidium monoazide exclusion, and by apoptotic changes in nuclear heterochromatin using Hoechst 33342. Morphine (10nM, 100nM or 1microM) significantly increased Tat-induced (100 or 200nM) neuronal losses by about two-fold at 24h following exposure. The synergistic effects of morphine and Tat were prevented by naloxone (3microM), indicating the involvement of opioid receptors. Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia.

Animals↗

Quantitative analysis of dimethyl titanocene by iodometric titration, gas chromatography and NMR.

In this study we report the use of an automated iodometric titration method and a novel gas chromatography (GC) method for the quantitative analysis of dimethyl titanocene (DMT), a key raw material in drug synthesis. Both approaches are based on the reaction of DMT in toluene or tetrahydrofuran solutions with iodine. In the case of iodometric titration, excess iodine is titrated with a standardized aqueous sodium thiosulfate solution to a potentiometric end-point for the determination of DMT concentration. Alternatively, GC is employed to measure the concentration of iodomethane, a product of the reaction between DMT and iodine, in order to determine the concentration of DMT in the solution. Excellent agreement between iodometric titration, GC and NMR results using several DMT samples confirms the accuracy of the two methods and strongly supports the use of either method as a replacement to the expensive NMR for quantitative DMT analysis. The relatively few sources of error associated with the two methods, their ubiquitous nature and ease of application in routine analysis make them the analytical methods of choice, among all. Both methods have been validated according to ICH requirements. The use of iodometric titration method for DMT analysis is demonstrated with a couple of applications.

Chromatography, Gas↗

Determination of active component in silymarin by RP-LC and LC/MS.

Silybin, isosilybin, silydianin and silycristin in silymarin were separated and quantitatively determined by RP-HPLC. Two diastereoisomers of silybin and isosilybin were respectively separated by RP-HPLC and confirmed by LC/MS. Chromatographic condition consisted of column: Shim-pack VP-ODS (150 x 4.6mm i.d. 5 microm) and Pre-column (10 x 4.6 mm i.d. 5 microm); mobile phase: methanol and solvent mixture (water: dioxane=9:1) by gradient; flow rate: 1.5ml/min; column temp.: 40 degrees C; detector wavelength: 288 nm; The recovery of 99.66% for silycristin, 99.48% for silydianin, 100.0% for silybin and 98.72% for isosilybin was respectively obtained.

Antioxidants↗

Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal.

We studied the cognitive effects of antiepileptic drugs (AED), by investigating epileptic children who were seizure-free for at least 2 years and who had undergone fixed monotherapy. Seventy consecutive epileptic children (25 with carbamazepine (CBZ), 22 with phenobarbital (PB), and 23 with valproate (VPA)) were examined by Wechsler Intelligence Scale for Children-Revised (WISC-R) and auditory event-related potentials (P(300)) at three sessions: before AED reduction, then 1 and 7 months after complete withdrawal of treatment. There were no significant differences in IQ and subtests scores of WISC-R in any group at any of the three sessions. P(300) latencies were significantly increased in the children receiving PB but not in children receiving CBZ or VPA. P(300) amplitudes were increased but not significantly different among the three groups. These findings suggest that PB may affect cognitive function on children, but the changes of P(300) latencies may improve after discontinuation.

Anticonvulsants↗

Increased XRALDH2 activity has a posteriorizing effect on the central nervous system of Xenopus embryos.

Retinoic acid (RA) metabolizing enzymes play important roles in RA signaling during vertebrate embryogenesis. We have previously reported on a RA degrading enzyme, XCYP26, which appears to be critical for the anteroposterior patterning of the central nervous system (EMBO J. 17 (1998) 7361). Here, we report on the sequence, expression and function of its counterpart, XRALDH2, a RA generating enzyme in Xenopus. During gastrulation and neurulation, XRALDH2 and XCYP26 show non-overlapping, complementary expression domains. Upon misexpression, XRALDH2 is found to reduce the forebrain territory and to posteriorize the molecular identity of midbrain and individual hindbrain rhombomeres in Xenopus embryos. Furthermore, ectopic XRALDH2, in combination with its substrate, all-trans-retinal (ATR), can mimic the RA phenotype to result in microcephalic embryos. Taken together, our data support the notion that XRALDH2 plays an important role in RA homeostasis by the creation of a critical RA concentration gradient along the anteroposterior axis of early embryos, which is essential for proper patterning of the central nervous system in Xenopus.

Aldehyde Dehydrogenase 1 Family↗

Tissue-specific expression of an Ornithine decarboxylase paralogue, XODC2, in Xenopus laevis.

Ornithine decarboxylase (ODC) is involved in the biosynthesis of polyamines and hence has been found in almost all types of cells studied. Therefore it is frequently used as internal standard. We isolated a cDNA, XODC2, which is a paralogue to ubiquitous ODC and expressed in a spatial and temporal manner during the early embryogenesis of Xenopus laevis. Expression of XODC2was first detected at the animal pole at stage 9. During neurula stages the signals were found both in the extreme anterior and posterior part of the dorsal body axis. In tailbud stages the expression is further shifted to both the tail and head areas and gradually restricted to distinct tissues: forebrain, inner layer of epidermis of the head area, stomodeal-hypophyseal anlage, frontal gland, ear vesicle, branchial arches, the front tip of neural tube and proctodeum. In addition, signals were also found in the inner layer of epidermis underneath the cement gland during early tailbud stages while in later tailbud stages signals were detected at the apical zone of the cement gland. Comparative studies indeed could confirm that XODC1 in contrast to XODC2 is expressed ubiquitously throughout the whole embryos during early development of Xenopus laevis.

Amino Acid Sequence↗

Cis-acting elements regulate alternative splicing of exons 6A, 6B and 8 of the alpha1(XI) collagen gene and contribute to the regional diversification of collagen XI matrices.

Consecutive exons 6A, 6B, 7 and 8 that encode the variable region of the amino-terminal domain (NTD) of the col11a1 gene product undergo a complex pattern of alternative splicing that is both tissue-dependent and developmentally regulated. Expression of col11a1 is predominantly associated with cartilage where it plays a critical role in skeletal development. At least five splice-forms (6B-7-8, 6A-7-8, 7-8, 6B-7 and 7) are found in cartilage. Splice-forms containing exon 6B or 8 have distinct distributions in the long bone during development, while in non-cartilage tissues, splice-form 6A-7-8 is typically expressed. In order to study this complex and tissue-specific alternative splicing, a mini-gene that contains mouse genomic sequence from exon 5 to 11, flanking the variable region of alpha1(XI)-NTD, was constructed. The minigene was transfected into chondrocytic (RCS) and non-chondrocytic (A204) cell lines that endogenously express alpha1(XI), as well as 293 cells which do not express alpha1(XI). Alternative splicing in RCS and A204 cells reflected the appropriate cartilage and non-cartilage patterns while 293 cells produced only 6A-7-8. This suggests that 6A-7-8 is the default splicing pathway and that cell or tissue-specific trans-acting factors are required to obtain pattern of the alternative splicing of alpha1(XI) pre-mRNA observed in chondrocytes. Deletional analysis was used to identify cis-acting regions important for regulating splicing. The presence of the intact exon 7 was required to generate the full complex chondrocytic pattern of splicing. Furthermore, deletional mapping of exon 6B identified sequences required for expression of exon 6B in RCS cells and these may correspond to purine-rich (ESE) and AC-rich (ACE) exonic splicing enhancers.

Alternative Splicing↗

Growth factors in the treatment of wasting in kidney failure.

Protein-energy malnutrition is relatively common in patients with advanced renal failure and is associated with an increase in morbidity and mortality. Accordingly, there is a need to develop more effective treatments to enhance the nutritional status of these patients. One such approach is the use of recombinant growth factors and anabolic steroids for malnourished patients refractory to standard nutritional therapy. In this article, we review the current state of our knowledge regarding the potential use of these agents in malnourished renal failure patients and conclude that although the studies performed to date are indeed encouraging, further and more extensive clinical trials are required to firmly establish their efficacy and safety profile and the indications for clinical use.

Anabolic Agents↗

Novel enzyme activities and functional plasticity revealed by recombining highly homologous enzymes.

BACKGROUND: Directed evolution by DNA shuffling has been used to modify physical and catalytic properties of biological systems. We have shuffled two highly homologous triazine hydrolases and conducted an exploration of the substrate specificities of the resulting enzymes to acquire a better understanding of the possible distributions of novel functions in sequence space. RESULTS: Both parental enzymes and a library of 1600 variant triazine hydrolases were screened against a synthetic library of 15 triazines. The shuffled library contained enzymes with up to 150-fold greater transformation rates than either parent. It also contained enzymes that hydrolyzed five of eight triazines that were not substrates for either starting enzyme. CONCLUSIONS: Permutation of nine amino acid differences resulted in a set of enzymes with surprisingly diverse patterns of reactions catalyzed. The functional richness of this small area of sequence space may aid our understanding of both natural and artificial evolution.

Aminohydrolases↗

Optimal electrocardiographically triggered phase for reducing motion artifact at electron-beam CT in the coronary artery.

RATIONALE AND OBJECTIVES: The authors performed this study to (a) investigate coronary movement with electron-beam computed tomography (CT) and (b) find the optimal electrocardiographic (ECG) triggering phase for eliminating motion artifact. MATERIALS AND METHODS: One hundred fifty-one patients without arrhythmia were examined with electron-beam CT. First, movie scans were obtained to create displacement and velocity graphs of coronary artery movement. Then, a volume scan with an exposure time of 100 msec was obtained with various ECG trigger settings. RESULTS: Movement patterns of coronary arteries varied with heart rate. Optimal triggering phase was before atrial systole (near 71% of the R-R interval) when heart rate was slower than 68 beats per minute and at ventricular end systole when heart rate was fast. Rate of severe motion artifacts decreased from 43% to 0% when triggering was altered from 80% of the R-R interval to the individual optimal value. Experimental values of the optimal phase at different heart rates were derived, and severe motion artifact was only 3.0% with these values. CONCLUSION: ECG triggering set according to the heart rate enables a great reduction in motion artifacts at electron-beam CT with a 100-msec exposure time. The results may have implications for magnetic resonance imaging of the coronary artery.

Adult↗

A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube.

Cell pattern in the ventral neural tube is organized by Sonic hedgehog (Shh) secreted by floor plate cells. To assay the range of direct Shh action, we developed a general method for blocking transduction of Hedgehog (Hh) signals through ectopic expression of a deleted form of the Hh receptor Patched (Ptc), termed Ptc(Deltaloop2). We validated this method in Drosophila and used mouse Ptc1(Deltaloop2) (mPtc1(Deltaloop2)) to block Shh transduction in the chick neural tube. mPtc1(Deltaloop2) expression caused cell-autonomous ventral-to-dorsal switches in progenitor identity and neuronal fate throughout the ventral neural tube, supporting a gradient mechanism whereby Shh acts directly and at long range. mPtc1(Deltaloop2) expression also caused the abnormal spread of Shh to more dorsal cells, indicating that Shh in the neural tube, like Hh in Drosophila, induces a feedback mechanism that limits its range of action.

Animals↗

Solvent effects on the absorption and fluorescence characteristics of tin(IV) mesoporphyrin.

The absorption and fluorescence characteristics of tin(IV) mesoporphyrin (SnMP) and its analog tin(IV) protoporphyrin (SnPP) were studied in a series of organic solvents. Fluorescence quantum yields were calculated using the Strickler-Berg equation. Good correlation was found between calculated values and measured relative values. Fluorescence lifetime, radiative lifetime and non-radiative lifetime were also calculated. The parameters showed variation depending on ligation as well as H-bonding. Unusual long lifetime and high quantum yields were found in alcohol solvents. This finding might contribute to elucidation of the nature of tin porphyrins to inhibit heme oxygenase.

Enzyme Inhibitors↗

Mining time dependency patterns in clinical pathways.

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length of hospital stay of each patient. The development of clinical pathways is a lengthy process, and may require the collaboration among physicians, nurses, and staffs in a hospital. However, the individual differences cause great variances in the execution of clinical pathways. It calls for a more dynamic and adaptive process to improve the performance of clinical pathways. This paper reports a data mining technique we have developed to discover the time dependency pattern of clinical pathways for managing brain stroke. The mining of time dependency pattern is to discover patterns of process execution sequences and to identify the dependent relation between activities in a majority of cases. By obtaining the time dependency patterns, we can predict the paths for new patients when he/she is admitted into a hospital; in turn, the health care procedure will be more effective and efficient.

Algorithms↗

Three new peroxides from the sponge Plakinastrella species.

Two new five-membered-ring peroxide acids, plakinic acid F (3) and epiplakinic acid F (4), and a new peroxide-lactone, plakortolide F (5), were isolated from a sponge of the genus Plakinastrella collected from Felicite Island, Seychelles. The structures were elucidated through spectral analysis. The free acids 3 and 4 exhibit moderate antifungal activity against Candida albicans with minimum inhibitory concentrations of 25 micrograms/mL (SDB) and 3.1 micrograms/mL (RPMI) for 3, and 25 micrograms/mL (SDB) and 6.25 micrograms/mL (RPMI) for 4, respectively. Both also showed moderate in vitro inhibition of Aspergillus fumigatus with IC90's of 25 micrograms/mL.

Animals↗