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Biomedical subjects

S H Chen

Publications and source records attributed to S H Chen.

At least 145 records · Page 8Linked to original sources

Pharmacokinetic applications of capillary electrophoresis.

This review briefly discusses the use of capillary electrophoretic (CE) methods for the investigations of different aspects of pharmacokinetics. In most investigations, CE was the method of choice because of its unique features, including high resolving power for chiral or metabolite separation, small sample volume for pediatric pharmacokinetics or for cell-based investigations, in situ microdialysis sampling for rapid eliminations, low UV wavelength detection for nonderivatized analytes, fast and simplified sample processing for existing methods that require tedious sample preparation, or as a second method for verifications. Moreover, instrumental aspects of CE-based assays for pharmacokinetic studies, such as different modes of CE methods for analyzing biological samples, sample stacking for increasing detection sensitivity, and coupling techniques with microdialysis and mass spectrometry, are also discussed in this review. Furthermore, the advantages and limitations of CE methods as well as the future outlook for pharmacokinetic studies are summarized.

Animals↗

Maturational changes in gene expression for adenine nucleotide translocator isoforms and betaF1-ATPase in rabbit heart.

Maturational changes in myocardial respiratory control have been related to postnatal accumulation of adenine nucleotide translocator (ANT) in the inner mitochondrial membrane. Alternatively alterations in relative isoform distribution for this nuclear-encoded gene during myocardial maturation might be responsible for changing the kinetics of respiratory control. Rabbit hearts were analyzed for adenine nucleotide translocator isoform (ANT1, ANT2, ANT3) gene expression and distribution at four ages (fetal, 29/31 days of gestation; 1 h postnatal; 9 days postnatal; and 3-4 months postnatal). Transcript levels for the coordinately expressed betaF1-ATPase were also examined in these hearts. These studies demonstrated that mRNA expression for ANT1 in coordination with betaF1-ATPase increased substantially after 9 days of age in rabbit hearts. Expression of the minor isoform ANT3 parallels ANT1, though no change in expression of the kidney-specific isoform ANT2 occurs in heart during this developmental period. Previous work has demonstrated that ANT protein accumulation is closely coordinated with mRNA expression for ANT1. These results support previous studies, which indicate that the operational mode of myocardial respiratory control depends on adenine nucleotide mRNA expression. Changes in relative adenine nucleotide translocator isoform distribution do occur during fetal to mature transition and may contribute to observed changes in the mode of respiratory control.

Aging↗

Routine donor leg angiography before vascularized free fibula transplantation is not necessary: a prospective study in 120 clinical cases.

To evaluate the value of routine preoperative angiographies of donor sites, 120 patients with free fibula osteoseptocutaneous flap transplantations were included in this prospective study, which consisted of preoperative evaluation of dorsalis pedis and tibial posterior artery pulsation and angiographies of the donor legs (120 patients) and contralateral legs (111 patients). Both pedal pulses were palpable in 114 patients, and only one pulse was palpable in six patients. The respective nonpalpable foot pulses were detectable with pencil Doppler in five patients, but they were not detectable in one patient. Intraoperatively, the latter patient had a relatively hypertrophied peroneal artery as compared with both the tibial posterior and tibial anterior arteries. The angiographic result was arteria peronea magna. The other five patients showed intraoperatively and angiographically normal-sized major arteries of the lower leg. In three patients with normal pedal pulses, hypoplasias of either the tibial anterior or tibial posterior arteries were found intraoperatively. These findings corresponded with the angiographical results. In all patients (n = 119), except one with peroneal artery hemangioma, free osteoseptocutaneous fibula flap was harvested from the originally planned leg without subsequent sequelae to the respective donor leg. In 231 leg angiographies, only 7 cases (3 percent) with abnormalsized major lower leg arteries were described. The diagnoses in these cases were hypoplasia of either the tibial posterior or tibial anterior artery (4 cases), arteria peronea magna (2 cases, one of which was a false positive), absence of peroneal artery combined with hypoplastic tibial posterior artery (1 case), and hemangioma of the peroneal artery (1 case). From this prospective study, it was determined that routine preoperative angiography of the donor leg before fibula transplantation is not justified. It does not add relevant new information about donor leg vascularity, provided that the clinical evaluation of the pedal pulses is well conducted. The only two conditions that may require a preoperative donor leg angiography are abnormal pedal pulses or significant previous lower leg trauma.

Adolescent↗

Model for single-particle dynamics in supercooled water.

We analyze a set of 10 M-step molecular dynamics (MD) data of low-temperature SPC/E model water with a phenomenological analytical model. The motivation is twofold: to extract various k-dependent physical parameters associated with the single-particle or the self-intermediate scattering functions (SISFs) of water at a deeply supercooled temperature and to apply this analytical model to analyses of new high resolution quasielastic neutron scattering data presented elsewhere. The SISF of the center of mass computed from the MD data show clearly time-separated two-step relaxations with a well defined plateau in between. We model the short time relaxation of the test particle as a particle trapped in a harmonical potential well with the vibrational frequency distribution function having a two-peak structure known from previous inelastic neutron scattering experiments. For the long time part of the relaxation, we take the alpha relaxation suggested by mode-coupling theory. The model fits the low-temperature SISF over the entire time range from 1 fs to 10 ns, allowing us to extract peak positions of the vibrational density of states, the structural relaxation rate 1/tau of the cage (the potential well) and the stretch exponent beta. The structural relaxation rate has a power law dependence on the magnitude of the wave vector transfer k and the stretch exponent varies from 0.55 at large k to unity at small k.

Journal Article↗

Model for dynamics in supercooled water.

We propose a phenomenological model for the intermediate scattering function (ISF) associated with density fluctuation in low temperature water. The motivation is twofold: to extract various physical parameters associated with the ISF computed from extended simple-point-charge model water at supercooled temperatures, and to apply this model to analyze high resolution inelastic x-ray scattering data of water in the future. The ISF of the center of mass of low temperature water computed from 10 M-step molecular dynamics (MD) data shows clearly time-separated two-step relaxation with a well-defined plateau in-between. We interpret this result as due to the formation of a stable hydrogen-bonded, tetrahedrally coordinated cage around a typical molecule in low temperature water. We thus model the long-time cage relaxation by the well-known Kohlrausch form exp[-(t/tau)(beta)] with an amplitude factor which is a k-dependent Debye-Waller factor A(k), and treat the short-time relaxation as due to molecular collisional motions within the cage. The latter motions can be described by the generalized Enskog equation, taking into account the confinement effect of the cage. We shall show that the effect of the confinement changes the collisional dynamics by modifying certain input parameters in the kinetic theory by a factor [1-A(k)](1/2). We solve the generalized Enskog equation approximately but analytically by a Q-dependent triple relaxation time kinetic model. This kinetic model was previously shown to account for the large k behavior of Rayleigh-Brillouin scattering from moderately dense, simple fluids. We find that our model fits well with the MD generated collective as well as single-particle ISFs. For the short-time collisional dynamics, we fix values of the hard sphere diameter sigma and pair correlation function at contact g(sigma), without introducing any adjustable parameters. The calculated ISFs reproduce the correct Brillouin peak frequencies at low k values. From the long-time dynamics, we deduce values of the Debye-Waller factor A(k), the Kohlrausch exponent beta(k), and the cage relaxation time tau(k).

Journal Article↗

Interaction and percolation in the L64 triblock copolymer micellar system.

We present results of analyses of an extensive set of static light scattering (SLS), small angle neutron scattering (SANS), and viscoelastic (frequency dependent complex moduli) measurements of aqueous solutions of a triblock copolymer micellar system. We investigate Pluronic L64 (PEO(13)PPO(30)PEO(13))-water system in a wide range of composition and temperature. We determine phase diagram of the disordered micellar phase, including a cmc-cmt curve, a cloud point curve, the critical concentration, and the critical temperature by means of SLS and SANS. The microstructure and interaction between micelles are determined by analyses of SANS intensities. SANS intensity distributions are well described by combining the cap-and-gown model for the polymer segmental distribution within a micelle and the sticky hard sphere model for the intermicellar structure factor. The existence of percolation loci at well defined poins in the temperature-concentration plane is inferred from an abrupt increase of the stickiness parameter extracted from SANS data and from two order of magnitude jump of the complex moduli at the percolation point. Study of temperature dependence of real (storage) and imaginary (loss) part of the complex modulus at fixed concentration and frequency lends further support to the existence of a percolation line. We observe an increase of some order of magnitude of the real and imaginary part of viscosity at certain temperature and composition, a phenomenon usually ascribed to a gelation process in a polymer solution. The definitive confirmation of the percolation process is obtained by frequency dependent complex viscosity measured in a frequency range 0-160 (rad/sec). From these measurements we clearly observe a well defined frequency scaling behavior of the complex moduli and a loss angle (delta) independent of the frequency. Scaling exponents, determined for frequency-dependent complex moduli satisfy the scaling relations predicted by the scalar elasticity percolation theory.

Journal Article↗

MR cholangiography in the evaluation of neonatal cholestasis.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) cholangiography in excluding biliary atresia as the cause of neonatal cholestasis. MATERIALS AND METHODS: MR cholangiography was performed on 10 control and 16 jaundiced neonates and infants aged 3 days to 5 months. Diagnosis of biliary atresia (n = 6) was confirmed with surgery and liver biopsy, with or without surgical cholangiography. Diagnosis of neonatal hepatitis (n = 9) was confirmed with clinical follow-up until jaundice resolved. In one infant, paucity of intrahepatic ducts was diagnosed at liver biopsy. MR cholangiography was performed with respiratory-triggered, heavily T2-weighted turbo spin-echo and optional inversion-recovery turbo spin-echo sequences. Diagnosis of biliary atresia was based on nonvisualization of either the common bile duct or common hepatic duct. Cholescintigraphy with technetium 99m disofenin was performed in all 16 jaundiced patients. RESULTS: In the 10 controls, the nine patients with neonatal hepatitis, and the one infant with paucity of intrahepatic ducts, MR cholangiography clearly depicted the gallbladder and common hepatic and common bile ducts. MR cholangiography was 100% accurate in excluding biliary atresia as the cause of neonatal cholestasis, while 99mTc disofenin cholescintigraphic findings were false-positive in four of 10 patients with nonobstructive cholestasis. CONCLUSION: MR cholangiography can be used to depict the major biliary structures of neonates and small infants and to exclude biliary atresia as the cause of neonatal cholestasis by allowing visualization of the biliary tract.

Biliary Atresia↗

Detection of PAX3-FKHR and PAX7-FKHR fusion transcripts in rhabdomyosarcoma by reverse transcriptase-polymerase chain reaction using paraffin-embedded tissue.

BACKGROUND: Alveolar rhabdomyosarcoma (RMS) is associated with a characteristic chromosomal translocation t(2;13)(q35;q14). The genes involved in this translocation are paired box (PAX)3 on chromosome 2 and forkhead in RMS (FKHR) on chromosome 13. An occasional variant translocation t(1;13)(p36;q14) affecting PAX7 and FKHR on chromosomes 1 and 13, respectively, has also been described. Chromosomal translocations in RMS are detected using conventional cytogenetic analysis, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) on fresh or frozen tissue samples. We describe the results of RT-PCR analysis of PAX3-FKHR and PAX7-FKHR chimeric messages in formalin-fixed, paraffin-embedded tissue samples from 17 RMS cases. METHODS: RNA was extracted from formalin-fixed, paraffin-embedded RMS tissue. Oligonucleotide primers corresponding to the regions of PAX3, PAX7 and FKHR were used for the detection of PAX3-FKHR and PAX7-FKHR chimeric messages. A seminested PCR of the PCR products was used to increase the sensitivity of detection. The amplified fragments were purified and directly sequenced to confirm the specificity of the methods. RESULTS: The PAX3-FKHR chimeric message was detected in all three cases of alveolar RMS but not in any of the 12 embryonal and two pleomorphic RMS cases. The PAX7-FKHR fusion transcript was detected in one case of embryonal RMS. CONCLUSIONS: The results indicate that the RT-PCR assay is a reliable method for the detection of the PAX3-FKHR fusion transcript of alveolar RMS in formalin-fixed, paraffin-embedded tissue. This simple method enables pathologists to identify chromosomal rearrangements in RMS as a diagnostic aid in cases where fresh or frozen tissue is not available.

DNA-Binding Proteins↗

Herpes gestationis in a mother and child.

Herpes gestationis (pemphigoid gestationis) is a rare autoimmune disease that appears during pregnancy or in the immediate postpartum period. We report the cases of a mother and neonate with immunofluorescence confirmed herpes gestationis both of whom had extensive cutaneous involvement.

Autoimmune Diseases↗

Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa.

PURPOSE: To determine the mutation spectrum of the PDE6A gene encoding the alpha subunit of rod cyclic guanosine monophosphate (cGMP)phosphodiesterase and the proportion of patients with recessive retinitis pigmentosa (RP) due to mutations in this gene. METHODS: The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen all 22 exons of this gene for mutations in 164 unrelated patients with recessive or isolate RP. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS: Four new families were identified with five novel mutations in this gene that cosegregated with disease. Combining the data presented here with those published earlier by the authors, eight different mutations in six families have been discovered to be pathogenic. Two of the mutations are nonsense, five are missense, and one affects a canonical splice-donor site. CONCLUSIONS: The PDE6A gene appears to account for roughly 3% to 4% of families with recessive RP in North America. A compilation of the pathogenic mutations in PDE6A and those reported in the homologous gene PDE6B encoding the beta subunit of rod cGMP-phosphodiesterase shows that the cGMP-binding and catalytic domains are frequently affected.

3',5'-Cyclic-GMP Phosphodiesterases↗

Plastic microchip electrophoresis for analysis of PCR products of hepatitis C virus.

BACKGROUND: Electrophoresis on polymeric rather than glass microstructures is a promising separation method for analytical chemistry. Assays on such devices need to be explored to allow assessment of their utility for the clinical laboratory. METHODS: We compared capillary and plastic microchip electrophoresis for clinical post-PCR analysis of hepatitis C virus (HCV). For capillary electrophoresis (CE), we used a separation medium composed of 10 g/L hydroxypropyl methyl cellulose in Tris-borate-EDTA buffer and 10 micromol/L intercalating dye. For microchip electrophoresis, the HCV assay established on the fused silica tubing was transferred to the untreated polymethylmethacrylate microchip with minimum modifications. RESULTS: CE resolved the 145-bp amplicon of HCV in 15 min. The confidence interval of the migration time was <3.2%. The same HCV amplicon was resolved by microchip electrophoresis in <1.5 min with the confidence interval of the migration time <1.3%. CONCLUSION: The polymer microchip, with advantages that include fast processing time, simple operation, and disposable use, holds great potential for clinical analysis.

DNA, Viral↗

Combined third and fourth toe transplantation.

Multiple toe transplantation has been established as an effective technique for restoring prehensile ability in the metacarpal hand. The combined third and fourth toe transplant is a new toe transplant that has been developed for bilateral metacarpal hand reconstruction. Since 1991, the combined third and fourth toe transplant was added to the armamentarium of toe transplants for metacarpal hands, although its role in metacarpal hand reconstruction has not been described previously. This article introduces the indications for combined third and fourth toe transplant, outlines relevant vascular anatomy, and discusses technical considerations pertaining to toe harvest and transplantation.

Adult↗

Vascularized toe joint transplantation.

The vascularized toe joint transfer is an alternative to arthrodesis. For optimal functional results, the patient must have normal-functioning muscle and associated tendons, effecting joint motion. Although vascularized toe joint transfer permits long-term preservation of joint architecture and cartilage, the goal of achieving normal range of motion for a reconstructed digit is still elusive. Reconstruction of the extensor mechanism can be worthwhile in selected patients because more useful motion can be achieved even if the result falls short of normal.

Adolescent↗

A molecular perspective on the genera Paragonimus Braun, Euparagonimus Chen and Pagumogonimus Chen.

The status of the genera Euparagonimus Chen, 1963 and Pagumogonimus Chen, 1963 relative to Paragonimus Braun, 1899 was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit I (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer (ITS2). In the phylogenetic trees constructed, the genus Pagumogonimus is clearly not monophyletic and therefore not a natural taxon. Indeed, the type species of Pagumogonimus, P. skrjabini from China, is very closely related to Paragonimus miyazakii from Japan. The status of Euparagonimus is less obvious. Euparagonimus cenocopiosus lies distant from other lungflukes included in the analysis. It can be placed as sister to Paragonimus in some analyses and falls within the genus in others. A recently published morphological study placed E. cenocopiosus within the genus Paragonimus and probably this is where it should remain.

Animals↗

Mandibular osteomyelitis caused by Blastoschizomyces capitatus in a child with acute myelogenous leukemia.

A 6-year-old girl with acute myelogenous leukemia (AML) developed fungal mandibular osteomyelitis during chemotherapy. Blastoschizomyces capitatus was recognized histologically by its yeast-like morphology and formation of annelloconidia, and was confirmed by culture. The fungal osteomyelitis of the mandible was treated successfully with prolonged antifungal medication, extensive surgical debridement and an oral care program, without interrupting leukemia chemotherapy. B. capitatus osteomyelitis of the mandible may occur during chemotherapy in AML patients with poor dental condition. Successful treatment can be achieved by careful management without interruption of antineoplastic chemotherapy.

Child↗

Characterization of a novel immunocytolytic factor secreted by pancreatic adenocarcinoma.

We observed a putative immunocytolytic factor secreted in the supernatant of several pancreatic adenocarcinoma cell lines that induces apoptosis in lymphocytes. A marked reduction in the viability of the target splenocytes was evident after coincubation with the supernatants from various pancreatic adenocarcinoma cell lines (human, hamster, and murine). The immunocytolytic effect was not evident with the conditioned media of normal pancreatic duct epithelial cells or other nonpancreatic tumor cells. Biologic activity of the supernatants was determined to be heat sensitive and reside in a 30- to 50-kDa range. Immune and functional assays have excluded known immunosuppressive factors.

Adenocarcinoma↗