Biomedical subjects

S H Chen

Publications and source records attributed to S H Chen.

At least 37 records · Page 2Linked to original sources

PubMed2004

Antibody-mediated endothelial cell damage via nitric oxide.

Vascular disorders, resulting from endothelial cell dysfunction, may be caused by various stimuli, including infectious pathogens, cytotoxic reagents, and pathophysiological mechanisms mediated by immune responses. Endothelial cell dysfunction characterized by apoptosis and abnormal immune activation is, at least in part, induced by anti-endothelial cell antibody (AECA) in some cases of autoimmune disease. However, the molecular mechanisms of AECA-mediated pathogenetic damage to host vascular system remain unclear. The dual role of nitric oxide (NO) both in endothelial cell apoptosis and survival has been described. In this paper, endothelial cell apoptosis caused by the presence of cross-reactive AECA via a NO-mediated mechanism is demonstrated in dengue virus infection. Endothelial cells undergo apoptosis via the mitochondria-dependent pathway that is regulated by NO production. NO-regulated endothelial cell injury thus may play a role in the disruption of vessel endothelium and contribute to the AECA-induced pathogenesis of vasculopathy. The modulation of NO may provide the therapeutic strategies for autoimmune diseases by preventing the AECA-mediated endothelial cell damage.

Animals↗

PubMed2003

Primer Design Assistant (PDA): A web-based primer design tool.

Primer Design Assistant (PDA) is a web interface primer design service combined with thermodynamic theory to evaluate the fitness of primers. It runs in a Linux-Apache-MySQL-PHP structure on a PC equipped with dual CPU (Intel Pentium III 1.4 GHz) and 512 Mb of RAM. A succinct user interface of PDA is accomplished by built-in parameters setting. Advanced options on 5' GC content, 3' GC content, dimer check and hairpin check are available. The option of covered region constrains the PCR product to cover a user-defined segment. PDA accepts single sequence query or multiple ones in FASTA format. It produces optimal and homogenous primer pairs that meet the need in experimental design with large-scaled PCR amplifications. Considering the system loading, the size of a submitted sequence is limited to 10 kb and the total sequence number in a query is limited to 20. The authors may be contacted regarding other requirements for primer design. The web application can be found at http://dbb.nhri.org.tw/primer/.

DNA Primers↗

PubMed2003

Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist, reduces the infarct volume following transient middle cerebral artery occlusion in rats.

Recent studies using middle cerebral artery occlusion in the rat have suggested a role of neuropeptide Y in ischemic pathophysiology. In this study, we investigated the effects of an i.c.v. injection of a neuropeptide Y-Y2 receptor agonist, neuropeptide Y 3-36, a Y1 receptor agonist, [Leu(31),Pro(34)]-neuropeptide Y, or a Y1 receptor antagonist, BIBP3226, on infarct volume and hemodynamic parameters following middle cerebral artery occlusion. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 2 h. A single i.c.v. injection of neuropeptide Y 3-36 (15 microg/kg), [Leu(31),Pro(34)]-neuropeptide Y (30 microg/kg), or BIBP3226 (5, 15, or 45 microg/kg) was given at 30 min of ischemia. Blood pressure, heart rate, and regional cerebral perfusion were monitored during ischemia and reperfusion. The rats were decapitated after 70 h of reperfusion, and their brains were cut into 2-mm-thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. When compared with an infarct volume of 17.4+/-4.4% of the ipsilateral hemisphere following injection of neuropeptide Y 3-36, administration of the Y1 receptor analogs significantly modified the infarct volume (ordinary one-way analysis of variance (ANOVA), P<0.0001). [Leu(31),Pro(34)]-neuropeptide Y increased the infarct volume to 32.0+/-4.1% (Student-Newman-Keuls post-test, P<0.01), whereas BIBP3226 at 15 microg/kg decreased the infarct volume to 6.5+/-1.0% (post-test P<0.05). Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-neuropeptide Y tended to further reduce cerebral perfusion during ischemia, while injection of BIBP3226 at 15 microg/kg appeared to have the opposite effect. In addition to glutamate, calcium ion and nitric oxide, activation of the neuropeptide Y-Y1 receptors may mediate cerebral damage during focal ischemia. Conversely, inhibiting the Y1 receptors may protect the brain against ischemic injury. Further studies are warranted to confirm the neuroprotective potential of neuropeptide Y-Y1 receptor inhibition.

Animals↗

PubMed2002

Linear and time-dependent behavior of the gyrotron backward-wave oscillator.

Formation of axial modes in the gyrotron backward-wave oscillator is examined in the perspective of optimum conditions for beam-wave interactions. Distinctive linear properties are revealed and interpreted physically. Nonlinear implications of these properties (specifically, the role of high-order axial modes) are investigated with time-dependent simulations. Nonstationary oscillations exhibit self-modulation behavior while displaying no evidence of axial mode competition. Reasons for the erratic frequency tuning are investigated and stable tuning regimes are identified as a remedy.

Journal Article↗

PubMed2002

Cytomegalovirus infection in pregnancy.

OBJECTIVES: To investigate the effects of intrauterine human cytomegalovirus (HCMV) infection on pregnancy outcomes and infant development. METHODS: The study group consisted of the HCMV-IgM-positive offspring of 75 pregnant women, and a control group of the non-infected offspring of 73 pregnant women. Chorionic villi, amnionic fluid, and umbilical blood were obtained to detect HCMV-late mRNA with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The pregnancy outcomes were followed up. For all offspring, neurological development was evaluated with neurosonography, audiologic development with the brainstem auditory evoked potential (BAEP), and psychomotor development with the Beyley Scale of Infant Development (BSID). RESULTS: In the study group the positive rate of late mRNA was 50% in the chorionic villi and 67.65% in the amnionic fluid and the umbilical blood; the incidence of abnormal pregnancy outcomes (abortion, preterm delivery, stillbirth, etc.) was much higher than in the control group (40% vs. 6.57%; chi(2)=24.06; P=0.001); the abnormal rate of neurosonography results at birth and 3 months after birth was higher in the study group than in the control group (P<0.05), as were BAEP values 4 months after birth (chi(2)=8.960; P=0.003). Scores for the Infant Mental Development Index (MDI) were apparently lower than in the control group. When congenitally infected children were tested at the age of 5.5-6.5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), their rate of mental retardation was still found to be approximately 20%. CONCLUSIONS: Intrauterine HCMV infection is closely related to abnormal pregnancy outcomes, infant neurological damage, mental retardation, and hearing loss.

Abortion, Spontaneous↗

PubMed2002

A study on the friction of a self-correction ultrasonic stepping motor.

An experiment has been carried out to investigate the self-correction function of a self-correction ultrasonic stepping motor. When a slider (rotor) is placed on a vibrating beam (stator), it will stay at a stable equilibrium position. If the slider is slightly moved off the equilibrium position, a restoring force will urge the slider back towards its equilibrium position. The experimental result shows that the position of the maximum restoring force on the slider differs from that predicted by using the linear theory. Study found that when a quadratic form is assumed for the dynamic friction coefficient, the theoretical and experimental results are in good agreement.

Journal Article↗

PubMed2002

Observation of a re-entrant kinetic glass transition in a micellar system with temperature-dependent attractive interaction.

We detect in a tri-block co-polymer micellar system an ergodic-to-nonergodic-to-ergodic transition, as a function of temperature, in a range of concentrations, by photon correlation measurements. The shear viscosity is also shown to jump two order of magnitude at these transition temperatures. Surprisingly, the structure factor as measured by small angle neutron scattering shows a marked narrowing at the structural arrest state. Rationalization of these results with the existence of an attractive branch in the phase diagram of an attractive colloid system predicted by mode coupling theory is made.

Journal Article↗

PubMed2001

Dynamic scaling of quasielastic neutron scattering spectra from interfacial water.

A method for analysis of high-resolution quasielastic neutron scattering (QENS) spectra of water in porous media is proposed and applied to the case of water in hydrated tricalcium and dicalcium silicates. We plot the normalized frequency-dependent susceptibility as a function of a scaling variable [omega]/omega(p), where omega(p) is the peak position of the susceptibility function. QENS data have been scaled into a single master curve and fitted with an empirical formula proposed by Bergman to obtain three independent parameters describing the relaxation dynamics of hydration water in calcium silicates.

Journal Article↗

PubMed2001

Flow-through sampling for electrophoresis-based microfluidic chips using hydrodynamic pumping.

This work presents a novel electrophoretic microchip design which is capable of directly coupling with flow-through analyzers for uninterrupted sampling. In this device, a 3 mm wide sampling channel (SC) was etched on quartz substrate to create the sample inlet and outlet and the 75 microm wide electrophoretic channels were also fabricated on the same substrate. Pressure was used to drive the sample flow through the external tube into the SC and the flow was then split into outlet and electrophoretic channels. A gating voltage was applied to the electrophoretic channel to control the sample loading for subsequent separations and inhibit the sample leakage. The minimum gating voltage required to inhibit the sample leakage depended on the solution buffer and increased with the hydrodynamic flow-rate. A fluorescent dye mixture containing Rhodamine B and Cy3 was introduced into the sample stream at either a continuous or discrete mode via an on-line injection valve and then separated and detected on the microchip using laser-induced fluorescence. For both modes, the relative standard deviation of migration time and peak intensity for consecutive injections was determined to be below 0.6 and 8%, respectively. Because the SC was kept floating, the external sampling equipment requires no electric connection. Therefore, such an electrophoresis-based microchip can be directly coupled with any pressure-driven flow analyzers without hardware modifications. To our best knowledge, this is something currently impossible for reported electrophoretic microchip designs.

Electrophoresis↗

PubMed2001

Synthesis and evaluation of novel pseudomycin side-chain analogues. Part 3.

To increase the therapeutic utility of C-18 side-chain bearing pseudomycin analogue 2, we prepared additional analogues and prodrugs of 2 containing further modifications at various positions within its core structure. Each of the newly synthesized derivatives (10-15) exhibited reduced tail vein toxicity relative to the parent compound. Some of the new pseudomycin derivatives (e.g., 14) also showed improved in vivo antifungal activity relative to its corresponding parent compound.

Animals↗

PubMed2001

Short wavelength collective dynamics in phospholipid bilayers: a molecular dynamics study.

Short wavelength density fluctuations of hydrated multilamellar phospholipid bilayers have been studied by molecular dynamics simulations in both the gel and liquid crystalline phases, and the results compared to recent inelastic x-ray scattering data [Phys. Rev. Lett. 86, 740 (2001)]. We confirm the existence of a highly dispersive sound mode, whose frequency and damping depend on the lipid phase, that the scattering arises mainly from in-plane motion of hydrocarbon chains, and we also identify a nondispersive mode attributed to motions of the chain terminal carbons.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor.

The mammalian hairless (hr) gene plays a critical role in the maintenance of hair growth. Although the hr gene has been identified, the biochemical function of its encoded protein (Hr) has remained obscure. Here, we show that Hr functions as a transcriptional corepressor for thyroid hormone receptors (TRs). We find that two independent regions of Hr mediate TR binding and that interaction requires a cluster of hydrophobic residues similar to the binding motifs proposed for nuclear receptor corepressors (N-CoR and SMRT). Similarly, we show that Hr binds to the same region of TR as known corepressors. We show that Hr interacts with histone deacetylases (HDACs) and is localized to matrix-associated deacetylase (MAD) bodies, indicating that the mechanism of Hr-mediated repression is likely through associated HDAC activity. Thus, Hr is a component of the corepressor machinery, and despite its lack of sequence identity with previously described corepressors, its mode of action is remarkably conserved. On the basis of its thyroid hormone-inducible and tissue- and developmental-specific expression, Hr likely defines a new class of nuclear receptor corepressors that serve a more specialized role than ubiquitous corepressors. The discovery that Hr is a corepressor provides a molecular basis for specific hair loss syndromes in both humans and mice.

Amino Acid Sequence↗

PubMed2001

Dynamics of inherent structure in supercooled liquids near kinetic glass transition.

We present a description of the dynamics of a supercooled binary Lennard-Jones liquid in term of the potential landscape of the system. The slowing down of the dynamics in supercooled liquids near the kinetic glass transition is related to the existence of basins in the potential landscape. The inherent structures that are the local potential minima in the configuration space obtained by a quench process are employed to represent the configurations of the basins. We present time correlation functions of the inherent structure, both the self and the coherent part, as a function of wave vector. We also calculated the mean-square displacement, and the non-Gaussian parameter of the van Hove self-correlation function. Compared with the dynamics of original configurations, the short-time relaxation has almost been eliminated by the quench process. However, the long-time alpha relaxations remain essentially the same. We conclude that the long-time alpha relaxation is the result of cross-basin transition in the potential landscape in the configuration space.

Journal Article↗

PubMed2001

Video-assisted endoscopic lumbar discectomy.

BACKGROUND: The optimal management of symptomatic lumbar disc herniations (LDH) remains controversial. This study examines the feasibility and safety of a video-assisted endoscopic intracanalicular technique for managing symptomatic LDH. METHODS: From September 1999 to June 2000, we used the current technique, the Vertebroscope System, on 11 patients (six men, five women), aged from 18 to 61 years (mean, 45), who had suffered symptomatic LDH. The disc levels involved were at L4-L5 (n = 8), and L5-S1 (n = 3). The Vertebroscope, which has a 30 degrees viewing angle and a working channel 1.7 cm in diameter, was used for the minimally invasive endoscopic procedures. The mean follow-up period was 12 months (range, 6-15). RESULTS: The operating time ranged from 60 to 335 min (mean, 136.5), and the estimated blood loss during operation was minimal to 200 ml. The mean length of the paramedian skin incisions was 2 cm. No drainage tube was used postoperatively. The mean hospital stay was 3 days (range, 2-5), with five patients discharged on the 1st postoperative day. Complications included one superficial wound infection, one conversion to an open procedure when muscle herniation into the working channel created a technical difficulty in approaching the ligamatum flavum, and one minor tear of the nerve root sleeve that did not require further surgery. In the first five patients studied herein, the mean operating time was significantly longer than that for the later five patients (201 vs 72 min, p < 0.001). CONCLUSIONS: The advantages of the current endoscopic disectomy technique include its minimally invasive character, with less paraspinal muscle trauma, direct address to the lesion site that resembles the open technique, and enhanced operative field visualization with a paramedian skin incision of just 2 cm. Practice is needed to perfect such an endoscopic approach for lumbar disc excision, so the operating time decreased significantly as the surgeons became more familiar with this endoscopic technique. It has proved to be safe and effective for treating patients with symptomatic LDH.

Adult↗

PubMed2001

Independent contributions of GR-1+ leukocytes and Fas/FasL interactions to induce apoptosis following interleukin-12 gene therapy in a metastatic model of prostate cancer.

In a mouse model of prostate cancer, adenovirus-mediated interleukin-12 (Ad.mIL-12) gene therapy resulted in significant growth inhibition of both the injected primary tumor and synchronous metastases. Within 2 days of vector injection, two distinct patterns of apoptosis were detected within the primary tumor, the inhibition of which with a caspase inhibitor substantially negated growth suppression. The dominant pattern displayed localized sheets of apoptotic cells in close association with necrosis containing polymorphic neutrophils (PMNs). Depletion of PMNs resulted in the loss of this pattern of apoptosis and reduced growth suppression. A second major wave of growth suppression within the primary tumor was mediated by an immune response. Natural killer (NK) cell activity was detected within tumor-infiltrating lymphocytes (TIL) by the eighth day post-vector injection, the depletion of which resulted in a significant loss of survival enhancement. A more modest role for T cells was identified, which in the absence of documented cytotoxic T lymphocyte (CTL) activity may be related to a significant reduction in interferon-gamma (IFN-gamma) levels found in mice depleted of T cells, thereby reducing the secondary influences of IFN-gamma. However, depletion of NK cells or T cells had no discernible negative effect on IL-12-mediated anti-metastatic activity. Attention focused on the role of IFN-gamma, observed following Ad.mIL-12 therapy, to mediate the diffuse pattern of apoptosis seen in the primary and metastatic lesions. In vitro studies noted the ability of IFN-gamma to up-regulate tumor cell expression of Fas and FasL to mediate apoptosis, whereas in vivo blockage of Fas/FasL interactions with soluble Fas resulted in a modest reduction in primary tumor growth suppression but complete abrogation within metastatic lesions.

Adenoviridae↗

PubMed2001

Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins.

With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesized prodrugs described herein (e.g., 2a, 2e, and 4e) exhibited comparable in vivo efficacy to that achieved by the parent compounds, yet free of tail vein irritation and histamine induced toxicity in vivo.

Animals↗

PubMed2001

Theory of the generalized dynamic structure factor of polyatomic molecular fluids measured by inelastic x-ray scattering.

We describe a theory for the calculation of the generalized dynamic structure factor S(k,omega) as measured by an inelastic x-ray scattering (IXS) experiment on single-component molecular or polyatomic molecular fluids. IXS spectrum of a simple fluid is proportional to the dynamic structure factor of a single species of atom. In the case of a molecular fluid, however, IXS spectrum is a weighted sum of partial dynamic structure factors of pairs of atomic species. The weighting factors are products of the atomic form factors of the pairs. We call this weighted average dynamic structure factor the generalized dynamic structure factor. We extend the formalism of a three effective eigenmode theory (TEE) developed previously for simple fluids to derive an approximate evolution equation for the generalized dynamic structure factor, which can be considered as a generalized hydrodynamic equation for molecular fluids. As examples, we first study the contributions of the partial dynamic structure factor to the generalized dynamic structure factor computed from molecular dynamics simulation of SPC/E model water. We found that the generalized dynamic structure factor of water measured by IXS can be well approximated by the center of mass or the oxygen atom dynamic structure factors. The generalized TEE model was then employed to analyze IXS spectra of nearly fully hydrated dilauroylphosphatidylcholine. The theory is able to fit all of the spectra in the k range from 5 to 32 nm(-1) quantitatively and gives their deconvoluted generalized dynamic structure factors.

Journal Article↗

PubMed2001

N-acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents.

We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved via simple N-acylation of PSB (1) or PSC' (2) with various prodrug linkers (7-9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed.

Animals↗