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Biomedical subjects

C H Tsao

Publications and source records attributed to C H Tsao.

15 recordsLinked to original sources
PubMed2003

Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients.

To determine whether the serum levels of anti-double strand DNA (anti-dsDNA) autoantibodies detected using a newly developed fluorescence immunoassay (FIA) in patients with systemic lupus erythematosus (SLE) correlated more with clinical parameters, such as SLE disease activity index (SLEDAI), complement and the occurrence of nephritis when compared with traditional enzyme-linked immunosorbent assay (ELISA), we prospectively collected 124 serum samples from 31 patients who had juvenile-onset SLE and were regularly monitored every 2 months at our outpatient clinic. At every visit, clinical manifestations and laboratory parameters were assessed and the SLEDAI was determined. Correlation analyses between the two different measurements of anti-dsDNA antibodies and SLEDAI, serum complement levels and the occurrence of nephritis were performed. The results showed that anti-dsDNA autoantibodies detected using both ELISA and FIA significantly correlated with SLEDAI, and significantly and inversely correlated with the serum levels of C3 and C4. FIA had significantly higher correlation with SLEDAI and C4 than did ELISA. The mean values of anti-dsDNA antibodies detected using FIA in patients with nephritis were significantly higher than in those without nephritis. In contrast, the values of anti-dsDNA antibodies detected using ELISA did not show significant differences between these two groups. We conclude that FIA had better correlation with SLEDAI, C4 and the occurrence of nephritis, and comparable correlations with C3 that were similar to the results found using ELISA. Thus, it is worthwhile developing the FIA method for clinical evaluation of disease activity in SLE patients.

Adolescent↗
PubMed2001

The effect of human bcl-2 and bcl-X genes on dengue virus-induced apoptosis in cultured cells.

Infection of dengue viruses (DENs) can cause human dengue fever, hemorrhagic fever, or shock syndrome. Although DEN-induced apoptosis has been implicated in pathogenesis of the DEN-related diseases, the underlying mechanism remains largely unexplored. In this study, we investigated the effect of ectopic expression of human bcl-2 and bcl-X genes on DEN-induced apoptosis in cultured cells. We employed a human isolate of DEN serotype 2 (DEN-2), PL046, which not only caused cell-cycle arrest in the G1 phase but also induced apoptosis in infected baby hamster kidney (BHK-21) cells, murine neuroblastoma N18 cells, and human neuronal NT-2 cells. Our results reveal that overexpression of bcl-2 in fibroblast-like BHK-21 cells, although not inhibiting virus yields, delayed the process of DEN-induced apoptosis, thereby permitting surviving cells to become persistently infected. In contrast, stable bcl-2 expression in neuronal N18 cells failed to block DEN-induced apoptosis. On the other hand, Bcl-X(L), expressed predominantly in the nervous system, appeared to delay DEN's killing effect in neuronal N18 cells but not in fibroblast-like BHK-21 cells. In addition, inducible expression bcl-X(s), despite its proapoptotic property in other reported system, was found to merely accelerate cell death in DEN-infected N18 but not in infected BHK-21 cells. Thus, through studying the effect of human bcl-2-related genes, our results suggest that DEN infection may trigger target cells to undergo morphologically similar but biochemically distinct apoptotic pathways in a cell-specific manner.

Animals↗
PubMed2001

Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

Animals↗
PubMed1999

Membrane permeabilization by small hydrophobic nonstructural proteins of Japanese encephalitis virus.

Infection with Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. We observed that JEV replication rendered infected baby hamster kidney (BHK-21) cells sensitive to the translational inhibitor hygromycin B or alpha-sarcine, to which mock-infected cells were insensitive. However, little is known about whether any JEV nonstructural (NS) proteins contribute to virus-induced changes in membrane permeability. Using an inducible Escherichia coli system, we investigated which parts of JEV NS1 to NS4 are capable of modifying membrane penetrability. We found that overexpression of NS2B-NS3, the JEV protease, permeabilized bacterial cells to hygromycin B whereas NS1 expression failed to do so. When expressed separately, NS2B alone, but not NS3, was sufficient to alter bacterial membrane permeability. Similarly, expression of NS4A or NS4B also rendered bacteria susceptible to hygromycin B inhibition. Examination of the effect of NS1 to NS4 expression on bacterial growth rate showed that NS2B exhibited the greatest inhibitory capability, followed by a modest repression from NS2A and NS4A, whereas NS1, NS3, and NS4B had only trivial influence with respect to the vector control. Furthermore, when cotransfected with a reporter gene luciferase or beta-galactosidase, transient expression of NS2A, NS2B, and NS4B markedly reduced the reporter activity in BHK-21 cells. Together, our results suggest that upon JEV infection, these four small hydrophobic NS proteins have various modification effects on host cell membrane permeability, thereby contributing in part to virus-induced cytopathic effects in infected cells.

Animals↗
PubMed1996

Calculations of depth-dose distributions, cross sections and momentum loss.

The ability to know with precision the depth-dose, dose average LET, fluence and energy distributions is of great importance in many research fields, including therapeutic and diagnostic medicine when using heavy ion beams, as well as in space research. We have therefore developed a model and a computer code for calculating these distributions when using high energy proton or heavy ion beams. In this model, we use semi-empirical total reaction and partial cross section formulas developed by us and a new prescription to take into account the energy and momentum loss of the secondary nuclei. In this paper, we will also present an empirical equation for the total inelastic 4He-p cross section, as well as the partial cross sections for the production of 3He, 3H, 2H, p and n.

Algorithms↗
PubMed1990

Spallation processes and nuclear interaction products of cosmic rays.

Most cosmic-ray nuclei heavier than helium have suffered nuclear collisions in the interstellar gas, with transformation of nuclear composition. The isotopic and elemental composition at the sources has to be inferred from the observed composition near the Earth. The source composition permits tests of current ideas on sites of origin, nucleosynthesis in stars, evolution of stars, the mixing and composition of the interstellar medium and injection processes prior to acceleration. The effects of nuclear spallation, production of radioactive nuclides and the time dependence of their decay provide valuable information on the acceleration and propagation of cosmic rays, their nuclear transformations, and their confinement time in the Galaxy. The formation of spallation products that only decay by electron capture and are relatively long-lived permits an investigation of the nature and density fluctuations (like clouds) of the interstellar medium. Since nuclear collisions yield positrons, antiprotons, gamma rays and neutrinos, we shall discuss these topics briefly.

Astronomical Phenomena↗
PubMed1989

Model analysis of Space Shuttle dosimetry data.

An extensive model analysis of plastic track detector measurements of high-LET particles on the Space Shuttle has been performed. Three shuttle flights: STS-51F (low-altitude, high-inclination), STS-51J (high-altitude, low-inclination), and STS-61C (low-altitude, low-inclination) are considered. The model includes contributions from trapped protons and galactic cosmic radiation, as well as target secondary particles. Target secondaries, expected to be of importance in thickly shielded space environments, are found to be a significant component of the measured LET (linear energy transfer) spectra.

Cosmic Radiation↗
PubMed1989

Radiation hazards on space missions outside the magnetosphere.

Future space missions outside the magnetosphere will subject astronauts to a hostile and unfamiliar radiation environment. An annual dose equivalent to the blood-forming organs (BFOs) of approximately 0.5 Sv is expected, mostly from heavy ions in the galactic cosmic radiation. On long-duration missions, an anomalously-large solar energetic particle event may occur. Such an event can expose astronauts to up to approximately 25 Gy (skin dose) and up to approximately 2 Sv (BFO dose) with no shielding. The anticipated radiation exposure may necessitate spacecraft design concessions and some restriction of mission activities. In this paper we discuss our model calculations of radiation doses in several exo-magnetospheric environments. Specific radiation shielding strategies are discussed. A new calculation of aluminum equivalents of potential spacecraft shielding materials demonstrates the importance of low-atomic-mass species for protection from galactic cosmic radiation.

Aluminum↗
PubMed1988

A comparison of neutron-induced SEU rates in Si and GaAs devices.

The single-event-upset rates due to neutron-induced nuclear recoils have been calculated for Si and GaAs components using the HETC and MCNP codes and the ENDF data base for (n, p) and (n, alpha) reactions. For the same critical charge and sensitive volume, the upset rate in Si exceeds that of GaAs by a factor of about 1.7, mainly because more energy is transferred in neutron interactions with lighter Si nuclei. The upset rates due to neutrons are presented as functions of critical charge and atmospheric altitude. Upsets induced by cosmic-ray nuclei, secondary protons and neutrons are compared.

Arsenic↗
PubMed1987

Distributed reacceleration of cosmic rays.

We develop a model in which cosmic rays, in addition to their initial acceleration by a strong shock, are continuously reaccelerated (e.g., by weak shocks) while propagating through the galaxy. The equations describing this acceleration scheme are solved analytically (approximating ionization losses by a cutoff) and numerically. Solutions for the spectra of primary and secondary cosmic rays are given in a closed analytic form, and they allow a rapid search in parameter space for viable propagation models with distributed reacceleration included. The observed boron-to-carbon ratio can be reproduced by the reacceleration theory over a range of escape parameters, some of them quite different from the standard "leaky box" model. It is also shown that even a very modest amount of reacceleration by strong shocks causes the boron-to carbon ratio to level off at sufficiently high energies, and this effect may be observed in the CRNE data. Several other curiosities in the data may be explained naturally if a modest amount of distributed reacceleration is invoked, including (a) the apparent truncation at low energy in the otherwise exponential pathlength distribution associated with the leaky box model, (b) the sub-iron isotopic anomalies and other effects noted by Silberberg et al., and (c) the discrepancy between the reported 10Be lifetime and the lifetime of cosmic rays in the dense strata of the galactic disk.

Acceleration↗
PubMed1984

LET-distributions and doses of HZE radiation components at near-Earth orbits.

Among cosmic rays, the heavy nuclei ranging from carbon to iron provide the principal contribution to the dose equivalent. The LET-distributions and absorbed dose aid dose equivalent have been calculated and are presented as a function of shielding and tissue self-shielding. At solar minimum, outside the magnetosphere, the unshielded dose equivalent of nuclei with atomic number Z > or = 6 is about 47 rem/year. The contribution of the target nuclei adds 7 rem/year. With 4 g/cm2 aluminum shielding, and at a depth of 5 cm in a biological phantom of 30 cm diameter, the respective values are 11 and 10 rem/year. Corresponding dose rates for orbits with various inclinations are presented, as well as the LET distributions of various components of cosmic rays.

Cosmic Radiation↗
PubMed1984

Radiation doses and LET distributions of cosmic rays.

Among cosmic rays, the heavy nuclei ( HZE particles) like iron provide the dominant contribution to the dose equivalent during exposures in space. The LET distributions and radiation doses of cosmic-ray components have been calculated--with and without the quality factors--for a set of shielding and tissue self-shielding penetration depths. The relative contributions of heavy ions among solar flare particles to the dose equivalent are also explored. The transport calculations of the nuclei in air, shielding materials, and biological tissue-like material were carried out using the partial and total nuclear cross-section equations and nuclear propagation codes of Silberberg and Tsao . Outside the magnetosphere , at solar minimum, the product of the unshielded dose and the quality factors of cosmic-ray protons and heavy nuclei with atomic number Z greater than or equal to 6 are about 5 and 47 rem/year, respectively. With 4 g/cm2 aluminum shielding and at a depth of 5 cm in a biological phantom of 30 cm diameter, the respective values of the dose equivalents are about 4 and 11 rem/year. Due to the hard spectrum of cosmic rays, the attenuation of protons thus is relatively modest, while that of heavy nuclei is larger due to the larger interaction cross section. The dose equivalent of neutrons in the shielded case mentioned above is similar to that of protons. The biological risks are tentatively assessed in terms of the BEIR 1980 report. Uncertainties in risks due to possible large RBE values at low doses of high-LET radiation and due to the microbeam nature of damage by heavy ions are pointed out. Certain experiments and studies by radiobiologists are suggested for reducing the uncertainties in the estimates of the risks.

Cosmic Radiation↗