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Biomedical subjects

S L Chang

Publications and source records attributed to S L Chang.

At least 19 recordsLinked to original sources

Development of Taenia asiatica cysticerci to infective stage and adult stage in Mongolian gerbils.

The development of metacestodes and adult worms of Taenia asiatica in Mongolian gerbils (Meriones unguiculatus) were observed. Cysticerci were recovered from gerbils subcutaneously injected with hatched oncospheres. The recovery rate ranged from 0.1 to 3.2%. No cysticerci were recovered from the orally inoculated gerbils. The infectivity of the cysticerci recovered at 48 weeks post-infection was evaluated. Tapeworms were recovered on day 14 post-infection from the small intestine of 5 of 11 gerbils, with a recovery rate of 27% (6 worms recovered/22 worms inoculated). Three and four adult worms were recovered from two human volunteers who ingested five cysticerci after 4 months post-infection. In worms recovered from gerbils, segmentation and genital primordia in the posterior proglottids and hooklets in the residual rostellum were observed. The results indicate that gerbils can serve as an alternative intermediate host and that partial development of the adult worm stage occurs in gerbils.

Adult↗

Mechanism for singular behavior in vibrational spectra of topologically disordered systems: short-range attractions.

At low-enough fluid densities, we have found some naive singular behavior, like the van Hove singularities in the phonon spectra of lattices, appearing in the instantaneous normal mode spectra of the Lennard-Jones (LJ) 2n-n fluids, which serve as a prototype of topologically disordered systems. The singular behavior cannot be predicted by the mean-field theory, but interpreted by the perturbed binary modes of some special pairs, called the mutual nearest neighbor pairs, at separations corresponding to the extreme binary frequencies, which are solely determined by the attractive part of the LJ 2n-n pair potential. By reducing the range of attraction in the pair potential under the conditions of the same particle diameter and well depth, the tendency for the appearance of the singular behavior shifts to higher fluid densities. From this study, we conclude that pair potential with a short-range attraction can be a mechanism to produce a counterpart of the van Hove singularity in the vibrational spectra of disordered systems without a reference lattice.

Journal Article↗

Development of Taenia saginata asiatica metacestodes in SCID mice and its infectivity in human and alternative definitive hosts.

Development of Taenia saginata asiatica metacestodes in SCID mice, and its infectivity in humans, golden hamsters, and Mongolian gerbils as alternative definitive hosts, were investigated. Cysticerci were recovered from SCID mice that were subcutaneously injected with hatched oncospheres of T. s. asiatica. The morphological changes of metacestodes were observed. The recovered cysticerci were fed to gerbils, hamsters and humans, to check for their infectivity. Tapeworms were recovered from gerbils and hamsters fed with 20 to 45 week-old cysticerci, and proglottids excretions were observed in human volunteers fed with 45 week-old cysticerci. However, no tapeworms were recovered from gerbils fed with 10 week-old cysticerci. Our results suggest that T. s. asiatica oncospheres needed more than 20 weeks to develop to maturity in SCID mice to be infective to both their natural and alternative definitive hosts.

Animals↗

Instantaneous normal mode analysis of orientational motions in liquid water: local structural effects.

We have investigated the effects of local structures on the orientational motions in liquid water in terms of the instantaneous normal mode (INM) analysis. The local structures of a molecule in liquid water are characterized by two different kinds of index: the asphericity parameter of its Voronoi polyhedron and the numbers of the H bonds donated and accepted by the molecule. According to the two kinds of index, the molecules in the simulated water are classified into subensembles, for which the rotational contributions to the INM spectrum are calculated. Our results indicate that by increasing the asphericity, the rotational contribution has a shift toward the high-frequency end in the real spectrum and a decrease in the fraction of the imaginary modes. Furthermore, we find that this shift essentially relies on the number of the donated H bonds of a molecule, but has almost nothing to do with that of the accepted H bonds. The local structural effects resulting from the geometry of water molecule are also discussed.

Journal Article↗

Calculations of cellular microdosimetry parameters for alpha particles and electrons.

The cellular microdosimetry parameters including the cellular S-value and the single-event specific energy distribution for alpha particles and electrons are important in radiation dosimetry and biology. These parameters may be used to determine the relative biological effectiveness of radiations in the boron neutron capture therapy. In the present work, such parameters were calculated for different source to target region combinations, i.e. cell surface, cytoplasm, nucleus and cell. Calculations were made using a semi-analytical model that simulated the emission of alpha particles or electrons by the Monte Carlo method and calculated the energy imparted to the target volume by the analytical method. Delta particle equilibrium and partial delta particle equilibrium were applied to alpha particles and electrons, respectively. Range-energy relations were employed to determine the incident and emerging energies of the primary particles. For electrons, the fraction in the energy loss resulting from the generation of bremsstrahlung and high-energy secondary electrons was estimated. The energy loss straggling of electrons entering and leaving a target volume was also estimated. Calculated cellular S-values were compared to corresponding data of the MIRD Committee. Calculated single-event specific energy distributions were also compared to results calculated using the Penelope code.

Alpha Particles↗

Characteristics of the new THOR epithermal neutron beam for BNCT.

A characterization of the new Tsing Hua open-pool reactor (THOR) epithermal neutron beam designed for boron neutron capture therapy (BNCT) has been performed. The facility is currently under construction and expected in completion in March 2004. The designed epithermal neutron flux for 1 MW power is 1.7x10(9)n cm(-2)s(-1) in air at the beam exit, accompanied by photon and fast neutron absorbed dose rates of 0.21 and 0.47 mGys(-1), respectively. With (10)B concentrations in normal tissue and tumor of 11.4 and 40 ppm, the calculated advantage depth dose rate to the modified Snyder head phantom is 0.53RBE-Gymin(-1) at the advantage depth of 85 mm, giving an advantage ratio of 4.8. The dose patterns determined by the NCTPlan treatment planning system using the new THOR beam for a patient treated in the Harvard-MIT clinical trial were compared with results of the MITR-II M67 beam. The present study confirms the suitability of the new THOR beam for possible BNCT clinical trials.

Boron Neutron Capture Therapy↗

Chronic morphine potentiates the inflammatory response by disrupting interleukin-1beta modulation of the hypothalamic-pituitary-adrenal axis.

Interleukin-1-beta (IL-1beta) can promote inflammation by up-regulating vascular adhesion molecules and inhibit inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis to produce anti-inflammatory glucocorticoids. In this study, chronic morphine was shown to suppress IL-1beta-induction of corticotropin releasing factor (CRF) mRNA and plasma corticosterone levels. Leukocyte-endothelial adhesion (LEA) in rat mesenteric venules increased during IL-1beta- and FMLP-induced inflammation. Chronic morphine potentiated the LEA response to either IL-1beta or FMLP alone, and greatly enhanced LEA in response to combined IL-1beta and FMLP. Thus, it appears that chronic morphine exposure may promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1beta-mediated local inflammation and the anti-inflammatory effects of the HPA axis.

Animals↗

Residues in Methylosinus trichosporium OB3b methane monooxygenase component B involved in molecular interactions with reduced- and oxidized-hydroxylase component: a role for the N-terminus.

Methane monooxygenase (MMO) is a non-heme-iron-containing enzyme which consists of 3 protein components: a hydroxylase (MMOH), an NAD(P)H-linked reductase (MMOR), and a 138-residue regulatory protein, component B (MMOB). Here, NMR spectroscopy has been used to derive interactions between MMOB and reduced and oxidized states of MMOH (245 kDa). Differential broadening of MMOB resonances in 1H-15N HSQC spectra acquired at different molar ratios of MMOH indicates interaction of both proteins, with MMOB binding more tightly to oxidized MMOH as observed previously. The most broadened backbone NH resonances suggest which residues in MMOB are part of the MMOH-binding interface, particularly when those residues are spatially close or clustered in the structure of MMOB. Although a number of different residues in MMOB appear to be involved in interacting with oxidized- and reduced-MMOH, some are identical. The two most common segments, proximal in the structure of MMOB, are beta-strand 1 with turn 1 (residues 36-46) and alpha-helix 3 going into loop 2 (residues 101-112). In addition, the N-terminus of MMOB is observed to be involved in binding to MMOH in either redox state. This is most strongly evidenced by use of a synthetic N-terminal peptide from MMOB (residues 1-29) in differential broadening 1H TOCSY studies with MMOH. Binding specificity is demonstrated by displacement of the peptide from MMOH by parent MMOB, indicating that the peptide binds in or near the normal site of N-terminal binding. The N-terminus is also observed to be functionally important. Steady-state kinetic studies show that neither a delta2-29 MMOB deletion mutant (which in fact does bind to MMOH), the N-terminal peptide, nor a combination of the two elicit the effector functions of MMOB. Furthermore, transient kinetic studies indicate that none of the intermediates of the MMOH catalytic cycle are observed if either the delta2-29 MMOB mutant or the N-terminal peptide is used in place of MMOB, suggesting that deletion of the N-terminus prevents reaction of reduced MMOH with O2 that initiates catalysis.

Amino Acid Sequence↗

Phase determination and extension using X-ray multiple diffraction and the maximum-entropy method.

The extension of the phases of the structure factors of the organic crystal C(25)H(25)NO(2) from 77 starting individual phases using the maximum-entropy method is reported. These starting phases were determined from 90 experimental triplet phases calculated from 215 measured psi-scan three-beam and four-beam diffraction profiles obtained with a rotating-anode X-ray source, where the psi scans were around the reciprocal-lattice vectors of the 001, 002 and 003 reflections. The extension of the structure factors with phase values was carried out using the maximum-entropy method for 2040 measured two-beam Bragg diffraction intensities with 77 starting phases and the symmetry of the space group as the constraints. Use of structure-factor triplets as constraints for entropy maximization was also attempted. The minimum chi(2) criteria were applied to the maximum-entropy extrapolation to discern the best phase set to be used as the new constraints for the next step of generating new phases. With this phase-extension procedure, more than 100 phases were determined and an electron-density map at 1.97 A was deduced.

Journal Article↗

Polarization-resolved output analysis of X-ray multiple-wave interaction.

The polarization suppression of the interfering components in X-ray multiple-wave interaction is observed for the first time by using a polarization analyzer with an arbitrary inclination of the diffraction plane with respect to that of the investigated crystal. The condition for total suppression of the multiple-wave interaction outside the investigated crystals by a polarization analyzer is derived theoretically from the modified Born approximation. By means of the partial suppression of the strong interfering component, the increase in the visibility of multiple-wave interference is experimentally and theoretically demonstrated. The proposed experimental polarization-resolved technique provides an operational way to enhance the visibility of X-ray multiple-wave interaction outside the investigated crystals for direct phase determination.

Journal Article↗

Anomalous dispersion behavior of multiple-wave X-ray diffraction at absorption edges: determination of phase change at resonance.

The effects of anomalous dispersion (resonance) on multiple reflection of x rays and their interference in crystals at atomic absorption edges are studied. Intensity ratios of two inversion-symmetry-related multiple diffractions at or near absorption edges exhibit highly phase-sensitive profiles with strong asymmetric characteristics, unlike those far from the edges. A new resonance perturbation Bethe approach is developed to explain this behavior. This leads to direct determination of the phase change for x-ray reflections at resonance.

Journal Article↗

Dexamethasone affects cytokine-mediated adhesion of HL-60 human promyelocytic leukemia cells to cultured dermal microvascular endothelial cells.

Leukocyte endothelial adhesion (LEA) is the prelude to a complex cascade of reactions following an immunological challenge. Recently, LEA has been implicated in the molecular basis of several dermatological disorders. While the role of proinflammatory cytokines, such as interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), in LEA has been investigated using nondermal models, limited data exist regarding their effects on LEA in dermal models. This study shows that cotreatment of cultured human dermal endothelial cells (CADMEC) with IL-1beta and TNF-alpha resulted in a marked increase in the adherence of human promyelocytic leukemia (HL-60) cells to CADMEC and an increase in expression of intercellular adhesion molecule-1 and E-selectin. Pretreatment of CADMEC with dexamethasone, a long-lasting glucocorticoid, resulted in a decrease in both HL-60 cell adhesion to CADMEC and adhesion molecule expression. Taken together, these data demonstrate that LEA may play a role in inflammatory skin conditions and in the mechanisms underlying the potential use of glucocorticoids as a treatment option.

Cell Adhesion↗

Actions of endotoxin and morphine.

In summary, our current studies show that treatment with a bacterial endotoxin, lipopolysaccharide (LPS), induces the expression of mu opioid receptors in the rat mesentery. This induction may be mediated through IL-1's actions on mu opioid receptors. Morphine stimulates the expression of adhesion molecules in human brain microvascular endothelial cells (HBMEC) isolated from pathological tissues. Under pathological conditions, mu opioid receptor-dependent pathways may be modulated through the induction of mu opioid receptors, especially in endothelial cells. Treatment with morphine increases [14C]-inulin permeability of an in vitro microvascular endothelial cell barrier, and decreases endothelial cell viability. Morphine pre-treatment potentiates the effects of LPS on endothelial cell viability, and on LPS induction of IL-1beta secretion from 1alpha, 25-dihydroxy-vitamin D3-treated HL-60 human leukemia cells. Previously, it was suggested that an opioid-dependent pathway may be involved in the recovery from endotoxin shock (D'Amato and Holaday, 1984). Induction of mu opioid receptors by treatment with high doses of endotoxin suggests that mu opioid receptor-dependent pathways may be involved in mediating the response to endotoxins. Taken together, these data provide valid evidence for an association between endotoxins and opioid actions. These studies suggest that opioid-dependent pathways in disease or in endotoxin exposure may be modified by cytokine-induced expression of opioid receptors in endothelial cells. In a pathological condition, an alteration of the opioid-dependent pathway may be expected. When morphine is used for its therapeutic values, it may, indeed, potentiate LPS' effects in an adverse manner. From a clinical perspective, these data indicate that morphine and an endotoxin, such as LPS, may interact in a positive 'feedback type of reaction, and thereby modulate the body's immune responses with unexpected and detrimental results.

Animals↗

The origin of Minnan and Hakka, the so-called "Taiwanese", inferred by HLA study.

The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggests that this haplotype is the most well-conserved ancient haplotype of the Yueh.

Alleles↗

Diversity of HLA among Taiwan's indigenous tribes and the Ivatans in the Philippines.

Taiwan's indigenous tribes, especially the east coast tribes are not only closely related to Oceania but also with the Australian aborigines. The Ivatans of the Batan Islands in the Philippines are closely related to the Yami tribe of Taiwan as cultural and anthropological studies have shown. Many DRB1 alleles (*15021, *16021, *0404, *04051, *11011, *12021, *1401, *08032) have high allele frequencies (>20%) in certain tribes, suggesting Taiwan's indigenous tribes are homogeneous populations. These high frequency DRB1 alleles and also some HLA-A-B-DR haplotypes found in Taiwan's indigenous tribes are also found in Oceania, Australian aborigines, south and north east Asians and American Indians, lending further support to our previous findings that Taiwan's indigenous tribes are more or less genetically related to both northern and southern Asians, possibly as well as Amerindians. HLA-A*2402 with a remarkably high frequency among Taiwan's indigenous tribes (52.1% approximately 86.3%), especially the central mountain tribes, possibly represents not only founder effects and population bottlenecks, but also positive selection of the allele. Although the Ami tribe has the highest ever reported frequencies of the DRB1*0404 and DRB1*0405, these alleles have not been found to be associated with rheumatoid arthritis as previously described for Caucasians. In addition, DRB1*1401 has a high frequency in most tribes but is not associated with psoriasis as previously indicated in some studies, suggesting the involvement of some additional genetic and/or environmental factors mechanism in the development of these diseases.

Alleles↗

Comparison of the antiviral activity of hydrophobic amino acid phosphoramidate monoesters of 2'3'-dideoxyadenosine (DDA) and 3'-azido-3'-deoxythymidine (AZT).

A series of hydrophobic, water soluble and non-toxic amino acid phosphoramidate monoesters of dideoxyadenosine (ddA) and 3'-azido-3'-deoxythymidine were shown to inhibit the replication of HIV-1 in human peripheral blood mononuclear cells (PBMC) from two donors. The tryptophan methyl ester phosphoramidates of AZT and ddA were equally potent (EC50S = 0.3-0.4 microM), while the phenyl methyl ester of ddA was 40- to 100- fold more potent than the AZT derivatives. The alaninyl methyl ester of AZT was found to be 70- fold more potent than the ddA derivative. The methyl amide derivatives were found to be 5-20 fold less active than the methyl esters for the ddA series, while for AZT the derivatives were found to be of similar potency or 60- to 166- fold more potent than the methylesters.

Amides↗

Endomorphin-1 and endomorphin-2 induce the expression of c-FOS immunoreactivity in the rat brain.

Using FOS immunoreactivity (FOSir) as an anatomical marker of neuronal activation, we examined the effects of intracerebroventricular (i.c.v.) injections of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in the rat brain to determine the sites of action of these two mu-opioid ligands. Radiant heat tail flick latency, as a measure of behavioral effects, was prolonged by either EM-1 or EM-2 administration. Dose-dependent EM-1- and EM-2-induced FOSir were observed in various nuclei throughout the rostral-caudal axis of the rat brain. While there was some overlap, EM-1-induced FOSir was more prevalent than EM-2. The pattern of EM-induced FOSir was similar to the distribution of EM immunoreactivity (EMir). However, some sites with little or no detectable EMir exhibited FOSir, while other nuclei with marked EMir showed only sparse FOSir. EM-induced FOSir was correlated with mu-opioid receptor location in most brain areas. However, EM-induced FOSir was absent in the caudate putamen and the accumbens nucleus, both areas of high mu-opioid receptor density.

Animals↗