Analysis of NMR relaxation data of biomolecules with slow domain motions using wobble-in-a-cone approximation.
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Calmodulin↗
Biomedical subjects
S L Chang
Publications and source records attributed to S L Chang.
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↗
MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer.
MDM2 is one of the downstream target genes for transcriptional activation by the product of the p53 tumor-suppressor gene. Transactivation of MDM2 gene expression is represented by the presence of a functional p53 protein. We hypothesized that MDM2 mRNA expression may be a more suitable prognostic factor than p53 or MDM2 protein expression and p53 gene mutations. In this study, expression of MDM2 mRNA, p53 protein, and MDM2 protein and mutations of the p53 gene were assessed in 81 lung tumor tissue specimens using RT-PCR, immunohistochemistry, and direct sequencing among exons 5-8, respectively. By immunohistochemistry, 33 and 42 of 81 patients with p53 (40.7%) and MDM2 (51.5%) protein expression were found in lung tumor specimens, respectively. The p53 direct sequencing data indicated that 13 of 81 patients (16.0%) had p53 mutations. However, Kaplan-Meier analysis showed that p53 protein and MDM2 protein expression and p53 mutation were not useful as prognostic factors. Interestingly, the survival of patients with MDM2 mRNA expression was longer than that of patients without MDM2 mRNA expression, though MDM2 mRNA expression was not associated with clinicopathological parameters, including tumor grade, tumor stage, tumor type, and TNM values. Moreover, Cox regression analysis showed that MDM2 mRNA expression was a significantly independent favorable prognostic factor in non-small-cell lung cancer (NSCLC) patients. Thus, measuring MDM2 mRNA expression using RT-PCR may be a simple, useful approach for predicting the survival of NSCLC patients.
Adenocarcinoma↗
The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones.
Electrically-assisted delivery by iontophoresis and/or electroporation was used in vitro to deliver the calcium regulating hormones, salmon calcitonin (sCT) and parathyroid hormone (1-34) (PTH) through human epidermis. Such delivery could be useful for chronic treatment of post-menopausal osteoporosis and other clinical indications as a superior alternative to parenteral delivery. sCT (50 microg/ml) or PTH (1-34) (100 microg/ml) formulation was prepared in citrate buffer (pH 4.0 or 5.0, respectively). Epidermis separated from human cadaver skin was used. Iontophoresis was applied using a constant current power source and electroporation with an exponential pulse generator. Silver/silver chloride electrodes were used. A combination of electroporation and iontophoresis resulted in higher transdermal permeation than either one technique alone. Electroporation also shortened the lag time of iontophoretic transdermal delivery of salmon calcitonin. Pulsing at lower voltages followed by iontophoresis did not result in increased transport (over iontophoresis alone), perhaps because the transdermal voltage was very low. The transdermal transport of salmon calcitonin by pulsing with 15 pulses (1 ppm) of 500 V (200 ms) followed by iontophoresis led to a quick input and high flux. The average transdermal voltage was only about 50 V for a 500 V study.
Administration, Cutaneous↗
Chronic cocaine alters hemodynamics and leukocyte-endothelial interactions in rat mesenteric venules.
We investigated the effects of chronic cocaine exposure on the microcirculation in the rat mesenteric venules under both non-inflammatory and FMLP-induced inflammatory conditions. Chronic cocaine significantly increased WBC rolling flux in both conditions, and potentiated FMLP-induced leukocyte-endothelial cell adhesion (LEA). In cocaine-treated animals, total WBC number increased by 91%, and the ratio of white blood cell to red blood cell velocity was significantly lower, while vessel diameter was unchanged. Chronic cocaine decreased serum levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), but had no effect on interleukin-1 beta (IL-1beta). Expression of intercellular adhesion molecule-1 (ICAM-1) was increased in mesenteric venules following chronic cocaine exposure, and may be one of the mechanisms underlying enhancement of FMLP-induced LEA. The increase in WBC count, WBC flux and LEA, and the change in cell velocity seen in the cocaine-treated animals could cause a decrease in effective vessel diameter and a change in intravascular resistance, and may underlie the progressive vascular damage seen in chronic cocaine-abusing individuals.
Animals↗
Management of scrap computer recycling in Taiwan.
It is estimated that approximately 300,000 scrap personal computers are generated each year in Taiwan [S.-L. Chang, A Study on the Scrap Computer Treatment Cost, Environment Protection Administration of Taiwan, December 1998 (in Chinese)]. The disposal of such a huge number of scrap computers presents a difficult task for the island due to the scarcity of landfills and incineration facilities available locally. Also, the hazardous materials contained (i.e., phosphor coatings of cathode ray tubes (CRTs), batteries, polychlorinated biphenyl capacitors, mercury-containing parts, liquid crystal display, high-lead content CRT funnel glass, and plastic containing flame-retardant bromine, etc.) in the scrap computers may seriously pollute the environment if they are not properly disposed of. Therefore, the EPA of Taiwan declared scrap personal computers the producer's recycling responsibility as of July 1997. Under this decree, the manufacturers, importers and sellers of personal computers have to properly recover and recycle the scrapped computers which they originally sell. On June 1, 1998, a producer responsibility recycling program for scrap computers was officially implemented in Taiwan. Under this program, consumers can bring their unwanted personal computers to the designated collection points and receive reward money. Currently, only six computer items are mandated to be recycled in this recycling program. They are notebooks, monitors, hard disks, power supplies, printed circuit boards and main frame shells. This article outlines the current scrap computer recycling system in Taiwan.
Bromine↗
Transdermal iontophoretic delivery of salmon calcitonin.
Electrically enhanced transdermal delivery of salmon calcitonin could be useful for chronic treatment of postmenopausal osteoporosis and other clinical indications as a superior alternative to parenteral delivery. Calcitonin (50 microg/ml) formulation was prepared in citrate buffer (pH 4.0). Epidermis separated from human cadaver skin was used. Most iontophoresis studies were done at a current density of 0.5 m A cm2. Silver/silver-chloride electrodes were used and calcitonin was found to be best delivered under the anode. The relationship between calcitonin flux and current density during iontophoresis was linear. Passive flux was zero. Flux increased with increasing concentration up to 250 microg/ml but then it levels off. Thus, transdermal delivery of salmon calcitonin may be accomplished to achieve therapeutic levels.
Administration, Cutaneous↗
In vitro biocytin injection into perinatal mouse brain: a method for tract tracing in developing tissue.
Injection of biocytin provides an effective method for labeling axonal projections. Several difficulties arise when this technique is employed in fetal or early postnatal animals in vivo, including limited access to injection sites and extended post-injection survival periods. To circumvent these problems, we adapted the technique of extracellular biocytin injection for use in explanted brain hemispheres of developing mice. Briefly, entire brain hemispheres from perinatal mice (E16-P9) were removed and placed in oxygenated aCSF in a brain slice recording chamber. Following visually guided injection of biocytin (2%) into the prelimbic cortex, the brains were then incubated in oxygenated artificial cerebrospinal fluid (aCSF) for varying periods of time and then immersion-fixed in 4% paraformaldehyde and 0.5% glutaraldehyde. The next day, the brains were sectioned and processed for biocytin histochemistry using the avidin-biotin-complex method. We examined the method of injection, electrode type, time of injection, and post-injection incubation period. We found that in E16-P9 animals iontophoresis of biocytin using 8- to 12-megaohm patch clamp electrodes for a duration of 10 min provides optimal axonal labeling. Post-injection incubation times of four or more hours are sufficient for labeling fine caliber collaterals as well as axon bundles that reach distances over 3 mm. In vitro injection of biocytin into explanted brain hemispheres provides a quick and easy method for tract tracing in developing brains.
Animals↗