Biomedical subjects
Publications and source records attributed to S Chung.
A series of 2,2-dimethyl-5-[4-(methylsulfonyl)phenyl]-4-phenyl-3(2H)furanones was prepared and evaluated for their ability to inhibit cyclo-oxygenase-2 (COX-2).
Residual saliva and minor salivary gland secretions are important for the maintenance of oral mucosal wetness. Salivary proteins and glycoproteins are the major components of the oral mucosal film, which functions as a moisture retainer and a protective barrier. Here, the correlations between the amounts of residual saliva and minor salivary gland secretions and their protein concentrations were investigated in 30 normal healthy individuals. The thickness of the mucosal film was measured at six mucosal surfaces and minor salivary gland secretion rate was measured at two mucosal surfaces. The thickness of residual saliva was determined by placing filter-paper strips against the mucosa at each site for 5 s and then measuring the volume electronically with a Periotron 8000 micro-moisture meter. The unstimulated rate of minor salivary gland secretion was measured for 30 s by the same method. Unstimulated whole salivary flow rate was measured with the spitting method. The total protein concentration of all salivary samples was measured by bicinchoninic acid assay. Before the experiment, the intra-/inter-examiner reliability of the method using the Periotron and the filter-paper strips was investigated. With a range of 0.4256-0.8846, the intraclass correlation coefficient, measured within and between examiners, was indicative of good reliability. The oral mucosal site with the thinnest coat of residual saliva was the anterior hard palate. Mucosal wetness on the hard palate and buccal mucosa showed significant positive correlations with the unstimulated whole salivary flow rate and significant negative correlations with the total protein concentration of residual saliva. Mucosal wetness on the upper and lower labial mucosa also showed significant negative correlations with the total protein concentration of residual saliva. Mucosal wetness on the soft palate was correlated with the minor salivary gland secretion rate (r=0.477, P<0.01). Among the minor salivary glands, the secretion rate of soft palate glands in females showed a significant correlation with the unstimulated whole salivary flow rate (r=0.563, P<0.05) and a significant negative correlation with its total protein concentration (r=-0.525, P<0.05). These data suggested that oral mucosal wetness and minor salivary gland secretions could be influenced by various factors differently according to mucosal sites.
OBJECTIVE: This study compared recidivism rates for alleged maltreatment perpetrators whose initial report was substantiated and those whose initial report was not substantiated, to determine whether they returned to the child welfare system at differing rates. METHOD: Statewide administrative child welfare services data over a period of 4 1/2 years was analyzed. The sample included 31,531 perpetrators of intrafamilial maltreatment. Separate analyses were conducted for each type of maltreatment (sexual abuse, physical abuse, and neglect). RESULTS: Bivariate relationships (substantiation status and recidivism) were analyzed using survival curves, and the study found that recidivism patterns differed by type of maltreatment and by substantiation status at the index event. Multivariate analyses using Cox Proportional Hazards models found that bivariate relationships held true even when controlling for neighborhood mean income, ethnicity, and gender. CONCLUSIONS: The study's finding that perpetrators whose index event was not substantiated return to the child welfare system at a high rate suggests the need to learn how to discriminate those unsubstantiated alleged perpetrators who are most at risk for recidivism. The finding of frequent cross-type recidivism indicates that intervention should focus on common themes across maltreatment types.
Focus groups were conducted to identify ways persons in recovery from chemical dependence think they have benefited from their struggles with addiction. Categories of positive by-products were identified independently by two sets of readers. Several of the positive by-products discussed by the focus group participants are commonly reported from other kinds of challenging life experiences. These include increases in self-efficacy, family closeness, closeness with others, compassion and spirituality, and changes in life priorities. Additional positive by-products were discussed by the focus group participants that may be more unique to substance abuse and other similar stressors, including increased self-knowledge, enhanced ability to help offspring with substance abuse-related issues, and decreased naïveté. Ways to incorporate knowledge about these positive by-products into substance abuse treatment programs are introduced.
A new therapeutic neurological and neurosurgical methodology involves cell implantation into the living brain in order to replace intrinsic neuronal systems, that do not spontaneously regenerate after injury, such as the dopaminergic (DA) system affected in Parkinson's disease (PD) and aging. Current clinical data indicate proof of principle for this cell implantation therapy for PD. Furthermore, the disease process does not appear to negatively affect the transplanted cells, although the patient's endogenous DA system degeneration continues. However, the optimal cells for replacement, such as highly specialized human fetal dopaminergic cells capable of repairing an entire degenerated nigro-striatal system, cannot be reliably obtained or generated in sufficient numbers for a standardized medically effective intervention. Xenogeneic and transgenic cell sources of analogous DA cells have shown great utility in animal models and some promise in early pilot studies in PD patients. The cell implantation treatment discipline, using cell fate committed fetal allo- or xenogeneic dopamine neurons and glia, is currently complemented by research on potential stem cell derived DA neurons. Understanding the cell biological principles and developing methodology necessary to generate functional DA progenitors is currently our focus for obtaining DA cells in sufficient quantities for the unmet cell transplantation need for patients with PD and related disorders.
In ongoing investigations to map and archive the microbial footprints in various components of the spacecraft and its accessories, we have examined the microbial populations of the Jet Propulsion Laboratory's Spacecraft Assembly Facility (JPL-SAF). Witness plates made up of spacecraft materials, some painted with spacecraft qualified paints, were exposed for approximately 7 to 9 months at JPL-SAF and examined the particulate materials collected for the incidence of total cultivable aerobic heterotrophs and heat-tolerant (80 degrees C for 15-min.) spore-formers. The results showed that the witness plates coated with spacecraft qualified paints attracted more dust particles than the non-coated stainless steel witness plates. Among the four paints tested, witness plates coated with NS43G accumulated the highest number of particles, and hence attracted more cultivable microbes. The conventional microbiological examination revealed that the JPL-SAF harbors mainly Gram-positive microbes and mostly spore-forming Bacillus species. Most of the isolated microbes were heat resistant to 80 degrees C and proliferate at 60 degrees C. The phylogenetic relationships among 23 cultivable heat-tolerant microbes were examined using a battery of morphological, physiological, molecular and chemotaxonomic characterizations. By 16S rDNA sequence analysis, the isolates fell into seven clades: Bacillus licheniformis, B. pumilus, B. cereus, B. circulans, Staphylococcus capitis, Planococcus sp. and Micrococcus lylae. In contrast to the cultivable approach, direct DNA isolation, cloning and 16S rDNA sequencing analysis revealed equal representation of both Gram-positive and Gram-negative microorganisms.
The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female homozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the spermatogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduction in the numbers of late spermatids. Extensive nuclear head deformation was noted in late spermatids as well as the sharing of a common acrosome in multinucleated cells. In some multinucleated cells, nuclei were separated from their acrosomes, with the acrosomes remaining attached to areas of ectoplasmic specializations, suggesting defects in intercellular cytoplasmic bridge integrity. Although the lumen of the epididymis was essentially devoid of spermatozoa and filled instead with spherical degenerating cells, the epididymal epithelial cells appeared normal. The few late spermatids present in the epididymis were abnormal. There was no morphological evidence, as judged by the absence of lipid droplets of triacylglycerol or cholesteryl ester accumulation in the testis. Together, the data suggest that hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility. We speculate that a metabolite downstream from the hormone-sensitive lipase reaction may be essential for membrane stabilization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells.
Effects of clonidine, an imidazoline derivative as well as alpha2-adrenoceptor agonist, on carbachol (CCh)-evoked contraction in guinea pig ileal smooth muscle were studied using isometric tension recording. To investigate the cellular mechanisms of the inhibitory effect of clonidine, its effects on CCh-evoked nonselective cationic current (I(CCh)), voltage-dependent Ca2+ current (I(Ca)) and voltage-dependent K+ current (I(K)) was also studied using patch-clamp recording techniques in single ileal cells. Clonidine inhibited the contraction evoked by CCh (1 microM) in a concentration-dependent manner with an IC50 valve of 61.7 +/- 2.5 microM. High K+ (40 mM)-evoked contraction was only slightly inhibited even when clonidine was used at 300 microM. Externally applied clonidine inhibited I(CCh) dose-dependently with an IC50 of 42.0 +/- 2.6 microM. When applied internally via patch pipettes, clonidine was without effect. An I(CCh)-like current induced by GTPgammaS was also inhibited by bath application of clonidine. None of KU14R and BU224, both imidazoline receptor blockers, and yohimbine, an alpha2-adrenergic blocker, significantly affects the inhibitory effect of clonidine on I(CCh). Clonidine (300 microM) only slightly decreased membrane currents flowing through voltage-gated Ca2+ channels or K+ channels. These data indicate that clonidine relaxes smooth muscle contraction produced by muscarinic receptor activation and suggest that the effect of clonidine seems due mainly to inhibition of I(CCh) via acting directly on the involved cationic channel.
A CO2-fixing bacterium, strain YN-1, that can fix CO2 under chemoautotrophic conditions but not photoautotrophic conditions was isolated from seawater. Identification of the isolate was carried out using biochemical tests and 16S rDNA sequence analysis, and its characteristics were investigated. From the results of partial 16S rDNA sequence analysis, strain YN-1 showed low identity with previously reported hydrogen-oxidizing bacteria, Hydrogenovibrio marinus MH-110 and Hydrogenophilus thermoluteolus. This result indicates that strain YN-1 may be a new hydrogen-oxidizing marine bacterium. Strain YN-1 showed considerable CO2 fixation ability during continuous cultivation even at high CO2 concentration. Strain YN-1 used H2 and CO2 as energy and carbon sources, respectively. Growth characteristics were examined in batch and continuous cultivation with a view to improving the CO2 fixation rate. The results showed that CO2 fixation occurred in the absence of a light source and that the strain exhibited good growth at high CO2 concentration (40%). On the other hand, the dry cell weight was 13.4 g/l following continuous cultivation for 76 h in 10% CO2 (0.1 l/min), and at that time the amount of fixed CO2 was 18.08 g CO2/l. This indicates that strain YN-1 can efficiently fix CO2 even at high CO2 concentrations, which would allow its application to the removal of industrially discharged CO2.
The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the guinea-pig ileum. CO (10%) inhibited the 40 mM KCl-induced contraction. This effect was antagonized by ODQ (1 microM), a soluble guanylate cyclase inhibitor. In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+ level ([Ca2+]i). Cumulative addition of KCl induced a graded increase in both [Ca2+]i and muscle tension. In the presence of CO, the increase in muscle tension was attenuated whereas the increase in [Ca2+]i was only slightly decreased. Thus, the [Ca2+]i-tension relationship constructed by cumulative addition of KCl shifted downwards in the presence of CO. Using the patch clamp, CO was found to have little effect on the peak Ba currents (I(Ba)) when voltage was stepped from -60 mV to 0 mV. From these results, we conclude that CO inhibits contraction of guinea-pig ileum mainly by the decrease in the sensitivity of contractile elements to Ca2+ via a cyclic GMP-dependent pathway but not by the inhibition of L-type Ca2+ channel.
The sequential association of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 with CD4 and a seven-transmembrane segment coreceptor such as CCR5 or CXCR4 initiates entry of the virus into its target cell. The N terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in the CD4-dependent association of gp120 with CCR5 and in viral entry. Here we demonstrate that a tyrosine-sulfated peptide based on the N terminus of CCR5, but not its unsulfated analogue, inhibits infection of macrophages and peripheral blood mononuclear cells by CCR5-dependent, but not CXCR4-dependent, HIV-1 isolates. The sulfated peptide also inhibited the association of CCR5-expressing cells with gp120-soluble CD4 complexes and, less efficiently, with MIP-1alpha. Moreover, this peptide inhibited the precipitation of gp120 by 48d and 23e antibodies, which recognize CD4-inducible gp120 epitopes, but not by several other antibodies that recognize proximal epitopes. The ability of the sulfated peptide to block 48d association with gp120 was dependent in part on seven tropism-determining residues in the third variable (V3) and fourth conserved (C4) domains of gp120. These data underscore the important role of the N-terminal sulfate moieties of CCR5 in the entry of R5 HIV-1 isolates and localize a critical contact between gp120 and CCR5.
Our recent study demonstrated that ginsenosides had antinociceptive effects by reducing some types of pain-related behavior in mice (Yoon et al., 1998. Ginsenosides induce differential antinociception and inhibit substance P-induced nociceptive response in mice. Life Science 62, PL319-PL325). In the present study we further investigated whether ginsenosides produce antinociceptive effects through an action at central or peripheral site(s) and whether these effects are mediated by the opioid system. Intraperitoneally injected ginsenosides suppressed in a dose-dependent manner the pain-related behavior produced by capsaicin injection into the plantar surface of the hind paw; the ED(50) was 49 mg/kg [26-92 mg/kg, 95% confidence interval (C.I.)]. Intrathecally or intracerebroventricularly administered ginsenosides also suppressed the capsaicin-induced pain-related behavior in a dose-dependent manner; the ED(50)s were 1.72 mg/kg (0.8-3.72 mg/kg, 95% C.I.) and 1. 48 mg/kg (0.8-2.6 mg/kg, 95% C.I.), respectively. On the other hand, subcutaneously injected ginsenosides to the plantar surface prior to the capsaicin injection did not alter the pain-related behavior. Naloxone pretreatment was without effect in blocking the antinociceptive effect of intrathecally administered ginsenosides. Intraperitoneally injected ginsenosides also did not significantly affect the motor response of animals. These results suggest that ginsenosides produce antinociceptive effects through their action at the spinal and/or supraspinal site(s), not at nociceptors in the periphery. In addition, the results suggest that the antinociceptive effects are not mediated by opioid receptors.
The translationally controlled tumor protein (TCTP) was first identified as a tumor-associated protein. Here we described the expression profile of TCTP mRNA using a panel of normal human tissues. We also investigated the cell-cycle-dependent expression of the TCTP mRNA using synchronized cultures of Saccahromyces cerevisiae. The TCTP gene was constantly expressed through the yeast cell cycle. The expression of TCTP mRNA from three human colon carcinoma cell lines and their tumors xenografted in a nude mouse was studied. Our data imply that the TCTP is a housekeeping gene and that its deregulation may be involved in the tumor development of colon carcinoma.
Ginsenosides isolated from ginseng are biologically active components. In this study, whole-cell and inside-out configurations of patch clamp technique had been used to test the effect of ginsenosides on the capsaicin-activated channels in cultured small diameter sensory neurons of young rat. Ginsenosides (100 microg/ml) decreased the amplitude of capsaicin-activated currents by 78.2% in whole cell mode. Similarly, ginsenosides decreased capsaicin-activated single-channel activities in a dose-dependent manner in inside-out patches. These results indicate that ginsenosides might directly block capsaicin-activated channels, resulting in attenuation of the currents in rat sensory neurons.
N-Linked glycosylation is a post-translational modification occurring in many eukaryotic secreted and surface-bound proteins and has impact on diverse physiological and pathological processes. Similarly important is the generation of glycosylphosphatidylinositol linkers, which anchor membrane proteins to the cell. Both protein modifications depend on the central nucleotide sugar UDP-N-acetylglucosamine (UDP-GlcNAc). The enzymatic reactions leading to generation of nucleotide sugars are established, yet most of the respective genes still await cloning. We describe the characterization of such a gene, EMeg32, which we identified based on its differential expression in murine hematopoietic precursor cells. We further demonstrate regulated expression during embryogenesis. EMeg32 codes for a 184-amino acid protein exhibiting glucosamine-6-phosphate acetyltransferase activity. It thereby holds a key position in the pathway toward de novo UDP-GlcNAc synthesis. Surprisingly, the protein associates with the cytoplasmic side of various intracellular membranes, accumulates prior to mitosis, and copurifies with the cdc48 homolog p97/valosin-containing protein.
The effects of N-ethylmaleimide (NEM), an alkylating reagent to protein sulfhydryl groups, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole cell configuration of patch-clamp technique. When currents were evoked by step depolarizations to 0 mV from a holding potential of -80 mV NEM decreased the amplitude of TTX-S sodium current, but exerted little or no effect on that of TTX-R sodium current. The inhibitory effect of NEM on TTX-S sodium channel was mainly due to the shift of the steady-state inactivation curve in the hyperpolarizing direction. NEM did not affect the voltage-dependence of the activation of TTX-S sodium channel. The steady-state inactivation curve for TTX-R sodium channel was shifted by NEM in the hyperpolarizing direction as that for TTX-S sodium channel. NEM caused a change in the voltage-dependence of the activation of TTX-R sodium channel unlike TTX-S sodium channel. After NEM treatment, the amplitudes of TTX-R sodium currents at test voltages below -10 mV were increased, but those at more positive voltages were not affected. This was explained by the shift in the conductance-voltage curve for TTX-R sodium channels in the hyperpolarizing direction after NEM treatment.
We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Abeta42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased Abeta42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease.
The dorsoventral axis of the Drosophila visual cortex is patterned by nonautonomous signals expressed at its dorsal and ventral margins. wingless (wg) expression at the margins induces decapentaplegic (dpp), optomotor blind (omb), and aristaless in adjacent domains. We show that Combgap, a zinc finger protein, represses Wg target gene expression in the visual cortex. Wg signal reception downregulates combgap expression and derepresses target gene transcription. Combgap participates in a Hedgehog-controlled circuit in the developing wing and leg by regulating the expression of Cubitus interruptus. Combgap is thus a tissue-specific relay between Wingless and its target genes for the determination of cell fate in the visual cortex.