Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 127 records · Page 7Linked to original sources

PubMed2001

Maternal outcomes of a randomized controlled trial of a community-based support program for families of children with chronic illnesses.

BACKGROUND: Parents of children with chronic illnesses are at high risk for secondary mental health problems, such as anxiety and depression. OBJECTIVE: To evaluate maternal outcomes of a support intervention for families of children with selected chronic illnesses. DESIGN: A randomized controlled clinical trial design with repeated measures 1 year apart. SETTING: A community-based family support intervention linked to subspecialty and general pediatric clinics and practices in a metropolitan area. PARTICIPANTS: A population-based sample of 193 mothers of children aged 7 to 11 years; the children were diagnosed as having diabetes, sickle cell anemia, cystic fibrosis, or moderate to severe asthma. About 15% of the persons contacted refused to participate in the research, and 14% of the families were lost to follow-up. INTERVENTION: The 15-month intervention, the Family-to-Family Network, was designed to enhance mothers' mental health by linking mothers of school-aged children with selected chronic illnesses with mothers of older children with the same condition. The program included telephone contacts, face-to-face visits, and special family events. MAIN OUTCOME MEASURES: Beck Depression Inventory score and the Psychiatric Symptom Index. RESULTS: Maternal anxiety scores for participants in the experimental group decreased during the intervention period for all diagnostic groups and for the total group; scores for the control group increased (F = 5.07, P =.03). In multiple regression analyses, the intervention group was a significant predictor of posttest anxiety scores (P =.03). Effects were greater for mothers with high baseline anxiety (P<.001) and for those who were themselves in poor health (P<.01). CONCLUSIONS: A family support intervention can have beneficial effects on the mental health status of mothers of children with chronic illnesses. This type of intervention can be implemented in diverse pediatric settings.

Anemia, Sickle Cell↗

PubMed2001

Dissolution of poorly crystalline apatite crystals by osteoclasts determined on artificial thin-film apatite.

Poorly crystalline apatite (PCA) crystals introduced into bone tissue should be stable for a definite period before they are dissolved as a result of a host response. In this report, the dissolution of PCA crystals by the action of osteoclasts was studied on artificial thin films. These consisted of PCA crystals having similar crystallographic properties to bone crystals which were developed for assaying the osteoclast activity in vitro. The dissolution of minerals by osteoclasts decreased along with the decreased amount of labile phosphate and hydrogen phosphate domains of apatite crystals, which were caused by the crystal maturation temperature. A profound effect on mineral dissolution by pH in the culture medium was also shown. Low acidity considerably increased mineral dissolution, whereas a slight alkalinity totally blocked mineral dissolution. There was little difference in the mineral dissolution behavior of osteoclasts near the physiologic pH. In addition, it was determined whether mineral dissolution by osteoclasts was dependent on the destruction of the organic matrix. Nocodazole was introduced to inhibit the secretion of hydrolytic enzymes, and acetazolamide was added to inhibit acid production by the osteoclasts. There was no significant change as a result of nocodazole addition on mineral dissolution or by the addition of acetazolamide on degradation of collagen. These results indicate that small changes in the physicochemical properties of apatite crystals can decrease resorption by osteoclasts, which can be highly activated at low pH. These results also suggest that mineral dissolution and organic degradation by osteoclasts are self-regulating.

Acetazolamide↗

PubMed2001

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children.

BACKGROUND: Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. OBJECTIVES: In children with acute diarrhoea, to compare reduced osmolarity glucose-based oral rehydration salt solution with international WHO formulation. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: Randomised controlled trials comparing reduced osmolarity ORS solution with the WHO formulation. Outcomes sought were unscheduled intravenous fluid infusion therapy and measures of clinical illness. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. We tested for heterogeneity using the chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. MAIN RESULTS: The primary outcome was reported in 12 trials. In a meta-analysis of nine trials, reduced osmolarity ORS was associated with fewer unscheduled infusions compared with standard WHO ORS (Mantel Haenzel odds ratio 0.61, 95% confidence interval 0.47 to 0.81) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Thirteen trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. REVIEWER'S CONCLUSIONS: In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO ORS is associated with fewer unscheduled intravenous infusions, smaller stool volume post randomisation, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO ORS was detected.

Bicarbonates↗

PubMed2001

Naphthazarin derivatives (VIII): Synthesis, inhibitory effect on DNA topoisomerase-I, and antiproliferative activity of 6-(1-acyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones.

6-(1-Acyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinone (DMNQ; 5,8-dimethoxy-1,4-naphthoquinone) derivatives were synthesized and examined for their inhibitory effect on DNA topoisomerase-I (Topo I) and their antiproliferative activity against L1210 cells. The Topo-I inhibitory effect of 6-(1-hydroxyalkyl)-DMNQ derivatives was found to be dependent on the size of the alkyl chains, suggesting that lipophilicity might be one important factor influencing the inhibitory effect. It was found that acylation of 6-(1-hydroxyalkyl)-DMNQ derivatives possessing alkyl chains of C2-C5 enhanced both bioactivities, suggesting that an increase of electrophilicity in the quinoid moiety makes the electrophilic arylation of bionucleophiles more favorable. It is noteworthy that 6-(1-heptanoyloxyethyl)-DMNQ exhibited both the most potent Topo I inhibitory activity (IC50, 11.5 microM) and the greatest antiproliferative activity (ED50, 0.05 microM) upon L1210 cells.

Animals↗

PubMed2001

Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA.

Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expressed via the prion protein promoter. Here, we report the first direct comparison of abnormalities in these models. The HD mice show abbreviated lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The DRPLA mice show severe tremors, are hyperactive, and are profoundly uncoordinated. Neuropathological analyses reveal that the distribution of diffuse nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were the major distinguishing neuropathological feature of the HD mice; mutant atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the distinct behavioral and neuropathological phenotypes in these mice reflect differences in the way these mutant proteins perturb neuronal function.

Aggression↗

PubMed2001

Sesquiterpenoids from the rhizome of Curcuma zedoaria.

In the course of searching for biologically active sesquiterpenoids from Curcuma genus, two sesquiterpenoids were isolated from the rhizome of Curcuma zedoaria (Zingiberaceae). Their structures were identified as ar-turmerone (1) and beta-turmerone (2). The structure elucidation of compounds 1 and 2 was carried out by comparison of their physical and spectral data with previously reported values.

Chromatography, Thin Layer↗

PubMed2001

Naphthazarin derivatives (VII): antitumor action against ICR mice bearing ascitic S-180 cells.

Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1-hydroxyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1-Hydroxyiminoalkyl)-DMNQ derivatives expressed greater antitumor action than (1-hydroxyalkyl)- or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ derivatives expressed higher antitumor action than 2-sudstituted ones, suggestive of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl group of butyl to octyl moiety showed T/C values of >400%

Animals↗

PubMed2001

Naphthazarin derivatives (VII): antitumor action against ICR mice bearing ascitic S-180 cells.

Animals↗

PubMed2001

A new anti-hemoglobin F antibody against synthetic peptides for the detection of F-cell precursors (F-blasts) in bone marrow.

To date there are few antibodies available for the detection of fetal hemoglobin (HbF)-containing erythroblasts (F-blasts) in paraffin-embedded hematopoietic tissues. Recently, we developed a new polyclonal antibody specific to F-blasts by immunization of a rabbit with synthetic peptides of human HbF. Specificity and reactivity of the antibody were confirmed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. ELISA confirmed that the antibody showed strong immunoreactivity to fetal hemoglobin but no reaction to adult hemoglobin. The antibody could detect the presence of fetal blood hemolysates (10 microg/mL) at a dilution of 10(-5). According to immunohistochemical analysis, there were strong positive reactions to fetal erythroblasts in the liver and the spleen at 29 weeks of gestation and to erythroblasts from patients with myelodysplastic syndromes and erythroleukemia but no reactions to normal adult erythroblasts in bone marrow. Fetal erythrocytes in fetal blood vessels of placental tissues were strictly distinguished from maternal erythrocytes in the same sections by their positive reactions, indicating the presence of HbF. This new antibody will be a useful tool for studying fetal hemoglobin synthesis and for detecting F-blasts in archival specimens of various hematological diseases.

Amino Acid Sequence↗

PubMed2001

The geographic distribution of population health and contaminant body burden in gulf of Mexico oysters.

As part of NOAA's National Status and Trends Mussel Watch Program, oysters were sampled along the Gulf of Mexico coast each winter from 1986 to 1993 (The present analysis deals with 1986-1993 Mussel Watch data; the Mussel Watch project itself continues at this printing) and analyzed for trace metal, polynuclear aromatic hydrocarbons and pesticide body burden, plus a series of biological variables designed to assess population status and health. We identified contaminant and biological variables in which large-scale spatial processes played an important role in establishing population values by examining the likelihood that neighboring bays tended to have populations with body burdens or population attributes more similar than expected by chance. Local or watershed-dependent factors, such as land use and freshwater inflow, are important in controlling the bay-to-bay variation in body burden in most contaminants. However, the bay-to-bay variations in body burden of some metals (As, Cd, Hg, Ni, Se) appear to be principally influenced by larger-scale climatic factors. These metals and the biological variable shell length demonstrated a strong degree of similarity between bays over a large regional area reminiscent of the pattern shown by climatic factors, such as temperature and precipitation. In contrast, among the organics, none of the PAHs showed even a moderately strong climatic signal. Among the pesticides, only two did (dieldrin, total DDTs). These pesticides and the biological variables, reproductive stage and Perkinsus marinus prevalence and infection intensity, had spatial patterns that suggested both a local and a regional influence to their geographic distributions. This same pattern is exhibited by freshwater runoff. Metal contaminants also behaved distinctively compared to organics in the temporal influence of climate in establishing the interannual variability in body burden. For the organics, trends in interannual variability were strongly influenced by climate, whereas spatial trends were not. In contrast, most metals were unaffected by climatic forcing both spatially and temporally. However, all of the metals having a spatial pattern strongly influenced by climate (As, Cd, Hg, Ni, Se) also exhibited interannual variations related to variations in climate.

Animals↗

PubMed2001

Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali.

TRAAK is a member of the tandem-pore K+ channel family, and is expressed mainly in the brain. Using rat TRAAK (rTRAAK), we studied its single-channel kinetics, interactive modes of activation, and the role of the C-terminus on its pressure-, fatty-acid- and pH-sensitivity. When expressed in COS-7 cells, rTRAAK showed a mildly inwardly rectifying single-channel current/voltage relationship in symmetrical 140 mM KCl. Unlike TREK-1 and TREK-2, which are activated by acidic conditions, rTRAAK was activated by alkali conditions, such that a change in intracellular pH from 7.3 to 8.3 and 8.8 increased channel activity 5- and 14-fold, respectively. Pressure and alkali produced a strong synergistic activation, and pressure and arachidonic acid (AA) produced a mild synergistic activation. The only additive effect was observed with alkali and AA. Replacing the C-terminus of rTRAAK with that of TASK-1 or TASK-3 did not affect the response to pressure, AA or alkali. In contrast, replacing the C-terminus of TREK-2 with that of TASK-3 abolished the sensitivity to AA and acid, but not to pressure. These results show that rTRAAK is an alkali-sensing K+ channel that shows synergistic activation with pressure, and that the mechanism of activation of rTRAAK and TREK by free fatty acids are different.

Amino Acid Sequence↗

PubMed2001

Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi.

TREK-2, a member of the tandem-pore K+ channel family, is activated by membrane stretch, unsaturated free fatty acids and acidic conditions, and exhibits unique open channel kinetics. To identify the regions responsible for these properties, we studied the role of the cytoplasmic regions of TREK-2. Deletion of the N-terminus had no effect on any aspect of TREK-2 function. Deletion of the C-terminus or its substitution with that of TASK-3 abolished the sensitivity to free fatty acids and intracellular pH (pHi), and reduced the sensitivity to pressure. The regions that allow activation by free fatty acids and low pHi were localized to 25- and 10-amino-acid domains, respectively, close to the fourth transmembrane segment. Substitution of KKTKEE, a charged region near the proximal C-terminus, with uncharged amino acids produced little change in TREK-2 function; however, its deletion abolished sensitivity to fatty acids and low pH, indicating that this region is structurally very important. The TREK-2 C-terminus was also found to be critical for its channel opening in bursts as well as for its increased basal activity. Thus, the C-terminus endows TREK-2 with unique channel kinetics and the ability to be gated by free fatty acids and low pHi, and with increased mechanosensitivity.

Animals↗

PubMed2001

Sequence variations of hepatitis B virus promoter regions in persistently infected patients.

The HBV in the sera of two chronic active hepatitis patients were analyzed for the promoter sequence heterogeneity. In most cases, the proportion of any particular clone in the total viral populations was less than 50%, showing high mutation rates. In contrast, promoter sequences of HBV from asymptomatic carriers revealed only a few point mutations with no deletions. HBV in chronic patient harbored variants with multiple mutations throughout promoters including 1762 (A-to-T), 1764 (G-to-A) double mutation in C promoter and deletions near CCAAT site in S promoter. Unlike other three promoter regions, C, pre-S1 and S, of HBV which revealed a high level of sequence heterogeneity, the X promoter region (from nt985 to 1430) showed little sequence heterogeneity within a patient. However, the predominant viral clones in two patients were quite different from each other. In addition to mutations in promoter regions, a deletion mutation in the translation start codon was also found in pre-S1 gene. The results in this report indicate that the mutation rates are not the same in all four promoters and that one of the strategies for maintaining persistent infection could be through mutations in viral promoters which then impair the balance of viral gene expressions.

Adult↗

PubMed2001

Chimeric HTH motifs based on EF-hands.

The design of a new peptide construct from two structurally equivalent basis motifs is reported. A chimera was designed from the helical regions of a helix-turn-helix (HTH) domain, incorporating the consensus EF-hand Ca-binding loop at the turn. Two 33-residue peptides were constructed: one (P3, designed) includes the 12-residue consensus EF-hand loop, while the other (P2, control) contains the reversed EF-hand loop sequence. The Eu(III) and Ca(II) binding properties of P2 and P3 were investigated by circular dichroism and NMR. The designed peptide (P3) is 25% helical in its Eu(III)-saturated form, and 14% helical with excess Ca(II). Both the free and Eu-bound peptides have inherent solution structure, as demonstrated by the helicity induced by the addition of trifluoroethanol solvent. While Eu(III) binding stabilizes the structure of P3, it destabilizes the structure of P2. The NMR titration of P3 with Eu(III) resulted in new resonances characteristic of Ca-bound EF-hand loops. As observed for isolated EF-hands, the resonances appear within the first 0.5 equivalents of Eu(III) added, suggesting that one metal ion organizes two equivalents of peptide to fold into the back-to-back dimer structure of native EF-hands. The EuP3 chimera, but not EuP2, has significant affinity for supercoiled plasmid DNA, causing a gel shift at concentrations as low as 10 microM EuP3 (50 microM base pairs). These results show our chimeric peptide combines the characteristics of the parent motifs, maintaining both metal binding and DNA affinity.

Amino Acid Motifs↗

PubMed2001

Analysis of residual saliva and minor salivary gland secretions.

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.

Adult↗

PubMed2001

Esters of chlorambucil with 2-substituted 1,4-dihydroxy-9,10-anthraquinones as multifunctional anticancer agents.

Novel twelve esters of chlorambucil with 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone were synthesized and tested for their antitumor activity in mice bearing S-180 ascitic cells as well as cytotoxic activity against L1210 cells. Eight of them were highly cytotoxic on L1210 cells (ED(50), <6 microg mL(-1)) and derivatives 1 and 12 (T/C, 200 and 205%) appeared more active in vivo than chlorambucil (T/C, 168%).

Animals↗

PubMed2001

A fast calibration method for 3-D tracking of ultrasound images using a spatial localizer.

We have developed a fast calibration method for computing the position and orientation of 2-D ultrasound (US) images in 3-D space where a position sensor is mounted on the US probe. This calibration is required in the fields of 3-D ultrasound and registration of ultrasound with other imaging modalities. Most of the existing calibration methods require a complex and tedious experimental procedure. Our method is simple and it is based on a custom-built phantom. Thirty N-fiducials (markers in the shape of the letter "N") embedded in the phantom provide the basis for our calibration procedure. We calibrated a 3.5-MHz sector phased-array probe with a magnetic position sensor, and we studied the accuracy and precision of our method. A typical calibration procedure requires approximately 2 min. We conclude that we can achieve accurate and precise calibration using a single US image, provided that a large number (approximately ten) of N-fiducials are captured within the US image, enabling a representative sampling of the imaging plane.

Calibration↗

PubMed2001

Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice.

Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble Abeta (1.45% of total cerebral Abeta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.

Age Factors↗