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Y Kim

Publications and source records attributed to Y Kim.

At least 361 records · Page 20Linked to original sources

TBAK-1 and TASK-1, two-pore K(+) channel subunits: kinetic properties and expression in rat heart.

A mammalian K(+) channel subunit (TBAK-1/TASK-1) containing two pore domains and four transmembrane segments and whose mRNA is highly expressed in the heart has been cloned recently. TBAK-1 and TASK-1 are identical except for the additional nine amino acids in the NH(2) terminus of TBAK-1. We examined their kinetic properties, pH sensitivity, and regional cardiac mRNA expression and determined whether a native cardiac K(+) channel with similar kinetic properties was present. When TBAK-1 or TASK-1 was transiently expressed in COS-7 cells, time- and voltage-independent whole cell currents were observed. Single-channel conductances of TBAK-1 and TASK-1 were 14.6 +/- 1.0 and 13.8 +/- 2.8 pS, respectively, at -80 mV in 140 mM extracellular K(+), and the mean open times were 0.8 +/- 0.1 and 0.6 +/- 0.1 ms, respectively. Both TBAK-1 and TASK-1 were highly sensitive to extracellular pH such that a decrease from 7.2 to 6.4 reduced their open probability (P(o)) by 81 +/- 14% and 80 +/- 16%, whereas a decrease in intracellular pH from 7.2 to 6.4 reduced the P(o) by 42 +/- 10% and 47 +/- 12%, respectively. TBAK-1/TASK-1 mRNA was expressed in all regions of the rat heart, with the highest level of expression in the right atrium. A 14-pS K(+) channel with kinetic properties similar to those of TBAK-1/TASK-1 was identified in rat atrial and ventricular cells. These results indicate that TBAK-1/TASK-1 represents a functional native K(+) channel in the rat heart.

Amino Acid Sequence↗

Induction of tolerance in macrophages by cholera toxin B chain.

Model systems of human type 1 diabetes have revealed an important role of cellular immune reactions involving macrophages and T cells in the destruction of autologous insulin-producing pancreatic beta cells. Recently, the cholera toxin B chain (CTB) was found to suppress T cell-dependent autoimmune diseases including autoimmune diabetes of nonobese diabetic mice. Therefore, we tested the hypothesis that CTB exerts much of its immunomodulatory activity by targeting macrophages. These studies are reviewed here. Cells of the human monocyte line Mono Mac 6 were exposed to CTB and subsequently tested for proinflammatory immunoreactivity in response to challenge with endotoxin (LPS from Escherichia coli, 10 ng/ml for 5 h). Incubation of monocytes with CTB (10 microgram/ml) suppressed a later proinflammatory response to LPS as demonstrated by suppression of TNFalpha release from 6.7 +/- 0.7 ng/ml in cultures without CTB preexposure to 1.8 +/- 1.1 ng/ml in CTB-pretreated cells (p < 0.001). In contrast, the release of IL-10 remained inducible after CTB pretreatment. RT-PCR analysis showed that the suppression of TNFalpha production occurred at the level of mRNA formation. Control experiments excluded a role of possible contamination of CTB by endotoxin or the intact cholera toxin. Tolerance induction was maximal after 5 h of CTB exposure and persisted for 24 h. The suppressive effect of CTB was dose-dependent and no more recognizable at </=1 microgram/ml. Incubation with IL-10- and TGFbeta-neutralizing antibodies during CTB pretreatment prevented tolerization of macrophages. IFNgamma (1,200 U/ml) was found to antagonize actions of CTB. In contrast to desensitization by low doses of LPS, tolerance induction by CTB occurred 'silently', i.e. in the absence of a measurable proinflammatory response. In view of the potent instructive role of the innate immune system on T cell responses these findings are important in understanding how CTB prevents the development of autoimmune diabetes and improves tolerance to islet autoantigens.

Cell Line↗

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.

Adult↗

Mucin gene expression in the rat middle ear: an improved method for RNA harvest.

Mucins are heavily glycosylated proteins characterized by high molecular weight and heterogeneous structure. Mucin genes are expressed in a tissue- or epithelium-specific manner. Although mucins are known to be important structural components of the mucociliary transport system that protects epithelium against invading microorganisms, very little is known about mucin gene expression unique to the middle ear. This study demonstrated that middle ear messenger RNA specifically hybridized with rat MUC2 and human MUC2 (SMUC-41) complementary DNA probes. MUC3 and MUC5AC mucin genes, dominantly expressed in rodent intestine and trachea, were not detected in the rat middle ears in this study. The middle ear MUC2 messenger RNA harvested by lavage was characterized by a single transcript--unlike its counterpart in intestine and airways, which is characterized by polydispersity--suggestive of a better method for RNA analysis. It was concluded that rat middle ears possess a MUC2 mucin gene or homologue of human MUC2 (SMUC-41).

Animals↗

Immunohistochemical distribution of extracellular matrix components and keratin in experimentally induced otitis media.

The distribution of collagen types I, III, and IV and of laminin, fibronectin, and keratin was studied in otitis media experimentally induced by Streptococcus pneumoniae in the chinchilla. The expression of interstitial collagen types I and III and of fibronectin was increased in the subepithelial space that was thickened by inflammation in the acute period of infection. The expression of collagen type IV in the subepithelial space could be seen in the early period. The epithelial cells in the middle ear changed from flat cuboidal to pseudostratified columnar in pneumococcus-inoculated ears, and the number of keratin-positive epithelial cells in the middle ear increased remarkably after infection. These results indicate that changes in epithelial cell differentiation effected by the extracellular matrix correlate with changes in expression of keratin. It is proposed that the extracellular matrix may contribute to tissue repair in the middle ear after bacterial infection by interfering with cell proliferation of epithelial cells and fibroblasts.

Animals↗

Competency in community-oriented health care. Instrument development.

To competently deal with changes in the health care system, health professionals for the future must have expanded abilities and new attitudes. Education of health professionals for community-oriented health care (COHC) is being promoted as one approach to achieve this focus. This article reports on the development and testing of the Community-Oriented Health Care Competency Scale, which measures knowledge, attitudes, and intention to practice COHC. Results of testing demonstrate adequate reliability for a new instrument: an alpha coefficient of .95 for the Knowledge subscale, .68 for the Attitude subscale, and .93 for the Intention to Practice subscale. Content Validity of the instrument is based on the literature review, focus group sessions, and expert opinion. The instrument may be used to assess competency of health professions students in COHC, but continued testing is needed.

Community Health Services↗

Studies of the chemical structure of gangliosides in deer antler, Cervus nippon.

The biological activity of deer antler has been considered to originate in the gangliosides, although the structures of gangliosides have not been well elucidated. The quality of deer antler as an Asian folk medicine has often been evaluated by the amount of gangliosides contained in the crude drug. We have completed the structural determination of five gangliosides isolated from deer antler in the present study. Five ganglioside fractions were isolated and purified from deer antler, Cervus nippon, by the Folch-Suzuki partition method, DEAE-Sephadex A-25, and further by silica gel column chromatography. High field proton nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and fast atom bombardment-mass spectrometry studies characterized the isolated ganglioside fractions. GM3 and GD3 were present in the isolated ganglioside fractions. Samples were hydrolyzed in trifluoroacetic acid for direct compositional analysis and analyzed for sialic acid and neutral sugar without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at a high pH. The resolved monosaccharides were identified using standard monosaccharides by pulsed amperometric detection. N-Acetyl GM3 (Neu5Ac), N-glycolyl GM3 (Neu5Gc), and N-acetyl GD3 (Neu5Ac) were present in the antler. The major ceramide moiety was composed of C16:0 or C22:0 fatty acids along with either C18 sphingosine or C20 eicosasphingosine.

Animals↗

Selecting the most informative items in the IIP scales for personality disorders: an application of item response theory.

The first goal of the present analyses was to shorten the five scales (Pilkonis, P. A., Kim, Y., Proietti, J. M., & Barkham, M. [1996]. Journal of Personality Disorders, 10, 355-369) for personality disorders (PDs) developed from the Inventory of Interpersonal Problems (IIP), thereby increasing their attractiveness for screening purposes. The second goal was to illustrate, for more general purposes, the utility of item response theory (IRT) for such scale refinement. IRT analyses were performed using data collected from six different samples (N = 1149) at five sites and a two-parameter (2P) graded model designed for multiple response items like those on the IIP. The five most informative items from each scale were identified, based on the magnitude of item discrimination parameters and the range and elevation of individual item information functions. Preliminary analyses of the reliability and validity of the short forms of the scales (totaling 25 items) supported their value as alternatives to the longer forms (consisting of 47 items), although definitive tests of their psychometric properties await crossvalidation in independent samples. Analyses of the quality receiver operating characteristics (QROC) of the long and short forms showed that both versions can be useful in predicting the presence versus absence of any PD diagnosis arrived at by using either a "best estimate" clinical consensus method or a structured Axis II interview.

Adult↗

Screening for personality disorders in a nonclinical population.

Based on the Inventory of Interpersonal Problems (IIP), the IIP-PD and the IIP-C screening scales were developed to distinguish personality disorder (PD) from non-PD and Cluster C from other PD, respectively, in a clinic population. Two studies were conducted to determine (a) validity and reliability of these IIP scales for PD screening in a nonclinical population, (b) specificity of IIP-C for identifying Cluster C, and (c) usefulness of the IIP scales for screening Cluster A. College students were screened using the IIP scales (Study 1, N = 454, Study 2, N = 87). High and low scorers completed PD-related questionnaires in Study 1 and a clinical interview for PD symptomatology in Study 2. Results indicated strong test-retest reliability, internal consistency, and factorial, convergent, and external validity. The scales tapped a common deficit in interpersonal relatedness, with some distinction between externalizing and internalizing dimensions, respectively, and both scales were positively and significantly associated with schizotypal traits. In conclusion, the IIP-PD and IIP-C are useful and valid screening instruments for identifying any versus no PD in nonclinical populations.

Adolescent↗

Early initiation of breastfeeding and the risk of infant diarrhea in rural Egypt.

BACKGROUND: Initiation of breastfeeding shortly after delivery may enhance breastfeeding's protective effect against diarrhea because of the protective properties of human colostrum contained in early breast milk. OBJECTIVE: To evaluate whether initiation of breastfeeding within the first 3 days of life, when breast milk contains colostrum, was associated with a lower rate of diarrhea in rural Egyptian infants during the first 6 months of life. METHODS: Infants initially breastfed (n = 198) were monitored prospectively with twice-weekly home visits to ascertain dietary practices and diarrheal illnesses. RESULTS: The burden of diarrhea during the first 6 months of life in the cohort was high: seven episodes per child-year of follow-up. Only 151 (76%) infants initiated breastfeeding during the first 3 days of life ("early initiation"). Infants in whom breastfeeding was initiated early had a 26% (95% CI: 2%,44%) lower rate of diarrhea than those initiated late. The protective association between early initiation and diarrhea was independent of the pattern of postinitiation dietary practices and was evident throughout the first 6 months of life. CONCLUSIONS: Early initiation of breastfeeding was associated with a marked reduction of the rate of diarrhea throughout the first 6 months of life, possibly because of the salutary effects of human colostrum. These data highlight the need for interventions to encourage early initiation of breastfeeding in less developed settings.

Breast Feeding↗

Viral-induced cirrhosis: grading of severity using MR imaging.

OBJECTIVE: The purpose of this study was to determine whether MR imaging can be used to grade the severity of cirrhosis. MATERIALS AND METHODS: The MR examinations of 46 patients with cirrhosis were retrospectively reviewed independently by two radiologists and correlated with clinical severity assessed by Child-Pugh classification. MR imaging analysis by reviewers who were unaware of clinical status included comparison of volume indexes (computed as the product of three axis measurements) of the spleen and each segment of the liver, and changes in hepatic contour, iron or fat deposition, and presence of varices and collaterals. RESULTS: Volume index of the spleen and the presence of ascites and varices were significantly and positively correlated (p = .008, .002, .0001, respectively) with the clinical severity of cirrhosis (Child-Pugh classifications), and volume indexes of the posterior, medial, and lateral segments of the liver were significantly and inversely correlated (p = .001, .049, .041, respectively). On an MR scoring system based on four items (volume index of the spleen; volume index of posterior + medial + lateral segments; presence of ascites; and presence of varices and collaterals), averaged total MR scores were 2.5 +/- 0.3, 4.9 +/- 0.6, and 7.9 +/- 0.8 for Child-Pugh grades A, B, and C, respectively (p < .0001). The accuracy of MR scoring in distinguishing between clinical Child-Pugh grade A cirrhosis and further grades was 89%, the sensitivity was 93%, and the specificity was 82%. CONCLUSION: An MR scoring system can be used to grade the severity of cirrhosis.

Contrast Media↗

Special medical examination program reform proposal in Korea.

We are at a time when reform in the special medical examination program in keeping with the changing times is desperately needed because the common perception of workers, employers, and medical examination facilities is "special medical examination is merely ritualistic and unproductive." Therefore, we have tried to set forth the basic structure for reforming the special medical examination program by taking a close look at the management status of the current program and analyzing its problems. The specifics of the special medical examination program reform proposal consist of three parts such as the types, health evaluation based on occupational medicine, and the interval, subject selection, items and procedure. Pre-placement medical examination and non-periodic medical examinations-as-necessary are introduced newly. Health evaluation based on occupational medicine consists of classification of health status, evaluation of work suitability, and post-examination measure. Details regarding the medical examination interval, subject selection, items and procedure were changed.

Government↗

Disposition and metabolism of 2-(2''(1'',3''-dioxolan-2-yl)-2- methyl-4-(2'-oxopyrrolidin-1-Yl)-6-nitro-2h-1-benzopyran (SKP-450) in rats.

The disposition and metabolism of the new antihypertensive agent 2-(2"(1", 3"-dioxolan-2-yl)-2-methyl-4-(2'-oxopyrrolidin-1-yl)-6-nitro -2H-1-benzopyran (SKP-450) were investigated in male rats after single oral and i.v. doses of 14C-labeled compound. After an oral 2.0 mg/kg dose, mean radiocarbon recovery was 98.2 +/- 2.3% with 31.1 +/- 7.3% in the feces and 67.1 +/- 14.3% in the urine. Biliary excretion of radioactivity for the first 24-h period was approximately 40%, suggesting that SKP-450 is cleared either by hepatobiliary excretion or by renal excretion. SKP-450 was well absorbed; bioavailability calculated on the basis of radioactivity was 68 to 97%. Tissue distribution of the radioactivity was widespread with high concentrations in the liver and kidney but low central nervous system penetration. Radio-HPLC analysis of bile and urine from rats indicated the extensive metabolism of SKP-450 into oxidative metabolites. Oxidative metabolism of the dioxolanyl ring resulted in an aldehyde intermediate, subsequently confirmed in vitro, which was further oxidized to the corresponding carboxylic acid (M1) or reduced to the corresponding alcohol (M3). No parent drug was detected in the urine or bile. Glucuronide conjugate of M3 was also detected in urine and bile, accounting for 5.8 +/- 2.1 and 8.9 +/- 3. 7% of the excreted radioactivity, respectively. Quantitative data obtained from plasma samples suggest that the majority of circulating radioactivity was associated with metabolites. Our results suggest that the long duration of pharmacological activity of SKP-450 (>10 h) is largely attributable to its metabolites.

Animals↗

New form of X-linked dominant hereditary nephritis in dogs.

OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.

Animals↗

A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy.

BACKGROUND: Lymphocytes are believed to play a role in the induction and perpetuation of membranous nephropathy. Fludarabine is a purine nucleoside analog with selective activity against both dividing and resting lymphocytes. We evaluated the tolerance, toxicity, pharmacokinetics, immunologic, and clinical effects of fludarabine in patients with membranous nephropathy in an single arm pilot study. PATIENTS AND METHODS: Eight patients with idiopathic (n = 7) or lupus (n = 1) membranous nephropathy who had failed high-dose prednisone (n = 8) and/or alkylating agents (n = 2), or cyclosporine (n = 1) were treated with 6-monthly cycles of fludarabine (cycles 1-2, 20 mg/m2/day x 2 days, cycles 3-6, 20 mg/m2/day x 3 days). Mean proteinuria was 9 g/day with a mean duration of disease of 25 months (range 12-48). Proteinuria, GFR and effective renal plasma flow were compared before and after completing the treatment. RESULTS: Seven patients completed the protocol. CD3, CD4, CD8 and B cell counts decreased by 53%, 46%, 61% and 84%, respectively, at the end of treatment and remained at lower than pretreatment levels 6 months after completing the trial. Despite lymphopenia, serum immunoglobulin levels remained unchanged. Both naive (CD45RA+) and memory CD4+ T cells (CD45RO+) were reduced (naive > memory). Proteinuria decreased by > or = 50% in 5 out of 7 patients (p = 0.11). Filtration fraction improved in all patients with decreased filtration fraction at baseline. The only side-effect observed was one episode of acute bacterial sinusitis that responded promptly to antibiotic therapy. CONCLUSION: We conclude that low-dose fludarabine treatment in patients with membranous nephropathy is well tolerated and results in significant lymphopenia involving B more than T cells. In this pilot study improvement in proteinuria and filtration rate were observed. Additional studies are required to determine the optimal dose and clinical efficacy of fludarabine.

Adult↗

[Pharmacological study of weekly docetaxel in patients with metastatic breast cancer].

A pharmacological comparison of weekly administrations of docetaxel (TXT) and standard/conventional TXT was carried out among patients with metastatic breast cancer. Fifteen patients were enrolled in this study of weekly TXT (TXT: 40 mg/body/week x 3 with 1 week interruptions in 10 patients) and standard TXT (TXT: 60 mg/m2/3 weeks in 5 patients). The median dose intensity (DI) of weekly TXT (20.63 mg/m2/week) was similar to that of standard TXT, and the median relative dose intensity (RDI) of weekly TXT was 0.98. The median area under the plasma concentration-time curve (AUC) of weekly TXT (1.20 micrograms.h/ml) was smaller than that of standard TXT (1.87 micrograms.h/ml). Therefore, there were remarkable decreases in both median percent of decrease in neutrophil counts and grade 3, 4 neutropenia with weekly TXT. These pharmacological data show that weekly TXT is a well-tolerated and feasible schedule for the treatment of metastatic breast cancer.

Adult↗

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.

Adult↗