Search PubMed⌕ Search

Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 271 records · Page 15Linked to original sources

Threshold dependence of mortality effects for fine and coarse particles in Phoenix, Arizona.

Daily data for fine (< 2.5 microns) and coarse (2.5-10 microns) particles are available for 1995-1997 from the U.S. Environmental Protection Agency (EPA) research monitor in Phoenix, AZ. Mortality effects on the 65 and over population were studied for both the city of Phoenix and for a region of about 50 mi around Phoenix. Coarse particles in Phoenix are believed to be natural in origin and spatially homogeneous, whereas fine particles are primarily vehicular in origin and concentrated in the city itself. For this reason, it is natural to focus on city mortality data when considering fine particles, and on region mortality data when considering coarse particles, and most of the results reported here correspond to those assignments. After allowing for seasonality and long-term trend through a nonlinear (B-spline) trend curve, and also for meteorological effects based on temperature and specific humidity, a regression of mortality was performed on PM using several different measures for PM. Based on a linear PM effect, we found a statistically significant coefficient for coarse particles, but not for fine particles, contrary to what is widely believed about the effects of coarse and fine particles. An analysis of nonlinear pollution-mortality relationships, however, suggests that the true picture is more complicated than that. For coarse particles, the evidence for any nonlinear or threshold-based effect is slight. For fine particles, we found evidence of a threshold, most likely with values in the range of 20-25 micrograms/m3. We also found some evidence of interactions of the PM effects with season and year. The main effect here is an apparent seasonal interaction in the coarse PM effect. An attempt was made to explain this in terms of seasonal variation in the chemical composition of PM, but this led to another counterintuitive result: the PM effect is highest in spring and summer, when the anthropogenic concentration of coarse PM is lowest as determined by a principal components analysis. There was no evidence of confounding between the fine and coarse PM effects. Although these results are based on one city and should be considered tentative until replicated in other studies, they suggest that the prevailing focus on fine rather than coarse particles may be an oversimplification. The study also shows that consideration of nonlinear effects can lead to real changes of interpretation and raises the possibility of seasonal effects associated with the chemical composition of PM.

Aged↗

Increased expression and shuttling of aquaporin-2 water channels in the kidney in DOCA-salt hypertensive rats.

An altered role of AQP2 water channels in DOCA-salt hypertension was investigated. DOCA-salt hypertension was induced in rats. Control groups were either treated with DOCA alone or subjected to a high-salt intake without DOCA. Four weeks after inducing the hypertension, AQP2 expression and shuttling were determined in the kidney. Adenylate cyclase activity was also determined to examine the upstream affecting the AQP2 system. The AVP-evoked cAMP generation in the cortex and outer medulla was augmented following the treatment with DOCA either alone or combined with high-salt intake. Accordingly, the expression and shuttling of AQP2 proteins were increased in the cortex and outer medulla. These findings suggest that DOCA enhances cAMP generation and expression/shuttling of AQP2 water channels in the kidney, which may be causally related with the development of hypertension.

Adenylyl Cyclases↗

Dual requirement for rho and protein kinase C in direct activation of phospholipase D1 through G protein-coupled receptor signaling.

G protein-coupled and tyrosine kinase receptor activation of phospholipase D1 (PLD1) play key roles in agonist-stimulated cellular responses such as regulated exocytosis, actin stress fiber formation, and alterations in cell morphology and motility. Protein Kinase C, ADP-ribosylation factor (ARF), and Rho family members activate PLD1 in vitro; however, the actions of the stimulators on PLD1 in vivo have been proposed to take place through indirect pathways. We have used the yeast split-hybrid system to generate PLD1 alleles that fail to bind to or to be activated by RhoA but that retain wild-type responses to ARF and PKC. These alleles then were employed in combination with alleles unresponsive to PKC or to both stimulators to examine the activation of PLD1 by G protein-coupled receptors. Our results demonstrate that direct stimulation of PLD1 in vivo by RhoA (and by PKC) is critical for significant PLD1 activation but that PLD1 subcellular localization and regulated phosphorylation occur independently of these stimulatory pathways.

ADP-Ribosylation Factor 1↗

Joint effects of genetic hitchhiking and background selection on neutral variation.

Due to relatively high rates of strongly selected deleterious mutations, directional selection on favorable alleles (causing hitchhiking effects on linked neutral polymorphisms) is expected to occur while a deleterious mutation-selection balance is present in a population. We analyze this interaction of directional selection and background selection and study their combined effects on neutral variation, using a three-locus model in which each locus is subjected to either deleterious, favorable, or neutral mutations. Average heterozygosity is measured by simulations (1) at the stationary state under the assumption of recurrent hitchhiking events and (2) as a transient level after a single hitchhiking event. The simulation results are compared to theoretical predictions. It is shown that known analytical solutions describing the hitchhiking effect without background selection can be modified such that they accurately predict the joint effects of hitchhiking and background on linked, neutral variation. Generalization of these results to a more appropriate multilocus model (such that background selection can occur at multiple sites) suggests that, in regions of very low recombination rates, stationary levels of nucleotide diversity are primarily determined by hitchhiking, whereas in regions of high recombination, background selection is the dominant force. The implications of these results on the identification and estimation of the relevant parameters of the model are discussed.

Alleles↗

Seroepidemiology of Helicobacter pylori infection in a population of Egyptian children.

BACKGROUND: To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. METHODS: A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. RESULTS: The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. CONCLUSIONS: Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection.

Anthropometry↗

Carboxyl-terminal fragment of Alzheimer's APP destabilizes calcium homeostasis and renders neuronal cells vulnerable to excitotoxicity.

Numerous lines of evidence indicate that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid beta peptide (Abeta). However, the possible role of other cleaved products of APP is less clear. We have previously shown that a recombinant carboxy-terminal 105 amino acid fragment (CT 105) of APP induced strong nonselective inward currents in Xenopus oocyte; it also revealed neurotoxicity in PC12 cells and primary cortical neurons, blocked later phase of long-term potentiation in rat hippocampus in vivo, and induced memory deficits and neuropathological changes in mice. We report here that the pretreatment with CT 105 for 24 h at a 10 microM concentration increases intracellular calcium concentration by about twofold in SK-N-SH and PC 12 cells, but not in U251 cells, originated from human glioblastoma. In addition, the calcium increase and toxicity induced by CT 105 were reduced by cholesterol and MK 801 in SK-N-SH and PC 12 cells, whereas the toxicity of Abeta(1-42) was attenuated by nifedipine and verapamil. CT 105 rendered SK-N-SH cells and rat primary cortical neurons more vulnerable to glutamate-induced excitotoxicity. Also, conformational studies using circular dichroism experiments showed that CT 105 has approximately 15% of beta-sheet content in phosphate buffer and aqueous 2,2, 2-trifluoroethanol solutions. However, the content of beta-sheet conformation in dodecyl phosphocholine micelle or in the negatively charged vesicles, is increased to 22%-23%. The results of this study showed that CT 105 disrupts calcium homeostasis and renders neuronal cells more vulnerable to glutamate-induced excitotoxicity, and that some portion of CT 105 has partial beta-sheet conformation in various environments, which may be related to the self-aggregation and toxicity. This may be significantly possibly involved in inducing the neurotoxicity characteristic of AD.

Amyloid beta-Peptides↗

Validation of the International Classification of Diseases 10th Edition-based Injury Severity Score (ICISS).

OBJECTIVE: To compare the predictive power of International Classification of Diseases 10th Edition (ICD-10)-based International Classification of Diseases 9th Edition-based Injury Severity Score (ICISS) with Trauma and Injury Severity Score (TRISS) and ICD-9CM-based ICISS in the injury severity measure. METHODS: ICD-10 version of survival risk ratios was derived from 47,750 trauma patients from 35 emergency centers for 1 year. The predictive power of TRISS, the ICD-9CM-based ICISS and ICD-10-based ICISS were compared in a group of 367 severely injured patients admitted to two university hospitals. The predictive power was compared by using the measures of discrimination (disparity, sensitivity, specificity, misclassification rates, and receiver operating characteristic curve analysis) and calibration (Hosmer-Lemeshow goodness-of-fit statistics), all calculated by logistic regression procedure. RESULTS: ICD-10-based ICISS showed a lower performance than TRISS and ICD-9CM-based ICISS. When age and Revised Trauma Score were incorporated into the survival probability model, however, ICD-10-based ICISS full model showed a similar predictive power compared with TRISS and ICD-9CM-based ICISS full model. ICD-10-based ICISS had some disadvantages in predicting outcomes among patients with intracranial injuries. However, such weakness was largely compensated by incorporating age and Revised Trauma Score in the model. CONCLUSION: The ICISS methodology can be extended to ICD-10 horizon as a standard injury severity measure in the place of TRISS, especially when age and Revised Trauma Score were incorporated in the model. For patients with intracranial injuries, the predictive power of ICD-10-based ICISS was relatively low because of differences in the classifying system between ICD-10 and ICD-9CM.

Adult↗

Dynamic stabilization in the double-well duffing oscillator

Bifurcations associated with stability of the saddle fixed point of the Poincare map, arising from the unstable equilibrium point of the potential, are investigated in a forced Duffing oscillator with a double-well potential. One interesting behavior is the dynamic stabilization of the saddle fixed point. When the driving amplitude is increased through a threshold value, the saddle fixed point becomes stabilized via a pitchfork bifurcation. We note that this dynamic stabilization is similar to that of the inverted pendulum with a vertically oscillating suspension point. After the dynamic stabilization, the double-well Duffing oscillator behaves as the single-well Duffing oscillator, because the effect of the central potential barrier on the dynamics of the system becomes negligible.

Journal Article↗

Dynamical self-affinity of damage spreading in surface growth models

The dynamical anisotropic scaling properties of the surface growth models are restudied by use of the damage spreading concept. For that the vertical damage spreading distance d( perpendicular) of a damaged column as well as the lateral damage spreading distance d(||) is introduced. The scaling Ansatze for &dmacr;( perpendicular)(d(||),t), D(||) identical with and D( perpendicular) identical with<&dmacr;( perpendicular)> are suggested. The critical property of the probability distribution P(d(||),t) for the survived damages is also suggested. The suggested scaling relations are tested by simulating various growth models with substrate dimension d=1. From these results it can be concluded that the critical property or dynamical self-affinity of a surface growth model can also be determined by investigating the damage spreading.

Journal Article↗

Edge-guided boundary delineation in prostate ultrasound images.

Accurate detection of prostate boundaries is required in many diagnostic and treatment procedures for prostate disease. In this paper, a new paradigm for guided edge delineation is described, which involves presenting automatically detected prostate edges as a visual guide to the observer, followed by manual editing. This approach enables robust delineation of the prostate boundaries, making it suitable for routine clinical use. The edge-detection algorithm is comprised of three stages. An algorithm called sticks is used to enhance contrast and at the same time reduce speckle in the transrectal ultrasound prostate image. The resulting image is further smoothed using an anisotropic diffusion filter. In the third stage, some basic prior knowledge of the prostate, such as shape and echo pattern, is used to detect the most probable edges describing the prostate. Finally, patient-specific anatomic information is integrated during manual linking of the detected edges. The algorithm was tested on 125 images from 16 patients. The performance of the algorithm was statistically evaluated by employing five expert observers. Based on this study, we found that consistency in prostate delineation increases when automatically detected edges are used as visual guide during outlining, while the accuracy of the detected edges was found to be at least as good as those of the human observers. The use of edge guidance for boundary delineation can also be extended to other applications in medical imaging where poor contrast in the images and the complexity in the anatomy limit the clinical usability of fully automatic edge-detection techniques.

Algorithms↗

Effect of age on sleep onset-related changes in respiratory pump and upper airway muscle function.

In normal young men, there is an abrupt fall in ventilation (VE), a rise in upper airway resistance (UAR), and falls in the activities of the diaphragm (Di), intercostals (IC), genioglossus (GG), and tensor palatini (TP) at sleep onset. On waking, there is an abrupt increase in VE and fall in UAR and an increase in the activities of Di, IC, GG, and TP. The aim of this study was to determine whether these changes are age dependent. Nine men aged 20 to 25 yr were compared with nine men aged 42 to 67 yr. Airflow, UAR, Di, and IC surface electromyograms (EMGs) and the intramuscular EMGs of GG and TP were recorded. It was found that the falls in IC, GG, and TP at the transition from alpha to theta electroencephalogram (EEG) activity were significantly greater in the older than in the younger men (P < 0.05) and that the fall in Di was also greater, although this was only marginally significant (P = 0.15). The rise in GG at theta-to-alpha transitions was also greater in the older than in the younger men, and there was a trend for TP to be higher.

Adolescent↗

Reduced frequencies of peripheral interferon-gamma-producing CD4+ and CD4- cells during acute Kawasaki disease.

BACKGROUND: This study was performed to analyze the frequencies of peripheral interferon (IFN)-gamma-producing cells at the single-cell level and to determine concentrations of circulating IFN-gamma in the acute and subacute phases of Kawasaki disease (KD). METHODS: Ten patients with KD were studied and seven healthy children were selected as control subjects. Using immunofluorescent detection of intracellular IFN-gamma in CD4-positive and CD4-negative cells, the frequencies of IFN-gamma-producing cells in peripheral blood mononuclear cells were studied. Circulating IFN-gamma levels were measured by enzyme-linked immunosorbent assay. RESULTS: The frequencies of peripheral blood CD4+ and CD4- IFN-gamma-producing cells in acute-phase KD patients were significantly lower than in subacute-phase KD patients and control children (p < 0.05). CD4- cells, thought to be mainly composed of CD8+ cells, appeared to be more responsible for the reduced frequencies of total IFN-gamma-producing cells than CD4+ cells. There were, however, no differences in the frequencies of IFN-gamma-producing cells between KD patients in the subacute phase and control children. In contrast, serum IFN-gamma levels were higher in KD patients in the acute phase than in the subacute phase (p < 0.05). CONCLUSIONS: The above results show increased levels of circulating IFN-gamma and decreased emergence of peripheral IFN-gamma-producing cells in acute KD patients, suggesting transient infiltration of activated IFN-gamma-producing cells into the inflammatory sites during acute KD. These findings also support the hypothesis that IFN-gamma plays an important role in the pathogenesis of KD-related vasculitis.

CD4-Positive T-Lymphocytes↗

Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment.

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.

Adrenal Cortex↗

Expression of functional markers in acute nonlymphoblastic leukemia.

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIalpha was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

Adolescent↗

Female sexual dysfunction associated with antidepressant administration: a randomized, placebo-controlled study of pharmacologic intervention.

OBJECTIVE: Few controlled trials of pharmacologic intervention in women with antidepressant-associated sexual dysfunction have been reported, and there is uncertainty about the usefulness of putative treatments and the assessment methodologies. The authors evaluated the efficacy of buspirone and amantadine in the treatment of sexual dysfunction associated with fluoxetine administration. METHOD: Women who had been successfully treated with fluoxetine for at least 8 weeks and who had reported a deterioration in sexual function not present before the initiation of fluoxetine entered a 4-week assessment period. After assessment they were randomly assigned to an 8-week treatment trial with buspirone (N=19), amantadine (N=18), or placebo (N=20). Outcomes were assessed by using a patient-rated daily diary and a clinician-rated structured interview. RESULTS: While the amantadine-treated women did report significantly greater improvements in energy levels than women in the placebo group, all treatment groups experienced improvement in overall sexual function as well as in most individual measures. There were no statistically significant differences among the three groups. CONCLUSIONS: Neither buspirone nor amantadine was more effective than placebo in ameliorating antidepressant-associated sexual dysfunction. All groups experienced marked nonspecific improvement during treatment, which suggests the importance of placebo-controlled trials for this condition.

Adult↗

Immunohistochemical localization of collagen types I, III, and IV, laminin, fibronectin, and keratin in the endolymphatic sac.

We have employed immunohistochemistry to obtain baseline information on the molecular constituents of the extracellular matrix (ECM) of the endolymphatic duct (ED) and endolymphatic sac (ES) of the chinchilla. The results demonstrated that collagen types I and III were distributed in the subepithelial layer in the ED and ES, type IV collagen and laminin in the basement membranes, and fibronectin in the subepithelial layer and partly in the conglomerated cells in the ES. Collagen type III was diffusely distributed in the whole subepithelial layer of the ES, whereas collagen type I was concentrated densely in the deep layer of the interstitium, although gradually, the cuboidal epithelium in the ES was transformed into a flatter type in the ED. The epithelial cells of the ED and ES were clearly positive for keratin. This study deals, in particular, with the normal distribution of ECM components of the ED and ES of the chinchilla.

Animals↗

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

Adult↗

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Antineoplastic Agents, Phytogenic↗