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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 19 recordsLinked to original sources
PubMed2007

Enhanced degradation and toxicity reduction of dihexyl phthalate by Fusarium oxysporum f. sp. pisi cutinase.

AIMS: This research aims to investigate the efficiency of two lipolytic enzymes--fungal cutinase and yeast esterase--upon the biodegradation of dihexyl phthalate (DHP). METHOD AND RESULTS: During the enzymatic degradation of DHP dissolved in methanol, several degradation products were detected and their time-course changes were monitored using GC/MS. The DHP-degradation rate of cutinase was surprisingly high; i.e. almost 70% of the initial DHP (500 mg l(-1)) was decomposed within 4.5 h. Although the same amount of esterase was employed, more than 85% of the DHP remained after 3 days. Almost all the DHP was converted by cutinase into 1,3-isobenzofurandione (IBF), whereas hexyl methyl phthalate and IBF were abundantly produced by esterase. In addition, the toxicities of the DHP-degraded products by esterase were evaluated using various recombinant bioluminescent bacteria, which caused oxidative and protein damage, whereas the hydrolysis products from cutinase never caused any cellular damage in the methanol-containing reaction system. CONCLUSIONS: Cutinase starts to act as a DHP-degrader much earlier and faster than esterase, with high stability in ester-hydrolytic activity, therefore a plausible approach to the practical application of cutinase for DHP degradation in the DHP-contaminated environments may be possible. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the enhanced degradation and detoxification of DHP using Fusarium oxysporum f. sp. pisi cutinase.

Biodegradation, Environmental↗
PubMed2007

Prevalence and trends of metabolic syndrome in Korea: Korean National Health and Nutrition Survey 1998-2001.

BACKGROUND: Metabolic syndrome (MetS) is a major international health problem. Limited information is available about the prevalence of MetS in Asia, especially in Korea. OBJECTIVE: To examine the prevalence and trends of MetS in a Korean population. In addition, we investigated the risk factors associated with MetS. DESIGN AND PARTICIPANTS: A total of 7445 participants aged >/=20 years from the Korean National Health and Nutrition Survey (KNHNS) 1998 and 5964 participants from the KNHNS 2001 were included in this analysis. The KNHNS is a cross-sectional health survey of a nationally representative sample of the Korean population. The prevalence of MetS was determined using the National Cholesterol Education Program Adult Treatment Panel III criteria and the Asia-Pacific criteria for obesity based on waist circumference (APC-WC). RESULTS: Using the ATP III criteria, the age-adjusted prevalence of MetS among Korean adults was 15.7% (13.7% male, 17.8% female) in 1998 and 14.4% (13.0% male, 16.2% female) in 2001. Using the APC-WC criteria, the prevalence was 21.6% (19.4% male, 23.9% female) in 1998 and 21.4% (20.1% male, 23.4% female) in 2001. Of the five MetS components, increasing trends were found between 1998 and 2001 in the prevalence of hypertriglyceridaemia, low high-density lipoprotein cholesterol and central obesity for both men and women. Age, sex, body mass index and a family history of diabetes were associated with MetS. CONCLUSIONS: These results from a representative sample show that MetS is common in Korean adults. A systemic public health programme is required to prevent future increases in diabetes and cardiovascular complications.

Adult↗
PubMed2006

Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation.

We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53(-/-) cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53(-/-) cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53(+/+) cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53(+/+) cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

Apoptosis↗
PubMed2006

Neuroplasticity of face primary motor cortex control of orofacial movements.

We have carried out a series of studies to address the role of the face primary motor area (MI) in the cerebral cortex in trained or semi-automatic orofacial motor behaviours and in behavioural adaptations to an altered oral environment. These studies have utilized intracortical microstimulation (ICMS), reversible cold block or single neurone recordings in face MI. Our studies in monkeys have revealed that face MI plays a strategic role in elemental and learned motor behaviours and in certain aspects of chewing and swallowing. Furthermore, successful training of awake monkeys in a novel tongue-protrusion task is associated with significant neuroplastic changes in face MI. These findings in monkeys are supported by correlated findings in humans which have revealed significantly enhanced corticomotoneuronal excitability when humans learn the novel tongue-protrusion task. Our related ICMS studies in rats reveal that trimming or extraction of the rat's lower incisors or damage to the rat's lingual nerve can result in significant changes in the MI representations of the tongue or jaw muscles. These various findings suggest that the face MI is important in orofacial motor skill acquisition and adaptation to an altered occlusion or loss of teeth or lingual sensory function, and that it reflects dynamic and modifiable constructs that are modelled by behaviourally significant experiences and that are critical to learning and adaptive processes.

Adaptation, Physiological↗
PubMed2006

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.

Aged↗
PubMed2006

The prevalence and risk factors associated with isolated untreated systolic hypertension in Korea: the Korean National Health and Nutrition Survey 2001.

Although isolated systolic hypertension (ISH) increases the risk of coronary heart disease and stroke, more than any other hypertension subtype, the prevalence and risk factors associated with ISH in the Korean population are not known. The 2001 Korean National Health and Nutrition Survey was a cross-sectional and nationally representative survey conducted in 2001. The prevalence of ISH by age and body mass index (BMI) was examined in 6601 Korean adults over 20 years of age. After adjusting for age, 4.32+/-0.32% of Korean adults had ISH, 5.28+/-0.37% had isolated diastolic hypertension and 5.82+/-0.36% had systolic/diastolic hypertension. The overall prevalence of ISH was found to increase directly with advancing age and increasing BMI. Although the ISH was found to be more common in men overall (4.81+/-0.50% in men, 4.12+/-0.37% in women), it was more common in women over 70 years of age. Independent variables associated with risk for ISH included advanced age, BMI, triglyceride (TG) levels, monthly income and alcohol intake. However, gender, fasting blood glucose, total cholesterol and high-density lipoprotein cholesterol levels, residential area, education level and smoking were found not to be significantly associated with ISH risk. The findings of the present study demonstrate that the prevalence of untreated ISH in Korea was lower than in Western countries. Age, BMI, TG levels, monthly income and alcohol intake were associated with ISH.

Adult↗
PubMed2006

Identification of differential melanocortin 4 receptor agonist profiles at natively expressed receptors in rat cortical astrocytes and recombinantly expressed receptors in human embryonic kidney cells.

Using cAMP accumulation as a functional readout, we pharmacologically characterized the response of native melanocortin receptors in cultured rat astrocytes, and found this response to be mediated by the melanocortin 4 receptor (MC4R). Melancortin agonists stimulate cAMP in a concentration-dependent manner in both astrocytes and human embryonic kidney cells recombinantly expressing rat MC4R (HEK-rMC4R), however, the relative potency and intrinsic activity of both small molecule and peptide agonists are reduced in the native system. As such, the small molecules THIQ, NBI-702 and MB243 display 43, 30 and 18% of the maximal response elicited by alpha-MSH in astrocytes. Likewise, the peptides MTII and ACTH display 55 and 72% of the maximal response elicited by alpha-MSH in these cells. In contrast, all of these compounds elicit full agonist responses with similar intrinsic activity to alpha-MSH in HEK-rMC4R cells. MC4R mRNA was detected in astrocytes, however radioligand binding experiments failed to detect measurable MC4R in astrocyte membranes, in contrast to membranes from HEK-rMC4R cells that display a binding site density of 18.1+/-1.5 fmol/mg. We propose that the divergent observations in functional activity between the cell types reflect differences in receptor expression and that caution should be exercised when interpreting agonist activity in over-expression systems for the purposes of drug discovery.

Animals↗
PubMed2006

N-halamine biocidal coatings.

Novel N-halamine siloxane and epoxide coatings are described. The coatings can be rendered biocidal by exposure to dilute bleach. Once the bound chlorine is lost from the coatings, it can be regenerated by further exposure to dilute bleach. Synthetic schemes and biocidal efficacy data are presented. The stabilities of the bound chlorine on the surfaces are also addressed. Substrates employed include sand, textiles, and paint. Potential uses for the technology are discussed.

Coated Materials, Biocompatible↗
PubMed2006

Acute and chronic changes in aquaporin 4 expression after spinal cord injury.

The effect of spinal cord injury (SCI) on the expression levels and distribution of water channel aquaporin 4 (AQP4) has not been studied. We have found AQP4 in gray and white matter astrocytes in both uninjured and injured rat spinal cords. AQP4 was detected in astrocytic processes that were tightly surrounding neurons and blood vessels, but more robustly in glia limitans externa and interna, which were forming an interface between spinal cord parenchyma and cerebrospinal fluid (CSF). Such spatial distribution of AQP4 suggests a critical role that astrocytes expressing AQP4 play in the transport of water from blood/CSF to spinal cord parenchyma and vice versa. SCI induced biphasic changes in astrocytic AQP4 levels, including its early down-regulation and subsequent persistent up-regulation. However, changes in AQP4 expression did not correlate well with the onset and magnitude of astrocytic activation, when measured as changes in GFAP expression levels. It appears that reactive astrocytes began expressing increased levels of AQP4 after migrating to the wound area (thoracic region) two weeks after SCI, and AQP4 remained significantly elevated for months after SCI. We also showed that increased levels of AQP4 spread away from the lesion site to cervical and lumbar segments, but only in chronically injured spinal cords. Although overall AQP4 expression levels increased in chronically-injured spinal cords, AQP4 immunolabeling in astrocytic processes forming glia limitans externa was decreased, which may indicate impaired water transport through glia limitans externa. Finally, we also showed that SCI-induced changes in AQP4 protein levels correlate, both temporally and spatially, with persistent increases in water content in acutely and chronically injured spinal cords. Although correlative, this finding suggests a possible link between AQP4 and impaired water transport/edema/syringomyelia in contused spinal cords.

Animals↗
PubMed2006

Effects of pairing potential scattering on Fourier-transformed inelastic tunneling spectra of high-Tc cuprate superconductors with bosonic modes.

Recent scanning tunneling microscopy (STM) experimentally observed strong gap inhomogeneity in Bi2Sr2CaCu2O(8+delta) (BSCCO). We argue that disorder in the pair potential underlies the gap inhomogeneity, and investigate its role in the Fourier-transformed inelastic tunneling spectra as revealed in the STM. We find that the random pair potential induces unique q-space patterns in the local density of states (LDOS) of a d-wave superconductor. We consider the effects of electron coupling to various bosonic modes and find the pattern of LDOS modulation due to coupling to the B(1g) phonon mode to be consistent with the one observed in the inelastic electron tunnneling STM experiment in BSCCO. These results suggest strong electron-lattice coupling as an essential part of the superconducting state in high-Tc materials.

Journal Article↗
PubMed2006

Study of J/psi-->pp[over],LambdaLambda[over] and observation of eta(c)-->LambdaLambda[over] at Belle.

We study the baryonic charmonium decays of B mesons B+-->etacK+ and B+-->J/psiK+, where the etac and J/psi subsequently decay into a pp[over] or LambdaLambda[over] pair. We measure the J/psi-->pp[over] and LambdaLambda[over] anisotropy parameters alphaB=-0.60+/-0.13+/-0.14 (pp[over]), -0.44+/-0.51+/-0.31 (LambdaLambda[over ]) and compare to results from e;{+}e;{-}-->J/psi formation experiments. We also report the first observation of etac-->LambdaLambda[over]. The measured branching fraction is B(etac-->LambdaLambda[over ])=(0.87(+0.24)/(-0.21)(stat)(+0.09/-0.14) (syst)+/-0.27(PDG))x10-3. This study is based on a 357 fb-1 data sample recorded on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider.

Journal Article↗
PubMed2006

Observation of new states decaying into Lambda(c)(+)Kappa(-)pi(+) and Lambda(c)(+)Kappa(0)/(s)pi(-).

We report the first observation of two charmed strange baryons that decay into Lambda(c)(+)Kappa(-)pi(+). The broader of the two states is measured to have a mass of 2978.5+/-2.1+/-2.0 MeV/c2 and a width of 43.5+/-7.5+/-7.0 MeV/c2. The mass and width of the narrow state are measured to be 3076.7+/-0.9+/-0.5 MeV/c;{2} and 6.2+/-1.2+/-0.8 MeV/c2, respectively. We also perform a search for the isospin partner states that decay into Lambda(c)(+)Kappa(0)/(s)pi(-) and observe a significant signal at the mass of 3082.8+/-1.8+/-1.5 MeV/c2. The data used for this analysis were accumulated at or near the Upsilon(4S) resonance, using the Belle detector at the e+ e- asymmetric-energy collider KEKB. The integrated luminosity of the data sample used is 461.5 fb(-1).

Journal Article↗
PubMed2006

Molecular characterization of human adenomyosis.

Adenomyosis is a common gynaecological disorder characterized by the abnormal growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia. Uterine fibroids are benign neoplasms of the myometrium, and they represent a diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium. Unsupervised principal component analysis (PCA) revealed that these four tissue types could be segregated from one another solely based on their gene expression profiles. Analysis of variance (ANOVA), followed by Tukey means separation test, significance analysis of microarrays (SAM) and 2-fold change threshold, identified 7415 probe sets as differentially expressed among the four groups of samples. Supervised cluster analysis based on these probe sets clustered adenomyosis most closely with endometrium and uterine fibroids with myometrium, consistent with the anatomic origin of these two diseases. The Tukey means separation post hoc testing found 2073 probe sets altered between adenomyosis and normal endometrium or myometrium, and 2327 probe sets altered in expression when comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in uterine fibroids. Notably, the top network in both cases was associated with functions implicated in cancer and cell death. Finally, we compared the gene expression profiles of adenomyosis and uterine fibroids and identified 471 differentially expressed probe sets that may represent potential biomarkers for the differential diagnosis of these diseases.

Analysis of Variance↗
PubMed2006

Midbrain pathways for prepulse inhibition and startle activation in rat.

The midbrain is essential for prepulse inhibition (PPI) of the startle reflex, but the exact neural circuits for PPI are not yet determined. Electrical stimulation of the superior colliculus (SC) or pedunculopontine tegmentum was used to characterize the neurons and pathways that mediate PPI and the activation of startle that also occurs at higher currents in the same sites. Startle was inhibited by prepulses in most, but not all SC sites, with the lowest intensity sites in intermediate layers of SC. PPI latencies in SC sites were 4-6 ms longer than in inferior colliculus, intercollicular nucleus or pedunculopontine sites. Contrary to previous serial models, there must be two parallel midbrain pathways for PPI, a faster auditory pathway from inferior colliculus to pedunculopontine tegmentum, and a slower multimodal SC output for PPI. Double-pulse stimulation of SC sites shows that PPI results from direct stimulation of neurons with moderate refractory periods (0.4-1.0 ms), similar to SC neurons that mediate contraversive turning responses. By contrast, startle activation occurring at higher currents in all SC sites (even sites where PPI could not be elicited) results from stimulation of very short refractory period neurons (0.3-0.5 ms) and very long refractory period neurons (1.0-2.0 ms), with startle inhibition often found from 0.5-1.0 ms. Startle activation appears to result from stimulation of short refractory period neurons in deep SC layers that mediate fear-potentiated startle, plus long refractory period substrates in more dorsal SC sites.

Animals↗
PubMed2006

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma.

BACKGROUND: This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. PATIENTS AND METHODS: Patients with histologically proven, metastatic gastric adenocarcinoma, aged 18-70 years, performance status zero to two, no prior chemotherapy, and with signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day 1, and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, which was repeated every 2 weeks. RESULTS: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24-69). In total, 386 cycles were administered with a median of nine cycles per patient (range 1-12 cycles) and 45 of 48 patients were assessable for treatment response. An independent review of tumor responses resulted in overall response rate of 66.7% (95% confidence interval=53.4% to 80.0%) by intent-to-treat analysis with one complete response and 31 partial responses. The median survival of all patients was 14.8 months and the median time to progression was 9.6 months. Most common grade 3/4 toxic effects were neutropenia (12% of all cycles) and emesis (8% of all cycles). Grade 2 peripheral neuropathy occurred in five patients. One (2%) patient had severe tumor bleeding and five (10%) patients experienced grade 3 diarrhea. CONCLUSIONS: The modified FOLFOXIRI combination chemotherapy showed a very promising preliminary antitumor activity and was generally well tolerated as a first-line treatment of patients with metastatic gastric cancer.

Adenocarcinoma↗
PubMed2006

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Animals↗
PubMed2006

Measurement of the quark mixing parameter cos2phi1 using time-dependent Dalitz analysis of B0 -->D[KS(0)pi + pi-]h0.

We present a measurement of the angle phi1 of the Cabibbo-Kobayashi-Maskawa unitarity triangle using a time-dependent Dalitz analysis of D-->KS(0)pi + pi- decays produced in neutral B meson decay to a neutral D meson and a light meson (B0-->D*h0). The method allows a direct extraction of 2phi1 and, therefore, helps to resolve the ambiguity between 2phi1 and pi-2phi1 in the measurement of sin2phi1. We obtain sin2phi1= 0.78 +/- 0.44 +/- 0.22 and cos2varphi1 = 1.87(-0.53-0.32)(+0.40 + 0.22). The sign of cos2phi1 is determined to be positive at 98.3% C.L.

Journal Article↗