Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 199 records · Page 11Linked to original sources

PubMed1999

Vapor recognition with small arrays of polymer-coated microsensors. A comprehensive analysis.

A comprehensive analysis of vapor recognition as a function of the number of sensors in a vapor-sensor array is presented. Responses to 16 organic vapors collected from six polymer-coated surface acoustic wave (SAW) sensors were used in Monte Carlo simulations coupled with pattern recognition analyses to derive statistical estimates of vapor recognition rates as a function of the number of sensors in the array (< or = 6), the polymer sensor coatings employed, and the number and concentration of vapors being analyzed. Results indicate that as few as two sensors can recognize individual vapors from a set of 16 possibilities with < 6% average recognition error, as long as the vapor concentrations are > 5 x LOD for the array. At lower concentrations, a minimum of three sensors is required, but arrays of 3-6 sensors provide comparable results. Analyses also revealed that individual-vapor recognition hinges more on the similarity of the vapor response patterns than on the total number of possible vapors considered. Vapor mixtures were also analyzed for specific 2-, 3-, 4-, 5-, and 6-vapor subsets where all possible combinations of vapors within each subset were considered simultaneously. Excellent recognition rates were obtainable for mixtures of up to four vapors using the same number of sensors as vapors in the subset. Lower recognition rates were generally observed for mixtures that included structurally homologous vapors. Acceptable recognition rates could not be obtained for the 5- and 6-vapor subsets examined, due, apparently, to the large number of vapor combinations considered (i.e., 31 and 63, respectively). Importantly, increasing the number of sensors in the array did not improve performance significantly for any of the mixture analyses, suggesting that for SAW sensors and other sensors whose responses rely on equilibrium vapor-polymer partitioning, large arrays are not necessary for accurate vapor recognition and quantification.

Chemistry Techniques, Analytical↗

PubMed1999

Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.

The underlying causes of obesity are poorly understood but probably involve complex interactions between many neurotransmitter and neuropeptide systems involved in the regulation of food intake and energy balance. Three pieces of evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an important component of this system. First, MCH stimulates feeding when injected directly into rat brains; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals; and third, mice lacking MCH eat less and are lean. MCH antagonists might, therefore, provide a treatment for obesity. However, the development of such molecules has been hampered because the identity of the MCH receptor has been unknown until now. Here we show that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels. We also show that SLC-1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus, consistent with a role for SLC-1 in mediating the effects of MCH on feeding.

Alternative Splicing↗

PubMed1999

Distinct localization of SAPK isoforms in neurons of adult mouse brain implies multiple signaling modes of SAPK pathway.

Various cellular and environmental stresses lead to the activation of stress-activated protein kinase (SAPK), which is also referred to as c-Jun N-terminal kinase (JNK). In mammals, multiple SAPK isoforms, encoded by three independent genes, were identified. To gain insight into the roles of SAPK pathway in adult mouse brain, detailed expression patterns of three SAPK isoforms in brain were examined by using immunohistochemical and cell biological analyses. SAPKbeta was heavily expressed in almost all regions of brain as previously reported. Interestingly, SAPKgamma was also widely expressed at high levels. SAPKgamma expression was generally overlapped with SAPKbeta although there were some exceptions such as in hippocampus, where SAPKgamma was restricted to CA3 and CA4 regions while SAPKbeta was evenly expressed. SAPKalpha was widely expressed, but at low levels. It is particularly intriguing to note the differential subcellular localization of SAPK isoforms in neurons. In brain of normally reared mice, SAPKbeta was identified in nucleus as well as in cytoplasm of neurons, while SAPKgamma was detected mainly in cytoplasm and dendrites. Biochemical and immunological analyses revealed extraordinarily high basal activities of all SAPK isoforms in brain compared to peripheral organs, indicating that SAPK pathway may play a role in normal brain physiology. In addition, differential regional and subcellular localizations of SAPK isoforms allow us to speculate multiple signaling modes for SAPK activation in brain.

Animals↗

PubMed1999

Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway.

Serum and glucocorticoid-inducible kinase (SGK) is a novel member of the serine/threonine protein kinase family that is transcriptionally regulated. In this study, we have investigated the regulatory mechanisms that control SGK activity. We have established a peptide kinase assay for SGK and present evidence demonstrating that SGK is a component of the phosphoinositide 3 (PI 3)-kinase signaling pathway. Treatment of human embryo kidney 293 cells with insulin, IGF-1 or pervanadate induced a 3- to 12-fold activation of ectopically expressed SGK. Activation was completely abolished by pretreatment of cells with the PI 3-kinase inhibitor, LY294002. Treatment of activated SGK with protein phosphatase 2A in vitro led to kinase inactivation. Consistent with the similarity of SGK to other second-messenger regulated kinases, mutation of putative phosphorylation sites at Thr256 and Ser422 inhibited SGK activation. Cotransfection of PDK1 with SGK caused a 6-fold activation of SGK activity, whereas kinase-dead PDK1 caused no activation. GST-pulldown assays revealed a direct interaction between PDK1 and the catalytic domain of SGK. Treatment of rat mammary tumor cells with serum caused hyperphosphorylation of endogenous SGK, and promoted translocation to the nucleus. Both hyperphosphorylation and nuclear translocation could be inhibited by wortmannin, but not by rapamycin.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed1999

Dealing with a bleeding nuisance: a study of haemophilia care in New Zealand.

AIM: To describe the social and demographic characteristics of people with haemophilia in New Zealand and to identify key issues in their treatment. METHODS: The research (1994-6) used a combination of quantitative and qualitative methods, including key person interviews and focus groups, a national survey (n=193), interviews (80), participant observation and consultative report writing (30 participant-consultants). RESULTS: The study population was mainly (95%) male, somewhat younger than the general New Zealand population, and was 90% Caucasian but otherwise conformed closely to the socio-demographic profile of the general population. Participants clustered towards the severe end of the condition of haemophilia. There was great variation between participants in incidence of bleeds. Legs and arms were most commonly affected. The majority (61%) of bleeds were treated within six hours of detection. Despite considerable advances and an emphasis on the provision of adequate and prompt treatment, there is still much room for improvement to obviate problems such as joint damage, pain and the need for surgery. CONCLUSIONS: People with haemophilia and haemophilia health service providers struggle to achieve optimal care.

Adolescent↗

PubMed1999

Mechanism of Formation of Monodispersed Colloids by Aggregation of Nanosize Precursors.

It has been experimentally established in numerous cases that precipitation of monodispersed colloids from homogeneous solutions is a complex process. Specifically, it was found that in many systems nuclei, produced rapidly in a supersaturated solution, grow to nanosize primary particles (singlets), which then coagulate to form much larger final colloids in a process dominated by irreversible capture of these singlets. This paper describes a kinetic model that explains the formation of dispersions of narrow size distribution in such systems. Numerical simulations of the kinetic equations, with experimental model parameter values, are reported. The model was tested for a system involving formation of uniform spherical gold particles by reduction of auric chloride in aqueous solutions. The calculated average size, the width of the particle size distribution, and the time scale of the process agreed reasonably well with the experimental values. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Selective inactivation of protein tyrosine phosphatase PTP1B by sulfone analogue of naphthoquinone.

Protein tyrosine phosphatase inactivators are of interest as research tools and as therapeutic agents. In this study, the effect of sulfone analogue of naphthoquinone on the activities of PTP1B and other PTPs was examined. The results indicated that this compound selectively and irreversibly inactivated the PTP1B with the dissociation constant Ki of 3.5 microM and the inactivation rate constant kinact of 2.2 x 10(-2) sec-1.

Binding Sites↗

PubMed1999

Conscious sedation: a new approach for peritonsillar abscess drainage in the pediatric population.

OBJECTIVE: To assess the safety and efficacy of conscious sedation (CS) in children undergoing emergency department incision and drainage (I&D) of peritonsillar abscesses (PTAs). DESIGN: A 33-month retrospective chart review of all children presenting to the emergency department with the diagnosis of a PTA or peritonsillar cellulitis. Children who underwent CS prior to I&D were compared with children without CS for complications and efficacy. SETTING: St Louis Children's Hospital, an academic tertiary care pediatric hospital. PATIENTS: Fifty-two children were enrolled; 30 PTAs were drained with CS in 27 children (3 underwent I&D twice), and 25 PTAs were drained in 25 children without CS. INTERVENTIONS: The CS team included an otolaryngologist, a pediatric emergency department physician, and a registered nurse. A standardized CS protocol assessing vital signs and level of consciousness was employed during each procedure. A combination of midazolam, ketamine hydrochloride, and glycopyrrolate was used in appropriately weighted calculated doses. Patients were assessed for major and minor airway complications. MAIN OUTCOME MEASURES: Airway complications related to CS were reviewed. Patients who underwent I&D with and without CS were compared with regard to purulent drainage. RESULTS: There were no major airway complications in patients undergoing I&D with CS. There was 1 minor complication in this group, oxygen desaturation to 88%, which resolved with stimulation. Of the 55 procedures, 45 (82%) yielded purulence: 29 (97%) of 30 in the CS group and 16 (64%) of 25 in the non-CS group (chi2 = 9.8; P = .002). Of those children undergoing CS, 3 (10%) of 30 were admitted to the hospital from the emergency department as compared with 6 (24%) of 25 without CS (chi2 = 1.95; P = .16). In the CS group, PTAs had a low recurrence rate of 1 (3.3%) of 30 compared with 2 (8%) of 25 in the non-CS group (chi2 = 0.57; P = .45). No one in the CS group required a secondary procedure under general anesthesia. CONCLUSIONS: This preliminary study demonstrates CS to be a potentially safe and efficacious approach to drainage of PTAs in children. Given its efficacy and its associated lower levels of anxiety and pain for the patient, CS seems to be a promising new approach to caring for children with PTAs.

Adolescent↗

PubMed1999

Differential display, subtractive hybridization, and application of methodology to search for point mutations to identify genetic defects responsible for progression in MCF10AT model of human breast disease.

We describe initial studies utilizing three methods to detect differences in gene expression: (i) differential display with polyT-anchored primers; (ii) differential display with RNA arbitrarily primed polymerase chain reaction (RAP-PCR), and (iii) cDNA subtractive hybridization. Subtractive hybridization, which detects qualitative differences in gene expression, revealed no differences between a human cell line (MCF10A), originated by spontaneous immortalization of breast epithelial cells, and MCF10CA1 cells, a recently derived fully malignant, metastatic variant. The standard method of differential display with polyT anchored primers detected in excess of 100 differentially displayed bands but differential expression could seldom be verified by Northern blotting. However, RAP-PCR products frequently represent the coding region and fewer bands are detected. One gene of interest is a zinc finger protein which may be expressed more in the preneoplastic lesion-forming cells than in nonlesion-forming cells. Because most bands are not consistently differentially displayed among the variants of the MCF10 model, we suspect that point mutations rather than differential quantitative gene expression is responsible for some stage of progression. We propose that differential display of RAP-PCR products on nondenaturing gels might also detect point mutation differences.

Breast Diseases↗

PubMed1999

Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase.

The biliary epithelium is exposed to mediators of inflammation such as bacterial endotoxin or lipopolysaccharide (LPS) in a variety of inflammatory conditions. These conditions are also characterized by cholangiocyte proliferation and a predisposition to malignancy. Furthermore, LPS can enhance the expression of interleukin-6 (IL-6), a known biliary mitogen. However, the effects of LPS on cholangiocyte proliferation or IL-6 secretion are unknown. Thus, our aims were to determine if LPS stimulates cholangiocyte proliferation by IL-6-dependent signaling pathways. H69 cells derived from normal human intrahepatic cholangiocytes proliferated in response to LPS. Cholangiocytes responded to LPS (and other inflammatory cytokines such as tumor necrosis factor alpha [TNF-alpha] and IL-1beta) by increased secretion of IL-6, which had a mitogenic effect on H69 cells. Preincubation with anti-IL-6 neutralizing antibodies inhibited LPS-induced proliferation. Furthermore, cholangiocytes possessed the IL-6 receptor complex subunits and intact signaling mechanisms leading to activation of signal transducers and activators of transcription (STAT) factors. Although both p38 and p44/p42 mitogen-activated protein kinases (MAPKs) were constitutively present and active in cholangiocytes, IL-6 increased p44/p42, but not p38 MAPK activity. PD098059 inhibited activation of p44/p42 MAPK in cholangiocytes and completely blocked DNA synthesis in response to IL-6 or LPS. These studies identify a critical role for the p44/p42 MAPK in cholangiocyte proliferation and demonstrate that the proliferative response of cholangiocytes to inflammatory mediators such as LPS involves IL-6-mediated activation of the p44/p42 MAPK pathway.

Bile Ducts↗

PubMed1999

Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line.

Biliary tract malignancies represent challenges because of the lack of effective therapy and poor prognosis, in part because of the paucity of information regarding the mechanisms regulating their growth. We have recently identified a critical role for the p44/p42 mitogen-activated protein kinase (MAPK) pathway in interleukin 6 (IL-6)-stimulated growth of human cholangiocytes. Although IL-6 is a potential mitogen for cholangiocarcinoma, the role of this cytokine and its intracellular signaling pathways in cholangiocarcinoma growth is unknown. Thus, our aims were to determine the role of IL-6-mediated signaling mechanisms, and in particular the MAPK pathways, in the growth regulation of human cholangiocarcinoma. KMCH-1 cells (malignant cholangiocyte cells) secreted IL-6 constitutively, and increased IL-6 secretion in response to inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and IL-1beta. Stimulation with IL-6 resulted in proliferation of malignant cholangiocytes. These cells also possessed the IL-6 receptor complex subunits as directly assessed by immunoblot analysis. Furthermore, proliferation was completely inhibited by preincubation with anti-IL-6 neutralizing antibodies, indicating that the proliferative response to IL-6 involved receptor-mediated signaling. Both p38 and p44/p42 MAPKs were constitutively present and active in malignant cholangiocytes, and increased activity of both was observed within 15 minutes of stimulation with IL-6. Selective inhibition of either the p44/p42 MAPK pathway, by PD098059, or of the p38 MAPK pathway, by SB203580, blocked proliferation in response to IL-6. Thus, IL-6 can contribute to the autocrine and/or paracrine growth stimulation of malignant cholangiocytes via activation of either p38 or p44/p42 MAPK signaling pathways.

Bile Duct Neoplasms↗

PubMed1999

Reorganization of myosin and focal adhesion proteins in Swiss 3T3 fibroblasts induced by transforming growth factor beta.

Certain types of cells show a dramatic change in cell morphology cultured in the presence of transforming growth factor beta (TGF-beta). To identify cellular components or factors leading to morphological changes, we investigated if any members of cytoskeletal proteins and cell-adhesion molecules were redistributed in TGF-beta-treated Swiss 3T3 fibroblasts by indirect immunofluorescence and Western-blot analysis. Changes in cell morphology became apparent within 12 h of the addition of TGF-beta and new RNA and protein synthesis was necessitated by the changes. While TGF-beta induced reorganization of microfilaments as reported in earlier studies, one of the actin isoforms, alpha actin of smooth muscle, was induced to form stress fibers in Swiss 3T3 cells. It was observed that myosin light chain was relocated from cell periphery to cytoplasmic filamentous structures by TGF-beta treatment, with an increased amount. In addition, the cell-shape change was accompanied by an increase in the level of vinculin and tyrosine phosphorylation at focal adhesions. These results suggest that new protein synthesis is required for the cell-shape change, and acto-myosin filaments and focal adhesion proteins are involved in the alteration of cell morphology induced by TGF-beta in Swiss 3T3 fibroblasts.

3T3 Cells↗

PubMed1999

Remodeling of the occupational medical examination program in South Korea.

The South Korean government carried out reforms in the occupational medical examination program over a period of 2 years from 1997 to 1998 in a response to the discontent of workers, who had complained that occupational medical examinations were merely ritualistic and unproductive. The purposes of this manuscript are to describe the reason for the remodeling, with a historical review of the existing occupational medical examination program in South Korea, and to discuss the main issues involved in remodeling the program. The existing occupational medical examination program in South Korea was reviewed and criticized. The basic philosophy and the main issues in remodeling South Korea's occupational medical examination program were also discussed. In conclusion, the occupational medical examination program should not be conducted in a uniform manner according to legal regulations, but should be a part of overall occupational health services. Individual workplaces should be given the autonomy to perform medical examinations according to the characteristics of the workplace. An enabling approach based on the participation of labor and management should be taken into consideration.

Civil Rights↗

PubMed1999

Cascaded MRI-SPAMM for LV motion analysis during a whole cardiac cycle.

We present a new paradigm which incorporates multiple sets of tagged MRI data (MRI-SPAMM) acquired in a cascaded fashion in order to estimate the full 3-D motion of the left ventricle (LV) during its entire cardiac cycle. Our technique is based on an extension of our volumetric physics-based deformable models, whose parameters are functions. Using these parameters, we can characterize the local shape variation of an object with a small number of intuitive parameters. By integrating a cascaded sequence of SPAMM data sets into our modeling technique, we have extended the capability of the MRI-SPAMM technique and have provided an accurate representation of the LV motion during the full cardiac cycle (from end-diastole to end-diastole) to better understand cardiac mechanics.

Humans↗

PubMed1999

The tissue distribution of the human beta3-adrenoceptor studied using a monoclonal antibody: direct evidence of the beta3-adrenoceptor in human adipose tissue, atrium and skeletal muscle.

OBJECTIVE: To develop a monoclonal antibody that recognises an epitope of the native beta3-adrenoceptor expressed on the extracellular surface of human cells and tissues. DESIGN: A high affinity monoclonal antibody, Mab72c, was raised against the human beta3-adrenoceptor expressed on a transfected mammalian cell line. RESULTS: In CHO (Chinese hamster ovary) cells transfected with beta3-adrenoceptor cDNA, antibody labelling was found to be proportional to receptor density measured by the binding of the radiolabelled beta-adrenoceptor antagonist, [125I]-iodocyanopindolol. The use of Mab 72c has demonstrated the expression of the beta3-adrenoceptor in a variety of human tissues, including gall bladder, prostate and colon, where a mRNA signal had been detected previously. This study also provides the first direct demonstration of the expression of beta3-adrenoceptors in human skeletal muscle, atrium and adipose tissue. CONCLUSION: The development of this antibody represents an important addition to the armentarium of reagents that are available to study the localisation of beta3-adrenoceptors in human tissues.

Adipose Tissue↗

PubMed1999

Molecular cloning of multiple splicing variants of JIP-1 preferentially expressed in brain.

Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by a variety of cellular or environmental stresses. Proper regulation of the SAPK/JNK pathway may be critical for cell survival or death under various conditions. In this study, we report the molecular cloning of novel isoforms of JIP-1, which harbor a putative phosphotyrosine interaction domain and a helix-loop-helix domain, as well as an SH3 homologous region in the C terminus. Northern analysis indicates that transcription variant jip-1 is expressed in brain and kidney and transcription variants jip-2 and jip-3 are specifically expressed in brain. In situ hybridization data showed that the hybridized jip messages were heavily concentrated in adult brain, and were particularly enriched in the cerebral cortex and hippocampus, the brain regions vulnerable to pathological states such as hypoxia-ischemia, epilepsy, and Alzheimer's disease. All the deduced protein products of the jip transcription variants appear to have a similar property in that they inhibit the SAPK/JNK stimulation when overexpressed. Inhibition of SAPK activation by overexpression of the novel isoform JIP-2a resulted in suppression of etoposide-induced cell death in a neuroglioma cell line, N18TG. These findings suggest that JIP may play an important role in regulation of the SAPK pathway that is involved in stress-induced cellular responses.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Mutational analysis of bovine viral diarrhea virus RNA-dependent RNA polymerase.

Recombinant bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) produced in insect cells has been shown to possess an RNA-dependent RNA polymerase (RdRp) activity. Our initial attempt to produce the full-length BVDV NS5B with a C-terminal hexahistidine tag in Escherichia coli failed due to the expression of insoluble products. Prompted by a recent report that removal of the C-terminal hydrophobic domain significantly improved the solubility of hepatitis C virus (HCV) NS5B, we constructed a similar deletion of 24 amino acids at the C terminus of BVDV NS5B. The resulting fusion protein, NS5BDeltaCT24-His, was purified to homogeneity and demonstrated to direct RNA replication via both primer-dependent (elongative) and primer-independent (de novo) mechanisms. Furthermore, BVDV RdRp was found to utilize a circular single-stranded DNA as a template for RNA synthesis, suggesting that synthesis does not require ends in the template. In addition to the previously described polymerase motifs A, B, C, and D, alignments with other flavivirus sequences revealed two additional motifs, one N-terminal to motif A and one C-terminal to motif D. Extensive alanine substitutions showed that while most mutations had similar effects on both elongative and de novo RNA syntheses, some had selective effects. Finally, deletions of up to 90 amino acids from the N terminus did not significantly affect RdRp activities, whereas deletions of more than 24 amino acids at the C terminus resulted in either insoluble products or soluble proteins (DeltaCT179 and DeltaCT218) that lacked RdRp activities.

Amino Acid Sequence↗

PubMed1999

Complete sequence of enzootic nasal tumor virus, a retrovirus associated with transmissible intranasal tumors of sheep.

The sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. The genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type B and D oncoviruses. Enzootic nasal tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.

Amino Acid Sequence↗