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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 271 records · Page 15Linked to original sources
PubMed1997

Fluorescence polarization immunoassay of progesterone.

A homogeneous fluorescence polarization immunoassay (FPIA) was developed to measure levels of progesterone in urine using a TDx analyzer in photocheck mode (Abbott Labs). Two tracers of ethylenediamine fluorescein thiocarbamyl (EDF) were employed; one was synthesized from 11 alpha-hydroxyhemisuccinate progesterone (Prog-11OH-HS) and the other was synthesized from 3-(o-carboxymethyl)oxime progesterone (Prog-3CMO). Each derivative of progesterone was conjugated with bovine serum albumin and used as an immunogen which produced monoclonal antibody clone 15A (MAb 15A, anti-Prog-11OH-HS) and clone 2B7 (MAb 2B7, anti-Prog-3CMO), respectively. Different combinations of tracers and antibodies were investigated in the FPIA system. Similar sensitivity was observed when using the pair, MAb 2B7 and its homologous tracer, Prog-3CMO-EDF, or MAb 15A and its homologous tracer, Prog-11OH-HS-EDF. In this immunoassay, no separation step was required and the total time for an assay of 10 samples was approximately 7 min. The progesterone detection limit in a 10 microliters sample was 3 ng/ml. The cross-reactivity results indicate that the A-, B- and D-ring of a steroid are buried in the binding pocket of MAb 15A, while the C-ring faced outward, resulting in cross-reactivity with 11-alpha hydroxy progesterone. The A-, B- and C-ring of a steroid of MAb 2B7, in contrast, are buried deep in the pocket leaving the D-ring facing outward, resulting in some different degrees of cross-reactivity with C17 position substituted steroids.

Fluorescence Polarization Immunoassay↗
PubMed1997

Race, ethnicity, and access to health care, Rhode Island, 1990.

Differences in access to health care by race and ethnicity have been examined using data obtained from a statewide health interview survey conducted by Rhode Island Department of Health in 1990 (N = 6,536 individuals in 2,586 households), in which ethnic minorities were oversampled. Compared to White non-Hispanic (WNH) respondents, White Hispanics (WH) were more likely to lack a regular source of medical care at some time in the past twelve months (14.0% vs. 9.8%) and were much more likely to lack health insurance coverage (22.7% vs. 7.5%). Black respondents were more likely to lack regular source of care (10.4%) and health insurance coverage (17.4%). Asian respondents also had a high proportion without insurance (13.5%). Multivariate analysis has been employed to identify significant social, economic, and demographic determinants of inadequate access to care, including variables for race/ethnicity, age, sex, income, education, and employment status, and to quantify their independent contributions as predictors of level of access.

Black or African American↗
PubMed1997

A karyotype study on the Drosophila robusta species-group (Diptera: Drosophilidae).

The karyotypes of the Drosophila robusta species-group, especially its species-subgroup okadai, were studied by using brain cell-Giemsa staining method. Drosophila gani possessed a diploid number of 12 chromosomes, comprising 4 pairs of metacentric, 2 pairs of acrocentric chromosomes, and both D. okadai and D. neokadai did 2n = 12, with 3 pairs of metacentrics, 2 pairs of acrocentrics and 1 pair of microchromosomes. The okadai subgroup characteristically retained a middle-sized acrocentric X chromosome, which implies that this subgroup may occupy an ancestral position for the robusta group.

Animals↗
PubMed1997

[Salivary gland masses: dynamic MR imaging and pathologic correlation].

PURPOSE: To evaluate the efficiency of dynamic contrast-enhanced magnetic resonance imaging (MRI) for the diagnosis of salivary gland masses. MATERIALS AND METHODS: We retrospectively examined 19 salivary gland masses that were pathologically diagnosed by surgical operation or biopsy. We obtained T1- and T2-weighted images on MRI, performed dynamic studies on each mass and examined the correlation between enhancement patterns and pathological findings. RESULTS: Four enhancement patterns were recognized on contrast-enhanced MRI: type 1 showed marked, homogeneous enhancement; type 2 slight, homogeneous enhancement; type 3 marginal enhancement; and type 4 poor enhancement of the mass. Most pleomorphic adenomas had a type 1 enhancement pattern, but two had a type 2 pattern. Pathologically, each mass enhancement pattern had different tumor cell and matrix components. Warthin's tumor generally showed the type 4 pattern. Primary malignant tumors of the salivary gland all showed the type 3 pattern, and pathological specimens showed many tumor cells along the marginal portion of the tumor. One inflammatory cyst and one Warthin's tumor also showed the type 3 pattern. Except for metastatic renal cell carcinoma, the enhancement patterns of late phase images and dynamic study images were the same. CONCLUSIONS: Dynamic MRI added little diagnostic information about salivary gland masses, but the contrast-enhanced MR features correlated well with the pathological findings.

Adenolymphoma↗
PubMed1997

Metabolic disposition of the new fluoroquinolone antibacterial agent DW116 in rats.

The metabolic disposition of the new fluoroquinolone antibacterial agent DW116 has been studied in Sprague-Dawley rats. The compound was absorbed well and demonstrated excellent oral bioavailability. The plasma kinetic profiles were characterized by monoexponential elimination with an elimination half life of 3-4 hr. The apparent mean total clearance (CL(T)) and the volume of distribution (V(SS)) ranged from 221 +/- 55 to 274 +/- 27 ml/hr/kg and 1.0+/-0.1 to 1.5+/-0.2 l/kg, respectively, and were independent of dose between 4 and 20 mg/kg levels. The renal (CL(R)) clearance was 64.5 ml/hr/kg and the biliary (CL(B)) clearance was 33.8 ml/hr/kg. The combined value accounted for approximately one-half of the total clearance, indicating that the remaining one-half of the administered dose was eliminated via hepatic clearance. The major metabolite excreted in the bile was identified as the glucuromide ester of parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound, 19F-NMR and LC-MS methods. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were 28.6 +/- 2.7% and 36.4 +/- 1.8% of the administered dose and the corresponding biliary recoveries were 14.4 +/- 5.5% and 37.0 +/- 7.6%, respectively. The mass balance study after a single (100mg/kg) oral administration of 14C-DW116 indicated complete recovery of radioactivity over a 7-day period, accounting for approximately 60-70% in feces and 30-40% in urine. 14C-DW116 extensively distributed during a prolonged process into all tissues with a rather slower penetration into the brain, lung, and muscle. The compound also readily crossed the placenta and was transferred to the fetus.

Administration, Oral↗
PubMed1997

Chronic exogenous insulin and chronic carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats.

We have investigated hepatic de novo lipogenesis and the ratio of apoB-48/apoB-100 during chronic carbohydrate supplementation with or without administration of exogenous insulin in rats. Two groups received chronic (2 weeks) carbohydrate supplementation either as 10% glucose or 10% fructose (wt/v) in their drinking water. Two other groups received exogenous insulin chronically, in addition to the monosaccharides above. The insulin was given for 2 weeks as daily human ultralente insulin injections in increasing doses up to 6 units per day. A fifth group of rats (normal control) received only chow and water. The fractional synthetic rate (FSR), the fraction of very low density lipoprotein triglyceride (VLDL-TG) palmitate that was newly made during an 8-h infusion with sodium [1-13C]acetate, was evaluated. The glucose and fructose groups had a 4-fold (0.60%/h) and 7.5-fold (1.13%/h) increase in FSR from baseline, respectively, compared to chow-fed controls (0.15%/h). Chronic exogenous insulin administration resulted in a 11.5 (1.73%/h) and 11.0 (1.65%/h)-fold increase over baseline in the synthesis of newly made VLDL-TG palmitate in the glucose and fructose groups, respectively. The ratio of apoB-48/apoB-100, i.e. apoB-48 enrichment, in VLDL was positively correlated with insulin levels (r = 0.41, P < 0.01) and with FSR (r = 0.39, P < 0.01). The present study shows that carbohydrate supplementation significantly increases the FSR of newly made VLDL-TG palmitate and that this increase is further augmented by chronic hyperinsulinemia.

Acetates↗
PubMed1996

Excretion study of furazabol, an anabolic steroid, in human urine.

Furazabol and 16-hydroxyfurazabol represented the most abundant peaks in urinary metabolic profiles for two men obtained by gas chromatography-mass spectrometry (GC-MS) after oral administration of 5 mg furazabol. The excreted amounts of unchanged furazabol were determined and its response in GC-MS was compared with that of the 16-hydroxy metabolite. The maximum excretion rates of these compounds were reached 2-3 h after oral administration. The half-lives of unchanged furazabol for two human subjects, were 1.87 and 1.29 h respectively and the recovered amount in 48 h was 24% (33% for one, 15% for the other). Also the spectrum of an unidentified metabolite is reported.

Administration, Oral↗
PubMed1996

Identification of a pyrovalerone metabolite in the rat by gas chromatography-mass spectrometry and determination of pyrovalerone by gas chromatography-nitrogen-phosphorus detection.

Pyrovalerone and its hydroxylated metabolite have been identified by gas chromatography-mass spectrometry in rat urine and plasma. A sensitive gas chromatographic method for the quantitative analysis of pyrovalerone in rat urine and plasma is described. The method also permits the quantitative monitoring of the urinary excretion of the drug and its metabolite. Pyrovalerone and its hydroxylated metabolite are detected up to 18 h after a single oral administration to the rat at a dose of 20 mg/kg.

Animals↗
PubMed1996

Analysis of mesocarb analogues in urine and plasma of rats by high-performance liquid chromatography and thermospray liquid chromatography-mass spectrometry.

The pharmacokinetics and metabolism of synthetic 2-hydroxymesocarb and 4-methyl-2-hydroxymesocarb analyzed by HPLC-DAD and thermospray LC-MS were studied in rats. Multistep liquid-liquid extraction (LLE) was used with diethyl ether at pH 7.0. The major metabolites of 2-hydroxymesocarb in both urine and plasma of the rat were the p-hydroxylated derivative of the phenylcarbamoyl group of the parent drug. The metabolites of 4-methyl-2-hydroxymesocarb in urine of rats may be the oxidized forms at the phenylcarbamoyl group of the parent drug. Absorption (ka) and elimination (ke) rate constants in plasma of 2-hydroxy-mesocarb were 0.0300 and 0.00485 min-1, respectively; those of 4-methyl-2-hydroxymesocarb were 0.0546 and 0.00797 min-1, respectively. The half-lives (t1/2) of 2-hydroxymesocarb and 4-methyl-2-hydroxymesocarb in plasma were 144 and 86 min, respectively.

Animals↗
PubMed1996

Erythropoietin: physico- and biochemical analysis.

A hormone, erythropoietin, mainly produced in adult kidneys and fetal livers, acts on bone marrow erythroid progenitor cells to regulate the production of erythrocyte in mammals. As a result, the oxygen carrying capacity of blood increases and the increased oxygen supply raises the cardiac function and physiological working capacity. Erythropoietin is possibly misused by athletes in sports for the purpose of improving performance. Presently there is no discernible and specific method to identify erythropoietin administration for doping control. To address this practical problem, this paper presents a summary of the applications of analytical biotechnology, especially the structural characterization of erythropoietin.

Animals↗
PubMed1996

The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade.

Vascular endothelial growth factor (VEGF) is an angiogenic inducer that mediates its effects through two high affinity receptor tyrosine kinases, Flt-1 and KDR. Flt-1 is required for endothelial cell morphogenesis whereas KDR is involved primarily in mitogenesis. Flt-1 has an alternative ligand, placenta growth factor (PlGF). Both Flt-1 and KDR have seven immunoglobulin (Ig)-like domains in the extracellular domain. The significance and function of these domains for ligand binding and receptor activation are unknown. Here we show that deletion of the second domain of Flt-1 completely abolishes the binding of VEGF. Introduction of the second domain of KDR into an Flt-1 mutant lacking the homologous domain restored VEGF binding. However, the ligand specificity was characteristic of the KDR receptor. We then created chimeric receptors where the first three or just the second Ig-like domains of Flt-1 replaced the corresponding domains in Flt-4, a receptor that does not bind VEGF, and analyzed their ability to bind VEGF. Both swaps conferred upon Flt-4 the ability to bind VEGF with an affinity nearly identical to that of wild-type Flt-1. Furthermore, transfected cells expressing these chimeric Flt-4 receptors exhibited increased DNA synthesis in response to VEGF or PlGF. These results demonstrate that a single Ig-like domain is the major determinant for VEGF-PlGF interaction and that binding to this domain may initiate a signal transduction cascade.

3T3 Cells↗
PubMed1996

The carboxyl terminus of GLUT4 contains a serine-leucine-leucine sequence that functions as a potent internalization motif in Chinese hamster ovary cells.

To characterize the trafficking motifs contained in the carboxyl terminus of GLUT4, a chimera (GTCTR) was constructed in which the carboxyl-terminal 30 amino acids of GLUT4 were substituted for the amino-terminal cytoplasmic domain of the transferrin receptor (TR). The endocytic behavior of this chimera was characterized in Chinese hamster ovary cells. The GTCTR chimera had a more predominant intracellular distribution compared to the TR. Only 20% of the GTCTR chimera is on the surface at steady-state compared to 35% of the TR. The GTCTR chimera is internalized 50% more rapidly and recycled 20% more slowly than the TR. Acidification of the cytosol inhibited internalization of the GTCTR chimera, indicating that the chimera is internalized through clathrin-coated pits. Mutations of GTCTR were constructed in which a di-leucine sequence of the carboxyl domain of GLUT4 was mutated to a di-alanine sequence (GTCTR-AA) and serine residue 488, immediately preceding the di-leucine sequence, was mutated to either an alanine or aspartate residue. In each case, albeit to varying degrees, the substitutions shifted the distribution of the mutated GTCTR constructs toward the surface. The shift in the distribution of GTCTR-AA resulted from a 10-fold reduction in internalization, and the shift of serine 488 mutants resulted from a 3-fold reduction in the internalization rate compared to GTCTR. None of these mutations affected the recycling rate. These results demonstrate that the carboxyl terminus of GLUT4 contains a serine-leucine-leucine-based motif that, when expressed in non-insulin responsive cells, functions as a potent internalization motif which promotes more rapid internalization than does the native TR internalization motif.

Amino Acid Sequence↗
PubMed1996

Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc.

The cyclosporin A (CsA)/FK506-sensitive nuclear factor of activated T cells (NFAT) plays a key role in the inducible expression of cytokine genes in T cells. Although NFAT has been recently shown to be inducible in several non-T immune cells, the NFAT gene family members characterized to date have been isolated only from T cells. To further characterize NFAT function in human B cells and to demonstrate cytokine gene specificity of NFAT proteins, we report here the isolation and characterization of a cDNA clone from the Raji B cell line. The cDNA clone encodes a new isoform, NFATc.beta, of the NFAT gene family member NFATc (designated here NFATc.alpha). The amino acid sequence of NFATc.beta differs from that of NFATc. alpha in the first NH2-terminal 29 residues and contains an additional region of 142 residues at the COOH terminus. Northern analysis using a probe encompassing a common region of both isoforms showed two mRNA species of 2.7 and 4.5 kilobase pairs, while an NFATc.beta-specific probe detected only the 4.5-kilobase pair mRNA which was preferentially expressed in the spleen. Transient expression of NFATc.beta was capable of activating an interleukin-2 NFAT-driven reporter gene in stimulated Jurkat cells in a CsA-sensitive manner. However, NFATc.beta neither bound to the kappa3 element (an NFAT-binding site) in the tumor necrosis factor-alpha promoter nor activated the tumor necrosis factor-alpha promoter in cotransfection assays. These data suggest that different members or isoforms of NFAT gene family may regulate inducible expression of different cytokine genes.

Amino Acid Sequence↗
PubMed1996

Effects of human immunodeficiency virus type 1 infection on programmed cell death in the presence or absence of Bcl-2.

The effect of human immunodeficiency virus (HIV-1) infection on the programmed cell death of CD4+ lymphocytes was studied by using Jurkat cells stably expressing high levels of the Bcl-2 protein (Jurkat-Bcl2) or control cells (Jurkat-P). Both Jurkat-Bcl2 and Jurkat-P cells exhibited surface CD4 expression adequate to support HIV-1 infection. We observed no differences between HIV-1-infected Jurkat Bcl2 cells and control cells with respect to kinetics of virus replication, protein expression, and processing. Severe cytopathic effects, which were typical of acute HIV-1 infection and consisted of syncytium formation followed by single-cell lysis, were observed in both cell types. However, several lines of evidence, such as cell viability analysis by trypan blue dye exclusion, chromosomal DNA laddering, and morphologic analysis by acridine orange/ethidium bromide or Giemsa staining, indicated that HIV-1 did not induce a significant amount of programmed cell death in either cell type. These results suggest that apoptosis is at most a minor element in HIV-1-induced cytopathicity in Jurkat lymphocytes.

Apoptosis↗
PubMed1996

A non-enzymatic p21 protein inhibitor of stress-activated protein kinases.

The stress-activated protein kinases (SAPKs), which are identical to the c-Jun amino-terminal kinases (JNKs), are activated in response to a variety of cellular stresses, including DNA damage, heat shock or tumour-necrosis factor-alpha. SAPK, a subfamily of the mitogen-activated protein (MAP) kinases, is a major protein kinase that phosphorylates c-Jun and other transcription factors. SAPK phosphorylation of transcription factors is important in stress-activated signalling cascades. Here we report that the protein p21 WAF1/CIP1/Sd:1, a DNA-damage-inducible cell-cycle inhibitor, acts as an inhibitor of the SAPK group of mammalian MAP kinases. This highlights a new biochemical activity of p21, which may provide the first evidence for a non-enzymatic inhibitory protein for SAPK. We suggest that p21, by inhibiting SAPK, may participate in regulating signalling cascades that are activated by cellular stresses such as DNA damage.

Amino Acid Sequence↗
PubMed1996

Identification of vascular endothelial growth factor determinants for binding KDR and FLT-1 receptors. Generation of receptor-selective VEGF variants by site-directed mutagenesis.

Vascular endothelial growth factor (VEGF) expression in various cell types is induced by hypoxia and other stimuli. VEGF mediates endothelial cell proliferation, angiogenesis, vascular growth, and vascular permeability via the endothelial cell receptors, kinase insert domain-containing receptor (KDR)/fetal liver kinase 1 (Flk-1) and FLT-1. Alanine-scanning mutagenesis was used to identify a positively charged surface in VEGF that mediates binding to KDR/Flk-1. Arg82, Lys84 and His86, located in a hairpin loop, were found to be critical for binding KDR/Flk-1, while negatively charged residues, Asp63, Glu64, and Glu67, were associated with FLT-1 binding. A VEGF model based on PDGFb indicated these positively and negatively charged regions are distal in the monomer but are spatially close in the dimer. Mutations within the KDR site had minimal effect on FLT-1 binding, and mutants deficient in FLT-1 binding did not affect KDR binding. Endothelial cell mitogenesis was abolished in mutants lacking KDR affinity; however, FLT-1 deficient mutants induced normal proliferation. These results suggest dual sets of determinants in the VEGF dimer that cross-link cell surface receptors, triggering endothelial cell growth and angiogenesis. Furthermore, this mutational analysis implicates KDR, but not FLT-1, in VEGF induction of endothelial cell proliferation.

Amino Acid Sequence↗