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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 541 records · Page 30Linked to original sources

Hepatitis C virus NS5A protein is phosphorylated by casein kinase II.

Hepatitis C virus (HCV) has a positive-strand RNA genome that encodes a polyprotein, which is post-translationally processed by cellular and viral proteinases into three structural and six non-structural (NS) proteins. The NS5A protein, expressed in mammalian cells, exists as two phosphorylated forms of 56 kDa and 58 kDa. In this study, we provide evidence for a stable association between NS5A and a protein kinase from rat-1 cells by affinity to immobilized glutathione-S-transferase (GST)-NS5A fusion protein. This protein kinase was associated through the N-terminus of NS5A and was not regulated by cell cycle. The GST-NS5A was also phosphorylated in vitro by the purified casein kinase II (CKII), a member of the CMCG kinase family. Since CKII and the NS5A-associated protein kinase have the same molecular size and property by In-gel kinase assay and an inhibitor treatment test, we conclude that HCV NS5A protein is phosphorylated by CKII.

Animals↗

Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.1 and GATA-2.

In adult vertebrates, fibroblast growth factor (FGF) synergizes with many hematopoietic cytokines to stimulate the proliferation of hematopoietic progenitors. In vertebrate development, the FGF signaling pathway is important in the formation of some derivatives of ventroposterior mesoderm. However, the function of FGF in the specification of the embryonic erythropoietic lineage has remained unclear. Here we address the role of FGF in the specification of the erythropoietic lineage in the Xenopus embryo. We report that ventral injection of embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses ventral blood island (VBI) formation, whereas expression of the dominant negative form of the FGF receptor in the lateral mesoderm, where physiologically no blood tissue is formed, results in a dramatic expansion of the VBI. Similar results were observed in isolated ventral marginal zones and animal caps. Bone morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus embryo. Therefore, we examined how the BMP-4 and FGF signaling pathways might interact in the decision of ventral mesoderm to form blood. We observed that eFGF inhibits BMP-4-induced erythropoiesis by differentially regulating expression of the BMP-4 downstream effectors GATA-2 and PV.1. GATA-2, which stimulates erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively regulate transcription of each other. Thus, BMP-4 induces two transcription factors which have opposing effects on blood development. The FGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage.

Animals↗

Hanbury brown and twiss-type experiment with electrons

Fermion anti-bunching was directly observed by measuring the cross-covariance of the current fluctuations of partitioned electrons. A quantum point contact was used to inject single-mode electrons into a mesoscopic electron beam splitter device. The beam splitter output currents showed negative cross-covariance, indicating that the electrons arrived individually at the beam splitter and were randomly partitioned into two output channels. As the relative time delay between the outputs was changed, the observed ringing in the cross-covariance was consistent with the bandwidths used to monitor the fluctuations. The result demonstrates a fermion complement to the Hanbury Brown and Twiss experiment for photons.

Journal Article↗

Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces cerevisiae.

The proper spatial and temporal coordination of mitosis and cytokinesis is essential for maintaining genomic integrity. We describe the identification and characterization of the Saccharomyces cerevisiae IBD1 gene, which encodes a novel protein that regulates the proper nuclear division and bud separation. IBD1 was identified by the limited homology to byr4, a dosage-dependent regulator of cytokinesis in Schizosaccharomyces pombe. IBD1 is not an essential gene, and the knock-out cells show no growth defects except for the reduced mating efficiency [1]. However, upon ectopic expression from an inducible promoter, IBD1 is lethal to the cell and leads to abnormal nuclear division and bud separation. In detail, approximately 90% of the IBD1 overexpressing cells arrest at large bud stages with dividing or divided nuclei. In some IBD1 overexpressing cells, spindle elongation and chromosome separation occur within the mother cell, leading to anucleated and binucleate daughter cells. The anucleated cell can not bud, but the binucleate cell proceeds through another cell cycle(s) to produce a cell with multiple nuclei and multiple buds. Observations of the F-actin and chitin rings in the IBD1 overexpressing cells reveal that these cells lose the polarity for bud site selection and growth or attain the hyper-polarity for growth. Consistent with the phenotypes, the IBD1 overexpressing cells contain a broad range of DNA content, from 2 to 4 N or more. A functional Ibd1p-GFP fusion protein localizes to a single dot at the nuclear DNA boundary in the divided nuclei or to double dots in dividing nuclei, suggesting its localization on the spindle pole body (SPB). The cross-species expressions of IBD1 in S. pombe and byr4 in S. cerevisiae cause defects in shape, implicating the presence of a conserved mechanism for the control of cytokinesis in eukaryotes. We propose that Ibd1p is an SPB associated protein that links proper nuclear division to cytokinesis and bud separation.

Cell Cycle Proteins↗

Future of bradyarrhythmia therapy systems: automaticity.

Since the first fixed-rate ventricular pacemaker was introduced in the late 1950s, pacing systems have evolved rapidly. Current developments focus on making devices more sophisticated and less complex--a challenging combination. Automaticity features such as beat-by-beat capture verification, sensitivity threshold adaptation, and algorithms to govern dynamically the maximum sensor rate have either recently been introduced or are likely to be introduced in the near future. Technologic advances are likely to allow meaningful improvements in current drain, battery performance, memory capacity, signal processing, telemetry, and programmer interface. Bradyarrhythmia therapy devices of the future promise to go beyond the pacemaker. Ultimately, pacing systems will become part of integrated cardiac rhythm management systems.

Bradycardia↗

The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region, with a 5-year survival level of approximately 65%. To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether this strategy, combined with ionizing radiation (XRT), was more effective than either treatment alone. METHODS AND MATERIALS: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming units (pfu)/cell of Ad5CMV-p53, respectively. These doses were isoeffective for beta-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered 24 h post-infection, and Western blot analyses were conducted for p53, p21WAF1/CIP1, bax, and bcl-2 2 days after XRT. Cell survival was assessed using a clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using DNA agarose gel electrophoresis, and cell cycle was analyzed using flow cytometry. RESULTS: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The two modalities appear to be interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts. XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21WAF1/CIP1 expression. No changes were observed for bax or bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that Ad5CMV-p53 infection did not perturb the cell cycle beyond that observed with XRT alone. CONCLUSION: p53 gene therapy and XRT appears to interact in a synergistic manner; underscoring the significant potential of this novel strategy in the treatment of NPC.

Adenoviridae↗

The inturned protein of Drosophila melanogaster is a cytoplasmic protein located at the cell periphery in wing cells.

The inturned (in) gene is a component of the frizzled (fz) signaling pathway that controls the polarity of hairs and bristles in the epidermis of Drosophila. It appears to act downstream of fz, which encodes a putative receptor for a tissue polarity signal. The in gene encodes a novel protein that had been suggested to contain two potential transmembrane domains. It has been suggested that the In protein interacts with the actin cytoskeleton to regulate the formation of the pupal wing prehairs that become adult hairs. The initiation of prehairs is normally restricted to the vicinity of the distal most vertex along the apical surface of the pupal wing cells. In an in mutant, prehairs initate at a variety of locations along the apical cell periphery. We have used immunofluorescence to study the subcellular localization of the In protein. When expressed in cultured cells, we found that In is a cytoplasmic protein. However, we found that it is localized in the vicinity of plasma membrane and the cortical actin cytoskeleton of Drosophila wing disc and pupal wing cells. Thus, in wing cells the In protein is localized to the region of the cell where it appears to function. This subcellular localization presumably requires the function of other proteins and may represent a regulatory mechanism. Our data suggest that fz does not play a major role in the subcellular localization of In. The In protein is notably insoluble in buffers containing high salt and nonionic detergents. This lack of solubility is significantly reduced in fz and mwh mutants, implying that it may be related to the mechanism of in function.

Animals↗

Enzymatic synthesis of a dihydrobenzofuran neolignan by oxidative coupling.

The oxidative dimerization of ferulic acid has been carried out using horse-radish peroxidase as catalyst to give a dihydrobenzofuran neolignan (1), the structure of which was elucidated as (2SR,3RS)-2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-n-buto xycarbonyl-5-(2E-carboxyethenyl)-7-methoxybenzofuran by spectroscopic analyses. This compound showed more potent cytotoxicity against several tumor cell lines than the starting material.

Acrylates↗

Biotransformation of theophylline in cirrhotic rats induced by biliary obstruction.

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the plasma concentration-time curve) and (t1/2)beta were increased 1.3 fold and 3.5 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophylline metabolism, were decreased to 67%, 53%, and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drug metabolizing enzymes in liver.

Animals↗

Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica.

The antioxidant activity of Eriobotrya japonica was determined by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl) radical and lipid peroxidation produced when mouse liver homogenate was exposed to the air at 37 degrees C, using 2-thiobarbituric acid (TBA). The methanol extract and its fractions of Eriobotrya japonica leaves showed strong antioxidant activity. The antioxidant activity of EtOAc and n-BuOH soluble fractions were stronger than the others, and were further purified by repeated silica gel, MCl gel CHP-20P, and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid, quercetin-3-sambubioside from n-BuOH fraction, and methyl chlorogenate, kaempferol- and quercetin-3-rhamnosides, together with the inactive ursolic acid and 2 alpha-hydroxyursolic acid from EtOAc fraction were isolated. Antioxidant flavonoids and chlorogenic acid also showed prominent inhibitory activity against free radical generation in dichlorofluorescein (DCF) method.

Animals↗

Age-related changes in thyroid hormone effects on glucose transporter isoforms of rat heart.

To determine the age-related changes in thyroid hormone (TH) effects on cardiac glucose transporter one (GLUT-1) and four (GLUT-4) isoforms, male Fischer 344 rats at 4, 12, and 25 months of age were studied at euthyroid, hyperthyroid and hypothyroid conditions. Hyperthyroidism was induced with daily intraperitoneal injections of triiodothyronine (15 microg/100 gm) for 10 days. Hypothyroidism was achieved with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis indicated that at euthyroid basal conditions GLUT-1 protein was not significantly altered with age while GLUT-4 protein was significantly reduced in 25 month old rats (82.0 +/- 28.8% of a 4 month old rat p <0.01). In 4 months old rats, GLUT-1 was increased in both hypothyroidism (432.5 +/- 208.7% of age-matched euthyroid control) and to a lesser extent in hyperthyroidism (242.0 +/- 93.3% of control) p<0.01. In 25 month old rats, hyperthyroidism was also associated with increased GLUT-1 mass (190.8 +/- 117.6% of age-matched euthyroid control) p<0.01. Hypothyroidism in this age group was not associated with significant change in GLUT-1 protein. The cardiac GLUT-4 protein was increased during both hypothyroidism and hyperthyroidism. The changes of GLUT-4 in aged rats were similar to those found in young rats. It is concluded that TH effect on GLUT-1 expression in the heart is altered with age while TH effects on GLUT-4 are age independent.

Aging↗

Optimal spatial frequencies for discrimination of motion direction in optic flow patterns.

Spatial frequency tuning functions were measured for direction discrimination of optic flow patterns. Three subjects discriminated the direction of a curved motion path using computer generated optic flow patterns composed of randomly positioned dots. Performance was measured with unfiltered patterns and with patterns that were spatially filtered across a range of spatial frequencies (center spatial frequencies of 0.4, 0.8, 1.6, 3.2, 6.4, and 9.6 c/deg). The same subjects discriminated the direction of uniform, translational motion on the fronto-parallel plane. The uniform motion patterns were also composed of randomly positioned dots, that were either unfiltered or filtered with the same spatial filters used for the optic flow patterns. The peak spatial frequency was the same for both the optic flow and uniform motion patterns. For both types of motion, a narrow band (1.5 octaves) of optimal spatial frequencies was sufficient to support the same level of performance as found with unfiltered, broadband patterns. Additional experiments demonstrated that the peak spatial frequency for the optic flow patterns varies with mean image speed in the same manner as has been reported for moving sinusoidal gratings. These findings confirm the hypothesis that the outputs of the local motion mechanisms thought to underlie the perception of uniform motion provide the inputs to, and constrain the operation of, the mechanism that processes self motion from optic flow patterns.

Computer Graphics↗

Serologic tumor markers, clinical biology, and therapy of prostatic carcinoma.

PSA has been a valuable tool in enhancing our understanding of the prevalence and virulence of prostate cancer. PSA also has contributed to the understanding of important phenomena related to the androgen regulation of the cancer; however, it has not been useful in detecting some forms of androgen-independent (neuroendocrine) progression and is of limited prognostic value in androgen-independent prostate cancer. PSA also has been valuable in the accelerated development of therapies for prostate cancer; however, it must be used cautiously for this purpose, because it may not reflect the most relevant clone. In addition, some agents may directly affect PSA release independent of their antitumor activity. Most importantly, before PSA is adopted as a surrogate end point in clinical trials in prostate cancer, it must be prospectively validated. Future studies must focus on the development of prospective serologic tumor markers that can predict virulence of disease and to reflect androgen-independent progression.

Androgen Antagonists↗

Physician fees and procedure intensity: the case of cesarean delivery.

While there is a large literature investigating the response of treatment intensity to Medicare reimbursement differentials, there is much less work on this question for the Medicaid program. The answers for Medicare may not apply in the Medicaid context, since a smaller share of a physician's patients will be Medicaid insured, so that income effects from fee changes may be dominated by substitution effects. We investigate the effect of Medicaid fee differentials on the use of cesarean delivery over the period 1988-1992. We find, in contrast to the backward-bending supply curve implied by the Medicare literature, that larger fee differentials between cesarean and normal childbirth for the Medicaid program leads to higher cesarean delivery rates. In particular, we find that the lower fee differentials between cesarean and normal childbirth under the Medicaid program than under private insurance can explain between one half and three-quarters of the difference between Medicaid and private cesarean delivery rates. Our results suggest that Medicaid reimbursement reductions can cause real reductions in the intensity with which Medicaid patients are treated.

Cesarean Section↗

Low prevalence of valvular heart disease in 226 phentermine-fenfluramine protocol subjects prospectively followed for up to 30 months.

OBJECTIVES: This investigation sought to determine the effect of phentermine-fenfluramine (phen-fen) on the prevalence of valvular heart disease in 226 obese subjects enrolled in a prospective, strict weight loss, research protocol. BACKGROUND: Early reports have suggested that the use of phen-fen for weight loss may be associated with increased valvular heart disease. Such reports were based on small numbers of patients, limited data on dose and duration of phen-fen therapy, and no correlation with matched controls. METHODS: All subjects underwent transthoracic echocardiography for significant valvular lesions within a mean of 97 days from the manufacturer's announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine. All echocardiograms were interpreted by two independent readers. RESULTS: The study population included 183 women and 43 men with a mean age of 46.9 +/- 8.9 years and mean starting body mass index of 39.8 +/- 7.7 kg/m2. Using the Food and Drug Administration criteria, significant aortic regurgitation was detected in 15 subjects (6.6%) and mitral regurgitation in 3 subjects (1.3%). Only one patient had significant regurgitation of both aortic and mitral valves. No valves had severe regurgitation. Significant valvular disease did not correlate with the dose or duration of phen-fen therapy. Furthermore, the prevalence of valvular regurgitation is comparable to the normal offspring in the Framingham Heart Study, who are similar in age, gender, and geographical location. CONCLUSIONS: Phen-fen therapy is associated with a low prevalence of significant valvular regurgitation. Valvular regurgitation in our subjects may reflect age-related degenerative changes.

Adult↗

Plain abdominal radiographs and abdominal CT scans for nontraumatic abdominal pain--added value?

We conducted a retrospective descriptive study to determine the value of plain abdominal radiographs in emergency department (ED) patients also receiving abdominal computed tomography scans (CT) for the evaluation of nontraumatic abdominal, back and flank pain (NTAP). Cases were identified through radiology log books. Medical records and radiology reports were reviewed to determine whether the CT confirmed the findings of the plain abdominal radiographs, and whether the clinical course confirmed the results of either. Test characteristics for the plain abdominal radiograph and for the CT, using the clinical course including subsequent invasive procedures as the gold standard, were calculated. Of 177 patients who received CTs, 97 (55%) also received plain abdominal radiographs. Among the 74 patients who were admitted to the hospital and had complete data, the sensitivity and specificity for the plain abdominal radiographs were .43 and .75 respectively, compared to .91 and .94 for the CT scan (P(sens.) < .05, P(spec.) < .05). In 4 patients (5%), both studies failed to identify pathology shown in a subsequent procedure. In ED patients with NTAP, the plain abdominal radiograph may have some value as a screening tool; however, in patients in whom a CT is likely to be ordered anyway, a plain abdominal radiograph is unhelpful and often misleading.

Abdominal Pain↗

Degeneration and transdifferentiation of human lens epithelial cells in nuclear and anterior polar cataracts.

PURPOSE: To study the possible mechanisms of cataractogenesis by evaluating the characteristics of cataractous lens epithelial cells (LECs) in different types of human cataract. SETTING: Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. METHODS: Lens epithelial cells attached to the anterior capsules in eyes with nuclear or anterior subcapsular were analyzed for morphological characteristics by electron microscopy and for cellular characteristics by immunohistochemistry. RESULTS: Human LECs beneath the anterior capsule were degenerated in nuclear cataracts and were transdifferentiated in anterior polar cataracts. In senile nuclear cataractous lenses, LECs beneath the anterior capsule showed degenerative changes in morphology. In nuclear cataracts, LECs were immunohistochemically positive for cytokeratin and vimentin, while those in anterior polar cataracts were positive for vimentin only. The LECs of anterior subcapsular cataracts were transdifferentiated into spindle-shaped fibroblast-like cells without cellular junctions and embedded within a fibrillar meshwork mass. The extracellular matrixes in the anterior capsule of anterior subcapsular cataracts were immunohistochemically positive for fibronectin, laminin, collagen type I, and collagen type IV. CONCLUSIONS: Lens epithelial cells in different types of cataracts have distinct cellular characteristics and may possess a bipotential nature with the ability to transdifferentiate into mesenchymal cells. This may be an underlying mechanism for the development of cataract and capsule opacification.

Adult↗