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Biomedical subjects

I Kim

Publications and source records attributed to I Kim.

At least 55 records · Page 3Linked to original sources
PubMed2000

Angiopoietin-1 induces endothelial cell sprouting through the activation of focal adhesion kinase and plasmin secretion.

Angiopoietin-1 (Ang1) is a strong inducer of endothelial cell sprouting, which is a first step in both angiogenesis and neovascularization. We examined the mechanisms underlying Ang1-induced cell sprouting using porcine pulmonary artery endothelial cells. Ang1 induced the nondirectional and directional migration of endothelial cells mediated through the Tie2 but not the Tie1 receptor. Ang1 induced tyrosine phosphorylation of p125(FAK), and this phosphorylation was dependent on phosphatidylinositol (PI) 3'-kinase activity. Ang1 induced the secretion of plasmin and matrix metalloproteinase-2 (MMP-2), which is inhibited by PI 3'-kinase inhibitors. Ang1 also induced the secretion of small amounts of proMMP-3 and proMMP-9 but not proMMP-1. Ang1 suppressed the secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), but not of TIMP-1. Addition of alpha(2)-antiplasmin, a combination of TIMP-1 and TIMP-2, or PI 3'-kinase inhibitors inhibited Ang1-induced sprouting activity. Therefore, Ang1-induced sprouting activity in endothelial cells may be accomplished by cytoskeletal changes and secretion of proteinases and may be largely mediated through intracellular PI 3'-kinase activation.

Angiopoietin-1↗
PubMed2000

Tumor necrosis factor-alpha upregulates angiopoietin-2 in human umbilical vein endothelial cells.

The angiopoietin-Tie2 system is an important regulator of vasculogenesis and vascular integrity. Angiopoietin-2 (Ang2) disrupts blood vessel formation in the developing embryo by antagonizing the effects of angiopoietin-1 (Ang1) on the Tie2 receptor. In this study, we examined the effect of a well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on Ang2 expression in human umbilical vein endothelial cells. Reverse transcriptase-polymerase chain reaction and Northern blot analyses indicated that TNF-alpha induced Ang2 mRNA expression in a time- and dose-dependent manner. Western blot analyses revealed that TNF-alpha treatment increased cellular Ang2 protein. TNF-alpha induced less Ang2 mRNA expression in the presence of nuclear factor-kappaB (NF-kappaB) inhibitor. These results suggest that TNF-alpha-induced inflammatory angiogenesis might be facilitated by the induction of Ang2.

Angiopoietin-2↗
PubMed2000

Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis.

Using degenerate PCR we isolated a cDNA encoding a novel 406- and 410-amino acid protein from human and mouse embryonic cDNAs and have designated it 'hepatic fibrinogen/angiopoietin-related protein' (HFARP). The N-terminal and C-terminal portions of HFARP contain the characteristic coiled-coil domains and fibrinogen-like domains that are conserved in angiopoietins. In human and mouse tissues, HFARP mRNA is specifically expressed in the liver. HFARP mRNA and protein are mainly present in the hepatocytes. HFARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence and one consensus glycosylation site. Recombinant HFARP expressed in COS-7 cells is secreted and glycosylated. HFARP protein is present not only in the hepatocytes, but also in the circulating blood. Recombinant HFARP acts as an apoptosis survival factor for vascular endothelial cells, but does not bind to Tie1 or Tie2 (endothelial-cell tyrosine kinase receptors). These results suggest that HFARP may exert a protective function on endothelial cells through an endocrine action.

Amino Acid Sequence↗
PubMed2000

The mouse Pdgfc gene: dynamic expression in embryonic tissues during organogenesis.

The signaling activity of Platelet-derived growth factors A and B (PDGF-A and PDGF-B) that is mediated through the two receptor kinases, PDGFR-alpha and PDGFR-beta has been shown to be critical for the development of the cardiovascular organs, the kidney, the lung and the central nervous system. During the cloning of genes for VEGF related proteins, we isolated a mouse cDNA that can encode for a protein of 345 amino acids. A comparison of the amino acid sequence reveals that this predicted gene product displays 95% identity to human PDGF-C. The mouse Pdgfc gene maps to a region of chromosome 17 that is syntenic to human chromosome 6p21.3 In E9. 5-E15.5 mouse embryo, Pdgfc is widely expressed in the surface ectoderm and later in the germinal layer of the skin, the olfactory and otic placode and their derivatives and the lining of the oral cavity. In the gut and visceral organs, such as the lung and the kidney, Pdgfc mRNA is first expressed in the endodermal epithelium and later in mesenchymal tissues associated with the endodermal structures. Similar to other PDGFs, Pdgfc is widely expressed in mesenchymal precursors and the myoblast of the smooth and skeletal muscles. Contrary to PDGF-A, Pdgfc is not expressed in the central nervous system, except in the cerebellum, and neurogenic derivatives of the neural crest cells. Pdgfc is also absent from the heart and the vascular endothelium

Amino Acid Sequence↗
PubMed2000

Interactions of a didomain fragment of the Drosophila sex-lethal protein with single-stranded uridine-rich oligoribonucleotides derived from the transformer and Sex-lethal messenger RNA precursors: NMR with residue-selective [5-2H]uridine substitutions.

Proteins that contain two or more copies of the RNA-binding domain [ribonucleoprotein (RNP) domain or RNA recognition motif (RRM)] are considered to be involved in the recognition of single-stranded RNA, but the mechanisms of this recognition are poorly understood at the molecular level. For an NMR analysis of a single-stranded RNA complexed with a multi-RBD protein, residue-selective stable-isotope labeling techniques are necessary, rather than common assignment methods based on the secondary structure of RNA. In the present study, we analyzed the interaction of a Drosophila Sex-lethal (Sx1) protein fragment, consisting of two RBDs (RBD1-RBD2), with two distinct target RNAs derived from the tra and Sxl mRNA precursors with guanosine and adenosine, respectively, in a position near the 5'-terminus of a uridine stretch. First, we prepared a [5-2H]uridine phosphoramidite, and synthesized a series of 2H-labeled RNAs, in which all of the uridine residues except one were replaced by [5-2H]uridine in the target sequence, GU8C. By observing the H5-H6 TOCSY cross peaks of the series of 2H-labeled RNAs complexed with the Sx1 RBDI-RBD2, all of the base H5-H6 proton resonances of the target RNA were unambiguously assigned. Then, the H5-H6 cross peaks of other target RNAs, GU2GU8, AU8, and UAU8, were assigned by comparison with those of GU8C. We found that the uridine residue prior to the G or A residue is essential for proper interaction with the protein, and that the interaction is tighter for A than for G. Moreover, the H1' resonance assignments were achieved from the H5-H6 assignments. The results revealed that all of the protein-bound nucleotide residues, except for only two, are in the unusual C2'-endo ribose conformation in the complex.

Animals↗
PubMed2000

Thin and thick filament regulation of contractility in experimental cerebral vasospasm.

OBJECTIVE: Cerebral vasospasm is a potentially fatal consequence of aneurysmal subarachnoid hemorrhage and influences the prognosis of the patient. The purpose of this study was to evaluate the status of thin (actin) and thick (myosin) filament regulation of smooth muscle contraction in the double-subarachnoid hemorrhage canine model of cerebral vasospasm and to determine the effects of a kinase inhibitor reported to be effective in vasospasm, HA1077, on thin and thick filament regulation. METHODS: Cerebral vasospasm was assessed by vertebral angiography. Myosin regulatory light chain phosphorylation was measured using glycerol-urea gels, whereas protein levels of the thin filament-associated protein calponin were measured by Western blot. RESULTS: The basilar arteries of dogs in which subarachnoid hemorrhage was induced narrowed to 36% +/- 2.0% of their size on the first day (n = 12). The phosphorylation of the regulatory light chain tended to increase, but the change did not reach statistical significance (35% +/- 5.9% [n = 12] versus 25% +/- 4.8% [n = 10] in control arteries). In contrast to this increase, significant degradation of calponin was observed in the samples from vasospastic dogs (85.4% +/- 5.45% [n = 5] versus 15.2% +/- 6.21% [n = 5]; P < 0.01). Prophylactic treatment with intravenous injections of HA1077 at 0.67 mg/kg b.i.d. significantly inhibited vasospasm (diameters, 65% +/- 10.2% of Day 1 diameters [n = 5]; P < 0.05), and calponin degradation (57.8% +/- 13.9% [n = 4]) was substantially reduced. CONCLUSION: These data suggest that degradation of the thin filament-associated protein calponin plays a role in cerebral vasospasm and that the antivasospastic action of HA1077 is, at least in part, due to prevention of calponin degradation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Phase synchronization with type-II intermittency in chaotic oscillators

We study the phase synchronization (PS) with type-II intermittency showing +/-2pi irregular phase jumping behavior before the PS transition occurs in a system of two coupled hyperchaotic Rossler oscillators. The behavior is understood as a stochastic hopping of an overdamped particle in a potential which has 2pi-periodic minima. We characterize it as type-II intermittency with external noise through the return map analysis. In epsilon(t) approximately exp(|epsilon(t)-epsilon|(2)), which agrees well with the scaling law obtained from the Fokker-Planck equation.

Journal Article↗
PubMed2000

Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization.

Using growth factors to induce vasculogenesis is a promising approach in the treatment of ischemic legs and myocardium. Because the vasculogenesis requires a cascade of growth factors, their receptors, and intracellular signals, such therapies may require the application of more than a single growth factor. We examined the effect of 2 endothelial cell-specific growth factors, angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), on primary cultured porcine coronary artery endothelial cells. VEGF, but not Ang1, increased DNA synthesis and cell number. Ang1 or VEGF induced migration and sprouting activity, increased plasmin and matrix metalloproteinase-2 secretion, and decreased tissue inhibitors of metalloproteinase type 2 secretion. A combination of the submaximal doses of Ang1 and VEGF enhanced these effects and was more potent than the maximal dose of either alone. In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone. Angiographic analyses revealed that larger blood vessels were formed after gene delivery of Ang1 or Ang1 plus VEGF than after VEGF gene delivery. These results suggest that combined treatment of Ang1 and VEGF could be used to produce therapeutic vascularization.

Angiopoietin-1↗
PubMed2000

Mucosal mast cell responses in the small intestine of rats infected with Echinostoma hortense.

Mucosal mast cell (MMC) responses and worm recovery rates in rats infected with Echinostoma hortense were investigated from day 3 to day 56 post-infection (p.i.). Experimental infected group showed apparently higher number of MMC in each part of the small intestine than that of the control group. The number of MMC in the duodenum increased gradually after the infection and reached a peak on day 35 p.i. Thereafter, the number of MMC continued to decrease at a slow pace. The kinetics of MMC responses in the upper and lower jejunum were similar to that of the duodenum, but the number of MMC in the jejunum was lower. The worm recovery rate decreased with respect to time of which it was markedly reduced on day 49 and 56 p.i. The duration in which a high number of MMC appeared was similar to that in which a low rate in worm recovery was recorded. These results indicate that intestinal mastocytosis may play an important role in the expulsion of E. hortense.

Animals↗
PubMed2000

Fas (APO-1/CD95) ligand and Fas expression in renal cell carcinomas: correlation with the prognostic factors.

BACKGROUND AND OBJECTIVE: Fas ligand (FasL, CD95L) is a type II transmembrane protein of the tumor necrosis factor family that induces cells to send an apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, conferring a survival advantage. It is important to understand FasL and Fas expression in tumors, because the growth of cancer might be controlled by Fas-mediated apoptosis. METHODS: The expressions of FasL and Fas were studied by immunohistochemical analyses in 51 cases of renal cell carcinomas and the adjacent normal renal tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and histologic types. RESULTS: In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cases, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunostaining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and low expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clinical stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P<.001). CONCLUSION: These data indicate that high expression of FasL and low expression of Fas protein in renal cell carcinomas may play a role in evading surveillance of the immune system. In addition, the FasL and Fas expressions appear to have a therapeutic implication for high-grade tumors rather than a prognostic one.

Adult↗
PubMed2000

Diffusion of high molecular weight compounds through sclera.

PURPOSE: To determine the in vitro permeability of the sclera to high molecular weight compounds and the relationship between scleral permeability and molecular size. METHODS: Fresh rabbit sclera was mounted in a two-chamber diffusion apparatus, and its permeability to sodium fluorescein, fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin, FITC-IgG, and FITC dextrans ranging in molecular weight from 4 to 150 kDa was determined by fluorescence spectrophotometry. Electron microscopy was used to assess the impact of the experimental design on scleral ultrastructural integrity. The effect of the diffusion apparatus on scleral hydration was examined. Rabbit scleral permeability was compared with previously reported data for human and bovine sclera. RESULTS: Scleral permeability decreased with increasing molecular weight and molecular radius, consistent with previous human and bovine data. Molecular radius was a better predictor of scleral permeability than molecular weight. The sclera was more permeable to globular proteins than to linear dextrans of similar molecular weight. The experimental apparatus did not alter scleral ultrastructure. Permeability of rabbit sclera was similar to human sclera but greater than bovine sclera. CONCLUSIONS: Large molecules, such as IgG, diffuse across sclera in a manner consistent with porous diffusion through a fiber matrix. Transscleral delivery of immunoglobulins and other large compounds to the choroid and retina may be feasible.

Animals↗
PubMed1999

Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting.

Using degenerate polymerase chain reaction, we isolated a cDNA encoding a novel 493-amino acid protein from human and mouse adult heart cDNAs and have designated it angiopoietin-related protein-2 (ARP2). The NH(2)-terminal and COOH-terminal portions of ARP2 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in angiopoietins. ARP2 has two consensus glycosylation sites and a highly hydrophobic region at the NH(2) terminus that is typical of a secretory signal sequence. Recombinant ARP2 expressed in COS cells is secreted and glycosylated. In human adult tissues, ARP2 mRNA is most abundant in heart, small intestine, spleen, and stomach. In rat embryos, ARP2 mRNA is most abundant in the blood vessels and skeletal muscles. Endothelial and vascular smooth muscle cells also contain ARP2 mRNA. Recombinant ARP2 protein induces sprouting in vascular endothelial cells but does not bind to the Tie1 or Tie2 receptor. These results suggest that ARP2 may exert a function on endothelial cells through autocrine or paracrine action.

Amino Acid Sequence↗
PubMed1999

Isozyme-specific inhibitors of protein kinase C translocation: effects on contractility of single permeabilized vascular muscle cells of the ferret.

1. The effects on contractility of three peptides reported to inhibit protein kinase C (PKC) translocation in an isozyme-specific manner were studied: a peptide from the C2 domain of conventional PKCs (C2-2), a peptide from the N-terminal variable domain of epsilonPKC (epsilonV1-2) and a peptide (ABP) from the actin-binding domain of epsilonPKC (epsilon(223-228)). 2. Isometric force was directly recorded from individual hyperpermeable ferret portal vein or aortic smooth muscle cells. 3. Phenylephrine contracted permeabilized portal vein cells at pCa 6.7 but not at pCa 7.0. However, phenylephrine did contract aortic cells at pCa 7.0. 4. C2-2 inhibited phenylephrine-induced contraction, but did not affect resting tension, in portal vein cells at pCa 6.7. In aortic cells at either pCa 6.7 or 7.0, C2-2 had no effect on either basal tension or phenylephrine-induced contraction. 5. ABP did not evoke any changes in phenylephrine-induced contraction or baseline tension in either portal vein or aortic cells. 6. epsilonV1-2 inhibited phenylephrine-induced contraction and decreased resting tension in aortic cells at pCa 7.0, but not in portal vein cells at pCa 6.7. 7. Western blots indicated that portal vein cells contained substantially more alphaPKC than aortic cells. Portal vein cells also contained small amounts of betaPKC, which was undetectable in aortic cells. In contrast, aortic cells contained more epsilonPKC than portal vein cells. Even though epsilonPKC was expressed in portal vein and alphaPKC in aorta, imaging studies indicated that they were not translocated in these cell types. 8. These results suggest that the Ca2+-dependent isozymes of PKC (alpha and/or beta) play a major role in contraction of the portal vein but not of the aorta. In contrast, the results are consistent with epsilonPKC, but not Ca2+-dependent PKC isozymes, regulating contractility of the aorta.

Amino Acid Sequence↗
PubMed1999

Two-dimensional photonic band-Gap defect mode laser

A laser cavity formed from a single defect in a two-dimensional photonic crystal is demonstrated. The optical microcavity consists of a half wavelength-thick waveguide for vertical confinement and a two-dimensional photonic crystal mirror for lateral localization. A defect in the photonic crystal is introduced to trap photons inside a volume of 2.5 cubic half-wavelengths, approximately 0.03 cubic micrometers. The laser is fabricated in the indium gallium arsenic phosphide material system, and optical gain is provided by strained quantum wells designed for a peak emission wavelength of 1.55 micrometers at room temperature. Pulsed lasing action has been observed at a wavelength of 1.5 micrometers from optically pumped devices with a substrate temperature of 143 kelvin.

Journal Article↗
PubMed1999

Auxiliary partial orthotopic living donor liver transplantation as an aid for small-for-size grafts in larger recipients.

BACKGROUND: In countries where living donors are the only source of liver grafts, restrictions on graft size are a serious obstacle for the expansion of indications for adult recipients. To overcome this problem, auxiliary partial orthotopic liver transplants (APOLT*) was performed on the basis of the concept that the residual native liver would support the graft function until the graft had grown enough to function by itself. METHODS: APOLT as an aid for small-for-size (SFS) grafts was reviewed retrospectively to evaluate its feasibility. Between April 1995 and March 1998, 20 recipients underwent APOLT, which was indicated because of a SFS graft in 15 of them. The indication was based on the estimated graft/recipient's body weight ratio (GRWR). If the ratio was <0.8%, APOLT was performed. The other 5 patients had a graft with a GRWR >0.8% and underwent APOLT on the basis of the residual native liver supporting the graft function temporarily, 4 for supplementation of the defective enzyme in metabolic liver diseases and one for leaving the potential of the regeneration of the native liver in fulminant hepatic failure. The recipients who underwent APOLT because of a SFS graft were categorized as the SFS group, and the others were the second group. RESULTS: In the SFS group, the age of the recipients ranged from 13 to 48 (median 23). The original indications of this group were fulminant hepatic failure in 2 recipients, acute deterioration of chronic liver diseases in 3, Wilson's disease in 2, biliary atresia in 4, primary biliary cirrhosis in 3, and primary sclerosing cholangitis (PSC) in one. The actual GRWR ranged from 0.45 to 0.72 (median 0.55). The graft was implanted after resection of the left lateral segment of the native liver. Except in the first two patients, the portal vein to the residual native liver was completely transected so that all of the portal blood drained into the graft liver. This procedure was successful in 9 patients. The cause of death in the other 6 was mainly infection. The mortality rate among the recipients with signs of advanced liver failure, such as massive ascites or hepatic coma, was higher, even though APOLT was used to support the SFS graft. In the second group, in the other five recipients who underwent APOLT for other indications, one recipient with fulminant hepatic failure died of sepsis caused by the dehiscence of bilio-enteric anastomosis. CONCLUSIONS: APOLT as an aid for a SFS graft is technically viable. This procedure can thus expand the indication of living donor liver transplants for adult recipients when the native liver retains some functional capability to support the grafted liver during the immediate postoperative period.

Adolescent↗
PubMed1999

Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein.

The Sex-lethal (Sxl) protein of Drosophila melanogaster regulates alternative splicing of the transformer (tra) messenger RNA precursor by binding to the tra polypyrimidine tract during the sex-determination process. The crystal structure has now been determined at 2.6 A resolution of the complex formed between two tandemly arranged RNA-binding domains of the Sxl protein and a 12-nucleotide, single-stranded RNA derived from the tra polypyrimidine tract. The two RNA-binding domains have their beta-sheet platforms facing each other to form a V-shaped cleft. The RNA is characteristically extended and bound in this cleft, where the UGUUUUUUU sequence is specifically recognized by the protein. This structure offers the first insight, to our knowledge, into how a protein binds specifically to a cognate RNA without any intramolecular base-pairing.

Amino Acid Sequence↗