Biomedical subjects

J E Kim

Publications and source records attributed to J E Kim.

At least 37 records · Page 2Linked to original sources

PubMed2001

The clinical significance of common bile-duct dilatation in patients without biliary symptoms or causative lesions on ultrasonography.

BACKGROUND AND STUDY AIMS: Although abdominal ultrasonography (US) is a good initial screening method for detection of biliary tract disease, we sometimes encounter patients who only have findings of dilatation of the common bile duct (CBD) on US, without specific biliary symptoms or jaundice. This study aimed to evaluate the causes and clinical significance of dilatation of the CBD in patients without biliary symptoms, jaundice, or causative lesions at US. PATIENTS AND METHODS: A total of 77 patients who had no biliary symptoms and whose internal CBD diameter was more than 7 mm, without definite causative lesions on US, were enrolled. Of these, 49 underwent endoscopic retrograde cholangiopancreatography (ERCP) and 28 underwent follow-up US or computed tomography (CT) instead of ERCP. We excluded patients whose bilirubin level had increased beyond the upper normal level or who had previous history of upper abdominal surgery including cholecystectomy. RESULTS: The ERCP findings were as follows: no lesion in 20 patients (40.8%), juxtapapillary duodenal diverticulum (JDD) in 11 (22.5%), benign stricture in ten (20.4%), distal CBD mass in two (4.1%), choledochal cyst in two (4.1%), anomalous union of the pancreaticobiliary duct (AUPBD) in two (4.1%), and choledochal cyst with AUPBD in two (4.1%). There were no differences in age or in alkaline phosphatase or gamma-glutamyl transpeptidase (GGT) levels between the patients who had causative lesions revealed at ERCP and those who did not. Among the 28 patients who did not undergo ERCP, 12 had returned to normal and eight had no change in CBD diameter on follow-up US. Among eight patients who underwent CT, there were four with normal findings, one with JDD, and three with suspected choledochal cysts. CONCLUSIONS: We detected a significant number of causative biliary tract lesions in asymptomatic adults with dilatation of the CBD on routine abdominal US; no laboratory or demographic parameters were useful for discrimination. Further diagnostic study will be helpful for the early diagnosis of biliary tract disease in such patients.

Adult↗

PubMed2001

Risk factors suggesting malignant transformation of gastric adenoma: univariate and multivariate analysis.

BACKGROUND AND STUDY AIMS: Since gastric adenomas are precancerous lesions, polypectomy is necessary. However, there have been no reports suggesting factors capable of predicting malignant transformation of gastric adenomas removed by endoscopic snare polypectomy (ESP) or endoscopic mucosal resection (EMR) in Korea, a country in which gastric cancer is a major problem. The aim of this paper was to elucidate the risk factors suggesting malignant transformation of gastric adenomas removed by ESP or EMR at our center. PATIENTS AND METHODS: Between November 1994 and June 1999, 118 gastric adenomas diagnosed on the basis of endoscopy and histological examinations of the forceps biopsy specimens obtained were treated by ESP or EMR at our department. Factors capable of predicting malignancy were searched for in the endoscopy reports, still photographs, and histopathological findings. RESULTS: Eight of the 118 adenomas ultimately proved to have malignant foci. In the univariate analysis, four of the variables studied--location, histological type, surface redness, and degree of dysplasia--had a statistically significant relationship with malignant transformation. In the multivariate analysis, only the degree of dysplasia had a statistically significant relationship with malignant transformation. CONCLUSIONS: These results suggest that a diagnosis of high-grade dysplasia in forceps biopsy material should be considered an absolute indication for ESP or EMR.

Adenoma↗

PubMed2001

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). METHODS: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.

Aged↗

PubMed2001

The analysis of resectability and survival in pancreatic cancer patients with vascular invasion.

One of the major limitations of curative resection in patients with pancreatic cancer is local tumor extension to the mesenteric vessels. Thus, the purposes of our study were to assess the clinical value of contrast-enhanced spiral computed tomography (CT) in predicting the resectability and survival of patients with pancreatic cancer with suspicious vascular invasion and to assess the influence of curative resection on the survival of these patients. We enrolled 40 patients with pancreatic cancer who were suspected of having an involvement of the adjacent large vessels and who subsequently underwent operation with curative intent in the study. Resectability and survival were correlated with CT findings such as segment length, degree of encasement, and type and number of vessels involved. The survival rate was compared between the curative and palliative resection groups, and survival rate was compared between the resected and unresected groups. Of the 40 patients with adenocarcinoma of the pancreas, 14 had curative resections and 26 had palliative resections. The probability of curative resection was higher in patients with segment lengths less than 2 cm, as compared with segment lengths more than 2 cm. However, there was no difference in survival between the two groups. There were no differences in resectability and survival according to the degree of encasement and type and number of vessels involved. There was no difference in survival between the curative and palliative resection groups. There was no difference in survival between the resected and unresected groups. A survival benefit was not achieved by curative resection in patients with pancreatic cancer with vascular invasion. Therefore, it would be better to avoid aggressive surgery in patients with pancreatic cancer with vascular invasion.

Humans↗

PubMed2001

Induction of cell death in human immunodeficiency virus-infected macrophages and resting memory CD4 T cells by TRAIL/Apo2l.

Because the persistence of human immunodeficiency virus (HIV) in cellular reservoirs presents an obstacle to viral eradication, we evaluated whether tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induces apoptosis in such reservoirs. Lymphocytes and monocyte-derived macrophages (MDM) from uninfected donors do not die following treatment with either leucine zipper human TRAIL (LZhuTRAIL) or agonistic anti-TRAIL receptor antibodies. By contrast, such treatment induces apoptosis of in vitro HIV-infected MDM as well as peripheral blood lymphocytes from HIV-infected patients, including CD4(+) CD45RO(+) HLA-DR(-) lymphocytes. In addition, LZhuTRAIL-treated cells produce less viral RNA and p24 antigen than untreated controls. Whereas untreated cultures produce large amounts of HIV RNA and p24 antigen, of seven treated CD4(+) CD45RO(+) HLA-DR(-) cell cultures, viral RNA production was undetectable in all, p24 antigen was undetectable in six, and proviral DNA was undetectable in four. These data demonstrate that TRAIL induces death of cells from HIV-infected patients, including cell types which harbor latent HIV reservoirs.

Antiretroviral Therapy, Highly Active↗

PubMed2001

Dimensions of child maltreatment and children's adjustment: contributions of developmental timing and subtype.

This investigation examined the dimensions of developmental timing, subtype, and severity of maltreatment and their relations with child adaptation. The 814 children who participated in a summer day camp, 492 of whom were maltreated and 322 of whom were nonmaltreated comparison children, were assessed by camp counselors on their internalizing and externalizing symptomatology, aggressive, withdrawn, and cooperative behavior, and on personality dimensions of ego resiliency and ego control, and were rated by peers on disruptive, aggressive, and cooperative behavior. The severity within each subtype of maltreatment and the developmental period in which each subtype occurred were examined through hierarchical regression analyses. Additionally, children with similar timing or subtype patterns were grouped to explore diversity in outcomes. Results highlighted the role of severity of emotional maltreatment in the infancy-toddlerhood period and physical abuse during the preschool period in predicting externalizing behavior and aggression. Severity of physical neglect, particularly when it occurred during the preschool period, was associated with internalizing symptomatology and withdrawn behavior. Additionally, maltreatment during the school-age period contributed significant variance after earlier maltreatment was controlled. Chronic maltreatment, especially with onset during infancy-toddlerhood or preschool periods, was linked with more maladaptive outcomes. The implications of measuring multiple dimensions for improving research in child maltreatment are discussed.

Age Factors↗

PubMed2000

Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation.

Translation initiation is one of the key events regulated in response to mitogenic stimulation and nutrient availability, tightly coupled to mammalian cell cycle progression and growth. FKBP12-rapamycin-associated protein (FRAP; also named mTOR or RAFT1), a member of the ataxia telangiectasia mutated (ATM)-related kinase family, governs a rapamycin-sensitive membrane-to-cytoplasm signaling cascade that modulates translation initiation via p70 S6 kinase (p70(s6k)) and eIF-4E binding protein 1 (4E-BP1). Our studies reported here reveal a surprising regulatory mechanism of this signaling, which involves cytoplasmic-nuclear shuttling of FRAP. By using leptomycin B (LMB), a specific inhibitor of nuclear export receptor Crm1, we show that FRAP is a cytoplasmic-nuclear shuttling protein. Inhibition of FRAP nuclear export by LMB coincides with diminished p70(s6k) activation and 4E-BP1 phosphorylation. Further investigation by altering FRAP's nuclear shuttling activity with exogenous nuclear import and export signals has yielded results that are consistent with a direct link between nuclear shuttling of FRAP and mitogenic stimulation of p70(s6k) activation and 4E-BP1 phosphorylation. Furthermore, by using a reporter system, we provide evidence suggesting that nuclear shuttling of FRAP regulates mitogen-stimulated rapamycin-sensitive translation initiation. These findings uncover a function for the nucleus in the direct regulation of the protein synthesis machinery via extracellular signals.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, betaig-h3.

betaig-h3 is a transforming growth factor-beta-inducible cell adhesion molecule that has four characteristic homologous repeated domains. We made recombinant betaig-h3 proteins, which were highly active in mediating human corneal epithelial (HCE) cell adhesion and spreading. The 2nd and the 4th repeated domains were sufficient to mediate HCE cell adhesion. A sequence analysis showed that aspartic acid (Asp) and isoleucine (Ile) of the 2nd and the 4th domains are highly conserved in many fasciclin 1 homologous (fas-1) domains. Substitution mutational study identified these two amino acids are essential for cell adhesion. Synthetic peptides containing Asp and Ile, NKDIL and EPDIM derived from the 2nd and the 4th domains, respectively, almost completely blocked cell adhesion mediated by not only wild type betaig-h3 but also each of the 2nd and the 4th domains. These peptides alone were fully active in mediating cell adhesion. In addition, we demonstrated the functional receptor for betaig-h3 is alpha(3)beta(1) integrin. These results, therefore, establish the essential motifs within the 2nd and the 4th domains of betaig-h3, which interact with alpha(3)beta(1) integrin to mediate HCE cell adhesion to betaig-h3 and suggest that other proteins containing Asp-Ile in their fas-1 domains could possibly function as cell adhesion molecules.

Amino Acid Sequence↗

PubMed2000

An elongation factor-associating domain is inserted into human cysteinyl-tRNA synthetase by alternative splicing.

The amino acid sequence of human cytoplasmic cysteinyl-tRNA synthetase (CRS) was examined by analyzing sequences of genomic and expressed sequence tag fragments. From theses analyses, a few interesting possibilities were suggested for the structure of human CRS. First, different isoforms of CRS may result from alternative splicing. Second, the largest one would comprise 831 amino acids. Third, a new exon was identified encoding an 83 amino acid domain that is homologous to parts of elongation factor-1 subunits as well as other proteins involved in protein synthesis. Northern blot analysis showed three different mRNAs for CRS (of approximately 3.0, 2.7 and 2.0 kb) from human testis while only the 2.7 kb mRNA was commonly detected in other tissues. Expression of the exon 2-containing transcript in testis was confirmed by RT-PCR and northern blotting. CRS containing the exon 2-encoded peptide retained catalytic activity comparable to that lacking this peptide. This peptide was responsible for the specific interaction of CRS with elongation factor-1gamma.

Acylation↗

PubMed2000

Catalytic peptide of human glutaminyl-tRNA synthetase is essential for its assembly to the aminoacyl-tRNA synthetase complex.

Human glutaminyl-tRNA synthetase (QRS) is one of several mammalian aminoacyl-tRNA synthetases (ARSs) that form a macromolecular protein complex. To understand the mechanism of QRS targeting to the multi-ARS complex, we analyzed both exogenous and endogenous QRSs by immunoprecipitation after overexpression of various Myc-tagged QRS mutants in human embryonic kidney 293 cells. Whereas a deletion mutant containing only the catalytic domain (QRS-C) was targeted to the multi-ARS complex, a mutant QRS containing only the N-terminal appended domain (QRS-N) was not. Deletion mapping showed that the ATP-binding Rossman fold was necessary for targeting of QRS to the multi-ARS complex. Furthermore, exogenous Myc-tagged QRS-C was co-immunoprecipitated with endogenous QRS. Since glutaminylation of tRNA was dramatically increased in cells transfected with the full-length QRS, but not with either QRS-C or QRS-N, both the QRS catalytic domain and the N-terminal appended domain were required for full aminoacylation activity. When QRS-C was overexpressed, arginyl-tRNA synthetase and p43 were released from the multi-ARS complex along with endogenous QRS, suggesting that the N-terminal appendix of QRS is required to keep arginyl-tRNA synthetase and p43 within the complex. Thus, the eukaryote-specific N-terminal appendix of QRS appears to stabilize the association of other components in the multi-ARS complex, whereas the C-terminal catalytic domain is necessary for QRS association with the multi-ARS complex.

Adenosine Triphosphate↗

PubMed2000

Inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-stimulated Cyp1a1 promoter activity by hypoxic agents.

Since hypoxia-inducible factor-1alpha (HIF-1alpha) and the arylhydrocarbon receptor (AhR) shared the AhR nuclear translocator (Arnt) for hypoxia- and AhR-mediated signaling, respectively, it was possible to establish the hypothesis that hypoxia could regulate cytochrome P450 1a1 (Cyp1a1) expression. In order to test this hypothesis, we undertook to examine the effect of hypoxia on Cyp1a1 transcription in Hepa-I cells. Mouse Cyp1a1 5'-flanking DNA, 1.6 kb was cloned into pGL3 expression vector in order to construct pmCyp1a1-Luc. Hepa-I cells were transfected with pmCyp1a1-Luc and treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence or absence of various hypoxic agents such as 1-100 microM cobalt chloride, 1-100 microM picolinic acid, and 1-100 microM desferrioxamine. Luciferase activity of the reporter gene was measured from pmCyp1a1-Luc-transfected Hepa-I cell lysate which contains 2 microgram total protein using luciferin as a substrate. Hypoxic agents such as cobalt chloride, picolinic acid, and desferrioxamine showed inhibition of luciferase activity that was induced by 1-nM TCDD treatment in a dose-and time-dependent manner. Concomitant treatment of 150 microM ferrous sulfate with 1-100 microM desferrioxamine or 1-100 microM picolinic acid recovered luciferase activity from that inhibited by hypoxic agents or induced by TCDD. These data demonstrated that iron-chelating and hypoxic agents inhibited dioxin-induced Cyp1a1 transcription in Hepa-I cells. Thus, we might suggest that hypoxia inhibits TCDD-induced Cyp1a1 expression due to the competition between HIF-1alpha and the AhR for the Arnt in Hepa-I cells.

Animals↗

PubMed2000

The effect of pore formers on the controlled release of cefadroxil from a polyurethane matrix.

The effect of various pore formers on the controlled release of an antibacterial agent from a polymeric device was examined in order to develop a novel biomaterial that prevents bacterial adhesion and growth on its surface. Cefadroxil was chosen as the model antibiotic and was incorporated into a polyurethane matrix by the solvent-casting method. Polyethylene glycol (PEG) 1450, D-mannitol, or bovine serum albumin (BSA) was used as a pore former. The amount of cefadroxil released from various formulations at 37 degrees C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activities of matrices against Escherichia coli and Bacillus subtilis was evaluated by measuring the diameters of the inhibition zone. Changing the weight fraction and particle size of the pore formers/drug mixtures could control the release of cefadroxil from the matrix. The release rate of cefadroxil increased as the loading dose of the pore former increased (15<20<25%). Cefadroxil released from these devices exhibited antibacterial activity for 5-6 days. These results imply that an antibiotic-loaded polymeric device that could prevent bacterial infection on its surface can be formulated using appropriate pore formers.

Bacteria↗

PubMed2000

Protective effect of topiramate against hippocampal neuronal damage after global ischemia in the gerbils.

The purpose of this study was to examine whether topiramate would reduce neuronal damage after transient global ischemia in the gerbils because topiramate blocks voltage sensitive sodium channels and non-N-methyl-D-aspartate receptors and enhances gamma-aminobutyric acid-mediated inhibitory transmission. Both common carotid arteries were occluded for 3 min with microaneurysmal clips. The gerbils were treated with topiramate (50, 100, or 200 mg/kg, i.p.) immediately after ischemia. Neuronal cell damage in the hippocampal CA1 region was evaluated quantitatively 7 days after ischemia. Topiramate at the dose of 50 mg/kg failed to reduce hippocampal neuronal damage. However, topiramate when administered at the dose of 100 or 200 mg/kg significantly reduced hippocampal neuronal damage in dose-dependent manner (P<0.001 and P<0.0005, respectively). These results suggest that topiramate has a neuroprotective effect against neuronal damage following global ischemia in the gerbils.

Animals↗

PubMed2000

Potent growth inhibition of leukemic cells by novel ribbon-type antisense oligonucleotides to c-myb1.

We studied the effects of antisense oligonucleotides (AS oligos) with a novel structure. The AS oligos were covalently closed to avoid exonuclease activities by enzymatic ligation of two identical molecules. The AS oligos of a ribbon type (RiAS oligos) consist of two loops containing multiple antisense sequences and a stem connecting the two loops. Three antisense sequences targeting different binding sites were placed in a loop that was designed to form a minimal secondary structure by itself. RiAS oligos were found to be stable because they largely preserved their structural integrity after 24 h incubation in the presence of either exonuclease III or serums. When a human promyelocytic cell line, HL-60, was treated with RiAS oligos to c-myb, c-myb expression was effectively ablated. Cell growth was inhibited by >90% determined by both the 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and [(3)H]thymidine incorporation. Further, when the leukemic cell line K562 was treated with c-myb RiAS oligos, colony formation on soft agarose was reduced by 92 +/- 2%. These results suggest that RiAS oligos may be employed for developing molecular antisense drugs as well as for the functional study of a gene.

Base Sequence↗

PubMed2000

A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis.

Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved bone lesion is often tense, shiny, erythematous, and scleodermatous. In order to look for genes differentially expressed between the normal and involved skin, we cultured skin fibroblasts from the skin lesions of several afflicted patients, and identified differentially expressed genes by reverse dot-blot hybridization. We found that the genes human TGF-beta-induced gene product (betaig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblasts, with betaig-h3 the most significantly affected. The expression of betaig-h3 was induced by TGF-beta in both affected and normal fibroblasts. In an effort to determine the mechanism of bone and skin abnormalities in melorheostosis, we made recombinant betaig-h3. Both immobilized and soluble recombinant betaig-h3 proteins with or without an RGD motif inhibited bone nodule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of melorheostosis, with betaig-h3 in particular playing an important role in osteogenesis.

Animals↗

PubMed2000

Expression and purification of an active, full-length hepatitis C viral NS4A.

The nonstructural protein 3 (NS3) of the hepatitis C virus (HCV) is a bifunctional protein with protease and helicase activities. Nonstructural protein 4A (NS4A) is preceded by NS3 and augments the proteolytic activity of NS3 through protein-protein interaction. The central domain of NS4A has been shown to be sufficient for the enhancement of the NS3 protease activity. However, investigations on the roles of the N-terminal and the C-terminal regions of NS4A have been hampered by the difficulty of purification of full-length NS4A, a polypeptide that contains highly hydrophobic amino acid residues. Here we report a procedure by which one can produce and purify an active, full-length NS4A using maltose-binding protein fusion method. The full-length NS4A fused to the maltose binding protein is soluble and maintains its NS3 protease-enhancing activity.

ATP-Binding Cassette Transporters↗

PubMed2000

Dehalogenation of xenobiotics as a consequence of binding to humic materials.

Chlorinated phenols and anilines were transformed by oxidoreductive catalysts with release of chloride ions in both the absence and the presence of humic substances (syringaldehyde, catechol, and humic acid). Dehalogenation of these xenobiotics resulted from oxidative coupling reactions occurring at the chlorinated sites of the substrates. The effect of humic substances on dehalogenation depended on the mechanism of oxidative coupling. In a free-radical reaction mediated by peroxidase, laccase, or birnessite (delta-MnO2), syringaldehyde enhanced the dehalogenation of most of the chlorinated phenols, but it did not enhance the dehalogenation of the chloroanilines. With catechol, which does not form free radicals, dehalogenation was reduced or remained the same for both the chlorophenols and the chloroanilines. However, in tyrosinase-mediated reactions controlled by nucleophilic addition, catechol enhanced the dehalogenation of most of the chlorophenols, whereas syringaldehyde had little effect. Humic acid in most cases enhanced the dehalogenation of the chlorophenols, but it had little effect on the dehalogenation of the chloroanilines. On a molar basis, changes in dehalogenation caused by humic substances were proportional to the respective changes in substrate transformation. Only syringaldehyde was capable of releasing disproportionately high amounts of chloride ions from chlorophenols, apparently as a result of multiple crosscouplings to one molecule of the substrate.

Benzaldehydes↗

PubMed2000

Nonstructural protein 5A of hepatitis C virus inhibits the function of karyopherin beta3.

It has been suggested that nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) plays a role in the incapacitation of interferon by inactivation of RNA-dependent protein kinase PKR. In order to further investigate the role of NS5A, we tried to identify cellular proteins interacting with NS5A by using the yeast two-hybrid system. The karyopherin beta3 gene was isolated from a human liver cell library as a protein interacting with NS5A. The protein-protein interaction between NS5A and karyopherin beta3 was confirmed by in vitro binding assay and an in vivo coimmunoprecipitation method. The effect of NS5A on the karyopherin beta3 activity was investigated using a yeast cell line containing mutations in both PSE1 and KAP123, genes that are homologous to the human karyopherin beta3 gene. Human karyopherin beta3 complemented the loss of the PSE1 and KAP123 functions, supporting growth of the double mutant cells. However, expression of NS5A hampered the growth of the double mutant cells supplemented with human karyopherin beta3. On the other hand, expression of NS5A by itself had no effect on the growth of the double mutant expressing wild-type yeast PSE1. This indicates that NS5A may inhibit karyopherin beta3 function via protein-protein interaction. The role of NS5A in HCV replication is discussed.

Animals↗