Biomedical subjects
Publications and source records attributed to H Kim.
An expression plasmid carrying an alkaline lipase gene from Proteus vulgaris was constructed. The lipase content in Escherichia coli cells harboring the expression plasmid reached about 22% of total soluble protein. The purified enzyme displayed a partial interfacial activation toward p-nitrophenyl butyrate (PNPB).
OBJECTIVE: To assess the utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS. PATIENTS AND METHODS: This-section CT scans for suspicion of pulmonary tuberculosis were obtained from 226 patients. A total of 38 patients were excluded; the reasons were unavailability of final results (n = 18), patient unavailability for follow-up (n = 13), and coexistence of tuberculosis and aspergilloma (n = 7). The results from 188 patients were used for this study. After assessing the patterns of parenchymal lesion, involved segments, and presence of cavity, bronchiectasis, and bronchogenic spread of the lesion with CT, tentative diagnosis and disease activity were recorded. RESULTS: With CT, 133 of 146 patients (91%) with tuberculosis were correctly diagnosed as having pulmonary tuberculosis whereas 32 of 42 patients (76%) without tuberculosis were correctly excluded. CT diagnosis of lung cancer (n = 8), bacterial pneumonia (n = 2), pulmonary metastasis (n = 1), chronic hypersensitivity pneumonia (n = 1), and diffuse panbronchiolitis (n = 1) turned out to be tuberculosis. Conversely CT diagnoses of tuberculosis appeared pathologically as lung cancer (n = 5), bacterial pneumonia (n = 4), and pulmonary paragonimiasis (n = 1). Active (71/89, 80%) and inactive state (51/57, 89%) of disease respectively could be correctly differentiated by CT. CONCLUSION: CT can be helpful in the diagnosis of pulmonary tuberculosis in most cases. On the basis of CT findings, distinction of active from inactive disease can be made in most cases.
We report a case of primary fibroepithelial polyp of the right midureter. The patient was a 41-year-old-woman, complaining of right flank pain. An excretory urogram revealed right hydronephrosis and a filling defect of the the right midureter. The filling defect was produced by a large fibroepithelial polyp that was diagnosed and removed by ureteroscopy without open surgery. Large fibroepithelial ureteral polyps are relatively rare and ureteroscopy is the gold standard of diagnosis for ureteral filling defect.
It has recently been shown that nearly all cancers from hereditary nonpolyposis colorectal cancer syndrome (HNPCC), as well as a subset of sporadic colorectal cancers, have DNA replication errors (RER) at repeated sequences distributed throughout their genome. These RER-positive cancers had pathological characteristics of more frequent exophytic growth, large size and poor differentiation. However, the histogenesis and immunohistochemical characteristics of these RER-positive cancers are not known. The poorly differentiated colorectal carcinomas are heterogenous group of neoplasms that differ in their histologic appearance and prognosis. We therefore examined RER from 69 sporadic colorectal carcinomas of poor differentiation and detected in 23 cases (33%). The pathological features of RER-positive cancers differed from those without RER. The RER-positive cancers had marked preponderance of proximal location (16/23, 70%, vs. 20/46, 43%, p < 0.04), no glandular differentiation with intense peritumoral immune response (12/23, 52% vs. 6/46, 13%, p < 0.001). Immunohistochemically, most of the RER-positive cancers were reactive for cytokeratin (22/23, 96%) and CEA (17/23, 74%), and negative for NSE (2/23, 9%), chromogranin (3/23, 13%) and synaptophysin (0/23, 0%). In comparison to 46 RER-negative tumors, RER-positive cancer had less frequent CEA expression (17/23, 74% vs. 44/46, 96%, p = 0.01). We conclude that the RER-positive colorectal carcinomas have histologic characteristics of predominantly solid, poorly differentiated adenocarcinomas with intense peritumoral reaction and the tumors should be distinguished from neuroendocrine carcinomas and other more aggressive non-glandular tumors of the colon.
We report a case of sebaceous glands in the esophagus diagnosed by endoscopic biopsy. The patient was a 47-year-old Korean man presented with postprandial pain of several months duration. An endoscopic examination disclosed an early gastric carcinoma in the gastric antrum and a 0.4 x 0.4 cm sized irregular lobulated nodule in the middle esophagus. Microscopically, the lobule was proven to be sebaceous glands in the submucosa. Possible histogenesis of this lesion is discussed.
To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acinar response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.
Obstructive jaundice is rarely a presenting symptom of hepatocellular carcinoma (HCC). Most of the cases in the literature describing obstructive jaundice by HCC have a major hepatic component. Extrahepatic HCCs without primary hepatic parenchymal lesions are extremely rare. We encountered a case of extrahepatic HCC without primary hepatic parenchymal lesions in a 36-year-old man who presented with jaundice. We extensively sought primary hepatic parenchymal lesions preparatively and postoperatively with hepatic angiography and combined computed tomography (CT) studies, such as CT arterioportography and lipiodol-CT. The patient has been followed up for 1 year without definite evidence of recurrence. We herein report an unusual manifestation of HCC.
OBJECTIVES: The purpose of this study was to describe hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane. METHODS: Detailed medical and occupational histories were taken and thorough physical examinations with clinical laboratory tests were done for 33 workers (8 men and 25 women). Previous and present exposure was investigated in detail by industrial hygienists. RESULTS: Of the 25 female workers, 16 were shown to have secondary amenorrhea with high follicle-stimulating hormone levels, normal prolactin levels, and hot flashes. A total of eight workers with amenorrhea concurrently showed findings of pancytopenia. Among eight male workers, two showed azoospermia and another four showed some degree of oligospermia (normal > 20 million. ml-1) or reduced sperm motility (normal > 50%). The bone marrow effects and the testis or ovarian failure was shown to be the main health hazards in this workplace. Except for the cleaning solution containing 97.4% 2-bromopropane, no other known physical or chemical agents could be identified as responsible for the gonadal and bone marrow effects, including ionizing radiation, lead, ethylene glycol ether and its acetates, benzene, and dibromochloropropane. CONCLUSIONS: No previous studies have reported human toxicity for 2-bromopropane, but the results of this study lead to the tentative conclusion that the causal agent for the gonadal and bone marrow effects among the workers might be 2-bromopropane.
This study focuses on the influence of social support exchange through informal networks on Quality of Life (QOL) of the elderly. A total of 740 community residents aged 60 and over living in a rural area in Korea were interviewed from July 12 to July 15, 1993. Subjects were asked about the frequency of providing and receiving support to and from their spouse, children, and friends (24 items). The interview also included two QOL items (morale and life satisfaction) as well as instrumental ADL (five items), sex, age, education, and living arrangement. ANOVA showed that providing support to their children was strongly related to high morale score in female subjects. The elderly providing support to their friends were more likely to score high in morale. Analysis showed that the female elderly with greater support from their husbands had higher life satisfaction score. On the other hand, the male elderly group who provided support to their spouses but did not receive equal support in return from their spouses had low life satisfaction score. Providing support to their children was found to relate to high life satisfaction in both males and females, while receiving support from their children improved life satisfaction only in the females. Overall, the elderly group who exchanged support frequently with their spouses, children and friends showed the highest QOL score than any other group. These findings highlight the importance of supportive behavior by the elderly in order to improve their QOL.
Radical cystectomy followed by a urinary diversion or an orthotopic neobladder remains standard treatment for patients with muscle-invasive bladder cancer. The advances in surgical technique and reconstructive options allow many patients to enjoy a high quality of life after surgical extirpation. For those unable or unwilling to undergo a radical cystectomy, several treatment alternatives exist, using aggressive TUR and combinations of chemotherapy and/or radiation. Continued investigations into the biological behavior of this malignancy, as well as the identification of more effective chemotherapeutic agents, will allow more definitive treatment approaches with improved outcomes.
Rat cytochrome P450 2B1 antipeptide antibodies were produced by immunizing rabbits with a synthetic peptide antigen. The anti-CYP2B1 IgG obtained did not cross-react with CYP2B2, which has 97% identity in primary sequence of CYP2B1. This result demonstrates that a difference of 2 amino acid residues among 12 is sufficient to produce a form-specific antibody. The CYP2B1 antipeptide IgG inhibited pentoxyresorufin O-dealkylase activity of microsomes obtained from phenobarbital-treated rats in a dose-dependent manner, whereas it did not inhibit ethoxyresorufin O-deethylase activity of microsomes obtained from 3-methylcholanthrene-treated rats. These results suggest that the selected amino acid sequence, which coincides with one of the substrate binding sites of Pseudomonas putida CYP101A (P450cam) and one of the putative substrate binding sites of CYP2B2, is located on the surface of the CYP2B1 molecule, as opposed to inside the molecule or in the lipid bilayer of microsomes.
The structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the trypanosomatid parasite Leishmania mexicana has been determined by X-ray crystallography. The protein crystallizes in space group P2(1)2(1)2(1) with unit cell parameters a = 99.0 A, b = 126.5 A, and c = 138.9 A. There is one 156,000 Da protein tetramer per asymmetric unit. The model of the protein with bound NAD+s and phosphates has been refined against 86% complete data from 10.0 to 2.8 A to a crystallographic Rfactor of 0.198. Density modification by noncrystallographic symmetry averaging was used during model building. The final model of the L. mexicana GAPDH tetramer shows small deviations of less than 0.5 degrees from ideal 222 molecular symmetry. The structure of L. mexicana GAPDH is very similar to that of glycosomal GAPDH from the related trypanosomatid Trypanosoma brucei. A significant structural difference between L. mexicana GAPDH and most previously determined GAPDH structures occurs in a loop region located at the active site. This unusual loop conformation in L. mexicana GAPDH occludes the inorganic phosphate binding site which has been seen in previous GAPDH structures. A new inorganic phosphate position is observed in the L. mexicana GAPDH structure. Model building studies indicate that this new anion binding site is well situated for nucleophilic attack of the inorganic phosphate on the thioester intermediate in the GAPDH-catalyzed reaction. Since crystals of L. mexicana GAPDH can be grown reproducibly and diffract much better than those of T. brucei GAPDH, L. mexicana GAPDH will be used as a basis for structure-based drug design targeted against trypanosomatid GAPDHs.
Cardiac L-type Ca2+ channels are multisubunit complexes composed of alpha 1C, alpha 2 delta, and beta 2 subunits. We tested the roles of these subunits in forming a functional complex by characterizing the effects of subunit composition on dihydropyridine binding, its allosteric regulation, and the ability of dihydropyridines to inhibit channel activity. Transfection of COS.M6 cells with cardiac alpha 1C-a (alpha 1) led to the appearance of dihydropyridine ([3H]PN200-110) binding which was increased by coexpression of cardiac beta 2a (beta), alpha 2 delta a (alpha 2), and the skeletal muscle gamma. Maximum binding was achieved when cells expressed alpha 1, beta, and alpha 2. Cells transfected with alpha 1 and beta had a binding affinity that was 5-10-fold lower than that observed in cardiac membranes. Coexpression of alpha 2 normalized this affinity. (-)-D600 and diltiazem both partially inhibited PN200-100 binding to cardiac microsomes, but stimulated binding in cells transfected with alpha 1 and beta. Again, coexpression of alpha 2 normalized this allosteric regulation. Therefore coexpression of alpha 1 beta and alpha 2 completely reconstituted high affinity dihydropyridine binding and its allosteric regulation as observed in cardiac membranes. Skeletal muscle gamma was not required for this reconstitution. Expression in Xenopus oocytes demonstrated that coexpression of alpha 2 with alpha 1 beta increased the potency and maximum extent of block of Ca2+ channel currents by nisoldipine, a dihydropyridine Ca2+ channel antagonist. Our results demonstrate that alpha 2 subunits are essential components of the cardiac L-type Ca2+ channel and predict a minimum subunit composition of alpha 1C beta 2 alpha 2 delta for this channel.
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Two conserved Trp-Cys-Gly-His-Cys (WCGHC) sequences are assigned to act as catalytic sites for protein disulfide isomerase. Peptides containing the active site sequence, Ala-Pro-Trp-Cys-Gly-His-Cys-Lys(APWCGHCK), were synthesized both in a mono-molecular form and on multiple antigen peptide (MAP) resin or Wang resin by the 9-fluoroenylmethoxycarbonyl (Fmoc)-based solid-phase method. With scrambled RNase as a substrate, the (APWCGHCK)8-MAP was first shown to mimic the PDI activity, which was one thousandth of that of bovine PDI and comparable to that of thioredoxin. APWCGPCK and APWCGHCK, however, did not display a disulfide isomerase activity even at a concentration 8 times higher than that of (APWCGHCK)8-MAP. It was assumed that a sterically proper proximity of at least two active site peptides with CXXC motif was required for the expression of PDI activity.
Mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3), a gene specifically not expressed in neoplastic JB6 cells, have been isolated recently through the use of the mRNA differential display technique (Sun, Y., Hegamyer, G., and Colburn, N. H. (1994) Cancer Res. 54, 1139-1144). We report here the full-length mTIMP-3 cDNA sequence, the promoter sequence and partial characterization, expression and induction of TIMP-3, and the possible molecular basis for the lack of mTIMP-3 expression in neoplastic JB6 cells. There are three transcripts arising from alternative polyadenylation of mouse TIMP-3 gene, having sizes of 4.6, 2.8, and 2.3 kilobase pairs, respectively. All three TIMP-3 transcripts are expressed in preneoplastic but not neoplastic JB6 cells. Computer analysis of cloned TIMP-3 promoter revealed six AP-1 binding sites, two NF-KB sites, a c-Myc site, and two copies of a p53 binding motif separated by eight base pairs with two mismatches at the second motif, along with many other cis elements. TIMP-3 gene expression was inducible by AP-1 and NF-KB activators, 12-O-tetradecanoylphorbol-13-acetate, and tumor necrosis factor-alpha only in preneoplastic cells with an induction peak at 2 h post-treatment, suggesting classification of mTIMP-3 as a member of the immediate early gene family. Southern blot, mutational analysis, and transient transcriptional activation experiments revealed that the lack of expression of mTIMP-3 in neoplastic JB6 cells was due neither to gross deletion nor to promoter mutation of the gene, nor was there a lack of transcription factors required for transcriptional activation. Instead, the lack of TIMP-3 expression in neoplastic JB6 cells may reflect an abnormal methylation of the gene. Both hyper- and hypomethylation of the mTIMP-3 gene are associated with complete down-regulation of gene expression in neoplastic JB6 cell lines. Treatment of neoplastic cells with the methylase inhibitor 5-azacytidine caused reexpression of the mTIMP-3 gene in a tumor cell line that showed hypermethylation but not in another that showed hypomethylation of the gene, suggesting a complex role for methylation in the silencing of gene expression.
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N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), serine protease inhibitors, block many cytotoxic functions of immune cells including superoxide anion production, cytokine release, cell-mediated cytolysis, and nitric oxide (NO)-related macrophage functions. IFN-gamma/LPS-induced NO production from murine peritoneal macrophages was inhibited by TPCK and TLCK in a dose-dependent manner (EC50s: approximately 20 microM for TPCK and approximately 30 microM for TLCK). Viability exceeded 91% with 25 microM TPCK and with 80 microM TLCK. When TPCK treatment was delayed until 1 h of activation, the inhibitory effect was markedly reduced. After 2 h of the activation, TPCK was not effective anymore. Addition of either TNF-alpha or conditioned media from IFN-gamma/LPS-activated macrophage culture did not prevent the inhibitory effect of TPCK. Neither TPCK nor TLCK reduced enzymatic NO production from macrophage lysates. Lysates from TPCK-treated cells did not generate NO even after supplementing necessary cofactors for NO synthase. Immunoblotting analysis showed that simultaneous treatment of TPCK with IFN-gamma/LPS abolished the NO synthase expression, whereas delayed addition of TPCK was either partially effective or not effective at all. Furthermore, TPCK treatment reduced the concentration of mRNA for NO synthase without decreasing mRNA stability. Thus, the serine protease inhibitors directly blocked an early event in expression of NO synthase. Electrophoretic mobility shift assay indicated that TPCK blocked the activation of nuclear factor-kappa B, a transcription factor necessary for NO synthase induction. TPCK also blocked disappearance of I kappa B from cytosolic fraction, and nuclear translocation of NF-kappa B subunits p50 and p65. Delaying the addition of TPCK by 10 min partially prevented the inhibition of the NF-kappa B activation process and allowed partial resuming of NO production. Thus, TPCK inhibited NO synthase induction by blocking NF-kappa B activation.