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Biomedical subjects

Y J Cho

Publications and source records attributed to Y J Cho.

At least 55 records · Page 3Linked to original sources

Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis.

Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.

Autoantibodies↗

Distributional patterns of phospholipase C isozymes in rat kidney.

As the first step to investigate the physiological function of phospholipase C (PLC), we determined the distribution patterns of PLC isozymes in normal rat kidneys using Western blotting analysis and immunohistochemistry. Western blotting analysis was performed in four regions (cortex, outer stripe and inner stripe of the outer medulla, and the inner medulla). PLC-beta1 and beta3 were detected in the inner stripe of the outer medulla and the inner medulla. PLC-gamma1 was distributed homogeneously along the corticomedullary axis. PLC-gamma2 was observed in the medulla and PLC-delta1 showed a gradual increase from the cortex to the inner medulla. In contrast, no PLC-beta4 was detected in all regions. On immunohistochemistry, the immunoreactivities to PLC antibodies were observed as follows: PLC-beta1, from the thick ascending limb (TAL) to the inner medullary collecting tubule (IMCT); PLC-beta3, in the glomerulus (Glm), the ascending thin limb (ATL) and the collecting tubule; PLC-beta4, Glm, the proximal convoluted tubule (PCT), ATL, the distal convoluted tubule, the connecting tubule, and the collecting tubules; PLC-gamma1, PCT, TAL and IMCT; PLC-delta1, homogeneously from PCT to IMCT. PLC-beta3 immunoreactivities were detected in the nuclei of the TAL, ATL, outer medullary collecting tubule (OMCT) and IMCT. PLC-beta4 and gamma2 were observed in Glm, MTAL, ATL, OMCT and IMCT. These results suggest the intrarenal site-specific existence of PLC isozymes that may regulate kidney functions through the PLC-mediated signal transductions.

Animals↗

Attenuation of renomedullary phospholipase C isozyme, PLC-delta 1, in spontaneously hypertensive rats.

The distributional patterns of PLC isozymes within the kidney were investigated using spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats at 4 and 12 weeks of age. PLC-beta 1, PLC-beta 3 and PLC-delta 1 quantified by Western blot analysis, were present in the highest concentrations in the inner medulla of rats at both 4 and 12 weeks of age. On the other hand, PLC-beta 4, PLC-gamma 1 and PLC-gamma 2 were distributed almost equally among the regions for the rats of both ages. When compared with WKY rats at 12 weeks of age, the amounts of PLC-beta 1, PLC-beta 3, PLC-gamma 1, PLC-gamma 2, and PLC-delta 1 in the inner medulla of SHRs were significantly lower, and the amount of PLC-delta 1 in the inner stripe of the outer medulla was also significantly lower. Even at the prehypertensive stage at 4 weeks of age, the inner medullary concentration of PLC-delta 1 was significantly lower in SHRs than WKY rats. These results suggest that PLC-delta 1 would play an important role in the development of hypertension.

Animals↗

Silica-induced oxygen radical generation in alveolar macrophage.

Silica is a well-known occupational fibrogenic agent and its primary target cell is alveolar macrophage. Particle-stimulated macrophages are believed to release various mediator which can regulate the inflammation as well as pulmonary fibrosis. Even though oxygen radicals play the major role among these mediators, the mechanisms concerning the stimulation of alveolar macrophages are not clear yet. The present study was carried out to investigate the signal transduction pathway on oxygen radical generation in silica-stimulated alveolar macrophages. Silica induced oxygen radical generation in a dose-response pattern. Extracellular calcium depletion, calcium channel blockers, and calcium release blocker decreased the effect of silica on oxygen radical generation. Silica increased intracellular calcium through the influx of calcium through the calcium channel and the calcium release from the intracellular calcium store. To know the role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin) suppressed the silica-induced oxygen radical generation. Silica increased the PLC activity at the concentration of 5 mg/ml. The inhibitors of PTK and PLC suppressed the action of silica on the PLC activity. From these results, we suggest that silica induces oxygen radical generation through PTK, PLC, and PKC in alveolar macrophages.

Animals↗

Renal potassium wasting and hypocalciuria ameliorated with magnesium repletion in Gitelman's syndrome.

A woman aged 45 years was presented with hypokalemic metabolic alkalosis and hypomagnesemia associated with renal potassium and magnesium wasting. Her 24-hour urinary calcium excretion was strikingly low despite normocalcemia and normal creatinine clearance, which is one of characteristic findings of Gitelman's syndrome (GS). She was evaluated for the responses following Mg supplementation for 10 days, which showed marked increments in serum potassium and magnesium as well as improvements of the degree of renal potassium wasting and hypocalciuria. This amelioration of abnormal biochemical pictures in this patient after Mg supplementation proposes that the hypokalemia with renal potassium wasting and hypocalciuria may be caused by abnormal Mg metabolism.

Bartter Syndrome↗

Flat depressed early colon cancer--a case report.

A flat depressed early colon cancer (FDEC) is characterized by non-polypoid growth pattern, no association of adenomatous tissues and a tendency of even small lesions toward submucosal invasion and lymph node metastasis. It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancers arise in pre-existing adenoma (adenoma-carcinoma sequence). There have been few reports of small depressed cancers because of the difficulty in colonoscopic detection and the rapid development to ulcerating advanced cancers. We report a case of flat depressed early colon cancer confined to mucosa detected by indigo carmine contrast colonoscopy.

Colonic Neoplasms↗

Gallbladder motility change in late pregnancy and after delivery.

OBJECTIVES: The incidence of gallstone disease has increased recently in Korea and there seems to be an increased prevalence of gallstones when in association with pregnancy. Although the pathogenesis is incompletely defined, and altered motility of the gallbladder may contribute to the increased risk of gallstones during pregnancy. METHODS: We measured gallbladder volume using real-time ultrasonography to find out the mechanism for the changes of gallbladder motility during late pregnancy. Eighteen pregnant women took the gallbladder ultrasonography during their last trimester of pregnancy and after delivery; gallbladder volume and ejection fraction were calculated in each patient. RESULTS: Fasting gallbladder volumes increased significantly in the last trimester of pregnancy (25.28 +/- 14.26ml) compared with postpartum (17.44 +/- 5.82 ml) (p < 0.05). Gallbladder volumes measured after fatty meals showed more increment in pregnant women (10.13 +/- 7.19 ml) than in those after delivery (4.34 +/- 3.36 ml) (p < 0.005). A significantly reduced gallbladder ejection fraction was found in the pregnant group (60.56 +/- 18.80%) compared with those after delivery (77.48 +/- 13.37%) (p < 0.005). CONCLUSION: Gallbladder motility in late pregnancy shows significant impairment compared with that in postpartum. Thus, we suggest that gallbladder hypomotility may occur during late pregnancy, and this impairment of gallbladder motility may play an important role in gallstone formation.

Adult↗

Properties of analogues of an intermediate in the process of mechanism-based inactivation of carboxypeptidase A.

Carboxypeptidase A (CPA), and other zinc-dependent proteases, facilitate an alpha deprotonation of judiciously designed ketones and amides. This adventitious reaction has been used in the development of effective mechanism-based inactivators for this family of enzymes. N-Acryloyl-L-phenylalanine, an intermediate in the process of mechanism-based inactivation of CPA by N-(3-chloropropionyl)-L-phenylalanine, was shown to be an affinity inactivator, but also a very poor substrate for the enzyme. Similarly, O-(acryloyl)-L-3-phenyllactate was shown to be both an affinity inactivator and a poor substrate for CPA. However, consistent with the trend established with other ester and amide substrates for CPA, O-(acryloyl)-L-3-phenyllactate is a better substrate than N-acryloyl-L-phenylalanine. N-(Propiolyl)-L-phenylalanine served only as a poor substrate for the enzyme. To gain insight into enzyme inactivation and the unexpected poor turnover of these molecules, molecular modeling of these compounds with the crystal structure of CPA was carried out. These analyses suggested that the smaller size of these molecules permits a binding mode which is somewhat different in the active site than with typical larger substrates, such that the transition-state species for hydrolysis is not greatly stabilized by the enzyme. The slow turnover of these species, along with their specific binding interactions with the enzyme active site have implications for the inactivation chemistry of CPA and other zinc proteases by this family of mechanism-based inactivators.

Carboxypeptidases↗

Pathological changes according to the severity of asthma.

BACKGROUND: There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. OBJECTIVE: This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histological abnormalities in asthmatics according to the severity of asthma. METHODS: Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inflammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultrastructural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina. CONCLUSION: These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.

Adult↗

Translocation of lipocortin (annexin) 1 to the membrane of U937 cells induced by phorbol ester, but not by dexamethasone.

1. Induction of lipocortin 1 secretion by dexamethasone has been demonstrated, although the secretory mechanism is still unknown. We have studied the effects of 12-tetradecanoyl phorbol 13-acetate (TPA) and/or dexamethasone on the expression, translocation, and secretion of lipocortin 1 in U937 cells. 2. The expression of lipocortin 1 and its mRNA increased during TPA-induced differentiation of U937 cells to a maximum of 1.9 fold and 8.2 fold, respectively, after 48 h. Both the protein and the mRNA levels decreased after 48 h. 3. TPA caused the translocation of lipocortin 1 from the cytosol to the membrane of U937 cells in a time-dependent manner, as determined by Western blot analysis. The translocation was concurrent with the differentiation of the cells. After 48 h of TPA treatment, 82.6 +/- 6.5% of lipocortin 1 was present in the membrane fraction compared to 41.6 +/- 1.7% in untreated cells. 4. The amount of lipocortin 1 that was externally bound (associated) with the membrane increased to 3.2 fold as the cytosol to membrane translocation of lipocortin 1 increased. 5. Dexamethasone decreased the externally bound lipocortin 1, but had no effect on the cytosol to membrane translocation. 6. This offers a model system with which the function and the secretion mechanism of lipocortin 1 can be studied. Our data is consistent with the hypothesis that the secretory mechanism is through an unknown pathway, involving the translocation of lipocortin 1 from the cytosol to the internal membranes, and then, its secretion to the external membrane.

Animals↗

Epidermal surface antigen (MS17S1) is highly conserved between mouse and human.

A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, high-lighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5' and 3' untranslated sequences are conserved. Similar RNA folding patterns of the 5' untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene.

Amino Acid Sequence↗

[Interleukin-8 gene expression in the human colon epithelial cell line, HT-29, exposed to Entamoeba histolytica].

The protozoan parasite, Entamoeba histolytica, is one of major causative agents of intestinal disease all over the world. In acute experimental infection, the early host response to E. histolytica is characterized by an infiltration of neutrophils. However, the chemotactic signal for this response is not well known. Based on the finding that human epithelial cells produce the potent neutrophil chemoattractant and activator, interleukin-8 (IL-8), IL-8 gene expression was examined thoroughly in human colon epithelial cells exposed to E. histolytica trophozoites. Cellular RNAs were extracted from HT-29 or Caco-2 human colon epithelial cells exposed to E. histolytica trophozoites for 30 minutes, 1 and 3 hours. IL-8 mRNA transcripts were measured by reverse transcriptional polymerase chain reaction (RT-PCR) using synthetic standard RNA. The number of IL-8 mRNA molecules increased from 30 minutes to 3 hours of exposure period, reaching 3.1 x 10(7) molecules/micrograms of total RNA. Expression pattern of IL-8 mRNA transcripts was parallel to the amounts of IL-8 protein measured by enzyme-linked immunosorbent assay (ELISA). Lysates of E. histolytica also induced expression of mRNA for IL-8 in colon epithelial cells. These results suggest that acute inflammatory reaction by E. histolytica may be initially triggered by proinflammatory cytokines such as IL-8 secreted from epithelial cells of the colon.

Animals↗

Evidence suggesting a role for phospholipase C isozyme, PLC-delta 1 in corticomedullary osmotic gradients in rat kidneys.

We determined the distributional patterns of phospholipase C isozymes within the rat kidneys. PLC-beta1 was localized in the inner medulla at the highest degree followed by the inner stripe of the outer medulla, the cortex and the outer stripe of the outer medulla. PLC-gamma1 was distributed homogeneously along the corticomedullary axis. PLC-delta1 showed gradual increase from the cortex to the inner medulla. Tissue osmotic gradients were measured using 4 slices, resulting in gradual increase from the cortex to the inner medulla. The pattern of PLC-delta1 appeared very similar to the osmotic gradient in the kidney. The results suggest that the distinct patterns of the PLC isozymes may be associated with different signal transduction pathways along the corticomedullary axis and PLC-delta1 may play a role in the osmoregulation of the medullary region.

Animals↗

Effects of low density lipoprotein on type IV collagen production by cultured rat mesangial cells.

Hyperlipidemia, especially hypercholesterolemia, may contribute to glomerulosclerosis as it does to atherosclerosis. Low density lipoprotein (LDL) stimulates the production of extracellular matrix by mesangial cells in culture as well as the proliferation of mesangial cells. This study was carried out to examine the effects of LDL on the type IV collagen (CIV) production by cultured rat mesangial cells (CRMC). Subconfluent CRMC monolayers which were grown in RPMI with 20% lipid-free fetal calf serum for 48 h were challenged with LDL (0, 50, 100, 150 and 200 micrograms/ml) for another 48 h. LDL was prepared from normal human plasma. Mesangial cell proliferation was examined by [3H]-thymidine uptake. Production of CIV was evaluated as the expression of CIV on the cell surface by flow-cytometric analysis. The collagen synthesis was measured by the [3H]-proline uptake. Total RNA was extracted from CRMC at 6 and 24 h of incubation with 150 micrograms/ml LDL, and Northern blotting and hybridization was performed with cDNAs for alpha 1-CIV, for 72-kD collagenase and for tissue inhibitor of metalloproteinase (TIMP)-2. The amount of total mRNA was corrected with beta-actin mRNA. Mesangial cell proliferation increased in all concentrations studied and had a peak value of 221% with 150 micrograms/ml of LDL. Expression of CIV increased by 30-60% in 100-200 micrograms/ml of LDL. Collagen synthesis also increased by 50-70% in 150-200 micrograms/ml of LDL. The mRNA ratio (procollagen alpha 1(IV)/beta-actin) increased to 133% at 24 h. The mRNA ratio (TIMP-2/beta-actin) increased to 137% at 24 h. mRNA ratios at 6 h showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute lung disease after exposure to fly ash.

A 48-year-old man with no history of pulmonary disease developed acute lung disease after the intensive exposure of fly ash. He subsequently had progressive worsening of shortness of breath and hypoxemia to the point of requiring mechanical ventilation. Fly ash is a compound consisting of silicon dioxide and various other substances and is used in industrial settings to generate electricity. Exposure to fly ash may cause irritation to the mucous membrane of the respiratory tract and even pulmonary fibrosis in humans. To our knowledge, this is the first case report described in the medical literature of acute lung disease developing after fly ash exposure.

Accidents, Occupational↗

Intracellular induction pathways for CD23 antigen and surface immunoglobulins in human tonsillar B cells: the roles of protein kinase C and tyrosine kinase-mediated signals.

The expression of CD23 on human tonsillar B cells is increased following treatment with interleukin 4 (IL-4) or 12-O-tetradecanoylphorbol 13-acetate (TPA), while that of surface immunoglobulins (sIgs) is increased by IL-4 but decreased by TPA. This suggests that the signaling by these effectors may result from distinct second messenger-generating systems. In this study, we attempted to elucidate the signal transduction pathways responsible for the expression of CD23 and sIgs by using different protein kinase C (PKC) and tyrosine kinase (TK) inhibitors. Our results showed that B cells expressed varying amounts of sIgs depending on different activators and inhibitors. Sphingosine, a PKC inhibitor, almost completely reversed the TPA-induced decrease in sIgM and sIgD expression. Other PKC inhibitors, e.g., H7 and staurosporine, had similar but less profound effects. In comparison, the up-regulation of CD23 by IL-4 and TPA was only partially blocked by these PKC inhibitors. TK inhibitors, such as herbimycin A and genistein, decreased both the IL-4- and TPA-induced CD23 expression by 50-80%, but had modest effects on sIgs expression. These findings indicate that CD23 and sIgs expression is regulated by independent pathways; PKC is important for the regulation of sIgs expression while the signals through TK pathways might play the major role in CD23 expression.

B-Lymphocytes↗