Biomedical subjects

K Y Kim

Publications and source records attributed to K Y Kim.

At least 19 recordsLinked to original sources

PubMed1992

Inhibition of protein phosphatases blocks myogenesis by first altering MyoD binding activity.

To examine the role of protein phosphatases in skeletal muscle differentiation, C2C12 myoblasts were treated with okadaic acid, a potent in vitro inhibitor of protein phosphatases 1 and 2A which regulate various cellular events in intact cells. We now show that okadaic acid treatment of the mouse myoblast C2C12 cell line reversibly altered the morphology of the cells and blocked differentiation. At a molecular level, it extinguished expression of the myogenic determination genes, MyoD1 and myogenin, but induced the expression of an inhibitor of differentiation, Id. Analysis of the MyoD1 promoter showed that inhibition of MyoD1 expression by okadaic acid occurs at the transcriptional level. These changes occur 10-20 h after okadaic acid treatment. However, within 1 h of treatment the ability of muscle extracts to support a specific MyoD-dependent gel mobility shift using a MyoD DNA binding site is lost. These data suggest that protein phosphatases play an important role during myogenic differentiation.

Animals↗

PubMed1992

Post-transcriptional regulation of the human transforming growth factor-beta 1 gene.

Since many lines of evidence suggest that expression of the transforming growth factor-beta 1 (TGF-beta 1) gene may be regulated post-transcriptionally, we examined the effect of the 5'-untranslated region (UTR) of this gene on TGF-beta 1 expression. For this purpose, fragments of the 840-nucleotide highly GC-rich TGF-beta 1 5'-UTR were inserted into the 5'-UTR of the structural gene for human growth hormone driven by the simian virus 40 early promoter. A portion of the 5'-UTR of TGF-beta 1 mRNA spanning the sequences from +11 to +147 was shown to inhibit growth hormone expression by as much as 22-fold. This effect was cell-specific; growth hormone production was inhibited in PC-3 human prostate adenocarcinoma and A-549 human lung adenocarcinoma cells, while no effect was seen in rat pheochromocytoma PC12 cells, which show efficient translation of endogenous TGF-beta 1 mRNA. Computer analysis showed that this region of the 5'-UTR contained a stable secondary stem-loop structure spanning sequences +49 to +76. This stem-loop region alone is sufficient to inhibit expression of the growth hormone gene, suggesting that it plays an important role in post-transcriptional regulation of TGF-beta 1 gene expression.

Animals↗

PubMed1992

Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3.

The standard therapy for advanced prostate cancer is androgen ablation. Despite transitory responses, hormonally treated patients ultimately relapse with androgen-independent disease that is resistant to further hormonal manipulation and cytotoxic chemotherapy. To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines. We report here that elevation of intracellular cAMP markedly inhibits the growth of the hormone-refractory cell line PC-3. To examine the mechanism of cAMP action in PC-3 cells, we tested the effect of the cAMP analog dibutyryl cAMP (Bt2-cAMP) on the regulation of the potent negative growth factor transforming growth factor beta (TGF-beta). Bt2-cAMP selectively induced the secretion of TGF-beta 2 and not TGF-beta 1 by PC-3 cells. This TGF-beta 2 was shown to be bioactive by using the CCL-64 mink lung cell assay. TGF-beta 1 was not activated despite being present at 3-fold higher concentrations than TGF-beta 2. Northern analysis showed that Bt2-cAMP induced an increase in the five characteristic TGF-beta 2 transcripts and had no effect on the level of TGF-beta 1 or TGF-beta 3 transcripts. TGF-beta 2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces the expression of active TGF-beta 2 by PC-3 prostate carcinoma cells, suggesting a new approach to the treatment of prostate cancer and a new molecular mechanism of cAMP action.

1-Methyl-3-isobutylxanthine↗

PubMed1992

Solid-phase immunoassay using a flow cytometer: quantitative and qualitative determination of protein antigens and a hapten.

A fluoroimmunoassay employing a flow cytometer as the fluorescence-detecting device is described. Three kinds of antigens, murine immunoglobulin (Ig), human chorionic gonadotropin (hCG) and progesterone were chosen as examples of the assay using fluorescein-labeled antibodies. Cyanogen bromide-activated agarose beads were used as solid-phase supporters. The flow cytometric immunoassay was applied to both qualitative and quantitative analyses; determination of murine Ig isotypes, quantitative determination of Ig, hCG and a hapten, progesterone. This assay produced very reproducible and less-fluctuating data since thousands of particles in the assay were collected and processed to produce a single value for fluorescence intensities. Furthermore, the working range of the assay in terms of antigen concentration was much broader than that of enzyme immunoassay. Therefore, we believe that microparticles like agarose beads could be useful solid-phase supporters in immunoassay, and the flow cytometer could provide a reliable alternative to the fluorescence-detecting device in immunoassay.

Animals↗

PubMed1992

The first report of diffuse panbronchiolitis in Korea: five case reports.

Diffuse panbronchiolitis (DPB), which is prevalent in Japan, is known to be rare outside Japan. Although a case of diffuse panbronchiolitis in a second generation Korean was reported in Japan in 1986, no case has been reported in Korea. Recently we found 5 cases of diffuse panbronchiolitis in Korea, two histologically proven and three clinically and radiologically suspected. All 5 cases had the typical respiratory symptoms and signs and a history of chronic sinusitis. In three clinically and radiologically suspected cases, high resolution computed tomography showed the typical findings of DPB and other diseases such as pulmonary emphysema, bronchial asthma, chronic bronchitis and bronchiectasis could be ruled out. More cases of DPB are expected to be found in Korea in the near future.

Adult↗

PubMed1992

Glucose-6-phosphate dehydrogenase deficiency--report of 4 cases.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary enzyme disorder and more than 200 million people have a deficiency in this enzyme. It is a globally important cause of neonatal jaundice and causes life-threatening hemolytic crisis in childhood. At later ages, certain drugs such as antimalarials, and fava beans cause hemolysis among G6PD deficiency patients. The frequency and severity is influenced by genetic and cultural factors. It is common in Mediterranean, African, and some East Asian populations but rare in Korea. Four cases of G6PD deficiency which were first noticed in Korea are investigated with their clinical features.

Child↗

PubMed1992

Arterial oxygen desaturation during esophagogastroduodenoscopy.

This prospective study evaluated the incidence and severity of arterial oxygen desaturation during esophagogastroduodenoscopy (EGD) and assessed clinical factors in relation to arterial oxygen desaturation. Following pulmonary function testing, 192 patients underwent elective EGD with continuous recording of arterial oxygen saturation (SaO2). 62 patients (32.3%) showed arterial oxygen desaturation (SaO2 decrease greater than 4% from baseline SaO2); severe arterial oxygen desaturation (SaO2 less than or equal to 85%) reflecting hypoxemia (arterial oxygen tension less than or equal to 50 mmHg) was found in 17 patients (8.9%). These changes were most frequent at the esophageal stage of EGD but most marked at the gastroduodenal stage of EGD. The incidence of arterial oxygen desaturation was not related to age, sex, preendoscopic pulmonary function tests, smoking, or duration of endoscopy. These data support that continuous monitoring of SaO2 should be standard procedure during endoscopy because there was no identifiable preendoscopic risk factor for arterial oxygen desaturation during EGD. But there was no persistent drop in SaO2 longer than 2 minute. We suppose that oxygen supplement may not be required during EGD even in patients with modestly impaired pulmonary function tests.

Adult↗

PubMed1992

Small airway disease in rheumatoid arthritis.

Variety of pulmonary lesions are thought to be associated with rheumatoid arthritis (RA). These lesions traditionally have included pleurisy with or without effusion, Caplan's syndrome, pulmonary rheumatoid nodules, diffuse interstitial fibrosis, and pulmonary arteritis and hypertension. But little attention has been paid to the airways in RA. Recently, several reports have suggested an association between airflow limitation and RA, but its incidence is not known. Also whether there exists a parameter of disease activity of RA, suggesting the presence of small airway disease (SAD) is not clear. To answer these questions, the serologic parameters which reflect the disease activity of RA and pulmonary function tests which reflect small airway dysfunction were performed on 36 lifetime nonsmokers with RA who had normal chest x-ray findings. The prevalence of SAD and the relationships between the disease activity parameters of RA and pulmonary function were observed. The results were as follows. The percentages of patients with abnormal values for diffusing capacity, frequency dependence of compliance (C1.0/C0.0), forced expiratory flow 25-75%, Vmax50% and Vmax 75% were 45.5%, 62.5%, 40%, 22.8% and 11.4%, respectively. There was statistically significant negative correlation between C1.0/C0.0 and ESR. But consistent correlation between other pulmonary function tests and clinical and serologic parameters of RA, and differences in pulmonary function between patients who were serologically positive and negative for CRP and FANA, were not found. In conclusion, SAD, without the influence of smoking, is frequently associated with RA, but the presence of SAD cannot be predicted from any clinical and serologic parameters of RA currently in use.

Adult↗

PubMed1992

MRI classification of lumbar herniated intervertebral disc.

A consecutive series of 28 patients with lumbar herniated intervertebral disc (HIVD) who exhibited positive magnetic resonance imaging (MRI) findings was analyzed and compared with operative findings to define the type of disc herniation. This prospective study showed that the overall accuracy of MRI in predicting the types of HIVD was 80.6%. Proton density image was the most helpful in differentiating protruded discs from extruded ones. Disruption of "posterior longitudinal ligament line," defined on T2-weighted sagittal image, was reliable in differentiating a transligamentous disc from subligamentous one. Sequestered disc could be more accurately diagnosed with Gadolinium-DTPA enhancement, which showed anterior rim enhancement of the sequestered portion on T1-weighted axial image.

Adolescent↗

PubMed1991

Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease?

We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.

Cognition↗

PubMed1991

Differential regulation of the expression of transforming growth factor-beta s 1 and 2 by retinoic acid, epidermal growth factor, and dexamethasone in NRK-49F and A549 cells.

Although most biological activities of transforming growth factor-beta s 1 and 2 (TGF-beta 1 and TGF-beta 2) examined in vitro are similar or identical, recent studies suggest that each of these factors may be independently regulated in vivo. In this study we have used highly sensitive and specific sandwich enzyme-linked immunosorbent assays for TGF-beta 1 and TGF-beta 2 to examine the effects of a variety of treatments on expression of these two TGF-beta isoforms. We show that epidermal growth factor (EGF) induces secretion of TGF-beta 1 and not TGF-beta 2, whereas retinoic acid (RA) induces secretion of TGF-beta 2 and not TGF-beta 1 in NRK-49F normal rat kidney fibroblasts and A549 human lung carcinoma cells. Moreover, treatment with EGF diminishes the levels of TGF-beta 2, while RA decreases the levels of TGF-beta 1 in both cell lines. Dexamethasone (Dex), on the other hand, inhibits the secretion of both TGF-beta 1 and TGF-beta 2 in A549 cells, while selectively inhibiting TGF-beta 1 secretion in NRK-49F cells. The interactive effects of EGF, RA, and Dex on the production of TGF-beta 1 and TGF-beta 2, which were studied on NRK-49F cells, demonstrate that EGF blocks the induction of TGF-beta 2 mRNA and peptide by RA, while Dex inhibits the induction of TGF-beta 1 mRNA and peptide by EGF. These results demonstrate that RA, EGF and Dex are each unique, differential, and interactive regulators of the expression of TGF-beta s 1 and 2.

Animals↗

PubMed1991

Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene.

Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo.

Animals↗

PubMed1991

Hodgkin's disease in a child with acute lymphoblastic leukemia.

Hodgkin's disease, manifested as a second malignant neoplasm in acute lymphoblastic leukemia, rarely occurs, with seventeen cases reported including this cases. We presented the clinical and pathological features of a nine-year-old male child with acute lymphoblastic leukemia in remission. He had cervical lymph node involvement 22 months after the diagnosis of leukemia as an initial presentation of Hodgkin's disease of mixed cellularity. A brief review of related literatures was also done.

Antineoplastic Agents↗

PubMed1990

Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

Cell Line↗

PubMed1990

Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis.

To localize the cellular sources of the collagens excessively deposited in the liver in the course of secondary biliary fibrosis, we have analyzed by in situ hybridization the distribution of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen and albumin RNA transcripts in rat livers up to 6 wk following common bile duct ligation and scission. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen RNA were found in nonparenchymal cells, while alpha 1(IV) procollagen gene expression was at the threshold of detection. Following bile duct obstruction, increasing amounts of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen gene transcripts were observed in cells of the expanding portal tracts and in perisinusoidal cells in areas of excessive collagen deposition. Procollagen gene expressing perisinusoidal cells were colocalized with desmin-immunoreactive cells, suggesting that Ito cells and transitional cells were among the collagen-expressing cell types. Only alpha 1(IV) procollagen transcripts were found in epithelial cells of newly formed bile ducts. Neither normal nor fibrotic liver showed any hybridization signal above background over hepatocytes, indicating that hepatocytes are unlikely to be a major source of hepatic collagen.

Animals↗

PubMed1990

Regulation of collagenase gene expression by okadaic acid, an inhibitor of protein phosphatases.

Human collagenase gene expression is regulated transcriptionally and is inducible by various mitogens in many cell types. To investigate the molecular mechanisms of this response, we examined the effects on collagenase gene expression of okadaic acid, a non-12-O-tetradecanoyl-phorbol-13-acetate (TPA)-type tumor promoter, which induces apparent "activation" of protein kinases by inhibition of protein phosphatases. Steady state levels of collagenase mRNA were markedly increased by okadaic acid treatment. We show that the AP-1 consensus sequence in the collagenase promoter is required for the induction of collagenase gene expression by okadaic acid, even though sequences upstream of the AP-1 consensus site have an additive effect. We also examined the regulation by okadaic acid of expression of the components of the AP-1 complex, c-fos and c-jun. c-fos expression is dramatically stimulated by okadaic acid, whereas c-jun expression is stimulated to a lesser extent. Induction of c-fos gene mRNA occurs through a region known to contain multiple regulatory elements. These results suggest that phosphorylation regulates collagenase gene expression mediated by an AP-1 binding site.

DNA-Binding Proteins↗

PubMed1990

Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex.

The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property of TGF-beta 1 is its ability to activate its own mRNA expression and thereby increase its own secretion. Two distinct regions of the promoter of the TGF-beta 1 gene are responsive to autoregulation: one 5' to the upstream transcriptional start site and another located between the two major start sites. In both promoter regions, autoinduction is mediated by binding of the AP-1 (Jun-Fos) complex. An important contribution to this positive regulation is the autoactivation of c-jun transcription by AP-1. Cotransfection of antisense c-jun or antisense c-fos expression vectors prevents TGF-beta 1 autoinduction. These results demonstrate that both components of the AP-1 complex are required for TGF-beta 1 autoinduction. Induction of jun expression by TGF-beta 1, as well as jun autoinduction, may amplify the action of TGF-beta 1 during normal development and oncogenesis.

Adenocarcinoma↗

PubMed1990

Pulmonary diffuse alveolar septal amyloidosis--diagnosed by transbronchial lung biopsy.

Diffuse alveolar septal involvement is a rare form of pulmonary amyloidosis. Antemortem diagnosis is unusual, and most of the reported cases were diagnosed at autopsy. It has recently been reported that transbronchial lung biopsy via a flexible fiberoptic bronchoscope was a relatively safe method to confirm diffuse alveolar septal amyloidosis. We report a case of pulmonary diffuse alveolar septal amyloidosis confirmed by transbronchial lung biopsy. The patient's chief complaints were dyspnea on exertion and epigastric pain aggravated over a one-year period, while a chest roentgenogram showed bilateral diffuse interstitial infiltration. This case also showed nephrotic syndrome, cardiac arrhythmia, congestive heart failure, a tingling sensation in both hands and multiple nodules in the gastrointestinal tracts, suggesting involvement of the kidney, heart, peripheral nerves and gastrointestinal tracts. We propose that when diffuse interstitial lung disease is present with systemic signs such as nephrotic syndrome or cardiac arrhythmia, amyloidosis should be considered as a possible diagnosis. Also, transbronchial lung biopsy may be a useful confirmative diagnostic tool.

Amyloidosis↗