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Biomedical subjects

T H Kim

Publications and source records attributed to T H Kim.

At least 91 records · Page 5Linked to original sources

Papular elastorrhexis in childhood improved by intralesional injections of triamcinolone.

Papular elastorrhexis is a rare disease developing asymptomatic skin-colored small papules in adolescence with histopathological loss of elastic fibers. There has been no established treatment for this disease. A 4-year-old Korean boy had multiple, hard, whitish papules on his chest and back for one year. Histopathologic examination revealed focal loss of elastic fibers in the dermis, and X-ray examination showed no bony abnormalities. His skin lesions were improved by intralesional injections of triamcinolone but recurred after four months.

Back↗

Dependence of malformation upon gestational age and exposed dose of gamma radiation.

In order to evaluate the importance of gestational age and the dose-incidence relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5 to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also at day 11.5 after conception, which was the most sensitive stage for the induction of major congenital malformations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. The only demonstrable effect of irradiation during the pre-implantation period was an increase in prenatal mortality. Resorptions were maximal on exposure at day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. A small head, growth retardation, a cleft palate, dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the extremities and tail after exposure were prominent during the organogenesis period, especially on day 11.5 of gestation. As for the dose-incidence relationship, the incidence of a small head, growth-retarded fetuses, a cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose as the radiation dose increased. The result indicated that the late period of organogenesis in the development of the brain, skull and extremities of a mouse was a particularly sensitive phase. The threshold doses of radiation that induced a cleft palate and dilatation of the cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively.

Abnormalities, Radiation-Induced↗

Role of inducible heat shock protein 70 in radiation-induced cell death.

We previously demonstrated the protective effect of inducible heat shock protein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth rate of inducible hsp70-transfected cells was 2-3 hours slower than that of control cells. Flow cytometric analysis of cells at G1 phase synchronized by serum starvation also showed the growth delay in the Hsp70-overexpressing cells. In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells, which were probably responsible for the reduction of cell growth. To find out if inducible Hsp70-mediated growth delay affected radiation-induced cell cycle regulation, flow cytometric and molecular analyses of cell cycle regulatory proteins and their kinase were performed. The radiation-induced G2/M arrest was found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced cyclin A or B1 expressions together with their kinase activities were also inhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apoptosis. When treated with nocodazole, radiation-induced mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase arrest, subsequently resulting in inhibition of radiation-induced cell death.

3T3 Cells↗

Effect of graded running on esophageal motility and gastroesophageal reflux in fed volunteers.

The effects of different grades of running on esophageal motility and gastroesophageal reflux in the fed state were evaluated. We studied healthy volunteers (male: 12, age: 27 +/- 5 yr) using ambulatory esophageal manometry, pH catheter and portable digital data recorder. Each exercise was performed 30 min after meal, with 20 min of rest between exercises. Subjects exercised on a treadmill at 40% and 70% maximal heart rate. The number of gastroesophageal reflux episodes, the duration of esophageal acid exposure and percent time pH below 4 were significantly (p < 0.01) increased during exercise at 70% maximal heart rate. The frequency of contraction (contraction/min) (p < 0.05), frequency of repetition (p < 0.01), percent of simultaneous contraction (p < 0.01), percent of above 100 mmHg amplitude (p < 0.05), and frequency of 2-peak contraction (p < 0.01) were significantly increased during exercise at 70% maximal heart rate. However, median amplitude and median duration showed no significant changes between each exercise session. Postprandial running exercises induce gastroesophageal reflux, which correlates with exercise intensity. These effects are mediated by disorganized esophageal motility.

Adult↗

Hepatopulmonary syndrome in poorly compensated postnecrotic liver cirrhosis by hepatitis B virus in Korea.

BACKGROUND: Hepatopulmonary syndrome (HPS) refers to the association of hypoxemia, intrapulmonary shunting and chronic liver disease. But there is no clear data about the prevalence of HPS in postnecrotic liver cirrhosis by hepatitis B virus (HBV), the most common cause of liver disease in Korea. The aim of this study was to investigate the prevalence of HPS in poorly compensated postnecrotic liver cirrhosis by HBV, and the correlation of the hepatopulmonary syndrome with clinical aspects of postnecrotic liver cirrhosis by HBV. METHODS: Thirty-five patients underwent pulmonary function test, arterial blood gas analysis and contrast-enhanced echocardiography. All patients were diagnosed as HBV-induced Child class C liver cirrhosis and had no evidence of intrinsic cardiopulmonary disease. RESULTS: Intrapulmonary shunt was detected in 6/35 (17.1%) by contrast-enhanced echocardiography. Two of six patients with intrahepatic shunts had significant hypoxemia (PaO2 < 70 mmHg) and four showed increased alveolar-arterial oxygen gradient over 20 mmHg. Only cyanosis could reliably distinguish between shunt positive and negative patients. CONCLUSIONS: The prevalence of intrapulmonary shunt in poorly compensated postnecrotic liver cirrhosis by HBV was 17.1% and the frequency of hepatopulmonary syndrome was relatively low (5.7%). 'Subclinical' hepatopulmonary syndrome (echocardiographically positive intrapulmonary shunt but without profound hypoxemia) exists in 11.4% of cases with poorly compensated postnecrotic liver cirrhosis by HBV. Cyanosis is the only reliable clinical indicator of HPS of HBV-induced poorly compensated liver cirrhosis. Further studies are required to determine if the prevalence and clinical manifestations of HPS varies with etiology or with geographical and racial differences.

Adult↗

Early stage onychomadesis presenting as painful swellings of proximal nail folds.

Two Korean men complained of painful erythematous swellings of the proximal nail folds. When we removed the overlying nail plates, we observed new ones growing under the old ones. These painful swellings disappeared after the affected nails were extracted. We found typical onychomadesis in another finger during the follow-up, suggesting that the initial condition marked the onset of onychomadesis. Because both patients had plaster casts removed recently and histories of trauma, it was hypothesized that trauma might be responsible for this peculiar condition.

Adolescent↗

Influence of gestational age at exposure on the prenatal effects of gamma-radiation.

The objective of this investigation was to evaluate the influence of gestational age at exposure on the prenatal effects of gamma-radiation. Pregnant ICR mice were exposed to a single dose of 2.0 Gy gamma-radiation at a gestational 2.5 to 15.5 days post-coitus (p.c.). The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, change in head size and any other morphological abnormalities. The only demonstrable effect of irradiation during the preimplantation period was an increase in prenatal mortality. Resorptions were maximal on post-exposure day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. Small head, growth retardation, cleft palate, dilatation of the cerebral ventricle, dilatation of the renal pelvis and abnormalities of the extremities and tail were prominent after exposure during the organogenesis period, especially on day 11.5 of gestation. Our results indicate that the late period of organogenesis in the mouse is a particularly sensitive phase in terms of the development of the brain, skull and extremities.

Abnormalities, Radiation-Induced↗

Bid-induced cytochrome c release is mediated by a pathway independent of mitochondrial permeability transition pore and Bax.

Bid, a pro-apoptosis "BH3-only" member of the Bcl-2 family, can be cleaved by caspase-8 after Fas/TNF-R1 engagement. The p15 form of truncated Bid (tBid) translocates to mitochondria and induces cytochrome c release, leading to the activation of downstream caspases and apoptosis. In the current study, we investigated the mechanism by which tBid regulated cytochrome c release in terms of its relationship to mitochondrial permeability transition and Bax, another Bcl-2 family protein. We employed an in vitro reconstitution system as well as cell cultures and an animal model to reflect the physiological environment where Bid could be functional. We found that induction of cytochrome c release by tBid was not accompanied by a permeability transition even at high doses. Indeed, inhibition of permeability transition did not suppress the activity of tBid in vitro nor could they block Fas activation-induced, Bid-dependent hepatocyte apoptosis in cultures. Furthermore, Mg(2+), although inhibiting permeability transition, actually enhanced the ability of tBid to induce cytochrome c release. We also found that tBid did not require Bax to induce cytochrome c release in vitro. In addition, mice deficient in bax were still highly susceptible to anti-Fas-induced hepatocyte apoptosis, in which cytochrome c release was unaffected. Moreover, although Bax-induced cytochrome c release was not dependent on tBid, the two proteins could function synergistically. We conclude that Bid possesses the biochemical activity to induce cytochrome c release through a mechanism independent of mitochondrial permeability transition pore and Bax.

Animals↗

Lysosomal protease pathways to apoptosis. Cleavage of bid, not pro-caspases, is the most likely route.

We investigated the mechanism of lysosome-mediated cell death using purified recombinant pro-apoptotic proteins, and cell-free extracts from the human neuronal progenitor cell line NT2. Potential effectors were either isolated lysosomes or purified lysosomal proteases. Purified lysosomal cathepsins B, H, K, L, S, and X or an extract of mouse lysosomes did not directly activate either recombinant caspase zymogens or caspase zymogens present in an NT2 cytosolic extract to any significant extent. In contrast, a cathepsin L-related protease from the protozoan parasite Trypanosoma cruzi, cruzipain, showed a measurable caspase activation rate. This demonstrated that members of the papain family can directly activate caspases but that mammalian lysosomal members of this family may have been negatively selected for caspase activation to prevent inappropriate induction of apoptosis. Given the lack of evidence for a direct role in caspase activation by lysosomal proteases, we hypothesized that an indirect mode of caspase activation may involve the Bcl-2 family member Bid. In support of this, Bid was cleaved in the presence of lysosomal extracts, at a site six residues downstream from that seen for pathways involving capase 8. Incubation of mitochondria with Bid that had been cleaved by lysosomal extracts resulted in cytochrome c release. Thus, cleavage of Bid may represent a mechanism by which proteases that have leaked from the lysosomes can precipitate cytochrome c release and subsequent caspase activation. This is supported by the finding that cytosolic extracts from mice ablated in the bid gene are impaired in the ability to release cytochrome c in response to lysosome extracts. Together these data suggest that Bid represents a sensor that allows cells to initiate apoptosis in response to widespread adventitious proteolysis.

Animals↗

Analysis of expressed sequence tags of Porphyra yezoensis.

Single direct partial sequencing of anonymous cDNA clones was performed to obtain genetic information on red algae Porphyra yezoensis of which genetic information is not available. This expressed sequence tags (EST) analysis revealed 81 clones (42%) had significant homologies to known genes in GenBank. Of these clones, eight are related to known algal genes, whereas above 90% of the EST clones were newly identified in algae. Putative functional categories of these clones showed that the most abundant genes were involved in stress and defense mechanisms and that the next abundant genes were associated with protein synthetic pathways.

DNA, Complementary↗

Augmentation of urea-synthetic capacity by inhibition of nitric oxide synthesis in butyrate-induced differentiated human hepatocytes.

We have recently developed an in vitro differentiation model of immortalized non-transformed human hepatocytes using butyrate, and observed the induction of inducible NO synthase (iNOS). In this study, we analyzed the effect of NO on the urea-synthetic capacity of these cells. The inhibition of iNOS during butyrate treatment significantly increased the urea-synthetic capacity as compared to that of butyrate treatment alone, possibly through the further induction of ornithine transcarbamylase expression. Therefore, the inhibition of NO production might be useful for obtaining more differentiated hepatocytes in the process of in vitro induction of hepatocyte-specific differentiation.

Argininosuccinate Synthase↗

Design and synthesis of anticonvulsive agents as gamma-vinyl GABA-based potential dual acting prodrugs and their biological activities.

For the development of new anticonvulsive agents, gamma-vinyl GABA (vigabatrin) and GABA mimetics derivatives were covalently coupled as potential dual acting prodrugs and evaluated for their anticonvulsive activities. Among the prepared compounds, 11 showed the most potent anticonvulsive activity, a shorter onset time and a broader spectrum compared to vigabatrin.

Animals↗

Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration.

Partial hepatectomy triggers a variety of biological phenomena, which culminate in regeneration of the liver mass. Hepatocyte proliferation is a major feature of the regenerating liver after partial hepatectomy. Previous studies in our laboratory suggested that hepatic matrix remodeling might be a prerequisite process for hepatocyte proliferation in the regenerating liver. In the present study we use immunohistochemical staining, Western blot analysis, and gelatin zymography to show that the inactive matrix metalloproteinases (MMPs), pro-MMP-2 and pro-MMP-9, are elevated at 30 minutes and activated at 6 to 12 hours and at 3 to 6 hours, respectively, after hepatectomy. Sham-operated livers did not show an increase in inactive pro-MMP-2 and pro-MMP-9 and did not contain active MMP-2 or MMP-9. To examine whether tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is changed to regulate the activities of MMPs after partial hepatectomy, the level of TIMP-1 protein was analyzed by both immunohistochemistry and Western blot analysis. The level of TIMP-1 protein appears to increase by 6 to 18 hours, implying that an increase in TIMP-1 regulates activities of active MMP-2 and MMP-9. Taken together, these results suggest that hepatic matrix remodeling is mediated by activated MMPs, which contribute to modulation of the environment surrounding hepatocytes during rat liver regeneration.

Animals↗

Wegener's granulomatosis presenting as mediastinal soft tissue mass invading the tracheal wall.

Wegener's granulomatosis (WG) is a clinicopathologic entity of unknown cause characterised by a necrotising granulomatous vasculitis affecting multiple organs, especially the upper and lower respiratory tracts, lung and kidney. The lung is the most frequently, and sometimes the only involved organ. Single or multiple nodules, with or without cavitation, are the most common pulmonary manifestations in WG, but mediastinal involvement is atypical. The sole tracheal involvement is rare and hilar and mediastinal involvement has been thought not to be part of the clinical feature. We experienced a rare case of WG presenting as paratracheal mediastinal lesions with tracheal wall invasion, which responded dramatically to corticosteroid treatment. We present this case with a review of the literature.

Adult↗

Seronegative spondyloarthropathy initiated by physical trauma.

We undertook this study to demonstrate the pattern of onset and the course of arthritis on the traumatised joint in spondyloarthropathy (SpA) initiated by physical trauma. Among 288 patients with SpA, 12 (4.2%) whose arthropathies were associated with trauma were reviewed retrospectively. There were seven patients with ankylosing spondylitis (AS), three with juvenile onset AS and two undifferentiated SpA. The type of trauma was direct injury to the joint and injuries at other sites, except in spinal surgery, for example. In eight cases the initial evidence of disease was peripheral arthritis. The disease first occurred in traumatised joints in five cases. Only three cases showed recurrent inflammatory episodes in the traumatised joints throughout the disease course. SpA initiated by trauma initially manifested as peripheral arthritis at the traumatised joints in about half of the cases. Inflammatory episodes preferentially involved other joints apart from the traumatised joints throughout the whole course of the disease.

Adolescent↗