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Biomedical subjects

C D Kim

Publications and source records attributed to C D Kim.

At least 19 recordsLinked to original sources

Expression profiling of radiation-induced genes in radiodermatitis of hairless mice.

BACKGROUND: Radiation induces many cellular events leading to radiodermatitis. OBJECTIVES: The aim of this study was to establish a radiodermatitis model using experimental animals, and to examine the expression profile of radiation-induced genes. METHODS: Hairless mice were irradiated on the dorsal skin; then total RNAs were isolated and microarray hybridizations were performed. RESULTS: Irradiation with a total of 40 Gy (10 Gy day-1 for four consecutive days) provokes radiodermatitis in the hairless mouse. After microarray analysis, 130 genes that showed upregulation by radiation were selected and organized into four different clusters, depending on the time-kinetic pattern. Classification of these genes into several functional categories revealed that various biological processes were globally affected by radiation. These include transcription regulation, signal transduction, cell communication, cell death regulation and metabolism. CONCLUSIONS: These results demonstrate the complexity of the transcriptional profile of the radiation response, providing important clues on which to base further investigations of the molecular events underlying radiodermatitis.

Animals↗

The effects of the overexpression of recombinant uncoupling protein 2 on proliferation, migration and plasminogen activator inhibitor 1 expression in human vascular smooth muscle cells.

AIMS/HYPOTHESIS: Increased oxidative stress in vascular smooth muscle cells (VSMCs) has been implicated in the pathogenesis of accelerated atherosclerosis in patients with diabetes mellitus. Uncoupling protein 2 (UCP-2) is an important regulator of intracellular reactive oxygen species (ROS) production. We hypothesised that UCP-2 functions as an inhibitor of the atherosclerotic process in VSMCs. METHODS: Overexpression of human UCP-2 was performed in primary cultured human VSMCs (HVSMCs) via adenovirus-mediated gene transfer. Its effects on ROS production, AP-1 activity, plasminogen activator inhibitor 1 (PAI-1) gene expression, and cellular proliferation and migration were measured in response to high glucose and angiotensin II (Ang II) concentrations, two major factors in the pathogenesis of atherosclerosis in patients with diabetes and hypertension. Mitochondrial membrane potential and NAD(P)H oxidase activity were also measured. RESULTS: High glucose and Ang II caused transient mitochondrial membrane hyperpolarisation. They also significantly stimulated ROS production, NAD(P)H oxidase activity, mitochondrial membrane potential, AP-1 activity, PAI-1 mRNA expression, and proliferation and migration of HVSMCs. Adenovirus-mediated transfer of the UCP-2 gene reversed all of these effects. CONCLUSIONS/INTERPRETATION: The present study demonstrates that UCP-2 can modify atherosclerotic processes in HVSMCs in response to high glucose and Ang II. Our data suggest that agents increasing UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes and hypertension.

Aorta, Thoracic↗

Analysis of genes responding to ultraviolet B irradiation of HaCaT keratinocytes using a cDNA microarray.

BACKGROUND: Ultraviolet (UV) B irradiation causes many important biological changes in skin, which lead to pathophysiological alterations of the homeostatic environment. OBJECTIVES: To gain more insight into the molecular events provoked by UVB irradiation, we performed cDNA microarray analysis. METHODS: Immortalized HaCaT keratinocytes were irradiated with a high cytotoxic dose of UVB (50 mJ cm(-2)), and total RNA was isolated. Fluorescently labelled probes were prepared by reverse transcription and were hybridized with cDNA microarray slides made using 840 cDNA clones. RESULTS: Time-course cDNA microarray analysis revealed the global gene expression profile after UVB exposure. Of 840 genes tested, 192 genes showed changes in their expression levels at one or more of four time points. The genes were clustered into four groups according to their expression patterns in a self-organizing maps analysis. Classification of these genes into nine functional categories revealed that UVB irradiation affected several biological processes. The genes that were first upregulated and then returned to normal levels included several genes related to the inhibition of cell growth and the proteasome pathway. Conversely, the expressions of many genes involved in the cytoskeleton, signal transduction, metabolism and transcription were first downregulated or unchanged and then upregulated later, reflecting the recovery of UVB-damaged cellular activities. CONCLUSIONS: These results demonstrate the complexity of the transcriptional profile of the UVB response, and provide a basis for the global characterization of UV-regulated gene expression.

Adult↗

Phenotypic variation among three broiler pure lines for Marek's disease, coccidiosis, and antibody response to sheep red blood cells.

To identify candidate genes, chicken lines with the most divergent phenotypes are usually crossed to generate resource mapping populations, for example, either backcrossed or F2 populations. Linkage between the genetic marker and the phenotypic trait locus is then tested in the mapping population. As an initial step in the development of a mapping population from commercial broilers, the goal of the current research was to evaluate the phenotypic variation among three pure lines for antibody response to SRBC and in resistance to two economically important poultry diseases, Marek's disease (MD) and coccidiosis (Eimeria acervulina). Chicks from each line were received and separated into three experimental studies to evaluate each of their responses. In summary, broiler Line 3 had significantly lower antibody responses to SRBC immunizations compared to the other two lines, and nonvaccinated birds from Line 3 were also more susceptible to MD. With coccidiosis, the response was complex, and ranking of the lines was dependent on the age of infection, and whether it was a first or second challenge. With the first challenge, Line 1 was most susceptible at the younger age (Day 30), whereas Line 3 was susceptible at the older age (Day 58). Upon the second challenge, broiler Line 1 remained susceptible at the younger age, but Line 2 was more susceptible at the older age. Line 3 was completely resistant to the second challenge at the older age. Thus, although the broiler lines have been intensively selected for productivity and general livability, this study also demonstrates that the lines differ for immune response and disease resistance. Based on the phenotypic differences between Lines 1 and 3, they were chosen to establish a mapping population for identifying candidate genes that affect MD and coccidiosis in commercial broiler chickens.

Age Factors↗

Involvement of NADH/NADPH oxidase-derived superoxide in experimental vasospasm induced by periarterial blood in rat femoral artery.

To elucidate the mechanism(s) involved in periarterial blood-mediated vasospasm in the rat femoral artery, vascular production of superoxide and related expression of intercellular adhesion molecule-1 (ICAM-1) were assessed with subsequent perivascular mobilization of granulocytes and macrophages. Arterial vasospasm characterized by increased wall thickness and decreased lumen size was observed on the side exposed to blood at 7 to 12 days, and these vascular changes were significantly ameliorated by pretreatment with NADH/NADPH oxidase inhibitor, diphenyleneiodonium (200 microM, locally). Increased mobilization of granulocytes was paralleled with the expression of ICAM-1 in the vessels at 24 hours after periarterial application of blood to the femoral artery, and then both declined. Subsequently, infiltration of macrophage progressively increased at all layers throughout 7 to 12 days. In in vitro study, a large amount of superoxide that was inhibitable by diphenyleneiodonium (20 and 100 microM) was produced at 3 hours upon application of 10% autologous blood to the aortic segments. Furthermore, ICAM-1 expression by autologous blood was well correlated with generation of superoxide anion in the aortic segment (r=0.975, P<0.05). Taken together, it is suggested that NADH/NADPH oxidase-derived superoxide is implicated in periarterial blood-induced vasospasm via increased expression of ICAM-1 with subsequent mobilization of granulocyte/macrophage.

Animals↗

Prevalence of endoscopic reflux esophagitis among Koreans.

BACKGROUND AND AIM: Although reflux esophagitis is believed to be common in the Western population, very few epidemiologic data on reflux esophagitis in Koreans are available. The aims of this study were to evaluate the prevalence of endoscopic reflux esophagitis in patients who came for a physical check-up at Korea University Hospital, and to study the relationship between various factors relevant to reflux disease. METHODS: This study was carried out prospectively on 7,015 patients who received an esophagogastroduodenoscopy from September 1996 to December 1997. Most of the patients were free of symptoms and had come for their self-paid check-up. RESULTS: The overall prevalence of reflux esophagitis was 3.4%, and most of the patients had a mild degree of esophagitis representing grade 1 in 98.3% and grade 2 in 1.7%. The male: female ratio for esophagitis was 7 : 1, and the body mass index (BMI) was significantly higher in patients with reflux esophagitis. A hiatal hernia was found in 166 patients with esophagitis (68.6%), but only in 9.2% patients without esophagitis (P < 0.05). Smoking and alcohol consumption were associated with the development of reflux esophagitis (P < 0.05). CONCLUSIONS: The prevalence of endoscopic reflux esophagitis among Koreans is 3.4%, and most of the patients had a mild grade esophagitis. Smoking, alcohol consumption, the presence of a hiatal hernia and a higher BMI are associated with the development of reflux esophagitis.

Esophagitis, Peptic↗

Endoscopic removal of sharp foreign bodies impacted in the esophagus.

BACKGROUND AND STUDY AIMS: Impacted sharp foreign bodies in the esophagus can be very difficult to manage. When attempts are made to remove such objects inappropriately, life-threatening complications such as perforation can occur. The aim of this study was to evaluate the safety and efficacy of endoscopic removal of impacted sharp foreign bodies in the esophagus using proximal dilatation with an oral side balloon or transparent cap. PATIENTS AND METHODS: A total of 22 patients (10 men, 12 women) with impacted sharp foreign bodies in the esophagus underwent endoscopic extraction. The following technique was successfully performed at our hospital. An oral side balloon (Top Co., Japan) for esophageal variceal sclerotherapy was attached to the distal part of the endoscope. With the patient under local anesthesia, the endoscope was inserted as far as the proximal part of the esophageal foreign body. The oral side balloon was then gradually inflated. Dilatation of the proximal part of the esophagus made it possible to release the impacted sharp foreign body from the esophageal wall. A transparent cap was used for foreign bodies in the upper esophagus when there were difficulties with the oral side balloon. RESULTS: The types of foreign body removed were fish bones (n = 9), press-through packages (n = 8), chicken bones (n =3), dentures (n = 1), and a wrist watch (n = 1). Endoscopic removal was successful in all but one of the cases, in which a fish bone had to be extracted surgically. CONCLUSIONS: The proximal dilatation method using an oral side balloon or transparent cap is safe and effective in removing sharp foreign bodies from the esophagus, avoiding surgery and possible perforation.

Adult↗

Incomplete pancreas divisum: is it merely a normal anatomic variant without clinical implications?

BACKGROUND AND STUDY AIMS: Incomplete pancreas divisum (PD) has been generally regarded as merely a normal anatomic variant, without clinical implications. This study compares the prevalence, symptom occurrence rate, clinical presentation, and outcomes of endoscopic treatment in patients with incomplete PD and those with complete PD. PATIENTS AND METHODS: The study population consisted of 56 patients (27 with complete PD and 29 with incomplete PD), identified from 4473 newly performed endoscopic retrograde cholangiopancreatography examinations. Endoscopic treatment (minor papilla sphincterotomy with stents or nasopancreatic drainage tube insertion) was attempted in 25 symptomatic patients with PD, which was suspected to be causing the associated pancreatic diseases: acute recurrent pancreatitis (ARP) (n = 13; five patients with complete PD and eight with incomplete PD); chronic pancreatitis (CP) (n = 10: five patients with complete PD and five with incomplete PD); and pancreatic-type pain (PP) (n = 2; one patient with complete PD and one with incomplete PD). The mean follow-up period was 17 months (range 9 - 49 months). RESULTS: In 12 of the 27 patients with complete PD--six with ARP, five with CP, and one with PP--it was suspected that PD was the cause of pancreatic disease. Ten of the 11 symptomatic patients with complete PD underwent successful endoscopic treatment (five with endoscopic minor papilla sphincterotomy and stenting, and five with endoscopic minor papilla sphincterotomy and endoscopic nasopancreatic drainage), and seven of these ten patients benefited from the endoscopic treatment. In 14 of the 29 patients with incomplete PD--eight with ARP, five with CP, and one with PP--it was suspected that pancreas divisum was the cause of pancreatic disease. Thirteen of the 14 symptomatic patients with incomplete PD underwent successful endoscopic treatments (six with endoscopic minor papilla sphincterotomy and stenting, and seven with endoscopic minor papilla sphincterotomy and endoscopic nasopancreatic drainage), and eight of these 13 patients experienced clinical improvement. CONCLUSIONS: The prevalence rate, symptom occurrence rate, clinical presentation, and outcomes of endoscopic treatment were similar in patients with complete PD and incomplete PD. Incomplete PD may therefore have similar clinical implications to those of complete PD.

Adult↗

Inconsistent association of esophageal symptoms, psychometric abnormalities and dysmotility.

OBJECTIVES: The aim of this study was to characterize the psychometric profiles of symptomatic patients with abnormal esophageal motility and symptomatic patients with normal manometric findings compared to asymptomatic controls. METHODS: A total of 113 patients with abnormal esophageal motility (7 achalasia, 8 diffuse esophageal spasm, 27 nutcracker esophagus, 37 hypertensive lower esophageal sphincter, 21 hypotensive peristalsis, 13 failed peristalsis), 23 symptomatic controls with similar esophageal symptoms but normal manometry, and 27 asymptomatic controls were enrolled. Validated questionnaires assessing depression (Beck Depression Inventory), anxiety (Spielberger State Anxiety Inventory or Trait Anxiety Inventory), and somatization (Psychosomatic Symptom Checklist) were administered to all subjects. RESULTS: Patients with both esophageal symptoms and either hypertensive lower esophageal sphincter, nutcracker esophagus, or hypotensive contractions exhibited increased somatization, acute anxiety, or depression compared to asymptomatic controls but not compared to symptomatic controls. On the other hand, the psychometric profiles of patients with achalasia and diffuse esophageal spasm were strikingly normal. Among esophageal symptoms, chest pain was closely correlated with psychometric abnormalities. CONCLUSIONS: The esophageal symptoms of patients with abnormal esophageal motility may relate to the underlying psychological abnormalities, independent of manometric abnormalities.

Analysis of Variance↗

Restoration of vasodilation and CBF autoregulation by genistein in rat pial artery after brain injury.

This study determined whether, after fluid percussion injury (FPI), tyrosine kinase activation is coupled to inhibition of K(+) channels and alteration in cerebral blood flow (CBF) autoregulation in the rat pial artery. Injury of moderate severity (2--2.5 atm) was produced by FPI in anesthetized rats equipped with a closed cranial window. The suppressed vasodilation of the pial arterioles to calcitonin gene-related peptide (CGRP) and levcromakalim (LMK) and altered lower limit of CBF autoregulation after FPI were restored by genistein but not by daidzein, an inactive analog. Vasodilation to S-nitroso-N-acetyl penicillamine (0.1--10 micromol/l) was, however, little influenced after FPI. The restored vasodilation was decreased by sodium orthovanadate, suggesting the reciprocal action of tyrosine phosphorylation and dephosphorylation. After FPI, CGRP-induced vasodilation restored by genistein (10 micromol/l) was strongly antagonized by iberiotoxin but not by glibenclamide, whereas LMK-induced vasodilation was, in contrast, inhibited by glibenclamide but not by iberiotoxin. Taken together, we suggest that, after FPI, activation of tyrosine kinase links the inhibition of K(+) channels to impaired autoregulatory vasodilation in response to acute hypotension and alteration in CBF autoregulation in the rat pial artery.

Animals↗

Effects of taurine on cerulein-induced acute pancreatitis in the rat.

Taurine, or 2-aminoethane sulfonic acid, is an intracellular amino acid and has been suggested to have a function in protecting biological systems from oxidative tissue damage. The aim of this study was to determine the effect of taurine against cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by administering three subcutaneous injections of cerulein (40 microg/kg body weight) at 1-hour intervals, while taurine was administered intravenously at graded doses (30, 100, or 300 mg/kg, respectively) following the first cerulein injection. The severities of pancreatitis and lung injury were determined by measuring biochemical parameters, tissue myeloperoxidase (MPO), and histological changes. To clarify the mechanism of taurine, serum IL-1beta and TNF-alpha levels and tissue concentrations of malondialdehyde (MDA) were evaluated. In cerulein-induced acute edematous pancreatitis, treatment with taurine significantly decreased hyperamylasemia, tissue MPO, pancreatic edema, and the extent of pancreatic and pulmonary injury. Taurine decreased MDA concentration in the pancreas and lung, but not the serum cytokine concentration. We would conclude that taurine has beneficial effects in cerulein-induced acute pancreatitis and lung injuries by preventing the production of oxygen free radicals.

Acute Disease↗

Differentiation between reinfection and recrudescence of helicobacter pylori strains using PCR-based restriction fragment length polymorphism analysis.

The aim of this study was to evaluate whether PCR-based restriction fragment length polymorphism (RFLP) analysis was effective in differentiating between reinfection and recrudescence of H. pylori strains. Following a 1-2 week regimen of omeprazole 20 mg, amoxicillin 1.0 g, and clarithromycin 500 mg twice daily, twenty patients with duodenal ulcer were enrolled in the study. Ten patients (group 1, control) were not successfully treated, and another 10 patients (group 2) exhibited recurrence of infection 6-24 months following the therapy. Follow-up diagnosis was performed by Giemsa stain and CLO test. RFLP profiles of antral and midbody biopsy specimens were compared before and after therapy. PCR products using the ureC gene were digested with restriction enzymes Hha I, Mbo I, and Hind III, and the fragments generated were analyzed by agarose gel electrophoresis. Hha I, Mbo I, and Hind III digestion produced 13, 7, and 2 distinguishable digestion patterns, respectively. There was no difference in RFLP profiles seen before and after the therapy in 17 duodenal ulcer patients, while different RFLP profiles were discovered in 3 patients. Following treatment, one (group 2) patient differed in Mbo I, and two (one each from both groups) patients differed in Hha I and Mbo I RFLP patterns. Eight of group 2 patients showed recrudescence of previous infection and two patients had reinfection by another strain. This study supports the hypothesis that PCR-based RFLP analysis can be effective for differentiating reinfection and recrudescence of H. pylori strains following triple therapy.

Adult↗

A case of primary adenosquamous carcinoma of the liver presented with liver abscess.

Primary adenosquamous carcinoma of the liver is a very rare type of cholangiocarcinoma and is defined as a cancer containing both squamous and adenomatous components in the same lesion. Recently, we experienced a primary adenosquamous carcinoma of the liver presented as liver abscess. A 63-year-old man was presented with a 4-day history of fever and chill. The radiologic study showed a 4 cm-sized, central hypoattenuated mass with peripheral rim enhancement in the left lobe of the liver. Ultrasonography-guided aspiration and biopsy suggested an adenocarcinoma with abscess in the liver. At laparotomy, the tumor occupied the left lobe of the liver and invaded the right diaphragm. An extended left lobectomy and a partial excision of the involved diaphragm were done. Grossly, the tumor was 6 x 5 x 5 cm in size and had an eccentric necrosis. Microscopically, the tumor was composed of adenocarcinoma and squamous cell carcinoma with a transitional area.

Carcinoma, Adenosquamous↗

Antiangiogenic effect of KR31372 in rat sponge implant model.

A rat sponge implant model was used to examine the antiangiogenic effect of KR31372. Topical administration of angiotensin II (AII, 100 ng, daily) into the sponges enhanced the basal sponge-induced neovascularization, leading to higher clearance of (99m)Tc, increased retention of dye in the vessels, and increased numbers of blood vessels. These AII-induced changes were significantly suppressed by oral administration of KR31372 (1 mg/kg for 7 days). Angiogenic effect of recombinant human VEGF(165) (200 ng) was modestly higher than that of AII, which was also significantly inhibited by KR31372. KR31372-mediated suppression of (99m)Tc clearance was reversed by glibenclamide. Levcromakalim showed a modestly suppressive effect on the AII-induced angiogenesis. In conclusion, KR31372 exerted a strong inhibitory effect on the sponge-induced neovascularization, in part, through mediation of glibenclamide-sensitive K(+) channel activation. It is suggested that it may have therapeutic potential in the treatment of angiogenic disorders.

Angiogenesis Inhibitors↗

Expression of intracellular adhesion molecule-1 linking superoxide to mobilization of granulocytes and macrophages after periarterial blood in rat femoral artery: effect of rebamipide.

OBJECT: To clarify the mechanism(s) involved in the perivascular mobilization of granulocytes and macrophages by periarterial autologous blood (PAAB) in the vicinity of the femoral artery (FA) in rats, superoxide production as well as expression of intercellular adhesion molecule-1 (ICAM-1) were determined by conducting both in vitro and in vivo experiments. METHODS: In an in vitro study, a significant amount of superoxide inhibited by diphenyleneiodonium (20 microM and 100 microM) was identified at 3 hours after application of 10% whole blood to the aortic segments, and these results were correlated with in vitro ICAM-1 expression. High expression of ICAM-1 was subsequently demonstrated in these segments at 24 hours in in vitro and in vivo studies. In the in vivo study, an increased mobilization of granulocytes paralleled with a high expression of ICAM-1 in the vessels at 24 hours after administration of PAAB to the FA and then declined. Subsequently, macrophage infiltration progressively increased at all layers throughout a period of 7 to 12 days. Pretreatment with rebamipide (100 and 300 mg kg(-1) day(-1), orally) significantly inhibited the expression of ICAM-1 with inhibition of mobilization of granulocyte/macrophage. CONCLUSIONS: These findings suggest that application of PAAB to the rat FA causes superoxide-linked expression of ICAM-1 and mobilization of granulocyte and macrophages. Thus, the potential value in suppressing these variables stimulated by PAAB is indicated in therapeutic strategies for prevention and possible regression of vasospasm after subarachnoid hemorrhage.

Alanine↗

Enhancement of adenoviral transduction with polycationic liposomes in vivo.

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.

Adenocarcinoma↗