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Biomedical subjects

J H Park

Publications and source records attributed to J H Park.

At least 19 recordsLinked to original sources

Depression in vascular dementia is quantitatively and qualitatively different from depression in Alzheimer's disease.

BACKGROUND/AIMS: To compare the prevalence and characteristics of depression in vascular dementia (VaD) and Alzheimer's disease (AD) after adjusting for dementia severity and gender. METHODS: One hundred and eight pairs of VaD and AD patients matched for dementia severity and gender were assessed. RESULTS: Major depressive disorder (MDD) was more prevalent in the VaD group than in the AD group (20.4% in VaD, 10.2% in AD, p = 0.04, Cochran-Mantel-Haenszel, CMH, test) regardless of the dementia severity and gender. The odds ratio for developing MDD in the VaD group versus the AD group was estimated to be 2.20 (95% confidence interval = 1.02-4.74). Neurovegetative symptoms such as 'felt tired and weak all the time' (30.6% in VaD, 13.9% in AD, p = 0.003, CMH test) and 'changed weight without trying' (16.7% in VaD, 6.5% in AD, p = 0.02, CMH test) were more prevalent in the VaD group than in the AD group. CONCLUSION: Depression in VaD was quantitatively and qualitatively different from that in AD regardless of the severity of dementia and gender; depression was more prevalent, severer and more retarded and vegetative in VaD than in AD.

Aged↗

Endothelial progenitor cells in pterygium pathogenesis.

PURPOSE: The pathogenesis of pterygium is not well known, and controversy exists about the cell origins and the nature of initial trigger required for its development. We investigated whether endothelial progenitor cells (EPCs) are involved in pathogenesis of pterygium and the mechanism underlying the selective recruitment of EPCs during this process. METHODS: We studied 13 normal controls and 28 pterygium patients (primary (n=15), recurrent (n=13)). Substance-P, vascular endothelial growth factor (VEGF), and stem cell factor (SCF) were measured in plasma and tears using ELISA, and circulating CD34(+) and c-kit(+) mononuclear cells (MNCs) by flow cytometry. Anterior segment fluorescein angiography (FAG) was performed to evaluate hypoxic conditions in the early stage of pterygium. Surgically removed pterygial tissues were analyzed immunohistochemically using the progenitor cell markers, CD34, c-kit, VEGFR-1, and VEGFR-2. RESULTS: Anterior segment FAG findings showed an increase in non-perfusion areas and attenuated vessels in the nasal limbus during early-stage pterygium. Circulating CD34(+) MNCs and c-kit(+) MNCs were increased in pterygium groups compared with normal controls. Systemic and local cytokines including SP, VEGF, and SCF in pterygium groups were also elevated and showed positive correlations with CD34(+) and c-kit(+) MNC numbers. Immunohistochemical analysis of pterygium showed strong progenitor cell marker immunoreactivities. CONCLUSIONS: EPCs might be involved in pterygium development, and ocular hypoxia triggers this neovascularization by recruiting EPCs derived from the bone marrow via the production of systemic and local cytokines.

Age Distribution↗

An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Alkaline Phosphatase↗

Activation of NF-kappaB by HDAC inhibitor apicidin through Sp1-dependent de novo protein synthesis: its implication for resistance to apoptosis.

Histone deacetylase (HDAC) inhibitors are promising anti-cancer drugs, but these exert differential responses depending on the cell types. Here, we demonstrate a new mechanism for activation of nuclear factor-kappaB (NF-kappaB) by HDAC inhibitor apicidin and the role of NF-kappaB signaling pathway for mediating differential cellular responses, especially, apoptosis. Treatment of HeLa cells with apicidin increases transcriptional activity of NF-kappaB and its target gene IL-8 and cIAP-1 induction, which involves the activation of IKK-IkappaBalpha signaling pathway through Sp1-dependent de novo protein synthesis. In parallel, apicidin treatment leads to histone hyperacetylation in the IL-8 promoter region independent of NF-kappaB signaling pathway, which is not sufficient for full transcription of IL-8 gene. This NF-kappaB activation contributes to resistance of HeLa cells to apoptotic potential of apicidin. Collectively, our results suggest that activation of NF-kappaB signaling cascade functions as a critical modulator to determine cell fate on apoptosis in response to HDAC inhibitors.

Apoptosis↗

Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast-like cells.

Parathyroid hormone (PTH) is a major regulatory factor in skeletal physiology. However, the molecular mechanism underlying the effects of PTH on bones has yet to be elucidated in detail. Recently, some reports have demonstrated the crucial role of bone vasculature with regard to bone density. Angiopoietin-1 (Ang-1), along with VEGF, has been established as a primary angiogenic regulatory agent. In this study, we have attempted to characterize the effects of PTH (1-34) on Ang-1 expression and signaling molecules, employing primary-cultured human osteoblast-like cells. Quiescent osteoblasts were exposed to PTH (1-34), after which Ang-1 expression was determined at the mRNA and protein levels. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that Ang-1 mRNA expression increased as the result of PTH (1-34) treatment. The expression of the Ang-1 protein was also augmented as the result of treatment with PTH (1-34). An adenylyl cyclase activator, forskolin, was shown to induce Ang-1 mRNA expression, whereas the protein kinase A inhibitor, H-89, blocked the PTH (1-34)-mediated expression of Ang-1 mRNA. These findings indicate that PTH (1-34)-mediated Ang-1 expression involves adenylyl cyclase-protein kinase A dependent signaling. Our observations also show that Ang-1 may perform a crucial role in the effects of PTH (1-34) on bones, possibly involving alterations in bone vasculature.

Angiopoietin-1↗

Different radiological findings with the same pathologic diagnosis due to different age in primary osteosarcoma.

PURPOSE: To examine the imaging characteristics of osteoblastic osteosarcoma in older patients, we compared them with those in adolescents because the radiological features of osteosarcoma can be atypical in elderly patients. MATERIAL AND METHODS: 29 cases of adolescent patients and 12 patients older than 40 years of age were reviewed. All cases were pathologically confirmed as osteoblastic osteosarcoma. The comparative factors were tumor location, plain radiological features including periosteal reactions, and the degree of soft tissue mass with magnetic resonance (MR) imaging. RESULTS: Older patients demonstrated frequent osteolytic findings (83.3%), and none of the tumors showed a significant major periosteal reaction. Seven (58.3%) of the 12 tumors had no soft tissue mass (grade 0) and only three (25%) had a grade 3 mass. The differences in the two groups were statistically significant (P<0.001). CONCLUSION: In older patients, primary osteosarcoma should be considered when making a differential diagnosis of osteolytic lesions without any periosteal reactions and small soft-tissue extensions. In cases with atypical findings, the morphology of specimens (aspiration, core, or surgical biopsy) from the lesion should be recommended when making an accurate diagnosis.

Adolescent↗

Determination of the optimal angle for needle insertion during caudal block in children using ultrasound imaging.

Using ultrasound imaging, the optimal angle for needle insertion during caudal epidural injection in children was estimated. After general anaesthesia, ultrasonography was performed at the sacral hiatus in 130 children aged 2-84 months positioned in the lateral position. The median [range] values for the intercornual, caudal space depth and the distance from skin to the posterior sacral bony surface were 17.0 [9.6-24] mm, 3.5 [1-8] mm and 21.0 [10-39] mm, respectively. The optimal angle showed no significant correlation with age, weight, height or body surface area. The median [range] calculated optimal angle for the needle was 21.0 [10-38] degrees. We conclude that the needle should be inserted at about 20 degrees to the skin to avoid puncture of the bone and potential intra-osseous injection.

Analgesia, Epidural↗

Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome.

The objective of this study was to determine whether or not the number of enteroendocrine cells (ECs) in the gut is related to visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS). Twenty-five subjects with D-IBS (mean, 43.1 years; 16 women, nine men) were recruited into our study, along with 13 healthy controls (mean, 40.7 years; nine women, four men). Maximally tolerable pressures were evaluated via barostat testing, and the levels of ECs were immunohistochemically identified and quantified via image analysis. The numbers of ECs between the D-IBS subjects and the controls were not significantly different in the terminal ileum, ascending colon and rectum. However, the maximally tolerable pressures determined in the D-IBS subjects were significantly lower than those of the control subjects (P < 0.01), and we detected a significant relationship between the maximally tolerable pressures and the numbers of ECs in the rectum (r = -0.37, P < 0.01). Rectal sensitivity was enhanced to a greater degree in D-IBS patients exhibiting an elevated level of rectal ECs. This study provides some evidence to suggest that ECs play an important role in visceral hypersensitivity.

Adult↗

Prevalence of and risk factors for extracranial internal carotid artery stenosis in Korean Type 2 diabetic patients.

AIMS: The objectives of this study were to evaluate the prevalence of and risk factors for extracranial internal carotid artery stenosis in Type 2 diabetic patients. METHODS: This study included 406 patients aged 40-79 years with Type 2 diabetes (male 55.4%, female 44.6%). Both carotid arteries of each patient were examined by carotid duplex scanning. The duplex ultrasound criteria based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) measurement method were used for the identification of carotid stenosis. RESULTS: Extracranial internal carotid artery stenosis >or= 40% by velocity criteria was detected in 5.2% of the patients. The prevalence of carotid stenosis increased with advancing age: 1.0% at 40-49 years of age, 5.0% at 50-59 years, 7.3% at 60-69 years and 9.5% at 70-79 years. The degree of stenosis was > 70% in 42.9% of patients with stenosis, Bilateral stenosis was detected in 14% of patients. Of the patients with >or= 40% carotid stenosis, 33% had a decreased ankle-brachial index, 38% had a previous history of stroke, and only one patient (5%) had a documented history of coronary artery disease. Multivariate analysis, including variables determined to be significantly different by univariate analysis between patients with or without >or= 40% stenosis, indicated that age, systolic blood pressure and high-density lipoprotein (HDL)-cholesterol (inverse correlation) were independent risk factors associated with carotid stenosis. CONCLUSIONS: Carotid duplex scanning is a useful strategy in identifying carotid stenosis in older Type 2 diabetic patients with high systolic blood pressure, or low levels of HDL cholesterol. The early identification and subsequent appropriate management of carotid stenosis, particularly in this group of patients, may facilitate efforts to reduce the incidence of macrovascular complications.

Adult↗

Evaluation of microbiological screening systems using dental plaque specimens from young children aged 6-36 months.

Using cotton swab specimens of dental plaque from children aged 6-36 months, four commercial chairside tests for oral bacteria were evaluated by comparison with conventional selective culture: mitis salivarius kanamycin bacitracin agar for mutans streptococci and Rogosa SL agar for lactobacilli. Representative colonies of all isolates were identified by commercial identification kits. According to qualitative evaluations, all chairside tests for mutans streptococci were effective in our population. Those for lactobacilli were not as effective, due mainly to a high recovery of yeast contaminants.

Bacterial Typing Techniques↗

Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features.

Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors. This study analysed the clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage. No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia. The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.

Acute Disease↗

Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects.

BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is prescribed for the management of angina and hypertension, and is sold as amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has recently been developed. Here, we evaluated the comparative pharmacokinetic and pharmacodynamic characteristics of the nicotinate and besylate forms of amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was conducted in 18 healthy male volunteers to compare the pharmacokinetics and pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and amlodipine besylate (reference), after administration of a single dose of 5 mg of each drug and a washout period between doses of 4 weeks. Blood samples for the pharmacokinetic analysis of amlodipine were obtained over the 144-hour period after administration. Systolic and diastolic blood pressures and pulse rates were recorded immediately prior to each blood sampling. RESULTS: All participants completed both treatment periods, and no serious adverse events occurred during the study period. After administering a single dose of each formulation, mean AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for the reference formulation, respectively. The 90% confidence intervals of test/reference mean ratios for AUC0- infinity and Cmax fell within the predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including systolic and diastolic blood pressures and pulse rates exhibited no significant differences between the two formulations. CONCLUSION: The two amlodipine formulations showed similar pharmacokinetic and pharmacodynamic characteristics and the new amlodipine formulation, amlodipine nicotinate, was found to be equivalent for pharmacokinetics to the currently available amlodipine besylate with respect to the rate and extent of amlodipine absorption.

Administration, Oral↗

Global physiological understanding and metabolic engineering of microorganisms based on omics studies.

Through metabolic engineering, scientists seek to modify the metabolic pathways of living organisms to facilitate optimized, efficient production of target biomolecules. During the past decade, we have seen notable improvements in biotechnology, many of which have been based on metabolically engineered microorganisms. Recent developments in the fields of functional genomics, transcriptomics, proteomics, and metabolomics have changed metabolic engineering strategies from the local pathway level to the whole system level. This article focuses on recent advances in the field of metabolic engineering, which have been powered by the combined approaches of the various "omics" that allow us to understand the microbial metabolism at a global scale and to develop more effectively redesigned metabolic pathways for the enhanced production of target bioproducts.

Biomedical Engineering↗

Comparison of the efficacy of Burch colposuspension, pubovaginal sling, and tension-free vaginal tape for stress urinary incontinence.

OBJECTIVE: To compare the cure rate and confirm the clinical efficacy of the 3 most frequently performed surgical procedures for stress urinary incontinence (SUI). METHODS: Between January 2001 and May 2003, 92 women with SUI were randomly assigned to undergo the Burch colposuspension (n=33), pubovaginal sling (n=28), or tension-free vaginal tape (n=31) at the Department of Obstetrics and Gynecology, Yonsei Medical Center, Seoul, Korea. Patient characteristics, urodynamic study results, cure rates at 3, 6, and 12 months, and complication rates were compared using the chi2 test. RESULTS: There were no statistically significant differences in the cure rates initially, but after 12 months the cure rate of the pubovaginal sling procedure was found to be significantly higher than those of the tension-free vaginal tape or Burch colposuspension procedures. CONCLUSION: The cure rate of the pubovaginal sling procedure was significantly higher after 1 year, but no difference in efficacy was observed between the 2 other procedures. A randomized prospective study of a larger population should be conducted.

Female↗

Depressive symptoms of type 2 diabetics treated with insulin compared to diabetics taking oral anti-diabetic drugs: a Korean study.

OBJECTIVE: The purpose of this study was to examine the depressive symptoms of type 2 diabetic patients who were treated with insulin compared to those diabetics treated with oral anti-diabetic drugs in Korea. METHODS: A total 204 outpatients with type 2 diabetes were invited to complete a questionnaire using the Beck depression inventory (BDI) to measure depressive symptoms. Age, gender, body mass index, serum lipid profile, and a social history including marital status, occupation and educational background were also assessed. The presence of diabetic complications was evaluated by examining the patients' medical records. Diabetic patients who were not treated with anti-diabetic drugs were excluded. All the study subjects were classified into two groups based on their mode of therapy: the oral drug group and insulin group. The insulin group included patients treated with insulin-oral drug combinations as well as those treated solely with insulin. RESULTS: Overall, 32.4% of our diabetic subjects showed depressive symptoms with the criterion being a BDI score > or = 16. Compared to the oral drug group, the insulin group showed a significantly higher frequency of depressive symptoms (insulin group, 48.0%; oral drug group, 27.3%; p<0.01) and higher BDI scores (insulin group, 16.6+/-10.7; oral drug group, 12.6+/-8.7; p<0.01). Moreover, after an adjustment for social factors, the degree of hyperglycemia and the presence of diabetic complications, the insulin group showed a significantly higher frequency of depression (odds ratio 4.38, 95% CI 1.66-11.6, p=0.003), compared to the oral drug group. CONCLUSIONS: The data showed that insulin treatment is related to the presence of depressive symptoms, and the importance of more careful psychological support of Korean insulin-treated type 2 diabetic patients is strongly suggested.

Administration, Oral↗

Microvascular tumor embolism: independent prognostic factor after liver transplantation in hepatocellular carcinoma.

Microscopic tumor cell dissemination may be a more important factor in the recurrence of hepatocellular carcinoma (HCC) after liver transplantation, probably because of posttransplant immunosuppression. The presence of microvascular tumor embolism was undetermined as a factor for HCC recurrence after orthotopic liver transplantation (OLT). This study evaluated whether microvascular tumor embolism affects recurrence-free survival and correlates with other clinicopathologic factors after OLT among patients with HCC. From September 1996 to June 2003, 72 OLTs for HCC were enrolled in this study. Median follow-up was 22.8 months. Among 41 patients without microvascular tumor embolism, 1-year, 2-year, and 5-year recurrence-free survival rates were all 97.6%, while these rates were 77.3%, 68.2%, and 59.7%, respectively, for 31 patients (43.1%) with microvascular tumor embolism (P = .0006). The 5-year recurrence-free survival rate showed significant differences for a pT2 tumor (P = .0073), for maximal tumor size <3 cm (P = .0328), for > or =5 cm solitary tumor (P = .0095), and for the presence of a tumor capsule (P = .0012), within the Milan criteria (P = .0376). At multivariate analysis, significant independent predictors for HCC recurrence were microvascular tumor embolism and histopathologic grade. In conclusion, microvascular tumor embolism is an independent predictor of HCC recurrence after liver transplantation. Although OLT is a safe and effective treatment for HCC within the Milan criteria, the presence of microvascular tumor embolism at pathologic examination can predict its recurrence. In these cases, the feasibility of immunosuppressive therapy or adjuvant chemotherapy must be considered to prevent tumor recurrence.

Adult↗

Macrophagic myofasciitis unrelated to vaccination.

Macrophagic myofasciitis (MMF) is known to be closely associated to vaccination containing aluminium as an adjuvant. Here we describe a case of MMF unrelated to vaccination, and presented as focal tender muscle in a 59-year-old woman. Magnetic resonance imaging showed evidence of unilateral myofasciitis involving muscles and fascias of the vastus lateralis. Open biopsy showed a unique pathological pattern of MMF. Our case suggests that other causes unrelated to vaccination need to be investigated in the pathogenesis of MMF, and MMF could be considered in the differential diagnosis of patients with focal muscle tenderness.

Biopsy↗