Current status of organ transplantations in Korea.
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Humans↗
Biomedical subjects
K Park
Publications and source records attributed to K Park.
Prospects of organ sharing and strategies for increasing transplants in Asia.
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Asia↗
Movement of fibrinogen receptors on the ventral membrane of spreading platelets.
We have used fibrinogen gold conjugates and fluorescein-labelled fibrinogen to examine the presence of fibrinogen receptors on the ventral membrane of spreading platelets and to visualize the redistribution of the receptors during platelet spreading. The movement of fibrinogen gold conjugates was observed in real time using video-enhanced interference reflection microscopy (VEIRM) and the redistribution of fluorescein-labelled fibrinogen was examined using video-intensified epifluorescence microscopy (VIFM). Fibrinogen was picked up by spreading platelets and moved towards the centre of the platelets. The velocity of the movement of fibrinogen-gold conjugates under the ventral membrane ranged from less than 0.1 microm min(-1) to more than 10 microm min(-1). The average velocity in the peripheral web region was more than 6 microm min(-1), and was reduced to around 1 microm min(-1) in the outer and inner filamentous zones. The centralized fibrinogen molecules were internalized and eventually removed from the platelets. Video microscopy in conjunction with colloidal gold particles provides a simple method for real-time observation of the movement of fibrinogen receptors on the ventral membrane of spreading platelets.
Adsorption↗
Accelerated study on lysozyme deposition on poly(HEMA) contact lenses.
A technique was developed to accelerate lysozyme deposition on poly(HEMA) contact lenses and measure the amounts of the deposited lysozyme. This technique was for evaluation of bendazac lysine solution, a contact lens cleaning and wetting solution. Effect of temperature on lysozyme deposition on poly(HEMA) contact lenses was examined. Five temperatures ranging from 25 degrees C to 90 degrees C were chosen to examine the temperature effect. The amounts of lysozyme deposited on poly(HEMA) contact lenses at 25 C and 60 C were 0.27 microg/lens and 0.61 microg/lens, respectively. The amount increased sharply to 23 microg/lens at 70 degrees C with the maximum of 31 microg/lens at 90 degrees C. Kinetics of lysozyme deposition on poly(HEMA) contact lenses was examined at 80 degrees C. Lysozyme deposition increased sharply during the first 2 h and reached a plateau after 2 h. Effectiveness of various cleaning procedures was examined using bendazac lysine solution. When the contact lenses were washed without rubbing with fingers, the bendazac lysine reduced the amount of deposited lysozyme by more than 40% from 18.3 microg/lens to 10.6 microg/lens. The effect of bendazac lysine was most prominent when the contact lenses were shaken during storage in the presence of lysozyme in solution. If the contact lenses were cleaned by rubbing with fingers, the effect of bendazac lysine solution on the prevention of lysozyme deposition was negligible.
Biocompatible Materials↗
Induction of pulmonary immunity in cattle by oral administration of ovalbumin in alginate microspheres.
Respiratory infectious diseases are an important cause of economic losses to the cattle industry. There is a need for an effective, easy to administer vaccine to the critical bacterial pathogens that cause pneumonia in cattle. An orally administered vaccine could be given to a large number of animals without significant stress to the animals and with minimal labor. The purpose of this study was to determine whether the oral administration of a model antigen (ovalbumin) in alginate microspheres could induce pulmonary immunity in cattle. Calves were vaccinated orally with ovalbumin (OVA) following either a subcutaneous (s.c.) or oral priming dose of OVA. Calves primed and boostered by oral administration (oral/oral) of OVA encapsulated in alginate microparticles had increased numbers of antigen-specific IgA ASCs (ASCs) in bronchoalveolar lavage (BAL) fluids. Calves that received a s.c. priming followed by an oral booster inoculation (s.c./oral) of OVA in alginate microspheres had a greater number of anti-OVA IgA, IgG1 and IgG2 ASCs in BALF. S.c./oral calves also had increased numbers of anti-OVA IgG1 ASCs in peripheral blood whereas oral/oral calves had none. S.c./oral calves had increased anti-OVA IgG1, IgG2, and IgA titers in BALF, and IgG1 and IgG2 in serum compared to both oral/oral and sham vaccinated calves. These results indicate that oral administration of antigen encapsulated in alginate microspheres results in a mucosal immune response in the respiratory tract of cattle. Furthermore, s.c. priming both enhanced the IgA response and stimulated an IgG1 and IgG2 response not seen in oral/oral calves. The difference in antibody isotype results suggest that design of the vaccination protocol can direct antibody responses as needed for a specific immunization program.
Administration, Oral↗
Synthesis and inhibitory action on HMG-CoA synthase of racemic and optically active oxetan-2-ones (beta-lactones).
A homologous series of both C3-unsubstituted and C3-methyl substituted oxetan-2-ones (beta-lactones) was investigated as potential inhibitors of yeast 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase. Several reported methods for racemic beta-lactone synthesis were studied for preparation of the target series. In addition, a novel aluminum-based Lewis acid obtained by combination of Et2AlCl with (1R,2R)-2-[(diphenyl)hydroxymethyl] cyclohexan-1-ol was studied for the asymmetric [2 + 2] cycloaddition of aldehydes and trimethylsilylketene. This Lewis acid exhibited good reactivity but variable enantioselectivity (22-85% ee). In in vitro assays using both native and recombinant HMG-CoA synthase from Saccharomyces cerevisiae, oxetan-2-ones mono-substituted at C4 with linear alkyl chains gave IC50s that decreased monotonically with chain length up to 10 carbons and then rose rapidly for longer chains. The trans isomers of 3-methyl-4-alkyl-oxetan-2-ones showed a similar trend but had 1.3- to 5.6-fold lower IC50s. The results imply a substantial hydrophobic pocket in this enzyme that interacts with both C-3 and C-4 substituents of oxetan-2-one inhibitors.
Enzyme Inhibitors↗
Immunohistochemical characterization of cellular infiltrate in nasal polyp from aspirin-sensitive asthmatic patients.
BACKGROUND: The immunopathologic mechanism of nasal polyp in aspirin-sensitive asthma remains to be further defined. OBJECTIVE: To characterize the features of the inflammatory cellular infiltrate in the nasal polyp tissue from aspirin-sensitive asthmatic patients. METHODS: We have taken nasal polyp tissue during nasal polyp resection from 13 aspirin-sensitive asthma, 6 allergic, and 12 non-allergic subjects. Immunohistochemistry was employed to stain and enumerate the individual inflammatory cell types using monoclonal antibodies against tryptase (AA1) to identify mast cells, against secreted forms of eosinophil cationic protein (EG2), to identify activated eosinophils, against neutrophil elastase (NE) for neutrophils and against T cell surface markers (CD3) to identify total T cells. RESULTS: There were no significant differences in AA1 + cells among three groups (P>.05). EG2 + cells tended to be higher in ASA-sensitive asthmatic patients than in allergic and non-allergic subjects, but no statistical significance was observed. NE+ cells were found in most subjects of the three groups and their numbers were significantly higher in allergic subjects than in aspirin-sensitive asthma (P<.05). Some patients had CD3+ cells with no statistical significance among the three groups. Significant correlation was found in numbers between NE+ cell and AA1+ cell (r=.44, P=.01), and between NE+ cell and EG2+ cell (r=.40, P=.02). CONCLUSION: These findings suggested that major effector cells such as mast cells and eosinophils might be placed in the center of the inflammatory response of nasal polyps, regardless of their association with aspirin sensitivity.
Adult↗
Fractal analysis of pharmaceutical particles by atomic force microscopy.
PURPOSE: Reliable methods are needed to characterize the surface roughness of pharmaceutical solid particles for quality control and for finding the correlations with other properties. In this study, we used fractal analysis to describe the surface roughness. METHODS: Atomic force microscopy (AFM) was used to obtain three-dimensional surface profiles. The variation method was used to calculate fractal dimensions. We have measured fractal dimensions of four granule samples, four powders, and two freeze-dried powders. RESULTS: A computer-program was written to implement the variation method. The implementation was verified using the model surfaces generated by fractional Brownian motion. The fractal dimensions of most particles and granules were between 2.1 and 2.2, and were independent of the scan size we measured. The freeze-dried samples, however showed wide variation in the values of fractal dimension, which were dependent on the scan size. As scan size increased, the fractal dimension also increased up to 2.5. CONCLUSIONS: Fractal analysis can be used to describe surface roughness of pharmaceutical particles. The variation method allows calculation of reliable fractal dimensions of surface profiles obtained by AFM. Careful analysis is required for the estimation of fractal dimension, since the estimates are dependent on the algorithm and the digitized model size (i.e., number of data points of the measured surface profile) used. The fractal dimension of pharmaceutical materials is also a function of the observation scale i.e., the scan size) used in the profile measurement. The multi-fractal features and the scale-dependency of fractal dimension result from the artificial processes controlling the surface morphology.
Algorithms↗
Use of a pharmacokinetic/pharmacodynamic model to design an optimal dose input profile.
A model for the pharmacodynamic effect of a drug (designated only X), and the use of the model to explore optimal input is described. The data analyzed here are from a crossover comparison study of the effect of 4 active treatments, yielding distinct concentration vs. time curves, plus placebo in 32 subjects. The model expresses total effect as the sum of placebo effect and (pure) drug effect. The latter allows for possible tolerance (found) and time effects (not found). Random effects allow interindividual differences to be expressed. Conditioning on the fitted model, a population optimal input profile is designed that obeys certain protocol constraints. The profile minimizes the expectation of a sum of squared differences between target effect and the resulting response over a given time interval. The target is a fixed constant, chosen to be either the individuals' maximum effect level in response to a baseline input regimen used in the study or the maximum effect level for the typical individual in the population in response to this regimen, as predicted from the model. The expectation is taken over the estimated nonparametric distribution of the 32 subjects' random effects. As one goal of early clinical studies of drugs may be to provide a basis for designing an optimal delivery profile (with respect to a specified loss function), we suggest this report as an example of a reasonable way to go about finding such a profile.
Analgesics↗
Characterization of dihydropyrimidine dehydrogenase in human colorectal tumours.
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for degradation of 5-fluorouracil (5-FU). DPD activity is highly variable in liver and peripheral mononuclear cells (PMNCs) and it has not been well studied in human tumours. Characterization of DPD in colorectal cancer is of clinical interest through its role in the regulation of 5-FU, the main chemotherapeutic agent used in this disease. Therefore, DPD activity was analysed in colorectal tumour and adjacent normal tissue from 63 patients, including three liver metastasis. DPD activity was highly variable in all tissues studied (coefficient of variation 43-61%) and was higher in normal tissue than in tumour. The tumour-normal activity ratio ranged from 0.19 to 3.32 (median 0.76). PMNC DPD activity was available for 57 patients and was correlated with tumour activity (r(s) = 0.29, P < 0.001). A higher correlation was observed between PMNCs and tumour samples that were both obtained in the morning (r(s) = 0.49), consistent with circadian variation in DPD activity. Normal tissue DPD activity was not correlated with either tumour (r(s) = 0.11) or PMNC activity (r(s) = -0.06). This study provides the first analysis of DPD activity in colorectal cancer and illustrates the large degree of variation in tumour activity. The tumour-normal activity ratio results suggest that elevated tumour DPD can play a role in 5-FU resistance through increased inactivation in tumour cells, but is an uncommon event in colorectal tumours. The results support the use of PMNCs for monitoring tumour DPD activity, particularly when circadian variation is taken into account. As a large degree of the variation in tumour DPD activity is not explained by PMNC activity, more accurate alternatives are needed before DPD activity can be used for targeting 5-FU therapy.
Adult↗
Comparative stereochemical analysis of glucose-binding proteins for rational design of glucose-specific agents.
There is a need for synthesizing glucose-sensitive molecules which can be used in glucose sensors and self-regulating insulin delivery devices. Currently, glucose-sensitive proteins, such as glucose oxidase and concanavalin A (Con-A), are used for detecting glucose molecules. For long-term in vivo applications, it is necessary to synthesize non-proteineous glucose-sensitive molecules which are biocompatible, nontoxic, cost-effective, and independent of environmental factors such as pH, ionic strength, or the presence of divalent cations. As a first step toward synthesizing glucose sensitive molecules, we have compared glucose-binding sites of four different types of glucose-binding proteins. They are human beta-cell glucokinase, D-xylose isomerase, lectins (Lathyrus ochrus isolectin I and Con-A), and glucose/galactose binding protein. Analysis of the glucose-binding sites of their 3-dimensional crystal structures showed that the hydrogen bonds between the hydroxyl groups of glucose and a few types of amino acid residues of proteins provided the main attraction. In some cases, the same atom was involved in multiple hydrogen bonds. Hydrophobic interactions between the pyranose ring of glucose and aromatic rings of hydrophobic amino acid residues also played an important role in the glucose specificity. A sandwich geometry was observed among the hydrophobic groups. This comparative stereochemical analysis suggests that a possible glucose binding site can be made by placing Asp and Asn around glucose for hydrogen bonding and Phe on both sides of glucose for hydrophobic interaction.
Binding Sites↗
Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature.
OBJECTIVE: To examine the clinical correlates of obsessive-compulsive disorder (OCD) in children and adolescents. METHOD: A systematic review of the extant literature on juvenile OCD was conducted examining age at onset, gender distribution, symptom phenomenology, psychiatric comorbidity, neurological and perinatal history, family psychiatric history, cognitive and neuropsychological profiles, and treatment and outcome in juvenile OCD subjects. RESULTS: Juvenile OCD was associated with a unique peak of age at onset indicating a bimodal incidence of the disorder, male preponderance, a distinct pattern of comorbidity with attention-deficit/hyperactivity disorder and other developmental disorders as well as frequent associated neuropsychological deficits, an increased familial loading for OCD, and frequent absence of insight. CONCLUSION: These findings show that juvenile OCD is associated with a unique set of correlates that appear to differ from findings reported in studies of adult OCD subjects. Although in need of confirmation, these findings suggest that juvenile OCD may be a developmental subtype of the disorder. Since juvenile OCD is likely to continue into adulthood, these findings stress the importance of considering age at onset in clinical and research studies of adults with OCD.
Adolescent↗
Small intestinal submucosa: a substrate for in vitro cell growth.
The extracellular matrix (ECM) of the small intestinal submucosa (SIS) was harvested by removing the superficial layers of the mucosa and the external muscular layers. The remaining 80 microns thick sheet was disinfected and sterilized by methods which removed all cellular components. The SIS-ECM, retaining its native 3-dimensional microarchitecture and composition, was evaluated for its ability to support in vitro cell growth. Six separate cell types were seeded either alone or in coculture with other cells upon this matrix, grown in selected media, a examined daily for time periods ranging from 48 h to 2 weeks. The six cell types tested were NIH Swiss mouse 3T3 fibroblast, NIH 3T3/j2 fibroblasts, primary human fibroblasts, primary human keratinocytes, human microvascular endothelial cells (HMECs), and an established rat osteosarcoma (ROS) cell line. All cell types showed the ability to attach a proliferate. All fibroblast cell line and the keratinocytes proliferated and/or migrated into the 3-dimensional scaffold of the SIS matrix. The ROS cells and the HMECs were confined in their growth pattern to the surface of the matrix. Coculturing of NIH 3T3/J2 fibroblasts and primary human keratinocytes resulted in a distinctive spatial orientation of the two cell types. The fibroblast populated the mid-substance of the 3-dimensional matrix and the keratinocytes formed an epidermal structure with rete ridge-like formation and stratification when the composite was lifted to an air liquid interface in culture. In summary, SIS provides a substratum with a 3-dimensional scaffold that allows for cell migration and spatial organization. The substratum is suitable for in vitro studies of the interaction between epithelial or mesenchymal cells and a naturally occurring extracellular matrix.
3T3 Cells↗
A discourse of relationships in bioethics: patient autonomy and end-of-life decision making among elderly Korean Americans.
A two-year, multidisciplinary study (N = 800) was conducted on attitudes about end-of-life decision making among elderly individuals in four ethnic groups (African American, European American, Korean American, and Mexican American). On a quantitative survey, Korean Americans reported negative attitudes about the use of life-sustaining technology for themselves but positive attitudes about its use in general. This article reports on an interview with a 79-year-old typical Korean American respondent to explain the contradiction in the survey data. Expectations among elderly Korean Americans include protecting family members with a life-threatening illness from being informed of their diagnosis and prognosis, and doing everything to keep them alive. Two conclusions, one substantive and the other methodological, are drawn: First, the bioethics discourse on individual rights (patient autonomy) is insufficient to explain the preferences of many Korean Americans and must be supplemented with a discourse on relationships. Second, the rigorous use of qualitative, narrative methods clarifies quantitative data and should not be dismissed as "anecdotal."
Advance Directives↗
Abnormally decreased HbA1c can be assessed with erythrocyte creatine in patients with a shortened erythrocyte age.
OBJECTIVE: To investigate whether erythrocyte creatine can serve as a corrective index for HbA1c in patients with a shortened mean age of erythrocytes. RESEARCH DESIGN AND METHODS: HbA1c and creatine in density-fractionated erythrocytes from 18 normal subjects were measured. HbA1c and erythrocyte creatine in the whole blood of 43 patients with liver cirrhosis (LC), 14 patients with hemolytic anemia (HA), 38 other patients with high reticulocyte counts (HRC) (>2.2%), and 59 normal subjects were also measured. The patients in this study all had normal blood glucose levels. A correction formula derived from the linear regression equation for the correlation between HbA1c and erythrocyte creatine was used to correct the patients' HbA1c values. RESULTS: Among density-fractionated erythrocytes, the young cells exhibited low HbA1c and high creatine values. With progressively increasing density, HbA1c gradually increased and creatine gradually decreased. In the whole blood samples, the HbA1c values were significantly lower (P < 0.001) in LC, HA, and HRC patients than in normal subjects. By contrast, the erythrocyte creatine values were significantly higher (P < 0.001) in LC, HA, and HRC patients than in normal subjects. A linear correlation between HbA1c (y) and erythrocyte creatine (x) was observed (y=-0.224x + 5.00; n=154; r=-0.70; P < 0.001). Based on the regression equation, a correction formula was obtained. Low HbA1c values (<4.3%) were found in 24 of the 43 LC patients, 12 of the 14 HA patients, and 20 of the 38 HRC patients. After correction of the HbA1c values, 15 of the 24 LC patients, 9 of the 12 HA patients, and 16 of the 20 HRC patients had HbA1c values within the normal range. CONCLUSIONS: HbA1c decreased in inverse proportion to the increase in erythrocyte creatine because of a shortened mean age of erythrocytes. The abnormally decreased HbA1c value could be assessed with erythrocyte creatine.
Adult↗
Desmoplastic cerebral astrocytoma of infancy: a case report.
We present a case of desmoplastic cerebral astrocytoma of infancy (DCAI) in a 9-month-old boy including immunohistochemical and proliferative activity studies. It was mainly composed of glial fibrillary acidic protein (GFAP)-positive astrocytes and desmoplastic stroma. Studies with Ki-67 and synthetic phase fraction disclosed a low proliferative activity. Flow cytometric study revealed diploidy pattern. These findings suggest a positive correlation with the favorable prognosis.
Astrocytoma↗
Membranoproliferative glomerulonephritis associated with HCV infection in native kidneys and renal allograft.
Hepatitis C viral infection occurs relatively low in Korea compared to hepatitis B. However, it progresses into chronic hepatitis and cirrhosis more frequently than HBV. It may be associated with cryoglobulinemia and glomerulonephritis, both in native and transplanted kidneys. We report three cases of membrano-proliferative glomerulonephritis type I in anti-HCV positive, but cryoglobulin-negative patients, presenting massive proteinuria, two in native kidneys and one in an allograft. HCV-RNA was positive in sera of two patients. Two were cirrhotic and ALT was mildly elevated in two. In addition to the characteristic membranoproliferative feature, two native kidneys overlapped with features of diabetic nephropathy. Immunofluorescence demonstrated mainly IgM and C3 deposits along the peripheral capillary walls. Subendothelial electron dense deposits were present in the glomeruli of all three cases with subepithelial and intramembranous deposits in two. HCV-RNA was associated not only with a greater amount of immune deposits but also with subepithelial and intramembranous deposits, indicating the role of active infection.
Adult↗
Is kidney graft biopsy indicated in recipients with newly developed, microscopic hematuria?
We actively performed renal allograft biopsies on 87 living donor renal transplant recipients presenting with stable serum creatinine but showing newly developed recurrent microscopic hematuria with a small amount of proteinuria during the maintenance phase of immunosuppression and found definite pathological lesions in 56 cases (64%). Chronic rejection of a mild grade (n = 27) and various kinds of glomerulonephritis (n = 27) were the major pathological diagnoses, and from 14 cases singular or complicated cyclosporine (CsA) toxicity was found. Twenty-four out of the 27 glomerulonephritis cases were IgA nephropathy, which is the most common glomerulonephritis in Korea. Through this study, the authors found chronic rejection or glomerulonephritis even in grafts which are generally considered to be normal. CsA nephrotoxicity, which was not expected clinically, could be found. In summary, renal allograft biopsy on patients, even with stable graft function when they start to show microscopic hematuria with or without a small amount of proteinuria, should be performed to document the early intragraft events if there are no medical contraindications.
Adult↗