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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 181 records · Page 10Linked to original sources
PubMed1999

Clear benefit of mycophenolate mofetil-based triple therapy in reducing the incidence of acute rejection after living donor renal transplantations.

BACKGROUND: According to a pooled analysis of three randomized clinical studies concerning the prevention of acute rejection in cadaveric renal transplantation, mycophenolate mofetil (MMF) proved superior to azathioprine or placebo in conjunction with cyclosporine (CsA) and steroids. MMF-treated patients showed reduced incidence and severity of acute rejection, similar graft survival, and better graft function over 12 months. However, the multicenter trials did not include the Asian recipients of living donor kidneys. METHODS: To assess the efficacy of MMF as the third component of a triple therapy in addition to CsA-Neoral and steroids in living donor renal transplantation recipients in Asians, a total of 100 recipients were randomized to receive CsA-Neoral and steroids (control group, n=50), or MMF-based triple therapy (1.0 g of MMF twice daily from postoperative day 2, MMF group, n=50). The dosing plan for Neoral and steroids was essentially same between groups. During 12 months of follow-up, we compared the incidence of acute rejection, adverse events such as infections, and 12-month actual graft and patient survival. RESULTS: The graft and patient survival at 1 year was excellent in both groups: 96/98% in the control group and 98/100% in the MMF group, respectively. MMF significantly reduced the proportion of patients with at least one episode of acute rejection (34% in the control group vs. 14% in the MMF group), cumulative incidence of acute rejection episodes (46% vs. 16%), and requirement of antilymphocyte antibody (21.7% vs. 12.5%). In the MMF group, viral infection such as herpes zoster or chicken pox was more prevalent than in the control group. CONCLUSIONS: Like cadaveric renal transplantation, this open clinical trial showed MMF to be effective in reducing the incidence and severity of acute rejection if used in conjunction with Neoral and steroids after living donor renal transplantation in Asian ethnicity.

Acute Disease↗
PubMed1999

Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)/H(+) exchanger.

Mutations in human DRA cause congenital chloride diarrhea, thereby raising the possibility that it functions as a Cl(-)/HCO(3)(-) exchanger. To test this hypothesis we cloned a cDNA encoding mouse DRA (mDRA) and analyzed its activity in cultured mammalian cells. When expressed in HEK 293 cells, mDRA conferred Na(+)-independent, electroneutral Cl(-)/CHO(3)(-) exchange activity. Removal of extracellular Cl(-) from medium containing HCO(3)(-) caused a rapid intracellular alkalinization, whereas the intracellular pH increase following Cl(-) removal from HCO(3)(-)-free medium was reduced greater than 7-fold. The intracellular alkalinization in Cl(-)-free, HCO(3)(-)-containing medium was unaffected by removal of extracellular Na(+) or by depolarization of the membrane by addition of 75 mM K(+) to the medium. Like human DRA mRNA, mDRA transcripts were expressed at high levels in cecum and colon and at lower levels in small intestine. The expression of mDRA mRNA was modestly up-regulated in the colon of mice lacking the NHE3 Na(+)/H(+) exchanger. These results show that DRA is a Cl(-)/HCO(3)(-) exchanger and suggest that it normally acts in concert with NHE3 to absorb NaCl and that in NHE3-deficient mice its activity is coupled with those of the sharply up-regulated colonic H(+),K(+)-ATPase and epithelial Na(+) channel to mediate electrolyte and fluid absorption.

Amino Acid Sequence↗
PubMed1999

Asp 280 residue is important in the activity of the Escherichia coli leader peptidase.

Leader peptidase is a novel serine protease in Escherichia coli, which catalyzes the cleavage of amino-terminal signal sequences from exported proteins. It is an integral membrane protein containing two transmembrane segments with its carboxy-terminal catalytic domain residing in the periplasmic space. Recently, the x-ray crystal structure of signal peptidase-inhibitor complex showed that Asp 280, a highly conserved consensus sequence of E. coli leader peptidase is the closest charged residue in the vicinity of two catalytic dyad, Ser 90 and Lys 145, and it is likely held in place by a salt bridge to Arg 282. Possible roles of Asp 280 and Arg 282 in the structure-catalytic function relationship were investigated by the site-directed mutagenesis of Asp 280 substituted with alanine, glutamic acid, glycine, or asparagine and of Arg 282 with methionine. All of mutants purified with nickel affinity chromatography were inactive using in vitro assay. It is surprising to find complete lose of activity by an extension of one carbon units in the mutant where Asp 280 is substituted with glutamic acid. These results suggest that Asp 280 and Arg 282 are in a sequence which constitutes catalytic crevice of leader peptidase and are essential for maintaining the conformation of catalytic pocket.

Aspartic Acid↗
PubMed1999

Oral vaccination of animals with antigens encapsulated in alginate microspheres.

Most infectious diseases begin at a mucosal surface. Prevention of infection must therefore consider ways to enhance local immunity to prevent the attachment and invasion of microbes. Despite this understanding, most vaccines depend on parenterally administered vaccines that induce a circulating immune response that often does not cross to mucosal sites. Administration of vaccines to mucosal sites induces local immunity. To be effective requires that antigen be administered often. This is not always practical depending on the site where protection is needed, nor comfortable to the patient. Not all mucosal sites have inductive lymphoid tissue present as well. Oral administration is easy to do, is well accepted by humans and animals and targets the largest inductive lymphoid tissue in the body in the intestine. Oral administration of antigen requires protection of antigen from the enzymes and pH of the stomach. Polymeric delivery systems are under investigation to deliver vaccines to the intestine while protecting them from adverse conditions that could adversely affect the antigens. They also can enhance delivery of antigen specifically to the inductive lymphoid tissue. Sodium alginate is a readily available, inexpensive polymer that can be used to encapsulate a wide variety of antigens under mild conditions. Orally administered alginate microspheres containing antigen have successfully induced immunity in mice to enteric (rotavirus) pathogens and in the respiratory tract in cattle with a model antigen (ovalbumin). This delivery system offers a safe, effective means of orally vaccinating large numbers of animals (and perhaps humans) to a variety of infectious agents.

Administration, Oral↗
PubMed1999

Molecular cloning and functional expression of a rat Na+/H+ exchanger (NHE5) highly expressed in brain.

We report here the cloning, primary structure, heterologous expression, tissue distribution, and localization of a cDNA encoding rat NHE5, a fifth member of the mammalian plasma membrane Na+/H+ exchanger (NHE) gene family. The full-length open reading frame as well as 34 nucleotides of 5'-untranslated and 1443 nucleotides of 3'-untranslated sequences were obtained using a polymerase chain reaction strategy involving reverse transcription-polymerase chain reaction and 5'/3'-rapid amplification of cDNA ends. The NHE5 cDNA encodes a protein of 898 amino acids with a calculated Mr of 99,044 and is predicted to contain 11-13 transmembrane domains. An amino acid comparison of the coding region of rat NHE5 reveals 95% identity with human NHE5. Northern hybridization analysis showed that high level expression of NHE5 mRNA is restricted to brain. Transfection of the coding region of rat NHE5 into NHE-deficient PS120 cells resulted in Na+/H+ exchange activity that was relatively insensitive to the amiloride analogue, 5-(N-ethyl-N-isopropyl) amiloride, with a half-maximal inhibitory concentration (IC50) of 1. 53 +/- 0.25 microM. In situ hybridization of rat brain sections revealed significant NHE5 mRNA levels in the dentate gyrus with lower levels observed in the hippocampus and cerebral cortex. These results suggest a specialized role for this fifth NHE isoform in neuronal tissues.

Amiloride↗
PubMed1999

Exchange donor program in kidney transplantation.

The donor organ shortage has been one of the major barriers to kidney transplantation in Korea, even though there has been a small but steady flow of cadaveric kidney donations for the last decade. To expand the donor pool in kidney transplantation, we have developed the exchange donor program at our institution and in Korea. The donor exchange program was first started for end-stage renal disease patients who had willing but incompatible related donors due to positive lymphocyte cross-match. The kidney transplantations were performed using exchanged kidneys between two families with successful results. Since this success, we have expanded the donor pool by accepting close relatives, spouses, friends of recipients, and willing voluntary donors as candidates for exchange donors with careful donor screening procedures. It helps relieve stress on donor supply. Particularly in those countries where brain death has not been socially or legally accepted, living donors including related, unrelated, and exchange donors should be considered as potential donors for kidney transplantation to relieve the pressure on donor organ shortage.

Family↗
PubMed1999

Expression of p27Kip1 and cyclin D1 proteins is inversely correlated and is associated with poor clinical outcome in human gastric cancer.

BACKGROUND AND OBJECTIVES: p27Kip1 is an inhibitor of cyclin-dependent kinases and is speculated to be a potential prognostic indicator in numerous human cancers. We investigated expression of p27Kip1 along with cyclin D1 in gastric cancer to estimate the clinical utility of p27Kip1. METHODS: Immunohistochemical assay for p27Kip1 and cyclin D1 proteins was performed in 64 patients with primary gastric cancer. Correlation between p27Kip1 expression and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients and cyclin D1 was overexpressed in 22 (34.4%) out of 64. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P = 0.015) and was also reduced in the tumors with high S-phase fraction (86.7%, 26/30) compared with tumors showing low S-phase fraction (41.2%, 14/34; P = 0.0002). Expression of p27Kip1 and cyclin D1 was inversely correlated (P = 0.021). In univariate analysis, extent of the disease (P < 0.001), expression of cyclin D1 (P = 0.0001), and reduced expression of p27Kip1 (P = 0. 0006), were statistically significant to predict patient's outcome, but depth of invasion (P = 0.008) and pathologic stage (P = 0.009) emerged as significant prognostic indicators in multivariate analysis. CONCLUSION: Expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 seems to have potential as a prognostic marker in the management of gastric cancer patients.

Adult↗
PubMed1999

Fractionated stereotactic radiation therapy for locally recurrent nasopharynx cancer: report of three cases.

BACKGROUND: This article reports on experience with fractionated stereotactic radiation therapy (FSRT) for locally recurrent nasopharynx cancer. METHODS: Three patients with locally recurrent nasopharynx cancer were given FSRT as reirradiation between September 1995 and August 1996. Application of FSRT was the third radiation therapy in two patients. Authors used the individually made relocatable Gill-Thomas-Cosman (GTC) stereotactic frame, and the radiation dose planning was performed using XKnife-3. The total doses to the recurrent tumor were 45 Gy/18 fractions in two patients, who were given concurrent chemotherapy as a radiosensitizer, and 50 Gy/20 fractions in the other patient. In all three patients the dose per fraction was 2.5 Gy, and the fraction schedule was to give five daily treatments per week. RESULTS: Authors observed satisfactory symptomatic improvement and remarkable objective tumor size decrease through the magnetic resonance (MR) images taken one month post-FSRT in all three patients. No neurological side effect was observed. All three patients died with regional and distant seeding outside the FSRT field at seven, nine, and nine months, respectively. CONCLUSION: FSRT as reirradiation for locally recurrent nasopharynx cancer seemed to be effective and safe.

Carcinoma↗
PubMed1999

Complement activation by PEO-grafted glass surfaces.

Activation of the complement system is one way in which the human body reacts to foreign materials that come in contact with blood. Poly(ethylene oxide) (PEO) has been used quite frequently to modify biomaterial surfaces to prevent protein adsorption and cell adhesion. Despite extensive use of PEO, however, PEO-induced complement activation has not been examined before. We examined the complement activation by PEO chains grafted to glass surfaces. PEO was grafted to trichlorovinylsilane-treated glass (TCVS-glass) by gamma-irradiation using PEO homopolymer, Pluronic F108 (PF108), and PEO-polybutadiene-PEO triblock copolymer (COP5000). Complement activation was assessed by measuring the plasma C3a level. Of the three polymers grafted (PEO, PF108, and COP5000), only PF108 showed significant increases in complement activation over controls. Complement C3a production on PF108-grafted glass was linearly dependent on surface concentration of grafted PF108. The C3a concentration increased from 46 ng/mL to 316 ng/mL as the surface PF108 concentration increased from 0-0.25 microg/cm(2). Kinetics of C3a generation by PF108-grafted surfaces show that 60% of the steady state C3a concentration was generated during the first hour of plasma exposure. When the same PF108-grafted glass surface was repeatedly exposed to fresh plasma, the amount of C3a generated decreased by 70% after the first exposure. This supports the "single-hit" mechanism in complement activation. PEO homopolymer did not activate complement in bulk solution, and, thus, it appears that C3a complement activation by PF108-grafted surfaces is due to the presence of poly(propylene oxide) units. Grafting of PEO using PEO-containing block copolymers requires examination of complement activating properties of the non-PEO segment.

Biocompatible Materials↗
PubMed1999

Synthesis of superporous hydrogels: hydrogels with fast swelling and superabsorbent properties.

We have been interested in the synthesis of hydrogels with fast swelling kinetics and superabsorbent properties. To increase the water absorption rate, interconnected pores were introduced to the hydrogels. Since the pore size in the dried hydrogels is in the order of hundreds of micrometers, these hydrogels are called "superporous" hydrogels. Superporous hydrogels were synthesized by crosslinking polymerization of various vinyl monomers in the presence of gas bubbles formed by the chemical reaction of acid and NaHCO3. The polymerization process was optimized to capture the gas bubbles inside the synthesized hydrogels. The use of the NaHCO3/acid system allowed easy control of timing for gelation and foam formation. We found that PF127 was the best foam stabilizer for most of the monomer systems used in our study. Scanning electron microscope (SEM) pictures showed interconnected pores forming capillary channels. The capillary channels, which were critical for fast swelling, were preserved during drying by dehydrating water-swollen hydrogels with ethanol before drying. The ethanol-dehydrated superporous hydrogels reached equilibrium swelling within minutes. The equilibrium swelling time could be reduced to less than a minute with the use of a wetting agent. In our study, water moisture was used as a wetting agent since the amount of moisture content in the dried hydrogels easily could be controlled. Preparation of superporous hydrogels using the right blowing system, foam stabilizer, drying method, and wetting agent makes it possible to reduce the swelling time to less than a minute regardless of the size of the dried gels. The superporous hydrogels can be used where fast swelling and superabsorbent properties are critical.

Absorption↗
PubMed1999

Signal transduction pathway in human middle ear cholesteatoma.

Phospholipase C-gamma1 plays a central role in signal transduction, and it is important in cellular growth, differentiation, and proliferation. Human cholesteatoma in the middle ear is characterized by the presence of a keratinizing epithelium that is believed to have hyperproliferative properties. The purpose of this study is to elucidate the distribution of phospholipase C-gamma1 in cholesteatoma matrix and deep meatal skin with Western blot analysis and immunohistochemistry. In conclusion, overexpression of phospholipase C-gamma1 in cholesteatoma matrix suggests a possible derangement of enhanced growth signal transduction in keratinocytes.

Antibodies, Monoclonal↗
PubMed1999

Reduced expression of p27Kip1 protein is associated with poor clinical outcome of breast cancer patients treated with systemic chemotherapy and is linked to cell proliferation and differentiation.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative regulator of cell proliferation. Its expression is known to be altered in a proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kip1 is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kip1 protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell-cycle analysis by flow cytometry. A total of 68 patients with invasive ductal cancer received adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU every 3 weeks for six cycles. In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kip1 is significantly reduced in poorly differentiated cancers and in the advanced stage of the disease. Levels of p27Kip1 expression correlated with cell populations in G0/G1 phase of the cell cycle. In survival analysis, p27Kip1 was useful to predict disease free survival but not overall survival of the patients after adjuvant chemotherapy. In summary, p27Kip1 seems to have a role in the cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of the present study suggest that p27Kip1 can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.

Adult↗
PubMed1999

Axial penile buckling forces vs Rigiscan radial rigidity as a function of intracavernosal pressure: why Rigiscan does not predict functional erections in individual patients.

AIM: An improved understanding of the relationship between radial and axial rigdity values would enable better appreciation of the clinical usefulness of RigiScantrade mark, the most widely utilized determination of erectile rigidity testing. Previous studies have shown that axial rigidity (measured by buckling forces) correlated well with radial rigidity (measured by RigiScantrade mark) for radial rigidity values below 60%. For radial rigidity exceeding 60%, there was poor correlation. Heretofore, there has been no physiologic explanation of this phenomenon. METHODS: During dynamic pharmacocavernosometry in 36 impotent patients, we investigated the relationship between axial buckling forces and RigiScan radial rigidity and, for the first time, how they both vary with pressure, (which we varied over over a wide functional range). In addition, we recorded multiple penile length and diameter values enabling us to relate, also for the first time, axial and radial rigidity to individual mechanical erectile tissue and penile geometric properties. RESULTS: Marked differences were found in the manner RigiScan radial rigidity units and axial buckling force magnitudes increased with increases in intracavernosal pressure values in each individual. The former asymptotically approached a maximum finite value while the latter increased continuously towards infinity. Based on data in this study, RigiScan radial rigidity values greater than 55% may be considered a necessary criteria for vaginal intromission capability in all partners but it is not a sufficient one. CONCLUSIONS: Axial and radial rigidity share a common dependency upon intracavernosal pressure, however, they are also dependent upon other unique physical determinants. For axial rigidity, additional dependent variables include cavernosal erectile tissue properties and penile geometry, while for radial rigidity, this may include tunical surface wall tension properties. Clinical devices which assess functional penile rigidity should utilize axial and not radial rigidity testing.

Equipment Design↗
PubMed1999

Immunohistochemical study of cell proliferation using BrdU labelling on tympanic membrane, external auditory canal and induced cholesteatoma in Mongolian gerbils.

The Mongolian gerbil is a well-known animal model for induction of aural cholesteatomas. This animal model is useful for studying changes in the keratinizing epithelium. It is not known whether keratin accumulation can increase the proliferative activity of the keratinizing epithelium in tympanic membrane and meatal skin. In this study, we investigated the proliferative activity of the epidermis in induced aural cholesteatoma at various stages and in different areas of the tympanic membrane and meatal skin in normal gerbils. Anti-5-bromo-2- deoxyuridine (BrdU) was injected intraperitoneally to detect the proliferative activity of keratinizing epithelium. Immunohistochemistry with monoclonal BrdU antibody in the normal gerbil showed intense immunolabelled keratinocytes at the handle of malleus, and the superior parts of pars tensa and pars flaccida. Also, mitotic activity in the deep meatal skin was more active than in the lateral meatal skin. The induced aural cholesteatoma showed more active proliferation centre of the epithelial cell than eardrum and external ear canal of the normal gerbil. These observations suggest that the accumulation of the keratin debris might induce changes of the cellular proliferation in the external auditory meatus.

Animals↗
PubMed1999

Expression of Fas/APO-1 and apoptosis of keratinocytes in human cholesteatoma.

OBJECTIVES: The Fas/APO-1 is a cell surface receptor protein known to trigger apoptosis when conjugated with Fas ligand or specific agonistic antibodies. The present study investigated the expression of Fas/APO-1 and apoptotic cell death in both normal and cholesteatoma epithelia. STUDY DESIGN: Ten cholesteatomas and retroauricular skins were taken during middle ear operations in the Ajou University Hospital for this study. METHODS: In situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) staining and agarose gel electrophoresis of genomic DNA were used for detection of apoptosis. The expression patterns of Fas/APO-1 protein were confirmed by immunoblot and immunohistochemical analysis. RESULTS: In situ TUNEL staining revealed many positively stained nuclei in 9 of 10 suprabasal layers of cholesteatoma epithelium, whereas few positively stained cells were found on the granular layer of retroauricular skins. Typical "ladder pattern" was seen on the gel electrophoresis of the genomic DNA of cholesteatoma. Immunoblot analysis and immunohistochemical studies revealed that Fas/APO-1 protein was expressed in 8 of 10 cholesteatoma epithelia, whereas retroauricular skin showed negative reaction. CONCLUSION: These results show the upregulated expression of Fas/APO-1 and increased apoptotic cell death in cholesteatoma epithelium. Because Fas/APO-1 is known as an apoptosis-triggering protein, it is suggested that the accumulation of keratin debris is due to increased apoptotic cell death related to Fas/APO-1 protein.

Apoptosis↗
PubMed1999

Self-organized growth model for a driven interface in random media.

We introduce a simple self-organized growth model in the quenched Edwards-Wilkinson universality class. The roughness and growth exponents are obtained for the model as alpha approximately 1.15 and beta approximately 0.89, respectively. These values of exponents are in good agreement with previous results obtained from numerical integrations or discretized model simulations of the quenched Edwards-Wilkinson equation. The velocity of a driven interface is found to be independent of the slope of the tilted substrate.

Journal Article↗