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K Park

Publications and source records attributed to K Park.

At least 253 records · Page 14Linked to original sources
PubMed1998

Relationship between area under the concentration versus time curve of cyclosporin A, creatinine clearance, hematocrit value, and other clinical factors in Japanese renal transplant patients.

We evaluated the relationship between the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) and several other clinical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal transplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis there was no correlation between the AUC and the daily dose of CsA (mg/kg/day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) activity level had no correlation with the posttransplant renal function evaluated according to creatinine clearance. In contrast, the renal function-related episodes significantly affected the AUC after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic function assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had significant positive correlations with the AUC, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjustment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUC, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors to be considered when therapeutic monitoring is performed.

Adult↗
PubMed1998

Sensitive enzymatic assay for erythrocyte creatine with production of methylene blue.

We developed a new, highly sensitive enzymatic method for quantifying creatine in erythrocytes, which comprises creatine amidinohydrolase, sarcosine oxidase, and peroxidase. In the present method, an N-methylcarbamoyl derivative of methylene blue, 10-N-methylcarbamoyl-3,7-bis(dimethylamino)phenothiazine (MCDP), was used as a sensitive chromogenic compound. Potassium ferrocyanide was used to prevent nonspecific oxidation of MCDP. The enzymatic method exhibited good analytical performance: precision, within-run CVs <1.0% and between-day CVs <2.0%; average analytical recovery, 99.3% +/- 1.8%; detection limit, 1.0 micromol/L in hemolysate; and linearity, at least up to 500 micromol/L as creatine concentration in hemolysate. Excellent agreement was observed between the present method (y) and HPLC (x), y = 1.029x - 0.002 micromol/g hemoglobin, r = 0.9998, S(y/x) = 0.053 micromol/g hemoglobin (n = 110). No significant interference was produced by various compounds, including guanidino compounds, amino acids, and reducing materials. The reference intervals (mean +/- 2 SD) for erythrocyte creatine obtained from 60 males and 60 females were (in micromol/g hemoglobin) 1.18 +/- 0.52 (0.66-1.70) for males and 1.35 +/- 0.49 (0.86-1.84) for females. Using this method, we documented changes in erythrocyte creatine in patients with various hemolytic conditions, including hemolytic anemia, liver cirrhosis, renal insufficiency, and chronic renal failure treated with hemodialysis with or without the administration of erythropoietin. We conclude that the use of MCDP allows sensitive measurement of erythrocyte creatine and that MCDP with potassium ferrocyanide can improve the sensitivity of assays that use peroxidase for detection of H2O2.

Adult↗
PubMed1998

Gastric retentive drug-delivery systems.

The development of a long-term oral controlled-release dosage form has been difficult mainly because of the transit of the dosage form through the gastrointestinal (GI) tract. Several approaches to extend gastric residence time have been tried. The most commonly used systems are (1) intragastric floating systems, (2) high-density systems, (3) mucoadhesive systems, (4) magnetic systems, (5) unfoldable, extendible, or swellable systems, and (6) superporous hydrogel systems. The concept of each approach is examined, and improvements that are needed for further development are discussed. Background materials in the GI physiology that are necessary for understanding the concept and usefulness of each approach are also provided.

Administration, Oral↗
PubMed1997

The 5'-upstream region of the rat phospholipase C-beta 3 gene contains two critical Sp1 sites and an HIV Inr-like element.

The 5'-upstream region of the rat phospholipase C-beta 3 gene (PLC-beta 3) has been cloned and characterized. Sequence analysis of the 5'-upstream region showed that it contains a GC-rich region (-166 to +1: 79%) and multiple binding sites for the transcription factors Sp1, AP-1 and AP-2, but does not contain a canonical TATA box. Primer extension analysis of total RNA isolated from rat glial cell C6Bul revealed that single transcription start point (tsp) is located at an initiator (Inr) element similar to that found in the HIV promoter. Gel mobility shift and competitive mobility shift assays indicated that this Inr element forms a DNA-protein complex with the HIV Inr-binding protein, LBP-1/CP2 or a homologue. In order to localize functional elements of the 5'-upstream region of the rat PLC-beta 3 gene, 5'-deletion fragments were cloned into a chloramphenicol acetyltransferase (CAT) reporter vector. Transient transfection analyses of the 5'-deletion mutants identified a crucial promoter element located at -128 to -14. Supershift mobility assays, site-directed mutagenesis and DNase I footprints indicated that Sp1 binds to three GC boxes within the sequence between -128 and -14 of the PLC-beta 3 promoter. Transient transfection analyses of promoter constructs containing site-specific mutation(s) of these three GC boxes demonstrated that two GC boxes, located proximal to the tsp, are important elements for normal promoter activity.

Animals↗
PubMed1997

Expression of transforming growth factor beta type II receptor reduces tumorigenicity in human gastric cancer cells.

Expression of transforming growth factor beta (TGF-beta) receptor type II (RII) is required for the growth-inhibitory effects of TGF-beta on proliferating epithelial cells. TGF-beta RII mutations have been identified in a broad spectrum of human epithelial malignancies, including colon and gastric cancers, and are highly correlated with development of TGF-beta resistance in cell lines derived from these tumors. In this study, the role of TGF-beta RII in regulating the tumorigenic potential of the SNU-638 human gastric cancer cell line was investigated by infecting these cells with retroviral construct (MFG) expressing TGF-beta RII. The SNU-638 cell line displays the DNA replication error phenotype and encodes a truncated, inactive TGF-beta RII protein. Infection of these cells with retroviral constructs expressing wild-type TGF-beta RII led to significant increases in TGF-beta RII mRNA and protein expression. These cells responded to exogenous TGF-beta with reduced proliferation compared to that of control cells infected with retroviral vector expressing chloramphenicol acetyltranferase. Addition of TGF-beta-neutralizing antibodies led to increased proliferation of wild-type TGF-beta RII-expressing SNU-638 cells but had no effect on control cells. The latter finding suggests that TGF-beta acts in an autocrine fashion to inhibit cell proliferation in SNU-638 cells. When transplanted into athymic nude mice, wild-type TGF-beta RII-expressing SNU-638 cells showed decreased and delayed tumorigenicity compared with control cells. This study suggests a strong association between the expression of wild-type TGF-beta RII and the degree of malignancy in human gastric cancer cells.

Animals↗
PubMed1997

Hemispheric asymmetries in reading Korean: task matters.

Native Korean readers were studied in a visual half-field paradigm. Subjects were to make speeded judgments on Hangul (syllabic) and Hanzza (logographic) scripts based on phonetic or visual properties of the stimuli. A task by visual field interaction was obtained indicating that, for both scripts, responses on the phonetic task were faster in the right visual field, whereas no visual field differences were found on the visual task. Script type did not interact with visual field. The results support a task-based account of hemispheric differences in verbal processing.

Adult↗
PubMed1997

Grafting of PEO to glass, nitinol, and pyrolytic carbon surfaces by gamma irradiation.

Glass, nitinol, and pyrolytic carbon surfaces were grafted with poly (ethylene oxide) (PEO) and PEO-containing Pluronic surfactants by gamma irradiation. These substrates were coated with a primer layer of trichlorovinylsilane (TCVS), which allows grafting of organic polymers. The TCVS-coated substrates were adsorbed with PEO or Pluronics and exposed to 0.3 Mrad of gamma radiation to graft the polymer to the surface. PEO-grafted substrates were characterized by contact angle measurement, X-ray photoelectron spectroscopy, fibrinogen adsorption, and platelet adhesion and activation. Surface modification with PEO reduced fibrinogen adsorption by as much as 99%. Platelet adhesion was significnatly reduced or prevented on the modified surfaces. Protein- and platelet-resistance effects were independent of hydrophilicity of the PEO-grafted surfaces. Polymer grafting by gamma radiation to TCVS-coated substrates provides a facile process to improve thromboresistance of inorganic biomaterials.

Alloys↗
PubMed1997

Effect of cadmium on Na-Pi cotransport kinetics in rabbit renal brush-border membrane vesicles.

Chronic exposure to cadmium impairs various renal functions, including phosphate (Pi) transport. To further investigate the mechanism of cadmium-induced alterations in renal Pi transport, kinetics of Na+-dependent Pi uptake were studied in renal cortical brush-border membrane vesicles (BBMV) exposed to CdCl2 in vitro. BBMVs isolated from rabbit renal outer cortex were preincubated in a buffer containing CdCl2 (50 microM in most cases) for 60 min at 37 degrees C and then tested for Pi uptake at 25 degrees C. CdCl2 treatment resulted in a marked attenuation of Na+-dependent Pi uptake with no changes in Na+-independent Pi uptake and membrane permeability to Na+. CdMt treatment induced no changes in Pi transport. The inhibition required preincubation of vesicles with CdCl2 for more than 30 min and was not reversed by extravesicular EDTA, suggesting that cadmium affects the transport system at the internal side of the membrane. Kinetic analysis indicated that two sodium ions and one phosphate ion interact with a carrier, and this stoichiometry was not altered by cadmium treatment. Cadmium treatment did not change the apparent Km for Na+ (K(Na)) and that for phosphate (K(Pi)), but it markedly reduced the Vmax of the Na+-dependent Pi transport. These results indicate that exposure of proximal tubular brush border membranes to cadmium impairs the Pi transport capacity, probably by reducing the effective number of Na-Pi cotransporter units without altering substrate affinities of the carrier.

Animals↗
PubMed1997

Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants.

It is well known that long-term use of steroids plays a decisive role in the development of glucose intolerance and diabetes mellitus (DM). Deflazacort, an oxazoline derivative of prednisolone, has been introduced as a potential substitute for conventional steroids in order to ameliorate glucose intolerance. We initiated a randomized study of conversion from prednisone to deflazacort in kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to ascertain whether or not the switch to deflazacort would ameliorate the diabetic state. Forty-two recipients in the conversion group were compared with 40 patients on prednisone (the control group) in a prospective manner. The dose reduction of insulin or oral blood glucose-lowering agents, the adequacy of glucose control, and the development of side effects were the criteria for evaluating outcome. In the conversion group, patients were switched to a deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the mean follow-up period of 13.2 months, neither graft dysfunction nor acute rejection developed in the conversion group. Improvement in blood glucose control in the conversion group was noted. When the conversion group was stratified into pre- or post-Tx DM, promising effects were clearly evident in the post-Tx DM patients. More than 50% dose reduction of blood glucose-lowering agents was possible in 42.3% of post-Tx DM patients. In conclusion, it was readily possible to control blood glucose better in post-Tx DM recipients without seriously affecting the immunosuppressive activity after conversion to deflazacort.

Adult↗
PubMed1997

Pancreatoblastoma.

BACKGROUND: Pancreatoblastoma is a rare pancreatic tumor with distinct acinar and squamoid cell differentiation that generally affects infants and young children. Just over 50 cases have been reported in the literature. METHODS: Five cases of pathologically proven pancreatoblastoma treated at Seoul National University Hospital from 1984 to 1994 were reviewed. There were three girls and two boys who were 2 years to 5 years of age. All cases came to medical attention because of an abdominal mass. RESULTS: Abdominal pain was observed in one case and anorexia, vomiting, and weight loss in one case. There was marked elevation of serum alpha-fetoprotein (27,000 ng/mL) in one case of liver metastases. Complete excision was performed in two cases in which the tumors were located in the tail of the pancreas. Partial excision was performed in two patients who had unresectable tumors of the head of the pancreas. One patient had an unresectable tumor at diagnosis and needle aspiration biopsy was carried out under ultrasound guidance. Electron microscopy was performed on pathological specimens of three cases and showed zymogen granules but not neuroendocrine granules. Immunocytochemical studies for alpha-fetoprotein, insulin, glucagon and somatostatin were performed in one patient, and results were all negative. Of two patients who underwent complete excision, one patient presented with liver metastases 4 months after operation and received chemotherapy, but died of tumor 6 months after operation. The other patient had local recurrence 1 year after operation. Reoperation and chemotherapy were performed, and the child is now alive without evidence of disease for 32 months. All three patients who had unresectable tumor died of tumor despite adjuvant radiotherapy and chemotherapy. CONCLUSIONS: The authors emphasize that the diagnosis of pancreatoblastoma in childhood should be suspected with palpation of an abdominal mass, and the chance for cure may be determined by complete excision of the tumor.

Child, Preschool↗
PubMed1997

Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy.

PURPOSE: We investigated forskolin, a direct adenylate cyclase activator, as an intracavernosal vasoactive agent in management of vasculogenic impotence. MATERIALS AND METHODS: Concentration responses for forskolin and prostaglandin E1 induced relaxation of phenylephrine precontracted strips of human corpus cavernosum smooth muscle were constructed in vitro. Cyclic adenosine monophosphate (cAMP) synthesis was determined with papaverine, phentolamine, prostaglandin E1 and forskolin in human corpus cavernosum smooth muscle cell cultures. Dose-dependent hemodynamic responses to intracavernosal forskolin (5 to 20 micrograms) were evaluated in a New Zealand White rabbit model. Safety and efficacy outcome data were obtained in vasculogenically impotent patients who signed informed consent and met strict inclusion and exclusion criteria that included having had standard self-injection therapies fail. RESULTS: In vitro forskolin and prostaglandin E1 alone caused concentration dependent relaxation with an EC50 of approximately 200 nm. and 16 nm., respectively. When the 2 agents were combined, the concentration response curve for relaxation shifted to the left. cAMP production was highest in cells treated with prostaglandin E1 and forskolin and was unaffected by papaverine or phentolamine. In 3 animals, equilibrium intracavernosal pressure and duration of erection had a dose dependent increase. Clinical investigation in 31 patients showed no adverse events with a mean of 14 +/- 4, range 11 to 18 months of followup. Overall 61% reported improvement in rigidity and/or erection duration using intracavernosal forskolin (98 micrograms./ml.), papaverine (29 mg./ml.), phentolamine (0.98 mg./ml.) and prostaglandin E1 (9.8 micrograms./ml.). CONCLUSIONS: Forskolin is a United States Food and Drug Administration nonapproved vasoactive agent that acts in synergism with prostaglandin E1 to induce smooth muscle relaxation. In combination with other vasoactive agents, forskolin has demonstrated preliminary safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent pharmacotherapy.

Alprostadil↗
PubMed1997

Evidence of Hop Japanese pollinosis in Korea: IgE sensitization and identification of allergenic components.

BACKGROUND: Hop Japanese (Hop J) pollens are abundant in the air of Korea during the autumn season. Their significance as a source of allergic sensitization is still unclear. OBJECTIVES: We sought to detect the sensitization rate to Hop J pollen as an inhalant allergen and to identify its allergenic components. METHOD: We carried out skin prick tests with Hop J pollen extract in 1287 patients with respiratory allergy who visited our hospital over the course of 1 year. The serum-specific IgE antibody to Hop J pollen antigen was detected by ELISA, and its binding specificity was confirmed by the ELISA inhibition test. To confirm the respiratory sensitization, bronchoprovocation tests were performed in 16 asthmatic patients sensitive to this pollen. To characterize allergenic components, Hop J pollen extract was analyzed by means of sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by IgE immunoblotting. RESULTS: A positive result on the skin prick test (> or = 2+ of the antigen to histamine ratio) was noted in 79 (6.1%) patients. The serum-specific IgE antibody was detected in 18 (41.9%) patients among 43 positive reactors tested. The ELISA inhibition test with the addition of Hop J pollen extract showed a dose-dependent response. Minimal inhibitions were noted with addition of ragweed and mugwort pollen extracts. Nine asthmatic patients showed significant bronchoconstriction after inhalation of the Hop J pollen extract (five early and four dual asthmatic responders), and all of them had high specific IgE binding. Immunoblot analysis revealed 12 IgE-binding components ranging from 13 to 89 kd. Three bands (13 kd, 74 kd, and 80 kd) were bound to the IgE among the sera tested from more than 50% of the patients. CONCLUSION: We believe that the Hop J pollen should be considered as a relevant allergen during the autumn season and thus included in skin test batteries in Korea. Some patients diagnosed as having "intrinsic" asthma or rhinitis might be sensitized to this pollen and other previously unknown allergens.

Adult↗
PubMed1997

Characterization of protein release through glucose-sensitive hydrogel membranes.

Glucose-sensitive phase-reversible hydrogels have been prepared based on the specific interaction between polymer-bound glucose and concanavalin A (Con-A). The main goal of this study was to characterize the release of model proteins (insulin and lysozyme) through the hydrogel membrane as the free glucose concentration in the environment was changed. The diffusion of the model proteins through the hydrogel membrane was examined using a diffusion cell. Porous poly(hydroxyethyl methacrylate) (PHEMA) membranes were used to sandwich the mixture of glucose-containing polymers and Con-A in between the donor and receptor chambers. The porous PHEMA membranes allowed diffusion of glucose, insulin and lysozyme, while preventing loss of glucose-containing polymers and Con-A in the sol state. The release rate of model proteins through the glucose-sensitive hydrogel membrane was dependent on the concentration of free glucose. The release rate of the proteins did not remain constant, however, due to the change in free glucose concentration resulting from diffusion of glucose from the receptor chamber to the donor chamber. This study demonstrated the possibility that the glucose-sensitive phase-reversible hydrogels can be used to regulate the insulin release as a function of the free glucose concentration in the environment.

Concanavalin A↗
PubMed1997

A semiparametric method for describing noisy population pharmacokinetic data.

We propose a semiparametric method to estimate model-independent pharmacokinetic (PK) measures such as area under concentration-time, peak concentration and time to peak concentration (Tpeak), for noisy population PK data from a sparsely sampled prospectively designed trial. The method is developed within the mixed-effect model framework, for the single-dose and steady-state case. We describe individual concentration vs. time using a longitudinal spline, consisting of a template spline, common to all individuals, and an individual-specific distortion spline accounting for individual differences. We impose a number of constraints on the longitudinal spline, including (i) it has a decreasing tail, (ii) its typical Tpeak is near the modal Tpeak observed in the population data, and (iii) its value is zero at time zero (single dose), or the same nonzero value at the beginning and end of a dosing interval (steady state). We test our method using simulated data and compare its performance to that of a parametric and a nonparametric method. An actual data example is also shown. The performance of the method is as good or better than that of a standard nonparametric method, and when the analysis model is misspecified, the method is superior to a standard parametric one. Since it is often not apparent that an analysis model is correct, we propose this approach as a general method for analysis.

Anti-HIV Agents↗
PubMed1997

Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency.

OBJECTIVE: Organic female sexual dysfunction may be related in part to vasculogenic impairment of the hypogastric-vaginal/clitoral arterial bed. The aim was to develop an animal model of vaginal engorgement insufficiency and clitoral erectile insufficiency. METHODS: Pelvic nerve stimulated vaginal engorgement and clitoral erection were achieved in control (normal diet, n = 8) and atherosclerotic (balloon injury of aorto-iliac arteries and 0.5% cholesterol diet, n = 7) New Zealand White female rabbits. After 16 weeks, novel hemodynamic variables including vaginal wall and clitoral blood flow, vaginal wall and clitoral intracavernosal pressure, vaginal length, vaginal luminal pressure, blood levels of cholesterol and triglycerides, aorto-iliac angiography and vaginal wall and clitoral erectile tissue histology were recorded in the two groups. RESULTS: Concerning pelvic nerve stimulated vaginal hemodynamic changes, there was significantly less increase in blood flow (ml/min/100 gm tissue), wall pressure (mmHg) and length changes (mm) in atherosclerotic (9.3 +/- 3.7, 4.8 +/- 3.8, 67.3 +/- 8.3) compared to control (13.9 +/- 4.5, 5.5 +/- 2.6, 74.1 +/- 10.0) animals respectively. Histologic examination of clitoral erectile tissue demonstrated cavernosal artery atherosclerotic changes and diffuse vaginal and clitoral fibrosis. Aorto-iliac angiography in atherosclerotic animals revealed diffuse moderate to severe atherosclerotic occlusion. CONCLUSIONS: Vaginal engorgement and clitoral erection depend on increased blood inflow. Atherosclerosis is associated with vaginal engorgement insufficiency and clitoral erectile insufficiency.

Adrenergic alpha-Antagonists↗
PubMed1997

Pharmacokinetics of saquinavir, zidovudine, and zalcitabine in combination therapy.

We investigated the pharmacokinetics of zidovudine, zalcitabine, and saquinavir in AIDS Clinical Trial Group protocol 229. Patients received either saquinavir, zalcitabine, or a combination of both, together with zidovudine three times a day. Approximately 100 patients were enrolled in each treatment arm, and intensive pharmacokinetic studies were performed on about 25 patients per arm at weeks 1 and 12. We estimated the pharmacokinetic parameters of all three drugs by using parametric and nonparametric methods. The mean values of the pharmacokinetic parameters of zidovudine (clearance [CL]/bioavailability [F], 168 liters/h; volume of distribution [V]/F, 185 liters; half-life, 0.76 h) and zalcitabine (CL/F, 25 liters/h; V/F, 92.2 liters; half-life, 2.7 h) were similar to those reported previously. For saquinavir, the mean pharmacokinetic parameter estimates using parametric methods were as follows: maximum concentration of drug in serum [Cmax], 70.8 ng/ml; time to Cmax, 3.11 h; area under the curve, 809 ng x h/ml; CL/F, 989 liters/h; V/F, 1,503 liters; half-life, 1.38 h. For all three drugs, clearance decreased with age. Weight did not influence the clearance of zidovudine, but the clearance of zalcitabine and saquinavir increased with weight. There were no differences in pharmacokinetic parameters between study weeks and arms, suggesting that there is no change in kinetics with chronic administration and that there are no significant pharmacokinetic interactions among these three drugs.

Adult↗