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Biomedical subjects

K H Yoo

Publications and source records attributed to K H Yoo.

At least 19 recordsLinked to original sources

Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction.

Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (alpha-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and alpha-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney will require targeting of specific renal compartments.

Animals↗

Synthesis and antibacterial activities of new 1beta-methylcarbapenems having aminopyrimidinylthioether moiety.

The synthesis of new 1beta-methylcarbapenems 1a-d bearing aminopyrimidinylthioether moiety at C-5 position of pyrrolidine ring and their antibacterial activities are described. All the compounds exhibited potent antibacterial activity. Of these carbapenems, 1d showed the best combination of antibacterial activity and stability to dehydropeptidase-I (DHP-I).

Anti-Bacterial Agents↗

Assessment of converting from intravenous to oral administration of cyclosporin A in pediatric allogeneic hematopoietic stem cell transplant recipients.

We studied the administration method during a transition period from continuous intravenous (i.v.) infusion to oral administration of cyclosporin A (CsA). Thirty-two pediatric hematopoietic stem cell transplant (HSCT) recipients, between the ages of 8 months and 15.6 years (median 7.1 years) participated in this study. The pharmacokinetic properties of CsA was evaluated during the transition period from i.v. to oral CsA. The daily oral dose of CsA was three times higher than the i.v. dose. Oral dosing began immediately after the continuous infusion was discontinued. Whole-blood CsA concentrations were measured by a monoclonal fluorescence polarization immunoassay (FPIA). The mean+/-s.d. value of bioavailability (F), maximum concentration (C(max)), half-life (t(1/2)) of CsA were 43.1+/-14.4%, 1135.3+/-340.6 ng/ml and 3.1+/-1.2 h, respectively. Mean clearance (CL)+/-s.d. was 480.9+/-103.7, 414.9+/-137.1 and 320+/-51.8 ml/h/kg in patients <20, 20-40 and >40 kg of body weight, respectively. The CsA CL of younger children was significantly greater than for older children (P=0.044). CsA trough levels were maintained within the therapeutic range throughout the transition period. Therefore, our findings suggest that the immediate administration of an oral formulation, after discontinuation of the continuous infusion, would be practical and effective for routine clinical use.

Administration, Oral↗

Successive double high-dose chemotherapy with peripheral blood stem cell rescue collected during a single leukapheresis round in patients with high-risk pediatric solid tumors: a pilot study in a single center.

In total, 18 of 26 double high-dose chemotherapies (HDCT) in pediatric solid tumors were rescued with peripheral blood stem cells collected during a single leukapheresis round (single-harvest group, SHG). In the remaining eight HDCT, additional leukapheresis were necessary after the first HDCT (HDCT1) to rescue the second HDCT (HDCT2) (double-harvest group, DHG). Stem cell collection after HDCT1 was inefficient and delayed in patients who had received prior chemotherapy before HDCT1. The interval between HDCT1 and HDCT2 was shorter in SHG than in DHG (median 62.5 days vs 178.5 days, P-value=0.002). Hematologic recovery in HDCT2 was delayed compared to HDCT1. However, there was no difference in hematologic recovery between SHG and DHG. A high rate of treatment-related mortality (TRM) was recorded during HDCT2, but there was no evidence that the shorter interval caused a higher rate of TRM (P-value=0.454). The probability of disease-free survival at 2 years after HDCT2 in the SHG and DHG were 66.7 and 25.0%, respectively (P-value=0.031). Therefore, to administer the second HDCT earlier in double HDCT, and thus to improve the survival of patients with high-risk solid tumors, the single-harvest approach is recommended rather than the double-harvest approach.

Adolescent↗

Infection after prosthetic reconstruction in limb salvage surgery.

Among 145 patients that underwent prosthetic reconstruction between 1985 and 1998, infection developed in 18. Osteosarcoma was the most common primary tumour, and staphylococci were the major pathogenic organisms. Infections were controlled in five patients with débridement only and in two patients with a two-stage revision. Arthrodeses were performed in three and amputations in two. In six patients, infection was suppressed with antibiotics but not cured. Pulmonary metastasis developed in four of ten patients in whom chemotherapy was delayed or interrupted. Infection controls were poor in cases of delayed débridement over 2 weeks, in cementless fixation of implant, and soft tissue defects ( P<0.01). Infection after prosthetic reconstruction is not only difficult to treat but also influences the prognosis reverse.

Adolescent↗

Electrical conduction through poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA molecules.

We report direct measurements of electrical transport through poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA molecules containing identical base pairs. The observed experimental results suggest that electrical transport through DNA molecules occurs by polaron hopping. We have also investigated the effect of gate voltage on the current-voltage curve. It demonstrates the possibility of a DNA field-effect transistor operating at room temperature. Moreover, the gate-voltage dependent transport measurements show that poly(dA)-poly(dT) behaves as an n-type semiconductor, whereas poly(dG)-poly(dC) behaves as a p-type semiconductor.

DNA↗

The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines.

We mixed various amounts of methotrexate with bone cement and measured the absorbance daily for 4 weeks. The cytotoxic effects on SaOS2 and MG63 osteosarcoma cells were examined by the MTT assay, and analysed according to the methotrexate concentration and the elapsed time. The amount of eluted methotrexate was greatest during the first day, and then decreased rapidly reaching a plateau in the third week. The number of viable tumour cells decreased significantly after 72 h, and they were hardly seen after 1 week.

Antimetabolites, Antineoplastic↗

Quantification of proteinuria in children using the urinary protein-osmolality ratio.

A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m2/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061 +/- 0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073 +/- 0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78 +/- 1.10 and Uprot/Uosm was 4.42 +/- 1.34. Twenty-four hour urinary protein excretion in group 2 was 1483.6 +/- 303.7 mg/m2/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r = 0.87, P < 0.001 and r = 0.88, P < 0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m2/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children.

Adolescent↗

Effect of graded running on esophageal motility and gastroesophageal reflux in fed volunteers.

The effects of different grades of running on esophageal motility and gastroesophageal reflux in the fed state were evaluated. We studied healthy volunteers (male: 12, age: 27 +/- 5 yr) using ambulatory esophageal manometry, pH catheter and portable digital data recorder. Each exercise was performed 30 min after meal, with 20 min of rest between exercises. Subjects exercised on a treadmill at 40% and 70% maximal heart rate. The number of gastroesophageal reflux episodes, the duration of esophageal acid exposure and percent time pH below 4 were significantly (p < 0.01) increased during exercise at 70% maximal heart rate. The frequency of contraction (contraction/min) (p < 0.05), frequency of repetition (p < 0.01), percent of simultaneous contraction (p < 0.01), percent of above 100 mmHg amplitude (p < 0.05), and frequency of 2-peak contraction (p < 0.01) were significantly increased during exercise at 70% maximal heart rate. However, median amplitude and median duration showed no significant changes between each exercise session. Postprandial running exercises induce gastroesophageal reflux, which correlates with exercise intensity. These effects are mediated by disorganized esophageal motility.

Adult↗

Synthesis and biological activity of 1beta-methyl-2-[5'-isoxazoloethenylpyrrolidin-3'-ylthio]carbapenems.

A new series of 1beta-methylcarbapenems 1a-i bearing isoxazoloethenyl groups on the pyrrolidine ring has been prepared and evaluated for in vitro antibacterial activity and stability to DHP-I. Most compounds showed excellent antibacterial activity and high stability to DHP-I superior to that of meropenem. Of these new carbapenems, 1a,b,h exhibited the best combination of antibacterial activity and DHP-I stability.

Animals↗

Synthesis and antibacterial activity of new carbapenems containing isoxazole moiety.

The synthesis and biological activity of a series of new 1beta-methylcarbapenems 1a-g containing 5'-isoxazolopyrrolidin-3'-ylthio derivatives as C-2 side chain are described. Most compounds exhibited potent and well-balanced antibacterial activity as well as high stability to DHP-I comparable to that of meropenem. 1e and 1c showed the best combination of antibacterial activity and stability to DHP-I, respectively.

Anti-Bacterial Agents↗

Angiotensin stimulates TGF-beta1 and clusterin in the hydronephrotic neonatal rat kidney.

Unilateral ureteral obstruction (UUO) induces activation of the renin-angiotensin system and upregulation of transforming growth factor-beta1 (TGF-beta1; a cytokine modulating cellular adhesion and fibrogenesis) and clusterin (a glycoprotein produced in response to cellular injury). This study was designed to examine the regulation of renal TGF-beta1 and clusterin by ANG II in the neonatal rat. Animals were subjected to UUO in the first 2 days of life, and renal TGF-beta1 and clusterin mRNA were measured 3 days later. Rats were divided into treatment groups receiving saline vehicle, ANG, losartan (AT(1) receptor inhibitor), or PD-123319 (AT(2) receptor inhibitor). ANG stimulated renal TGF-beta1 expression via AT(1) receptors, a response similar to that in the adult. In contrast, clusterin expression was stimulated via AT(2) receptors, a response differing from that in the adult, in which ANG inhibits clusterin expression via AT(1) receptors. We speculate that the unique response of the neonatal hydronephrotic kidney to ANG II is due to the preponderance of AT(2) receptors in the developing kidney.

Angiotensin II↗

HFE gene mutation, C282Y causing hereditary hemochromatosis in Caucasian is extremely rare in Korean population.

Hereditary hemochromatosis (HFE), which affects 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals in Western population, results in multiple organ damage caused by iron deposition, and is treatable if detected early. C282Y mutation in HFE gene has been known to be responsible for the most hereditary hemochromatosis cases and 5-10% of white subjects are heterozygous for this mutation. However, the prevalence of hemochromatosis in the Asian population was reported to be very low and ethnic heterogeneity has been suspected. The aim of our study was to determine the prevalence of heterozygosity and homozygosity for the C282Y HFE gene mutations in 502 unrelated Koreans. Results revealed that none of them had the mutant gene, suggesting a significant ethnic difference when compared with Caucasians. Our study excluded underlying possibility of hereditary hemochromatosis in Korean which could mimic the findings of alcoholic liver disease with iron overload or liver cirrhosis with chronic hepatitis C.

Alleles↗

Functional outcome following surgical treatment of metastatic tumors involving the femur.

Thirty-eight patients treated surgically for metastatic tumors of the femur were reviewed to evaluate the effects of surgical treatment on quality of life. Average age at surgery was 59 years. The most common origin site of metastatic tumors was the lung. The intertrochanteric area was involved in 14 patients, followed by the subtrochanteric area in 11, femoral neck in 7, and shaft in 6 patients. Surgery was based on the principles that tumor excision should be maximal, and to permit early postoperative ambulation, internal fixation should be rigid with cement augmentation. Types of internal fixation were applied according to lesion site to allow early ambulation and included intramedullary nailing (11), compression hip screw (9), and Rowe plates (7). Prosthetic replacement was performed in 9 patients. Average performance scores improved from 3.8 preoperatively to 2 postoperatively, based on the Functional Classification of the New York Heart Association. In 31 patients (82%), the degree of pain relief was more than a lot according to the criteria of Kaiko. Thirty-five patients survived >5 months postoperatively. In patients with a single metastatic lesion, survival was 21 months, and in patients with multiple lesions, survival was 10 months. Surgical stabilization of a pathologic lesion involving the femur resulted in improvement in the quality of life, including pain relief and early ambulation. In selected patients with a single metastatic lesion and a low-grade primary tumor, prolonged postoperative survival may be expected.

Adult↗

Synthesis and biological evaluation of novel 1beta-methylcarbapenems having a new moiety at C-2.

The synthesis and biological activity of the novel series of 1 beta-methylcarbapenems 1a-f, bearing a variety of 3",4"-disubstituted pyrrolidinamides as substituents at C-2, are described. Of these carbapenems, diol 1a showed the most potent and well balanced antibacterial activity against Gram-positive and Gram-negative. 1a was also evaluated for pharmacokinetics and in vivo therapeutic efficacy in systemic infections.

Animals↗

Indomethacin treatment decreases renal blood flow velocity in human neonates.

This study was designed to evaluate the effect of indomethacin (ID) on renal perfusion in 13 neonates with symptomatic patent ductus arteriosus (PDA). Serial blood flow velocity in the left renal artery was measured just before and at 10, 30, 45, 60, 75 and 90 min after ID administration. Serum creatinine (Cr), sodium (Na), and osmolarity were measured just before, at 12 and 24 h, and at 3 days after ID administration. Timed urine also was collected for measurement of amount, fractional excretion of Na (FE(Na)), and creatinine clearance (C(Cr)). ID decreased end-diastolic flow velocity of renal artery and increased Pourcelot's index, starting at 10 min and lasting for 75 min (p < 0.05). Serum Cr significantly increased at 12 h, and hourly urine output and C(Cr) decreased for 24 h. Serum Na and osmolarity decreased for a period of at least 3 days (p < 0.05). FE(Na) decreased at 12-24 h (p < 0.05). We conclude that ID treatment can induce significant renal dysfunction due to diminution of renal perfusion in human neonates.

Birth Weight↗