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H S Ahn

Publications and source records attributed to H S Ahn.

At least 19 recordsLinked to original sources
PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5&#xd7;10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25&#xd7;10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗
PubMed2006

Early engraftment kinetics of two units cord blood transplantation.

Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, limited cell doses may compromise outcome. To enhance engraftment, CBT has been conducted using two units with promising results. However, little is known about the mechanism of engraftment. Here, we analyzed the early engraftment kinetics of eight patients given two unit umbilical CBT. Early engraftment kinetics revealed dominancy of one of two units from the day of engraftment (absolute neutrophil count > 0.5 x 10(9)/l). The median value of percentage of the predominant unit by chimerism analysis at the time of engraftment was 88% (60-100%). Two units CBT was found to be a safe, effective and promising alternative treatment option with good engraftment potential. Dominancy occurred early after CBT and is probably influenced by multiple factors.

Acute Disease↗
PubMed2005

Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole.

The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K+ channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration-dependent manner with an IC50 of 39.69+/-2.37 microM. G-protein inhibitors (pertussis toxin and GDPbetaS) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the Shaw-type K+ channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98+/-9.74 microM and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel.

Animals↗
PubMed2005

Comparison of evidence-based therapeutic intervention between community- and hospital-based primary care clinics.

The purpose of this study was to compare the proportion of therapeutic interventions that is supported by scientific evidence between hospital-based and community-based primary care clinics. The study setting is a primary care clinic in university-affiliated tertiary hospital and community-based primary care clinic in a region in Seoul. A retrospective review of patients' medical records was done according to the primary diagnosis and treatment for 890 patients in community-based clinic and 307 in hospital-based clinic. The evidence for the intervention was searched for in Medline (1966-2001) and other evidence-based databases. The evidence was then classified as one of the three categories (i) evidence from randomised controlled trials (RCTs); (ii) convincing non-experimental evidence; and (iii) interventions without substantial evidence. In the hospital-based clinics, out of 356 primary diagnosis and treatment pairs, 59.6% were supported by evidence from at least one RCTs, and 19.4% were supported by convincing non-experimental evidence. In the community-based clinics, 47.1% out of 893 pairs and 10.5% fell into each category. As a result, the proportion of interventions in community settings that were based on evidence meeting our criteria was significantly lower than that of the hospital-based settings. To facilitate evidence-based practice, supportive activity should be focused on the primary care settings based on community where medical practices are less evidence-based.

Ambulatory Care↗
PubMed2004

Autologous peripheral blood stem cell transplantation with BCVAC conditioning in childhood acute myeloid leukemia.

Autologous peripheral blood stem cell transplantation (APBSCT) after intensifying conditioning is one of the post-remission therapeutic options in childhood acute myeloid leukemia (AML) patients without a matched family donor, but the optimal conditioning regimen has not been defined. This study was performed to evaluate the efficacy of a novel conditioning regimen without busulfan or total body irradiation. In total, 28 children with AML underwent APBSCT with BCVAC (BCNU, etoposide, cytosine arabinoside and cyclophosphamide) conditioning regimen during first remission. The event-free survival rate was 71.43% for all patients and the only cause of treatment failure was relapse. Eight male patients recurred at 1-11 months (median 5 months) after APBSCT. One patient remains alive with salvage therapy after relapse. With the exception of fever, mucositis and diarrhea, no serious complications occurred during APBSCT, including veno-occlusive disease (VOD), and there was no transplantation-related mortality. One patient developed secondary MDS after APBSCT but recovered hematologically on medication. APBSCT with BCVAC conditioning was found to be a safe and effective alternative option for patients with childhood AML in first remission, without a matched family donor.

Acute Disease↗
PubMed2004

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine-based conditioning regimens without total body irradiation have been reported to be promising for bone marrow transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 and -6), fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 and -2) and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 and -1) from HLA-matched unrelated donors. Complete donor type hematologic recovery was achieved in all patients. No serious complication occurred during BMT. Only one patient developed grade I acute GVHD resolved spontaneously. Except for one who had rupture of hepatic adenoma 78 days after BMT, all the other four patients are still alive with median 566 days. Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the promising results of good engraftment, tolerable toxicity and minimal GVHD.

Adolescent↗
PubMed2003

Measuring the burden of premature death due to smoking in Korea from 1990 to 1999.

This study estimated the burden of premature death due to smoking in Korea between 1990 and 1999 using the years of life lost (YLL) due to premature death method. To implement this study, age-group-specific YLL due to premature death were calculated by employing the standard expected years of life lost method. YLL due to smoking were calculated based on assumptions and methods developed by the Global Burden of Disease Study Group. The burden of premature death due to smoking was estimated by multiplying the population attributable risk by the YLL of smoking-related diseases. In 1999, the burden of premature death due to smoking was 57.7% in males and 11.4% in females in Korea. The burden of premature death due to smoking increased from 1643 person years per 100,000 in 1990 to 1888 person years in 1999 for males, and increased from 151 person years in 1990 to 225 person years in 1999 for females in Korea. Our results suggest that the method employed in this study, generated in quantified terms, enabled the burden of premature death due to smoking to be obtained comparably with methods used by other international studies in this field, and thus can provide a rational basis for national health policy planning regarding premature death from smoking and the related risk factors in Korea.

Adult↗
PubMed2003

Glanzmann's thrombasthenia due to a point mutation within intron 10 results in aberrant splicing of the beta3 gene.

Glanzmann's thrombasthenia (GT) is an hereditary bleeding disorder caused by a quantitative or qualitative defect in the integrin alphaIIbbeta3. We attempted to identify genetic defects responsible for a case of GT in Korea. The patient was a 6-year-old boy who had suffered from hemorrhage and purpura. The cDNAs of alphaIIb and beta3 were amplified by reverse transcription (RT)-PCR and were sequenced. RT-PCR of COS7 cells transfected with Exontrap vectors containing the beta3 genomic DNA fragments were performed to verify an aberrant splicing. Transient expression of alphaIIbbeta3 on transfected-COS7 cells was determined by flow cytometry, and the presence of alphaIIbbeta3 was confirmed by immunoprecipitation. We discovered an abnormality with the insertion of 38 bp between exon 10 and exon 11, including a stop codon, in beta3 cDNA. Sequence analysis of genomic DNA showed a point mutation, G-->T, at the position 29 107 of intron 10. RT-PCR analyses of COS7 cells transfected with Exontrap vector containing the mutant beta3 gene revealed that the point mutation at the position 29 107 of intron 10, G-->T, was responsible for an aberrant splicing in the beta3 gene. The transfection experiments and immunoprecipitation revealed the absence of alphaIIbbeta3 in the COS7 cells transfected with mutant gene. The mutation at the position 29 107 of intron 10, G-->T, in the beta3 genomic DNA was found to induce an aberrant splicing and to be responsible for GT in this patient.

Alternative Splicing↗
PubMed2002

The clinical relevance of sex hormone levels and sexual activity in the ageing male.

OBJECTIVES: To assess the changes in sex hormone levels with age and the relationship of sexual functioning to testosterone levels, evaluating serum testosterone levels and erectile function in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: The study included 213 men with LUTS (age range 31-78 years) who had no confirmed erectile dysfunction. Their serum total and free testosterone, and sex-hormone binding globulin (SHBG) levels were measured, and they completed the International Index of Erectile Function (IIEF) questionnaire. RESULTS: The total and free testosterone levels decreased and SHBG increased with age, but only the change in free testosterone and SHBG were statistically significant. The correlation with age was closer for free testosterone (r = - 0.356, P < 0.001) than for SHBG (r = 0.177, P = 0.010). Regression analysis of the five domain scores of the IIEF and three hormonal levels, after correcting for age, showed that free testosterone level was significantly correlated with erectile function (r = 0.2136, P = 0.005) and orgasmic function (r = 0.179, P = 0.020), but SHBG levels were significantly correlated only with orgasmic function (r = - 0.154, P = 0.046). Total testosterone levels showed no significant correlation with any of the five domains of the IIEF. CONCLUSIONS: Of the sex hormone levels, the change in free testosterone correlated most closely with ageing and had the closest correlation with sexual activity. Contrary to previous reports, free testosterone and SHBG levels were significantly correlated with orgasmic function and/or erectile function rather than sexual desire. A complete study of sex hormone levels is needed to evaluate patients with erectile dysfunction.

Adult↗
PubMed2001

Low incidence of TEL/AML1 fusion and TEL deletion in Korean childhood acute leukemia by extra-signal fluorescence in situ hybridization.

TEL/AML1 fusion in acute leukemia results from cryptic translocation of chromosome 12 and 21, the presence of which suggests a favorable prognosis. The incidence of TEL/AML1 fusion in B-lineage ALL is approximately 25%, but the incidence in Korea has not yet been reported. To investigate the incidence of TEL/AML1 fusion and TEL deletion, bone marrow specimens from 77 Korean children with newly diagnosed acute leukemia were analyzed by FISH. We applied extra-signal FISH to discriminate a true TEL/AML1 fusion from a false-positive fusion signal. To determine the cut-off value of the TEL/AML1 fusion signal, 20 normal bone marrow specimens and 28 normal peripheral blood specimens were also analyzed. The frequency of patients with TEL/AML1 fusion was 13.3% (4 cases) among 30 B-lineage ALL and 9.5% among 42 ALL. One TEL/AML1 fusion-positive patient was also found among 4 acute biphenotypic leukemias. TEL/AML1 fusion was not found in any samples from patients with T-lineage ALL or AML. The incidence of TEL deletion was 6.7% (2 cases) among 30 B-lineage ALL and 4.8% among 42 ALL. The incidences of TEL/AML1 fusion and TEL deletion in Korean children with acute leukemia appear to be lower than those in other countries, suggesting a racial difference.

Core Binding Factor Alpha 2 Subunit↗
PubMed2001

Ifosfamide nephrotoxicity in pediatric cancer patients.

The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine beta2-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). beta2-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m2) and high (>500 mg/m2) cumulative dose of previous cisplatin was 80 g/m2 (73-102 g/m2) and 45 g/m2 (11-76 g/m2), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by beta2-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress.

Adolescent↗
PubMed2001

Short-term phytohaemagglutinin-activated mononuclear cells induce endothelial progenitor cells from cord blood CD34+ cells.

Endothelial progenitor cells (EPCs) were recently demonstrated to exist in human cord blood. Phytohaemagglutinin (PHA), a potent mitogen for mononuclear cells was used to induce EPCs from unsorted cord blood mononuclear cells (CBMCs). Adherent cells in clusters appeared approximately 24 h after CBMCs were cultured in plain Roswell Park Memorial Institute media containing 10% fetal bovine serum (culture media) and PHA. Adherent cells were further propagated for 1 week in plain culture media. Flow cytometry and Di-I staining analyses showed that CD45-, CD34+, Flk-1+, CD31+ or VE-cadherin+ EPCs were induced and that they were mainly from the CD34+ cell compartment. When enriched CD34+ cells alone were stimulated with culture supernatant of the PHA-activated CBMCs, they neither proliferated readily nor induced EPCs. Because EPCs first appeared within the clustering cells that expressed high levels of fibronectin and vascular endothelial growth factor (VEGF), our data suggest that both cell-cell/cell-matrix interaction and the local VEGF action are important in the induction of EPCs. Thus, we demonstrate for the first time that EPCs are induced from human cord blood stem cell populations that interact with neighbouring PHA-activated CBMCs. This finding may have a significant implication in inflammatory cell-mediated vasculogenesis and angiogenesis in vivo.

Antigens, CD34↗
PubMed2001

Apoptosis and megakaryocytic differentiation during ex vivo expansion of human cord blood CD34+ cells using thrombopoietin.

Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, plays important roles in early haematopoiesis. Previously, we have demonstrated that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of cord blood (CB) CD34+ cells. In this study, we have demonstrated that the TPO-induced apoptotic cells belong to the megakaryocytic (MK) lineage and that initially expanding MK progenitors declined along with the appearance of TPO-induced apoptosis. Human CB CD34+ cells were expanded in serum-free conditions with TPO. Multidimensional flow cytometry using simultaneous measurement of apoptosis and immunophenotyping showed that the TPO-induced apoptotic cells appeared in CD61+ fractions. Immunocytochemical analysis of the fluorescent activated cell-sorted fractions showed that the apoptosis-associated CD44low fraction expressed CD61. Clonogenic assay revealed 7.4 +/- 0.50-fold increase of total megakaryocyte colony-forming units (CFU-MKs) during the initial 9 d. Thereafter, the number of CFU-MKs decreased in parallel with the increase of apoptosis. When the MK colonies were subdivided according to size, the proportion of large colonies progressively decreased, while that of medium and small colonies increased. In particular, from d 6 small colonies became predominant. These results suggested that the MK progenitors matured as they expanded during ex vivo expansion with TPO and then proceeded to apoptosis.

Antigens, CD↗
PubMed2001

Mobility shift assay of calcium-binding proteins of mouse epididymal spermatozoa.

The calcium-binding proteins (CBPs) of mouse epididymal spermatozoa were analysed by mobility changes in the presence of added Ca2+ in two-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The expression patterns of relatively high molecular weight CBPs (Mr > 20 kDa) were different between caput and cauda epididymal spermatozoa. There was a constitutive expression of low molecular weight CBPs (Mr < 20 kDa) regardless of the epididymal region. Most of the CBPs disappeared after the acrosome reaction (AR) induced by Ca2+ ionophore A23187, suggesting that they originated from the acrosome and/or the plasma membrane overlaying the acrosome. Taken together, it can be suggested that changes in CBPs of spermatozoa are important features of sperm maturation during epididymal transit, and that they may be related to the fertilizing ability of mouse epididymal spermatozoa.

Acrosome Reaction↗
PubMed2001

Cell cycling status of human cord blood CD34+ cells during ex vivo expansion is related to the level of very late antigen expression.

Very late antigen-4 (VLA-4), which binds to the extracellular matrix protein fibronectin, is an integrin molecule known to be modulated during mobilization of CD34+ cells, and to be involved in signaling the mobilization stimuli. On the hypothesis that cell cycling status might be different depending on the level of VLA-4 expression, we investigated the DNA contents of human cord blood CD34+ cells during ex vivo expansion by recombinant human thrombopoietin and flt3-ligand with simultaneous measurement of surface VLA-4 at the 1st and 4th week. During this ex vivo expansion, expression of VLA-4 increased and almost all cells became VLA-4+ until the 4th day of culture. Expression of VLA-4 was maintained in the major population of the cultured cells until the 4th week. The cells in S/G2/M phase were greater in number in VLA-4 high fraction than in VLA-4 low fraction (n=4, p<.001). Furthermore, the fraction of cells in S/G2/M phase increased as the expression of VLA-4 became higher. These results suggest that cord blood CD34+ cells expressing high levels of VLA-4 have more proliferative activities.

Antigens, CD34↗
PubMed2001

The value of cystoscopy and intravenous urography after magnetic resonance imaging or computed tomography in the staging of cervical carcinoma.

The clinical staging system for cervical carcinoma presently recommended by the International Federation of Gynecology and Obstetrics (FIGO) does not include MRI or CT findings and thus suffers limited accuracy. Recently however, the positive contributions of MRI and CT to preoperative staging have been reported. This study involves a determination of the value of routine cystoscopy and intravenous urography, in the detection of bladder invasion or hydronephrosis resulting from cervical carcinoma, among patients who had undergone MRI or CT. Among a total 296 patients with cervical carcinoma, 271 patients (92%) had undergone MRI and 25 (8%) CT. Bladder invasion was identified pathologically by cystoscopic biopsy in 8 (57%) of the 14 patients with suspected bladder invasion on MRI or CT. There was no bladder invasion in any of the other cases lacking in bladder invasion evidence on MRI or CT. Hydronephrosis was identified by intravenous urography in 18 patients, as it also was in all of these cases on MRI or CT, confirming a negative predictive value for MRI or CT, in detecting bladder invasion or hydronephrosis from cervical carcinoma, of 100%. Therefore, although MRI or CT cannot totally replace cystoscopy, the latter is unnecessary in the absence of bladder invasion evidence on MRI or CT. Intravenous urography, however, can be safely omitted whenever MRI or CT is performed.

Adult↗
PubMed2000

Inhibition of cellular action of thrombin by N3-cyclopropyl-7-[[4-(1-methylethyl)phenyl]methyl]-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine (SCH 79797), a nonpeptide thrombin receptor antagonist.

A growing body of evidence suggests an important contribution of the cellular actions of thrombin to thrombosis and restenosis following angioplasty. Recently we reported on SCH 79797 (N3-cyclopropyl-7-¿[4-(1-methylethyl)phenyl]methyl¿-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine) and its analogs as new potent, nonpeptide thrombin receptor antagonists. This study further characterizes the biochemical and pharmacological actions of pyrroloquinazoline inhibitors of protease activated receptor-1 (PAR-1) in human platelets and coronary artery smooth muscle cells (hCASMC). SCH 79797 and its N-methyl analog (SCH 203099) inhibited binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP, Ala-Phe(p-F)-Arg-ChA-HArg-[(3)H]Tyr-NH(2)) to PAR-1 with IC(50) values of 70 and 45 nM, respectively. SCH 79797 inhibited [(3)H]haTRAP binding in a competitive manner. SCH 79797 and SCH 203099 inhibited alpha-thrombin- and haTRAP-induced aggregation of human platelets, but did not inhibit human platelet aggregation induced by the tethered ligand agonist for protease-activated receptor-4 (PAR-4), gamma-thrombin, ADP, or collagen. SCH 203099 inhibited surface expression of P-selectin induced by haTRAP and thrombin, and it did not increase P-selectin expression or prevent thrombin cleavage of the receptor. Thrombin and TFLLRNPNDK-NH(2) (TK), a PAR-1-selective agonist, produced transient increases in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in hCASMC. This increase in [Ca(2+)](i) was inhibited effectively by SCH 79797. However, the Ca(2+) transients induced by SLIGKV-NH(2,) a PAR-2-selective agonist, were not inhibited by SCH 79797. Thrombin- and TK-stimulated [(3)H]thymidine incorporation also was inhibited completely by SCH 79797. The results of this study demonstrate that SCH 79797 and SCH 203099 are potent, selective antagonists of PAR-1 in human platelets and hCASMC. These data also suggest that the thrombin stimulation of Ca(2+) transients and mitogenesis in hCASMC is mediated primarily through activation of PAR-1.

Apoptosis Regulatory Proteins↗