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Biomedical subjects

M H Park

Publications and source records attributed to M H Park.

At least 19 recordsLinked to original sources
PubMed2006

Immunoglobulin GM and KM genotypes in Korean patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition. We genotyped immunoglobulin allotypes of G1M (f,z), G2M (n+,n-), G3M (b,g) and KM (1,3) in 142 Korean patients with SLE and 200 healthy controls to investigate the role of the allotypes in SLE. The allele frequency of G1M (z) was significantly higher in patients with SLE as compared to the healthy controls (94.6% vs. 84.3%, corrected P = 0.0004, OR 3.30, 95% CI 1.71-6.88). The frequency of G2M (n-) allele was also higher in patients with SLE (95.3% vs. 88.3%, corrected P = 0.008, OR = 2.71, 95% CI 1.38-5.72). Distribution of the tested allele frequencies for G3M and KM were not different between the patients and controls. In the respect of antibody production, there was increased genotype frequency of G1M (z/z) in anti-Sm(-) SLE (P = 0.023 vs. control, P = 0.042 vs. anti-Sm (+) SLE). In conclusion, particular genotypes at G1M (f,z) and G2M (n+,n-) loci are significantly associated with SLE. These immunoglobulin genes may contribute to the etiology of SLE and production of autoantibodies.

Adult↗
PubMed2006

Conserved extended haplotypes of the major histocompatibility complex: further characterization.

Since the complete sequencing of a human major histocompatibility complex (MHC) haplotype, interest in non-human leucocyte antigen (HLA) genes encoded in the MHC has been growing. Non-HLA genes, which outnumber the HLA genes, may contribute to or account for HLA and disease associations. Most information on non-HLA genes has been obtained in separate studies of individual loci. To comprehensively address polymorphisms of relevant non-HLA genes in 'conserved extended haplotypes' (CEH), we investigated 101 International Histocompatibility Workshop reference cell lines and nine additional anonymous samples representing all 37 unambiguously characterized CEHs at MICA, NFKBIL1, LTA, NCR3, AIF1, HSPA1A, HSPA1B, BF, NOTCH4 and a single nucleotide polymorphism (SNP) at HLA-DQA1 as well as MICA, NOTCH4, HSPA1B and all five tumour necrosis factor short tandem repeat (STR) polymorphisms. This work (1) provides an extensive catalogue of MHC polymorphisms in all CEHs, (2) unravels interrelationships between HLA and non-HLA haplotypical lineages, (3) resolves reported typing ambiguities and (4) describes haplospecific markers for a number of CEHs. Analysis also identified a DQA1 SNP and segments containing MHC class III polymorphisms that corresponded with class II (DRB3 and DRB4) lineages. These results portray the MHC where lineages containing non-HLA and HLA variants in linkage disequilibrium may operate in concert and can guide more thorough design and interpretation of HLA-disease relationships.

3' Untranslated Regions↗
PubMed2006

Staurosporin induces neurite outgrowth through ROS generation in HN33 hippocampal cell lines.

Staurosporin, a specific inhibitor of PKC, is widely used in studies of signal transduction pathways. Previous studies have shown that staurosporin induces neurite outgrowth, but the underlying mechanisms remain unclear. Here we report that staurosporin induces neurite outgrowth in HN33 hippocampal cells. Two other PKC inhibitors, Go 6976 (specific for alpha- and beta-isoforms) and rotterlin (a selective inhibitor of PKC delta), have no neuritogenic effect. In addition, staurosporin specifically increases ROS generation. NAC, which inhibits the generation of ROS, suppresses the staurosporin-induced neurite outgrowth in HN33 cells. Further, H(2)O(2) causes neurite outgrowth. Taken together, these results confirm a neuritogenic effect of staurosporin and point to ROS as the signal mediator of staurosporin-induced neurite outgrowth in HN33 hippocampal cells. Theme: Development and regeneration Topic: Neurotrophic factors: receptors and cellular mechanisms.

Animals↗
PubMed2005

Lesional location of lateral medullary infarction presenting hiccups (singultus).

BACKGROUND: Hiccups are an infrequent result of lateral medullary infarction. Their importance may be underestimated and they can cause distress, exhaustion, and aspiration. Hiccups in lateral medullary infarction remain poorly understood OBJECTIVE: To evaluate the relation between the lesional loci of lateral medullary infarction and hiccups. METHODS: 51 patients with lateral medullary infarction were investigated by magnetic resonance imaging within three days of the onset of infarction. Seven of the 51 patients developed hiccup. RESULTS: All patients with hiccups had middle level lateral medullary lesions, including two with lower level lesions and four with upper level lesions. In the middle level lateral medullary lesions, dorsolateral lesions were most often involved. All patients with lateral medullary infarction presenting with hiccups also had vertigo, dizziness, nausea, vomiting, and dysphagia. CONCLUSIONS: The observations suggest that middle level and dorsolateral lesion locations in lateral medullary infarction frequently induce hiccups.

Adult↗
PubMed2004

Ventricular-vascular uncoupling increases expression of B-type natriuretic peptide in heart transplantation.

BACKGROUND: Allograft adaptation to a foreign circulation is imperfect as noted from persistent limitations to stress. Effective arterial elastance (Ea), a measure of afterload, provides an estimate of aortic impedance. End systolic elastance (Ees) is a load-independent measure of ventricular performance as well as its interaction in the periphery. The ratio (Ea to Ees) characterizes ventricular-vascular coupling; a value close to unity signifies poor mechanical efficiency. The purpose of this investigation was to correlate mechanical efficiency of work with expression of B-type natriuretic peptide BNP, a specific marker of ventricular stress and strain. METHODS: We measured BNP levels in 40 consecutive stable heart transplant recipients free from rejection. In addition, echocardiography was performed to obtain Ea, Ees, and their ratio (Ea to Ees) by the single-beat method. We examined correlates of BNP expression by assessing Ea to Ees, while correcting for mean arterial pressure, body mass index, left ventricular mass index, ejection fraction, and serum creatinine. RESULTS: BNP levels were significantly and positively correlated (r=0.38, P=.05) with an increased Ea to Ees ratio. By multivariable analysis, this relationship persisted independently (t=2.1, P=.04), while the five other measures were insignificant predictors. CONCLUSION: This investigation indicated that the transplanted heart demonstrates poor contractile efficiency and operates at maximal left ventricular work. This is paralleled by a tandem increase in BNP, suggesting that elevation in this stress peptide is at least partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure.

Coronary Circulation↗
PubMed2004

Corticosteroid weaning in the tacrolimus and mycophenolate era in heart transplantation: clinical and neurohormonal benefits.

BACKGROUND: Compared with cyclosporine, tacrolimus-based immunosuppression yields improved metabolic outcomes in heart transplantation. Whether corticosteroid freedom provides incremental metabolic benefits in tacrolimus and mycophenolate mofetil immunoprophylaxis remains uncertain. METHODS: In a prospective trial, 41 heart transplant patients treated with tacrolimus and mycophenolate mofetil underwent steroid weaning immediately after transplantation until weaning was complete. Weaning was interrupted only for treated rejection with or without hemodynamic compromise. Benefits of steroid weaning assessed following the first year included B-type natriuretic peptide (BNP), late infections, lipids, blood pressure, hyperglycemia, and body mass index (BMI). RESULTS: Of this 41 patient cohort (age 53 +/- 9 years, 50% black American, 35% women) followed for a total of 47 +/- 5 months, 25 had corticosteroids discontinued (62%) by an average of 20 +/- 11 months. No differences between the two groups were noted in baseline characteristics. Significant predictors of failure to wean steroids included higher rejection, BNP, and lower dose of mycophenolate mofetil. No significant benefits of steroid weaning were noted on lipids, blood pressure, hyperglycemia, and BMI. However, late infections (after 1 year) requiring hospitalizations were more frequent in the failure to wean group (0.60.4 vs 0 infections/patient/y, P <.001). INFERENCES: Unlike known metabolic benefits of steroid withdrawal with cyclosporine, heart transplant recipients treated with tacrolimus and mycophenolate mofetil demonstrate no incremental metabolic benefits, but instead experience benefits of decreased serious late infections. Furthermore, failure to discontinue corticosteroids in this series is predicted by early allograft rejection, use of lower doses of mycophenolate mofetil, and higher BNP levels suggesting poor cardiac adaptation.

Adrenal Cortex Hormones↗
PubMed2004

TNF-alpha promoter polymorphisms and extended HLA and TNF-alpha haplotypes in Koreans based on 100 families.

We investigated five single-nucleotide polymorphism (SNP) sites of tumor necrosis factor-alpha (TNF-alpha) promoter, the distribution of five-locus TNF-alpha haplotypes, and extended human leukocyte antigen (HLA)/TNF-alpha haplotypes in 200 parents from 100 unrelated Korean families. TNF-alpha SNPs were typed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and PCR restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of -1031C, -863A, -857T, -308A, and -238A alleles were 0.185, 0.145, 0.140, 0.060, and 0.040, respectively. The allele frequencies in Koreans were similar to those of Japanese. A total of five TNF-alpha haplotypes (-1031/-863/-857/-308/-238) were detected in 196 parents: TCCGG (frequency 0.617), CACGG (0.143), TCTGG (0.143), TCCAG (0.061), and CCCGA (0.036). Five most common extended HLA/TNF-alpha haplotypes (frequencies >0.020) accounted for 16% (63/392) of the total haplotypes. A total of 223 HLA haplotypes and 239 HLA/TNF-alpha haplotypes were detected, indicating that most HLA haplotypes are exclusively associated with particular TNF-alpha haplotypes.

Family↗
PubMed2004

TNF-alpha and TGF-beta1 gene polymorphisms and renal allograft rejection in Koreans.

This study was performed in order to evaluate the association of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) gene polymorphisms with renal allograft rejection in Koreans. Five TNF-alpha (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) and two TGF-beta1 (codon 10 T/C and codon 25 G/C) single-nucleotide polymorphism (SNP) sites were studied by using polymerase chain reaction (PCR) single-strand conformation polymorphism and PCR restriction fragment length polymorphism methods in 100 controls and 164 patients. The patients underwent renal transplantation, having one or more Human leukocyte antigen (HLA)-A, HLA-B and HLA-DR antigens mismatched with their donors. For the TGF-beta1 gene, we also studied the polymorphism of donors. The allele frequencies of each SNP site in controls were not different from those of patients. The frequency of TNF-alpha high-producer genotype, -308GA, and TGF-beta1 lower (intermediate)-producer genotype, codon 10 CC and codon 25 GG, were significantly higher in patients with recurrent acute rejection episodes (REs), compared to those in patients with no or one RE. The highest risk group for developing recurrent REs showed the combination of TNF-alpha high- and TGF-beta1 lower-producer genotypes. Analysis of chronic renal allograft dysfunction (CRAD) revealed that TGF-beta1 high-producer genotype of donors, codon 10 TT/TC and codon 25 GG, is associated with CRAD especially in patients with recurrent REs. The highest risk group for developing CRAD showed the combination of recipient's TNF-alpha high- and donor's TGF-beta1 high-producer genotypes. These results would be useful for predicting high-risk group for acute rejection or CRAD in renal transplantation.

Chronic Disease↗
PubMed2003

Molecular evidence supporting the classification of Hosta virus X as a distinct species of the genus.

Apotexvirus, Hosta virus X (HVX-Kr), causing mosaic and mottle symptoms was isolated from hosta plants ( Hosta spp.) in Korea. The 3'-terminal 2,711 nucleotides excluding the poly (A) tail were determined and shown to include the partial viral replicase, triple gene block (TGB) 1 (26 kDa), TGB2 (13 kDa), TGB3 (8 kDa), and 23 kDa coat protein (CP) and the 3'-nontranslated region (NTR), typical of potexviruses. The CP gene of the type isolate of HVX (HVX-U) was amplified by RT-PCR and its nucleotide sequence was determined. The CPs of HVX-Kr and HVX-U had 100% and 98.9% identical amino acids and nucleotides, respectively. Most of the regions of the genome HVX had over 50% nucleotide identical to other sequenced potexviruses. This is the first report of sequence information of HVX and molecular evidence supporting the virus as a distinct species of the genus Potexvirus.

3' Untranslated Regions↗
PubMed2003

Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis.

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising of normal and malignant squamous epithelium, were generated and contributed to the Head and Neck Cancer Genome Anatomy Project (HN-CGAP). Initial analysis of the sequence information indicated the existence of many novel genes in these libraries [Oral Oncol 36 (2000) 474]. In this study, we surveyed the available sequence information using bioinformatic tools and identified a number of known genes that were differentially expressed in normal and malignant epithelium. Furthermore, this effort resulted in the identification of 168 novel genes. Comparison of these clones to the human genome identified clusters in loci that were not previously recognized as being altered in HNSCC. To begin addressing which of these novel genes are frequently expressed in HNSCC, their DNA was used to construct an oral-cancer-specific microarray, which was used to hybridize alpha-(33)P dCTP labeled cDNA derived from five HNSCC patient sets. Initial assessment demonstrated 10 clones to be highly expressed (>2-fold) in the normal squamous epithelium, while 14 were highly represented in the malignant counterpart, in three of the five patient sets, thus suggesting that a subset of these newly discovered transcripts might be highly expressed in this tumor type. These efforts, together with other multi-institutional genomic and proteomic initiatives are expected to contribute to the complete understanding of the molecular pathogenesis of HNSCCs, thus helping to identify new markers for the early detection of preneoplastic lesions and novel targets for pharmacological intervention in this disease.

Aged↗
PubMed2003

Association of HLA-DR and type II collagen autoimmunity with Meniere's disease.

To investigate HLA-associated genetic susceptibility to Meniere's disease in relation to type II collagen (CII) autoimmunity status, HLA-DRB1 genotyping and ELISA measurement of anti-CII antibody were performed in 41 Korean patients with Meniere's disease. In the anti-CII positive subgroup (20%) of patients, the frequency of HLA-DRB1*0405 was significantly increased (uncorrected) compared with both controls (63% vs 16%) and anti-CII negative patients (63% vs 12%). In the anti-CII negative subgroup, HLA-DRB1*1201 was significantly increased (uncorrected) (27% vs 10%) and DRB1*13 was decreased (6% vs 24%) compared with controls; these alleles appeared to confer susceptibility and resistance to the development of the disease. Association of HLA-DRB1*0405 with anti-CII positive Meniere's disease in this study suggests that it shares a specific HLA-DR sequence, QRRAA, as a genetic susceptibility factor with the anti-CII positive rheumatoid arthritis. In conclusion, whilst type II collagen autoimmunity may have a partial role in Meniere's disease, different HLA-DR alleles may also be associated with either susceptibility or resistance to the development of the disease in relation to anti-CII antibody status.

Adult↗
PubMed2003

Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans.

Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is occurring at high prevalence in most Asian endemic areas. There have been some reports on human leucocyte antigen (HLA) associations with HBV infections; however, HLA association with HBV-GN has been rarely reported. Forty-six adult Korean patients with HBV-GN (42 male and four female patients, age 20-66), 100 HBsAg (-) healthy controls, and 89 individuals with chronic HBV infection were studied for HLA-DRB1 and DQB1 gene polymorphisms using high-resolution DNA typing methods. In HBV-GN patients, a strong association with HLA-DR2 was observed compared with HBsAg (-) controls (OR = 4.0). Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8). HLA-DQB1*0601, strongly linked to DRB1*1502, was also associated with MPGN subtype of HBV-GN (OR = 4.3). All these associations were also significant compared with chronic HBV infection group. For chronic HBV infection per se, DRB1*1302, DQB1*0402, and DQB1*0604 had some protective effect (OR = 0.4, OR = 0.3, and OR = 0.1, respectively), and DRB1*1101 was weakly associated (OR = 4.6) in Koreans. These results suggest that HLA-DR or related genetic factor is associated with disease susceptibility to HBV-GN in Koreans, and different pathologic subtypes of HBV-GN are influenced by the genetic factors of the patients.

Adult↗
PubMed2002

The role of nitric oxide in ocular surface diseases.

For the first time, the current series of studies provide a possible pathophysiologic mechanism of NO-induced ocular surface disease. NO is present in tear and aqueous humor and is suspected of having an important physiological role in maintaining normal homeostasis of the ocular surface. NO concentrations are higher in aqueous humor compared to tears, though some variability exists between different species. When inflammation was induced by PTK wounding or LPS, three forms of NOS expression were seen in corneal cells. Each isoform of NOS was expressed uniquely according to the specific location of inflammation. When concentrations of NO peaked, the levels of iNOS were markedly increased in fibroblasts and inflammatory cells. The correlation between NO and inflammation was confirmed by treatment with NOS inhibitor, which abrogated the amount of both NO and inflammation. The tissue damage by NO was measured by nitrotyrosine formation. Damage was detected mainly in inflammatory cells, especially those localized in and around the limbal vessel. It is likely that expression of iNOS in limbal fibroblasts has other roles related to survival of limbal stem cells and fibroblasts as well. Because the main source of NO are fibroblasts, we were able to determine the effect of various concentrations of NO on cell viability using a fibroblast culture system. Cell viability increased in dose dependent manner from 10 microM to 500 microM of the NO generator SNAP, but decreased at concentrations above 1000 microM, suggesting that the in vivo mechanism of cell death was indirect, through specific biologic pathways. Therefore, the pathophysiological mechanism of NO action is bimodal with a toxicological component in ocular surface diseases. Furthermore, its concentration and interaction with other oxygen mediators appear to vary depending on the degree of inflammation.

Animals↗
PubMed2002

Hyaluronic acid and silver sulfadiazine-impregnated polyurethane foams for wound dressing application.

Five different kinds of PU foam wound dressings were prepared to investigate their wound healing capability. They include (i) PU+silver sulfadiazine (AgSD), (ii) PU+alginate (Al), (iii) PU+Al+AgSD, (i.v.) PU+hyaluronic acid (HA), and (v) PU+HA+AgSD. Physical properties and in vitro behaviors of AgSD release and fibroblast adhesion on those dressings were evaluated. From the drug release and fibroblast adhesion studies, it was observed that PU foam impregnated with both HA and AgSD shows good drug release behavior and low adhesion of the cells. Furthermore, the HA and AgSD-containing PU foam showed excellent wound healing effect without any inflammation or yellow cluster. The wound size decreased around 77% after 1 week application of that foam dressing onto a rat skin defect.

Journal Article↗
PubMed2002

HLA class II allele and haplotype frequencies in Koreans based on 107 families.

We have investigated the distribution of HLA class II alleles and haplotypes in 107 Korean families (207 parents and 291 children) for the HLA-DRB1, DRB3/B4/B5, DQA1, DQB1 and DPB1 loci. Numbers of alleles observed for each locus were DRB1: 25, DQA1: 14, DQB1: 15, and DPB1: 13. Only two to three alleles were observed for the DRB3 (*0101, *0202, *0301), DRB4 (*0103, * 0103102 N), and DRB5 (*0101, *0102) loci. These alleles showed strong associations with DRB1 alleles: DRB3*0101 with DRB1*1201, *1301 and *1403; DRB3*0301 with DRB1*1202 and *1302; DRB3*0202 with DRB1*0301, *1101, *1401 and *1405; DRB5*0101 and *0102 were exclusively associated with DRB1*1501 and *1502, respectively. The seven most common DRB1-DQB1 haplotypes of frequencies > 0.06 accounted for 52% of the total haplotypes. These haplotypes were exclusively related with the seven most common DRB1-DRB3/B4/B5-DQA1-DQB1 haplotypes: DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 (0.085), DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401 (0.082), DRB1*09012-DRB4*0103-DQA1*0302-DQB1*03032 (0.082), DRB1*0101-DQA1*0101-DQB1*0501 (0.075), DRB1*0701-DRB4*0103-DQA1*0201-DQB1*0202 (0.065), DRB1*0803-DQA1*0103-DQB1*0601 (0.065), and DRB1*1302-DRB3*0301-DQA1*0102-DQB1*0604 (0.065). When these haplotypes were extended to the DPB1 locus, much diversification of haplotypes was observed and only one haplotype remained with a frequency of > 0.06: DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401-DPB1*0501 (0.062). Such diversification would have resulted from cumulated events of recombination within the HLA class II region, and the actual recombination rate observed between the HLA-DQB1 and DPB1 loci was 2.3% (10/438 informative meioses, including 2 recombinants informative by analysis of TAP genes). Comparison of the distribution of DRB1-DQB1 haplotypes with other populations revealed that Koreans are closest to Japanese people. However, Koreans share a few haplotypes with white people and Africans, which are rare in Japanese: DRB1*0701-DQB1*0202 and DRB1*1302-DQB1*0609. The results obtained in this study will provide useful information for anthropology, organ transplantation and disease association studies.

Alleles↗