XPERNATO-TOX: an Integrated Toxicogenomics Knowledgebase

Toxicogenomics combines transcriptome, proteome and metabolome profiling with conventional toxicology to investigate the interaction between biological molecules and toxicant or environmental stress in disease caution. Toxicogenomics faces the problems of comparison and integration across different sources of data. Cause of unusual characteristics of toxicogenomic data, researcher should be assisted by data analysis and annotation for getting meaningful information. There are already existing repositories which claim to stand for toxicogenomics database. However, those just contain limited abilities for toxicogenomic research. For supporting toxicologist who comes up against toxicogenomic data flood, now we propose novel toxicogenomics knowledgebase system, XPERANTO-TOX. XPERANTO-TOX is an integrated system for toxicogenomic data management and analysis. It is composed of three distinct but closely connected parts. Firstly, Data Storage System is for reposit many kinds of '-omics' data and conventional toxicology data. Secondly, Data Analysis System consists of analytical modules for integrated toxicogenomics data. At last, Data Annotation System is for giving extensive insight of data to researcher.

Role of Immune-Inflammatory Mechanisms in Alzheimer's Disease and Other Degenerative Diseases

Recent studies suggest that alterations of the immune-inflammatory system contribute to the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Neuroinflammatory response initiated by innate immune mechanism that self-attack on neurons, known as "autotoxicity" could be an initial key mechanism of chronic neurodegenerative diseases. Numerous experimental and pathological evidences showing upregulated inflammatory cytokines and chemokines, and the activation of complement cascade and accumulation of activated microglia in damaged regions support the important role of immune-inflammatory mechanism in the pathogenesis of neurodegenerative diseases. Epidemiological studies on the non-steroidal anti-inflammatory drugs (NSAIDs), coupled with results from animal model of AD, PD and ALS, have prompted the studies to determine if immune-inflammatory modifying agents or molecules could be a new therapeutic paradigm of neurodegenerative diseases. Molecules inhibiting proinflammatory cytokines and chemokines released from microglia, agents that inhibit activation of microglia, COX2 and complement system are now considered as a good candidate of immune-inflammatory modulating treatment. By better understanding inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approach that may not completely cure AD, PD, and ALS but will likely help slow the progression or delay the onset of these devastating diseases.

Poly (ADP-Ribose) Polymerase immunoreactivity in Motor Neurons and Astrocytes in the Spinal Cord of Sporadic Amyotrophic Lateral Sclerosis Patients

BACKGROUND: The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly (ADP-ribose) polymerase (PARP) is increased in ALS. METHOD: Twenty Spinal cord specimens were obtained at the autopsy of sALS patients (n=11) and age-matched controls with non-neurological diseases (n=9). RESULTS: Using western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased three-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with the controls. PARP-IR was increased in the pellet fraction of sALS homogenates compared with the control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. CONCLUSIONS: The present results demonstrate glial alterations in sALS tissue and support the role of glial alterations in sALS pathogenesis.

Increased Neuronal and Glial Poly (ADP-Ribose) Polymerase Immunoreactivity in the Brain of Sporadic Amyotrophic Lateral Sclerosis

BACKGROUND: Over activation of the DNA repairing enzyme, poly (ADP-ribose) polymerase (PARP) in response to oxidative damage of DNA appears to play a role in cellular death in neurodegenerative diseases. Previous data suggested that PARP immunoreactivity (IR) was increased in the white and gray matter in spinal cord of the sporadic amyotrophic lateral sclerosis (sALS), predominantly in cells with astroglial morphology. METHODS: In the present study, we evaluated whether the PARP expression was present widespread in various regions of brain tissue including the motor cortex, parietal cortex and cerebellum. RESULTS: By western blot, PARP-IR in motor cortex from sALS patients, compared to the same region from age-matched normal controls, was also significantly increased (p=0.006). Importantly, PARP-IR was also increased in the parietal cortex, and cerebellum of sALS patients compared to the controls, in regions that are usually clinically unaffected in ALS (p=0.043, p=0.035, respectively). In addition, increased PARP expression in ALS was more prominent compared to Alzheimer's brain. Immunohistochemistry revealed that PARP staining was more significant in the cortical neurons and in the subcortical white matter glial cells from sALS patients compared to normal controls and Alzheimer's disease. CONCLUSIONS: The data demonstrate that increase in PARP-IR is not limited only to the vulnerable motor cortex. Furthermore, PARP-IR is present in both cortical neuronal and subcortical glial cells. The data suggest that widespread cellular stress on neuronal and glial cells is present in the brain of sporadic ALS patients.

Genetic Polymorphism of Xenobiotics Metabolizing Enzymes and Individual Susceptible Genes to Colorectal Cancer Patients in Korea

Individual susceptibility to cancers may result from several factors including differences in xenobiotics metabolism, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. To determine the frequencies of the genotypes of phase I (CYP1A1 and CYP2E1) and phase II (GSTM1 and NAT2) metabolizing enzymes and to identify the high-risk genotypes of these metabolic enzymes to colon cancer in Korean, we have analyzed 113 colorectal cancer patients and corresponding age and sex matched healthy controls using polymerase chain reaction-restriction fragment length polymorphi(PCR-RFLP). In analysis of phase I enzymes, m1/m2, m2/m2 and Val/Val genotypes in CYP1A1 enzyme polymorphisms and C1/C2 genotype in CYP2E1 polymorphism were associated with high relative risks to colorectal cancers (Odds ratio; 1.51, 1.59, 1.76 and 1.38, respectively). Among the phase II enzymes polymorphisms, GSTM (-) genotype of GSTM1 enzyme and slow acetylator (S/S) of NAT2 enzyme had 1.48 and 1.34 times of relative risks to colorectal cancers, respectively. In combined genotyping of phase I enzymes and GSTM1 polymorphisms, the patients with m1/m2 and GSTM (-), Val/Val and GSTM (-), and C1/C2 and GSTM (-) combined genotypes had higher relative risk than the patients with each baseline of combined genotypes (Odds ratio; 2.15, 5.81 and 2.20, respectively). In combined genotyping of phase I enzyme and NAT2 polymorphisms, the combined genotypes of m1/m2 with slow acetylator and C1/C2 with slow acetylator were more susceptible to colorectal cancer (Odds ratio; 3.5 and 4.5, respectively). These results suggest that the combined genotypes of Val/Val and GSTM (-), m1/m2 and slow acetylator, and C1/C2 and slow acetylator were more susceptible to colorectal cancer in Korean. And genotyping of xenobiotics metabolizing enzymes could be useful for predicting an individual susceptibility to colorectal cancer.

Inhibition of rac1 Reduces PDGF-induced Reactive Oxygen Species and Proliferation in Vascular Smooth Muscle Cells

In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC) stimulated by PDGF via decreasing intracellular ROS. RASMC were stimulated by PDGF (80 ng/mL) with or without N-acetylcysteine 1 mM or infected with 100 mutiplicity of infection of Ad.N17rac1. Intracellular ROS levels were measured at 12 hr using carboxyl-2', 7'-dichlorodi-hydrofluorescein diacetate confocal microscopy. At 72 hr, cellular proliferation was evaluated by cell number counting and XTT assay. Compared with control, ROS levels were increased by 2-folds by PDGF. NAC and Ad.N17rac1 inhibited PDGF-induced increase of ROS by 77% and 65%, respectively. Cell number was increased by PDGF by 1.6-folds compared with control. NAC and Ad.N17rac1 inhibited PDGF-induced cellular growth by 45% and 87%, respectively. XTT assay also showed similar results. We concluded that inhibition of rac1 in RASMCs could reduce intracellular ROS levels and cellular proliferation induced by PDGF.

The Differences Between Cyclosporine and Tacrolimus in the Generation of ROS and Extracellular Matrix Accumulation in Primary Cultured Human Mesangial Cells / 대한신장학회잡지

OBJECTIVE: Cyclosporine(CsA) and tacrolimus, albeit different in structure, exert immunosuppressive effect by similar mechanism. Although most of clinical manifestations, including nephrotoxicity, are similar in the patients using these drugs, there are some differences including gum hyperplasia, neurotoxicity, and hepatic fibrosis between two drugs. There are several reports about association between reactive oxygen species(ROS) and CsA. In contrast, tacrolimus is known to decrease ROS in central nervous system. Thus, we investigated the possibility of different effects of tacrolimus and CsA on the generation of ROS, on the synthesis and degradation of collagen. METHODS: Experiments were done in primary cultured mesangial cells between 4th and 8th passages. CsA was added to the culture dishes in different concentration(making final CsA concentration of 0, 2, 4, 8 microgram/milliliter) and N-acetylcysteine(NAC) was also added in another mesangial cell culture at 4 microgram/milliliter of CsA concentration; tacrolimus was added in similar pattern(making final tacrolimus concentration of 0, 0.1, 0.2, 0.4 microgram/milliliter, NAC in 0.2 microgram/milliliter of tacrolimus concentration). RESULTS: No significant decrease in viability was noted in both cell groups, but growth retardation was weak in tacrolimus treated cells comparing with CsA treated cells. By flow cytometry, we could find the generation of ROS in CsA treated cells, but not in tacrolimus treated cells. In RT-PCR, there is no significant difference in m-RNA expression for a number of molecules including collagen III, MMP-2, TIMP-2, MT1-MMP in either CsA treated cells or tacrolimus cells. But in zymogram, MMP-2 activities were decreased at higher CsA concentration, then increased with addition of NAC. In tacrolimus cells, MMP2 activity was not changed at 0.1 and 0.2 microgram/milliliter; but, at the concentration of 0.4 microgram/milliliter, changed and not reversed by NAC. MMP-9 activity was similar in both cells. CONCLUSION: We could find ROS generation in CsA treated human mesangial cells, but not in tacrolimus treated cells. We think this difference resulted in the decrease of post-transcriptional MMP-2 activity in CsA treated cells and we also think tacrolimus cells in our experiments were not influenced by ROS. From these results, tacrolimus and CsA are different in the generation of ROS that have some effects in the matrix accumulation in mesangial cells. These result does not mean that tacrolimus is superior to CsA in nephrotoxicity, because nephrotoxicity is similar between two drugs. In conclusion, the mechanisms of nephrotoxicity are different between CsA and tacrolimus.

The roles of inducible nitric oxide synthase expression in pancreatic cancer / 대한내과학회지

BACKGROUND: The finding of frequent inducible nitric oxide synthase (iNOS) expression in human cancer indicates that nitric oxide has a pathological role in tumor progression. Increased expression of iNOS in human pancreatic cancer cells was also recently reported, but the clinicopathological and biological significance of the iNOS expression remains unclear. The aim of our study was to look for possible roles and clinical significance of iNOS expression in pancreatic cancer. METHODS: 72 pancreatic adenocarcinoma tissue specimens were obtained from surgical resection. We investigated the immunohistochemical expression of iNOS in respect to variable clinicopathological characteristics, proliferation activity (assayed by Ki-67 expression), apoptosis (by TUNEL stain), and microvessel density (by CD34 expression; angiogenesis). RESULTS: Immunohistochemical positivity for iNOS in pancreatic epithelial cells was observed in 48/72 (66.7%). Apoptotic index (AI) of positive iNOS expressions were significantly higher than for negative expression (p <0.001) and increasing intensity of COX-2 expression showed a trend with increasing AI (p<0.001). No significant association was found between iNOS expression and proliferation index or microvessel density in pancreatic cancer. The expression of iNOS protein did not correlated with age, bilirubin, CA 19-9, location, size, AJCC stage, differentiation, distant metastasis or patient survival. CONCLUSION: The expression of iNOS enzyme in pancreatic cancer contributes to apoptosis of tumor cells. However, we could not find any correlation between iNOS expression and cell proliferation, angiognesis or clinical characteristics. Further in vivo investigations are necessary to determine the putative role of the iNOS expression for tumor progression in human pancreatic cancer.

Effect of Transforming Growth Factor-beta1 on Expressions of Epidermal Growth Factor and Transforming Growth Factor-alpha in DU145 Androgen-Independent Prostate Cancer Cells / 대한비뇨기과학회지

PURPOSE: This study was designed to identify the possible mechanism of insensitivity of DU145 prostate cancer cells to the transforming growth factor (TGF)-beta1-mediated growth inhibition. MATERIALS AND METHODS: DU145 cells were treated with 4, 40, 100 pM TGF-beta1 for 3, 6, 9 days. Initially we performed the growth assay. After that, we analysed the change of cell cycle using fluorescence flow cytometry. At each time point, Western blot analysis with cell pellets was performed to investigate the change of expressions of epidermal growth factor(EGF), TGF-alpha, EGF receptor(EGFR) and TGF receptorII(TbetaR-II) proteins. RESULTS: The growth rate of TGF-beta1-treated cells was initially suppressed, but over time returned to control level. Flow cytometric analysis revealed that TGF-beta1-treated cells showed an increase in apoptotic/G1 phases, and concurrent decrease in S, G2/M phases until 6days. On day 9, however, TGF-beta1-treated cells showed a persistent increase of apoptotic unclei in spite of recovery of apoptotic/G1, S and G2/M phases. Western blot analysis showed that the intensity of EGF or TGF-alpha band decreased in dose-sependent manner on day 6. However, the intensity of each band increased up to the control level on day 9. the expression of EGFR or TbetaR-II protein did not change after treatment of TGF-beta1. CONCLUSIONS: these results suggest that EGF and TGF-alpha sould mediate in part the escape fron the inhibitory effect of TGF-beta1 in DU145 cells.

Genetic susceptibilities of cytochrome P450 1A1, 2E1, and N-acetyltransferase 2 to the risks for Korean head and neck cancer patients

Effects of Human Recombinant Interferon-Gamma and Tumor Necrosis Factor-Alpha on Expressions of Matrix Metalloproteinases and Their Activity Human Bladder Cancer Cell Lines / 대한비뇨기과학회지

No abstract available.

Effects of Human Recombinant Interferon-Gamma and Tumor Necrosis Factor-Alpha on Expressions of Matrix Metalloproteinases and Their Activity Human Bladder Cancer Cell Lines / 대한비뇨기과학회지

No abstract available.

The Effects of Cyclosporine on the Generation of ROS and Extracellular Matrix Accumulation in Cultured Human Mesangial Cells / 대한신장학회잡지

OBJECTIVE: Treatment with cyclosporine(CsA) for a long-term period may induce renal glomerulosclersosis and interstitial fibrosis. Reactive oxygen species(ROS) seems to be involved in the process of glomerulosclersosis and interstitial fibrosis. We investigated the effect of CsA on the generation of ROS and extracellular matrix accumulation in cultured human mesangial cells. We also studied the relationship between ROS formation and extracellular matrix and the effect of antioxidant on ROS formation and/or extracellular matrix degradation. METHODS: Mesangial cells were treated with varying dose of Cyclosporine(0, 2.5, 5, 7.5 and 10microgram/ mL) and also with cyclosporine(5microgram/mL) plus N- acetylcysteine(1mM). ROS was measured by flow cytometric analysis. mRNA expression of MMP-2, TIMP-2, MT1-MMP and collagen III was assessed by RT-PCR method. MMP-2 activity was measured by gelatin zymography. RESULTS: No significant difference was noted in cell viability with each CsA concentration. CsA inhibited the cell proliferation in a dose dependent manner and induced the expression of ROS. Antioxidant NAC reversed the effect of cyclosporine. CsA had no effect on the mRNA expression of collagen III, MMP-2, TIMP-2, MT1-MMP. However CsA decreased the MMP-2 activity in a dose dependent manner, which was also reversed by NAC. CONCLUSION: Cyclosporine-induced ROS may be associated with the extracellular matrix accumulation, that is glomerulosclersosis and interstitial fibrosis by inhibiting the cell proliferation and by decreasing the degradation of extracellular matrix. Antioxidant, at least in vitro, may prevent some of the adverse effects of CsA on renal function.

Genetic Alterations of Human Oral Cancers Using Comparative Genomic Hybridization

The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: 3~13). High level amplification was present in 4 cases at 9p23, 12p21.1~q13.1, 3q and 8q24~24.3. Fourteen cases(78.9%, mean: 3.00, range: 1~8) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: 1~9) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at 3q24~26.7, 3q27~29, 1q22~31, 5p12~13.3, 8q23~24, and 11q13.1-13.3. The minimal common regions of losses were detected at 9q11~21.3, 17p31, 13q22~34, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q(1q22~31) and 11q(11q13.1~13.3) were mainly detected in higher stage group. The loss at 13q22~34 was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at 3q24~26.3, 1q22~31, and 5p12~13.3 and losses at 9q11~21.3, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at 3q24~26.3, 3q27~29, 5p12~13.3 and 5p are associated with the early progression of oral cancer. Gains at 1q22~31 and 11q13.1~13.3 and loss at 13q22-34 could be involved in the late progression of oral cancers.

The Frequency of CD34 and CD34 CD38 Hematopoietic Stem/Progenitor Cells in the Cord Blood and Adult Peripheral Blood / 대한소아혈액종양학회지

PURPOSE: The umbilical cord blood has been considered as an alternative source of hematopoietic stem cells for transplantation. The CD34+ is known as a common stem cell antigen and the CD34+ CD38- immunophenotype reportedly defines a primitive subpopulation of progenitor cells. In this study the frequency of CD34+ and CD34+ CD38- hematopoietic stem/progenitor cells in placental/cord blood (UCB), and adult peripheral blood (PB) were determined. METHODS: Between July and September 1998, 27 collections of UCB were performed at the obstetric units of Hanyang University Hospital. Fifteen adult PB samples were also obtained for control. RESULTS: The frequency of total CD34+ cells in UCB was higher (1.13+/-0.58% vs 0.46+/-0.30%, P=0.0002) than PB and the frequency of CD34+ CD38- cells in UCB was also greater (0.02+/-0.02 vs 0.01+/-0.01, P=0.035) than PB. The majority of UCB- and PB-derived CD34+ cells expressed CD38- antigen (98.22+/-2.11% in UCB and 97.85+/-2.56% in PB). The frequency of CD38- expression by UCB derived CD34+ cells was slightly higher (not statistically significant) than that by PB derived CD34+ cells. The frequency of CD34+ cells was increased linearly with birth weight (r=0.413). CONCLUSION: These results suggest that UCB could be a useful source of highly primitive hematopoietic stem cells for marrow reconstitution after bone marrow ablation.

A Demonhstration of a Tracheal Bronchus by Bronchoscopy and Computed Tompgraphy

Tracheal bronchus is an aberrant bronchus that arises most often from the right tracheal wall above the carina and is the result of an additional tracheal outgrowth early in embryonic life. It; incidence ranges between 0.1 and 5%. This anomaly is usually diagnosed incidentally during bronchoscopy, bronchography or computed tomography. Occasionally, it represents the underlying etiology for chronic pulmonary disease, especially if it involves the right upper lobe and reflects an abnorrnal pulmonary clearing mechanism. The tracheal bronchus may be associated with other bronchopulmonary anomalies, tracheal stenosis, or Down's syndrome. Asymptornatic tracheal bronchus does not require any treatment. In case of tracheal bronchus associated recurrent right upper lobe diseases, tracheal bronchus therapy should include resection of the aberrant bronchus as well as the lob it supplies. (J Korgan Pediatr Soc 2000;43:1501-1504)

Genetic Susceptibilities of Cytochrome P4501A1 and Glutathione S-transferase M1 to the Risk for Korean Head and Neck Squamous Cell Carcinoma Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione-S-transferase (GST) have been reported to be associated with risks to the smoking-related human cancers. The purpose of this study is to determine the frequencies of the genotypes of CYP1A1 and GSTM1 genes in healthy control of Koreans and to identify the high-risk genotypes of these metabolic genes in head and neck cancer patients. MAERIALS AND METHODS: Ninety-six healthy controls and 93 head and neck squamous cell carcinoma patients are analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distributions of CYP1A1 and GSTM1 in healthy controls according to the MspI site and absence or presence of PCR products were as following: m1/m1:m1/m2:m2/m2=39.6%:47.9%:12.5%, GSTM1 (-):GSTM1 (+)=45%:55%. GSTM1 (-) type and CYP1A1 m2/m2 types were more frequent in cancer patients than healthy controls. Among the combined genotypes of CYP1A1 and GSTM1 genes, the relative risk of CYP1A1 m1/m2, GSTM1 (-) genotypes was 2.13 times of relative odds' ratio in head and neck cancer patients. According to the tumor location, CYP1A1 m2/m2, GSTM1 (-) genotypes of larynx and CYP1A1 m1/m2, GSTM1 (-) genotypes of oral and pharynx were the highest risk groups to cancers in their locations. CONCLUSION: These results suggest that the genetic polymorphisms of CYP1A1 and GSTM1 were an important major factor to determine the individual susceptibility to head and neck cancers in Korean. And these polymorphisms and cancers susceptibile genotypes of CYP1A1 and GSTM1 in Korean population are very unique in comparison with the other ethinics.

Genetic Polymorphism of Cytochrome P4501A1 Exon 7 and Glutathione S-Transferase M1 in the Head and Neck Squamous Cell Carcinoma Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: An individual difference in susceptibility to chemically induced carcinomas is in part ascribed to genetic differences of metabolic activity of environmental procarcinogens. The cytochrome P450 family (CYPs) and glutathione S-transferase (GST) have been reported to be associated with human cancers related with smoking. The purpose of this study was to determine the frequencies of the genotypes of CYP1A1 and GSTM1 genes in healthy control of Koreans and to identify the high-risk genotypes of these metabolic genes in head and neck cancer patients. MATERIALS AND METHOD: The genetic polymorphism of CYP1A1 exon 7 and GSTM1 genes were analysed in a group of 115 healthy Koreans and 107 head and neck squamous cell carcinoma patients using allelic-specific polymerase chain reaction. RESULTS: The genotypes of CYP1A1 exon 7 (Ile/Ile, Ile/Val and Val/Val) were 59.1%, 36.5% and 4.4%, respectively, in the healthy control group, and 57.0%, 31.8% and 11.2%, respectively, in the cancer patients . The distributions of GSTM1 [GSTM1 (-), GSTM1 (+)] in healthy control group were 46.1%, 53.9% respectively, and 53.3%, 46.7%, respectively, in the cancer patients. The relative risk (odds ratio) for combination of CYP1A1 Val/Val and GSTM1 (-) genotype was estimated to be 5.17, taking the risk of combined genotype Ile/Ile and GSTM1 (+) as a reference in cancer patients. CONCLUSION: These results suggest that the genetic polymorphisms of CYP1A1 exon 7 and GSTM1 were an important major factor in determining the individual susceptibility to head and neck squamous cell carcinoma in Koreans.

Clinical Manifestations and Ultrasonographic Findings of Neonatal Septic Arthritis and Osteomyelitis

PURPOSE: This study was performed to evaluate clinical manifestations and findings of ultrasonogram of neonatal septic arthritis and osteomyelitis. We tried to determine the value of ultrasonogram as a tool for early diagnosis of septic arthritis and osteomyelitis. METHODS: We reviewed the records of 17 patients, who were diagnosed septic arthritis and/or osteomyelitis in Departments of Pediatrics and Orthopedic Surgery, Han dong University Sunlin Hospital in Pohang between Jan. 1994 and Sep. 1998. Radiologic findings were reviewed retrospectively according to the duration of symptoms at the onset. We compared the sensitivity of ultrasonogram with other radiologic tools done within 7 days of illness. RESULTS: We compared sensitivity of each imaging study done within 7 days of illness. 20%(3/5) had abnormality in plain radiographs, 78.6%(11/14) in ultrasonogram, 28.6%(2/7) in bone scan, and 100,0%(3/3) in MRI. Deep soft-tissue swelling around the bone was the earliest sign of acute osteomyelitis in ultrasonogram. Concurrently early septic arthritis showed deep soft tissue swelling around the joint and increased synovial effusion in ultrasonogram. CONCLUSION: Ultrasonogram is not so expensive, non-invasive, not harmful to patients, and there is no need to sedate patients for examination. Comparing with other imaging studies, the sensitivity of ultrasonogram is relatively high. Ultrasonogram is a useful diagnostic tool of septic arthritis and osteomyelitis in newbom infants.

Microsatellite Instability and Its Clinicopathologic Significance in Korean Gastric Cancer Patients

BACKGROUND: Genomic instability has been reported as a novel mechanism of tumorigenesis. Microsatellites are short tandemly repeated nucleotide sequences throughout the human genome. Widespread somatic mutations in these sequences due to the loss or gain of one or more repeated units are termed as microsatellite instabilites (MI). MI have been found to be the result of numerous replication errors due to mutations in mismatched repair genes. Recently, MI have been recognized as the causes of the increased mutation rates of cancer cells. An elevated mutation rate manifested by MI may also affect various genes that are essential for normal cell function and growth, thus contributing to tumor initiation, promotion, and progression. We investigated the frequency of MI in a series of 44 gastric carcinomas in an attempt to clarify the role of these genetic alterations in gastric carcinogenesis and to see whether the cases with MI displayed any clinical significance and morphologic features and/or whether they showed distinctive relations with any clinicopathologic characteristics. METHODS: We analyzed 44 gastric carcinomas and paired samples from non-neoplastic mucosa of Korean patients who had undergone a gastrectomy. The samples were immediately frozen in liquid nitrogen and stored at 70oC until use. High molecular weight DNAs were isolated by standard methods only from cases whose were composed of more than 50% tumor cells. Ten loci of microsatellites were used in this study: D3S1766, D3S1339, D3S1029, D9S162, D9S171, INF-a, D11S925, D11S1818, D11S35, and D11S1284. The MI analysis was performed by Polymerace Chein Reaction (PCR) with 33P-labelled primers. PCR products were separated on 6% polyacrylamide gel containing 7M urea, and autoradiographed. H-E stained sections were used to review the pathologic features. The relationships between MI incidence and clinicopathologic findings were statistically tested. RESULT: Analysis of the 44 cases at the 10 loci of microsatellites allowed us to identify 19 instabilities (43%): 15 cases at 1 locus, 2 cases at 2 loci, and 2 cases at multiple loci. The incidence of MI was remarkably increased in cases with poor differentiation and node metastasis (p=0.067 and p=0.007, respectively). Comparing the histologic type (diffuse vs. intestinal type), the diffuse type of carcinoma had a higher incidence; however, there was no statistical significance (55% vs. 33%, p=0.108). There was no significant correlation between MI and other prognostic variables including location, tumor size, and distant metastasis. CONCLUSIONS: These results confirm that the mutator phenotype plays in a certain role gastric carcinogenesis. The gastric cancers with MI were correlated with the worse prognostic variables of poor differentiation and node metastasis, suggesting that MI appear to be useful as possible indicators of the worst prognosis and represent important genetic alterations associated with tumor progression in gastric carcinogenesis.