• Korean Journal of Microbiology
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• v.34 no.3
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• pp.154-161
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• 1998

To investigate whether the introduced genetic marker is useful to detect the survivalship and activity of the natural bacteria under the stressed conditions, one Gram-negative isolate, KP964 was transformed to the luminous phenotype by transferring luxAB gene. Under the starvation-stress this luminous bacterial culturability (determined by colony-forming-units [CFU] on agar plate) decreased rapidly below the detection limit by 37 days, while its total cell number (determined by AODC) remained almost the same as its initial inocular size. At that time period, the viable cell number was estimated to be 1400 times higher than its CFU number. The bioiuminescence (determined by relative light units [RLU]) produced under the same condition was also monitored and found to decrease more rapidly than the culturability by 5-fold. Under the other stresses, e.g., osmotic shocks, acid shock, and exposure to toxic chemicals, this bacterial strain did not show the reliable correlation between CFU and RLU. These results might not suggest the direct estimation of bioiuminescence from the stressed bacteria be an index of both the survivalship and its activity. However, when the stressed bacterial cells were incubated under the favorable condition by relieving from the existing stress, the potential bioiuminescence (the lag periods before the increase of bioiuminescence, the increase rates of bioiuminescence, and the maximal levels of bioiuminescence) was shown to be highly dependent upon the strengths of the stresses exposed to the bacterial cells. Therefore, analysis of the potential bioiuminescence from the stressed bacteria revealed good relationships with survival as well as activity.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.695-701
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• 2003

Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.284-290
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• 2003

Purpose : A new airway inflammatory marker, exhaled nitric oxide(ENO) has been reported to correlate with bronchial hyperresponsiveness(BHR) and atopy. The purpose of this study was to analyze the relationship of ENO with BHR or atopy in patients with asthma and with allergic rhinitis. Methods : The subjects consisted of 55 children with asthma, 17 with allergic rhinitis, and 14 healthy controls. The asthma group was subdivided into the atopic asthma group(n=37) and the nonatopic asthma group(n=18) and the allergic rhinitis group into BHR group(n=7) and non-BHR group(n=10). All were investigated with spirometry and measurements of ENO concentration. The correlations between ENO concentration and both methacholine $PC_{20}$(provocative concentration causing a 20% decrease in forced expiratory volume in one second) and the number of allergen skin test positivity were analyzed. Results : ENO concentrations of both asthma and allergic rhinitis groups were significantly greater than that of control(P<0.01). ENO concentration of atopic asthma was significantly greater than that of nonatopic asthma(P<0.01). In allergic rhinitis, ENO concentration did not differ according to the presence or absence of BHR(P=0.50). ENO concentrations correlated significantly with the number of skin test positivity(r=0.32, P=0.02) or methacholine $PC_{20}$(r=-0.38, P<0.01) in asthma group, but not in the allergic rhinitis group(r=0.42, P=0.09; r=-0.06, P=0.83). Conclusion : In asthma patients, some pathogenetic mechanisms associated with atopy and BHR seem to influence ENO concentration. In allergic rhinitis patients, some factors other than BHR may be important in determining ENO concentration.

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.129-135
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• 2008

Purpose: The usefulness of serum tumor markers for assessing gastric carcinoma is very limited compared to that for neoplasms in other digestive organs. Many reports have shown that serum tumor markers are closely associated with the prognosis and tumor recurrence in gastric cancer patients. However, little is known about the usefulness of serum tumor markers as a predictor of distant metastasis for gastric carcinoma. Materials and Methods: With excluding the non-specific causes of elevated tumor markers, a total of 788 patients with gastric carcinoma and who were seen at our hospitals between 2004 and 2006 were included in this study. The correlation between the preoperative level of tumor makers and the clinicopathological features was analyzed. Results: CEA was significantly correlated with age, gender and nodal metastasis, but not with the depth of tumor. The CEA level was not correlated with distant metastasis, such as peritoneal or hematogenous metastasis. In contrast, the CA 19-9 level was significantly correlated not only with the depth of tumor and nodal metastasis, but also with peritoneal metastasis. Especially, the patients with over 500% elevation of the CA 19-9 level had a significant risk of peritoneal metastasis. Conclusion: CA 19-9 is useful for predicting peritoneal metastasis in gastric cancer patients. It can be used efficiently in making the diagnostic and the treatment plan, in combination with other diagnostic tools, for gastric cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.23-28
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• 1993

Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.180-189
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• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4517-4525
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• 2016

Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.909-913
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• 2013

Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, ${\gamma}$-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

• Journal of Life Science
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• v.18 no.12
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• pp.1733-1738
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• 2008

SLC6A18, one of the neurotransmitters, was reported the possible relationship to hypertension, and it contained eight blocks of minisatellites. In this study, SLC6A18-MS5 sequence which showed the highest heterozygosity among seven minisatellites was analyzed using the Transfac software, the putative binding sites for the transcription factor Pax4 and HNF4 were discovered as a result. The HNF4 is involved in the diabetes pathway and suggested the relationship to hypertension. Thus, we investigated the putative functional significance of allelic variation in this minisatellites with respect to susceptibility for hypertension. To address this possibility, we analyzed genomic DNA from the blood of 301 hypertension-free controls and 184 cases with hypertension. A statistically significant association was not identified between the allelic distribution of SLC6A18-MS5 and occurrence of hypertension. We then examined the meiotic segregation of SLC6A18-MS5 and it was transmitted following Mendelian inheritance. Therefore, this locus could be useful markers for paternity mapping and DNA fingerprinting. Moreover, we undertook a comprehensive analysis of the genomic sequence to address the evolutionary events of these variable repeats. SLC6A18 minisatellites regions are only conserved in human and primates. This result suggestedthat intronic minisatellites analysis is powerful evolution marker for the non-coding regions in primates and can provide a great insight to the molecular evolution of repeated region in primates.