• Childhood Kidney Diseases
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• 제10권1호
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• pp.58-64
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• 2006

최근 들어 모유 단독 수유의 장기화 및 잘못된 식이 제한 등으로 인한 비타민 D 결핍성 구루병의 발병이 점차 증가하고 있는 시점에서, 비타민 D 결핍성 구루병 및 이와 동반된 저칼슘혈증성 경련에 대한 예는 다소 보고된 바 있으나, 비타민 D 결핍으로 인해 골 병변 뿐 아니라 저칼슘 혈증, 부갑상선 기능 항진증, 나아가 신세뇨관성 산증까지 초래한 예는 보고된 바가 없었다. 저자들은 8개월간 모유 단독 수유만 유지하던 중 저칼슘혈증성 경련을 주소로 내원하여 골 병변을 동반한 비타민 D 결핍성 구루병과 부갑상선 항진 및 근위 세뇨관성 산증을 진단 받은 후, 적절한 칼슘, 비타민 D, 중탄산염 투여 후 완전히 회복된 환자의 1례를 경험하였기에 보고하는 바이다.

• Applied Microscopy
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• 제14권2호
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• pp.66-80
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• 1984

The organic phosphorus compounds have been widely used as an insecticide, since toxicity of these compounds is especially drastic to the insects than to men and other mammals. The organic phosphates are rapidly hydrolized and hence have little cumulative and ecologic effects. However, due to their acute toxic effects organophosphate have recorded rather high fatalities in men and domestic animals. The organic phosphorus compounds are powerful inhibitors to the carboxylic esterase enzymes such as acetylcholinesterase and pseudocholinesterase. As a result of firm binding characteristics of phosphate radicals to the active sites of enzyme, the activities of these enzymes are inhibited by the organophosphates. The organophosphates such as diazinon is easily observed from skin, gastrointestinal tract, conjunctivas and respiratory tract, and it is converted to more toxic form during metabolism in the liver The present study was carried out in order to investigate the hepatotoxicity of diazinon by observing the changes in the ultrastructure of cytoplasmic organelles of hepatic cells in albino mice. The animals were killed at 6, 12 and 24 hours after administration of 25mg/kg diazinon. The piece of hepatic tissue obtained from each animal was ultrathinly sectioned. The specimens stained by uranyl acetate and lead citrate double contrast methods were observed with JEM model 100B electron microscope. The results obtained were as follows: 1) A prominent dilatation and sacculation of the cisternae of rough endoplasmic reticulum associated with detachment of membrane bound-ribosomes, and disaggregation of the free ribosomes were recognized. 2) The hypertrophy of the smooth endoplasmic reticulum associated with depletion of the glycogen particles was observed. 3) The atrophy of cisternae of Golgi complex was observed. 4) A large number of secondary lysosomes (autophagic vacuoles and residual bodies) were formed. Consequently it is suggested that diazinon would induce disorganization of the cytoplasmic organelles of hepatocytes in albino mice.

• Molecules and Cells
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• 제25권1호
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• pp.64-69
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• 2008

Although the arthritis symptoms observed in the K/BxN model have been shown to be dependent on the functions of T and B cells specific to the self antigen glucose-6-phosphate isomerase, less is known about the in vivo roles of $CD4^{+}CD25^{+}$ regulatory T($T_{reg}$) cells in the pathology of K/BxN mice. We determined the quantitative and functional characteristics of the $T_{reg}$ cells in K/BxN mice. These mice contained a higher percentage of $Foxp3^+\;T_{reg}$ cells among the $CD4^+$ T cells than their BxN littermates. These $T_{reg}$ cells were anergic and efficiently suppressed the proliferation of $na\ddot{i}ve$ $CD4^+$ T cells and cytokine production by effector $CD4^+$ T cells in vitro. Antibody-mediated depletion of $CD25^+$ cells caused K/BxN mice to develop multi-organ inflammation and autoantibody production, while the symptoms of arthritis were not affected. These results demonstrate that despite the inability of the $T_{reg}$ cells to suppress arthritis development, they play a critical role protecting the arthritic mice from systemic expansion of autoimmunity.

• 한국수산과학회지
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• 제40권1호
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• pp.39-49
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• 2007

Species competition among the toxic dinoflagellates Alexandrium tamarense and Gymnodinium catenatum and the diatom Skeletonema costatum was simulated using a mathematical model. Prior to the model simulation competition experiments using the three species were conducted to obtain data for validation by the simulation model. S. costatum dominated at a density of ${\sim}10^{4}\;cells/mL$ compared to the other species in the medium with dissolved inorganic phosphorus (DIP). The growth of S. costatum was also stimulated by the addition of dissolved organic phosphorus (DOP), such as uridine-5-monophosphate (UMP) or glycerophosphate (Glycero-P), although this species is unable to take up DOP. This implies that the growth of S. costatum may be supported by DIP, which is hydrolyzed by alkaline phosphatase produced from A. tamarense and G. catenatum. The species competition model was run assuming the environmental conditions of northern Hiroshima Bay, Japan, during spring and summer. G. catenatum increased in cell density and neared the level of S. costatum at the end of the calculation. In the sensitivity analyses by means of doubling and halving parameters, depleted DIP had little effect on the cell density of G. catenatum. However the growth of A. tamarense and S. costatum was significantly affected by changes in the parameter values. These results indicate that if DIP depletion is ongoing, species that have a large phosphate pool in their cells, such as G. catenatum, will predominate in the community.

• 동아시아식생활학회지
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• 제6권3호
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• pp.295-305
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• 1996

This study was done to evaluate the effectiveness of dietary calcium level(a diet which met 100% or twice the calcium level in AIN-76 diet) on preventing bone loss in ovariectomized rats. Forty female Sprauge-Dawley rats(body weight 200$\pm$5g) were divided into two groups. One group were ovariectomized(Ovx) while the others received sham operation(Sham). Thereafter, each rat group was further divided into normal calcium diet(NCD, 0.52%) and high calcium diet(HCD, 1.04%) sub-groups. All rats were fed on experimental diet and deionized water ad libitum for 8 weeks. Urinary pyridinoline & creatinine and serum estradiol, luteinizing hormone, calcium, phosphate, total protein, albumin, alkaline phosphatase and osteocalcin were determined. There were no significant differences in serum calcium. total protein and albumin in the two groups(Ovx vs Sham) of rats. Ovariectomized rats had significantly lower estradiol than sham operated rats. There was a highly significant correlation between total bone mineral density(TBMD) and overall level of esteradiol(r=0.59, p<0.05). Total bone mineral density did not correlate significantly with ALP or osteocalcin, although a negative trend was evident. However, the rats fed high calcium diet had a lower crosslinks value and osteocalcine than the rats fed normal calcium diet. An increased rate of bone turnover is usually associated with a decrease in bone mass bexause bone formation at each remodeling site is never as great as resorption. Ovariectomized rats fed high calcium diet had a lower crosslink value and osteocalcin; it means high cacium diet decreased bone turnover rate. The findings from the present study demonstrated that bone loss due to ovarian hormonal deficiency can be partially prevented by a high calcium diet. Futhermore, these findings support the strategy of the use of a high calcium diet in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4981-4985
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

• 약학회지
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• 제58권1호
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• pp.21-27
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• 2014

We have developed 8 peptide derivatives as potential MC1R antagonists and their inhibitory effects on ${\alpha}$-MSH induced cell growth in cultured normal human melanocytes (NHM) were investigated. From these experiments, the two most potent peptide derivatives, 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_9NH_2$ (P 7) were selected for further studies. In ${\alpha}$-MSH depleted NHM cells, we have found that the treatment with 1 ${\mu}M$ of these two peptide derivatives, P 6 and P 7, inhibited the cell proliferation induced by the addition of 1 nM ${\alpha}$- MSH by 70% and 72%, respectively. In NHM cells without previous ${\alpha}$-MSH depletion, 1 ${\mu}M$ treatment in the presence of 10 nM ${\alpha}$-MSH resulted in 70% (P 6) and 80% (P 7) decrease in cell growth and 64% (P 6) and 71% (P 7) reduction in melanin synthesis, respectively. The peptide derivatives P 6 and P 7 were proved to have no apparent cytotoxicity and inhibited the elevation of intracellular cAMP concentration triggered by ${\alpha}$-MSH. In conclusion, our data suggest that the peptide derivatives reported in this study, 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His- Arg-Trp-$(Lys)_9NH_2$ (P 7) strongly antagonize ${\alpha}$-MSH, inhibit cell proliferation and melanin synthesis, and lower the intracellular cAMP concentration, hence have a promising potential as a novel skin lightening agent.

• Journal of Chest Surgery
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• 제25권7호
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• pp.693-701
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• 1992

Extracorporeal cardiopulmonary bypass[CPB] has been associated with a wide variety of hematologic derangements, including a transient deformation and hemolysis of red blood cells[RBCs], which is supposed to be due to mechanical trauma and/or metabolic alterations. Since membrane integrity is, in part, maintained by energy requiring process, inadequate function of erythrocyte glycolytic pathway, which is inevitalble during CPB, may cause depletion of high energy phosphate pool and result in hemolysis. The authors performed an investigation to assess whether administration of Fructose-l, 6-diphsphate [FDP], which has been known to enhance intracellular glycolytic activities, could counteract erythrocyte hemolytic events caused by CPB. Sixty pateints with cyanotic congenital heart diseases, who underwent open heart surgery under CPB longer than 60 minutes, were randomly divided into two groups depending on whether use of FDP[Group FDP] or not[Group Control]. The age, sex, CPB time, preoperative hemoglobin level, disease entities were all similar[Table 1], and membrane type oxygenators were used in all patients. In Group, FDP, a dose of 250mg/kg body weight of FDP was administered by intravenous dripping every 12 hours from the morning of the operation to postoperative 48 hours, To demonstrate the degree and pattern of hemolysis of erythrocyte, reticulocyte count, indirect /direct bilirubin, haptoglobin, plasma hemoglobin, lactate dehydrogenase were measured every 12 hours from the time of cessation of CPB to 48 hours and RBC morphologic study, osmotic fragility test were done every 24 hours. All parameters revealed less hemolytic in group FDP [Fig. 1~5], though the differences between two groups were not significant, except plasma hemoglobin, lactate dehydrogenase changes. A pattern of sequential changes of plasma hemoglobin, lactate deh-ydrogenase showed the highest level at the time of CPB stop and abrupt decrease in following 24 hours in both groups, and statistically significant differences were demonstrated in group FDP at least for the first 12 hours postoperatively[p<0.05]. The authors conclude that they can expect the benificial effect of FDP on the maintenance of membrane stability of RBC probably by energy enhancement during the shock status of CPB, but FDP could not completely prevent the damaging effect on RBC by cardiopulmonary bypass

• Toxicological Research
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• 제35권3호
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• pp.249-255
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• 2019

Cadmium is a strong toxic heavy metal which presents in paints and liquid wastes and causes oxidative stress in fish. On the other hand, lead is widely used for different purposes, e.g. lead pipes, it targets vital organs such as liver and kidney causing biochemical alterations. The present study evaluates the effects of 60 days exposure to Cd and Pb either single or combined together in African catfish. Sixty-four fishes were divided into 3 groups and exposed to $CdCl_2$ (7.02 mg/L) or $PbCl_2$ (69.3 mg/L) or a combination of them along with control group. Activities of acid phosphatase (ACP), lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were estimated. Moreover, gill, liver and kidney were assayed for activities of superoxide dismutase (SOD), catalase (CAT) and levels of glutathione (GSH) and malondialdehyde (MDA). Individual exposure showed that both Cd and Pb significantly decreased LDH activity and SOD activity in the kidney. Pb significantly increased G-6-PDH activity and decreased GSH level in the gill. CAT activity in liver and kidney elevated significantly on Cd exposure while lead caused a significant depletion in the liver and significant elevation in the kidney. Both Cd and Pb significantly increased MDA levels in liver and kidney while Pb increased its level in gills. The combined exposure resulted in normalization of LDH, G-6-PDH activity, and CAT activity in liver and kidney as well as GSH level in both tissues and MDA in gill and kidney. The combination increased SOD activity and MDA level in liver and decreased SOD activity in kidney and GSH level in gills. In conclusion, the antioxidant system of African catfish was adversely affected by prolonged exposure to Cd and Pb. The combined exposure caused less damage than individual exposure and returned most parameters to those of controls.

• BMB Reports
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• 제56권6호
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• pp.347-352
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• 2023

The protein family of poly (ADP-ribose) polymerases (PARPs) is comprised of multifunctional nuclear enzymes. Several PARP inhibitors have been developed as new anticancer drugs to combat resistance to chemotherapy. Herein, we characterized PARP4 mRNA expression profiles in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. PARP4 mRNA expression was significantly upregulated in cisplatin-resistant ovarian cancer cell lines, and this upregulation was associated with the hypomethylation of specific cytosine-phosphate-guanine (CpG) sites (cg18582260 and cg17117459) on its promoter. Reduced PARP4 expression was restored by treating cisplatin-sensitive cell lines with a demethylation agent, implicating the epigenetic regulation of PARP4 expression by promoter methylation. Depletion of PARP4 expression in cisplatin-resistant cell lines reduced cisplatin chemoresistance and promoted cisplatin-induced DNA fragmentation. The differential mRNA expression and DNA methylation status at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) according to cisplatin responses, was further validated in primary ovarian tumor tissues. The results showed significantly increased PARP4 mRNA expressions and decreased DNA methylation levels at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) in cisplatin-resistant patients. Additionally, the DNA methylation status at cg18582260 CpG sites in ovarian tumor tissues showed fairly clear discrimination between cisplatin-resistant patients and cisplatin-sensitive patients, with high accuracy (area under the curve = 0.86, P = 0.003845). Our findings suggest that the DNA methylation status of PARP4 at the specific promoter site (cg18582260) may be a useful diagnostic biomarker for predicting the response to cisplatin in ovarian cancer patients.