• 제목/요약/키워드: nuclear matrix

검색결과 532건 처리시간 0.03초

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

  • Yeo, Hyunjin;Lee, Jeong Yeon;Kim, JuHwan;Ahn, Sung Shin;Jeong, Jeong You;Choi, Ji Hye;Lee, Young Han;Shin, Soon Young
    • BMB Reports
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    • 제53권6호
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    • pp.323-328
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    • 2020
  • Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

아시아 몬순특성을 고려한 다중 GCMs 선정방법 개발 및 평가 (Development and assessment of framework for selecting multi-GCMs considering Asia monsoon characteristics)

  • 김정배;김진훈;배덕효
    • 한국수자원학회논문집
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    • 제53권9호
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    • pp.647-660
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    • 2020
  • 본 연구에서는 아시아 몬순특성을 고려한 전지구모형(General Circulation model, GCM) 선정방법을 개발하고 방법의 적정성을 평가하였다. 몬순기후와 연관된 12개의 기후변수를 선정하였으며, GCM의 과거 기후재현성을 기준으로 모의성능 평가 매트릭스 및 평가체계를 구성하였다. 19개 GCM으로부터 아시아 몬순지역 및 과거(1976 ~ 2005년) 몬순기간에 대한 12개 기후변수를 관측자료와 비교하여 GCM의 기후모의 성능을 평가하였다. GCM의 평가순위 및 강수량 모의성능을 고려하여 적정 5개 GCM (NorESM1-M, bcc-csm1-1-m, CNRM-CM5, CMCC-CMS, CanESM2)을 선정하였다. 과거 몬순계절 및 월 평균 기후에 대하여 선정된 GCM의 기후재현성을 검증하였다. 선정된 5개 GCM은 12개 기후변수에 대한 아시아 지역의 관측 기후특성을 잘 재현하였으며, 전체 GCM을 사용하는 경우에 비해 모의값과 관측값 간의 오차를 줄일 수 있는 것으로 확인되었다.

Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer

  • Min, Jimin;Choi, Boram;Han, Tae-Su;Lee, Hyuk-Joon;Kong, Seong-Ho;Suh, Yun-Suhk;Kim, Tae-Han;Choe, Hwi-Nyeong;Kim, Woo Ho;Hur, Keun;Yang, Han-Kwang
    • Molecules and Cells
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    • 제40권5호
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    • pp.346-354
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    • 2017
  • Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.

피부각질세포 HaCaT에서 진세노사이드 Rb1에 의한 유전자 발현 양상 (Gene Expression Profiling by Ginsenoside Rb1 in Keratinocyte HaCaT Cells)

  • 이동우;김정민;방인석
    • 생명과학회지
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    • 제29권5호
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    • pp.514-523
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    • 2019
  • 인삼(Panax ginseng C. A. Meyer)의 사포닌 진세노사이드 Rb1이 처리된 인간 피부각질세포 HaCaT에서 microarray 분석 및 발현이 증가된 세포사멸 반응에 대한 작용기전을 연구하였다. HaCaT 세포에 진세노사이드 Rb1의 처리로 세포사멸, 유사분열 세포주기의 G2/M 전이, 세포분열, 핵분열, 그리고 단백질 수송 등의 작용기전에 관여하는 유전자들이 2 배 이상 발현이 증가된 것으로 나타났으며, DNA 수선, 감수 핵분열, 그리고 세포외기질 체계 등의 작용기전에 관여하는 유전자들은 2 배 이상 발현이 감소된 것으로 나타났다. 특히 세포사멸 신호전달은 FAS와 PLA2G4A를 경유하는 것으로 나타났으며, 이들 유전자의 상위 조절자로 STAT3가 예측되었다. 세포사멸 반응 경유 유전자 FAS와 PLA2G4A의 활성을 qPCR로 확인한 결과, FAS 유전자는 $10{\mu}g/ml$의 진세노사이드 Rb1를 24시간 동안 처리하였을 경우 약 2 배의 발현 증가와, PLA2G4A 유전자는 6시간 처리부터 약 2 배로 증가되어 24시간 동안 처리시 2 배 이상의 유전자 발현이 증가되었다. 한편 STAT3-siRNA를 이용한 knock-down 실험에서 FAS의 발현 감소와 PLA2G4A의 발현 증가로 상위 조절자 STAT3로부터 FAS 만을 경유하는 것을 알 수 있었다. 이상의 결과 진세노사이드 Rb1의 처리에 의해 상위 조절자인 STAT3는 FAS를 경유하여 세포사멸을 유도하는 것임을 알 수 있다.

산수유의 최종당화산물 억제로 인한 주름 개선효과 (Corni Fructus Inhibits Wrinkle Formation by Reduced Advanced glycation end product (AGEs))

  • 이아름;김수현;김수지;김경조;권오준;최준영;노성수
    • 대한본초학회지
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    • 제32권5호
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    • pp.1-6
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    • 2017
  • Objectives : Corni Fructus (CF) is traditional herbal medicine used on polyuria, low back pain, and tinnitus. This study aimed to evaluate inhibits skin wrinkle formation effect of CF. Methods : To evaluate the produce inhibition effect of CF, SD-rats were distributed into four groups; normal rats (Nor), AGEs (advenced glycation end product)-induced rats (Con), AGEs-induced rats treated with 100mg/kg CF (CF). To induce AGEs, streptozotocin (50mg/kg) was administered intraperitoneally and after 3 days oral administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of CF suppressed the reactive oxygen specis (ROS) in serum. The AGEs in skin tissues was significantly reduced through treatment of CF. Furthermore, the expressions of AGEs related proteins such as polyclonal anti-$N^e$-(carboxymethyl)lysine (CML), anti-$N^e$-(carboxyethyl)lysine (CEL), AGE receptors (RAGE) were decreased in CF treated group compared with the control group in skin tissues. Inflammation-related proteins such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) reduced in CF treatment group than control group. AGE-induced rats exhibited that the significant decreased collagen however, CF treatment (100mg/kg of body weight) up regulated collagen by improved the expression levels of skin fibril-related genes such as Matrix metalloproteinase (MMP-1). Conclusion : Taken together, our study suggests that CF regulates ROS to prevent accumulation of AGEs and inhibits skin wrinkles. Our finding indicate that CF may be an effective agent for inhibits AGEs formation, and improved skin wrinkle.

화피(樺皮) 에탄올 추출물의 Ultraviolet B로 자극한 피부 각질 세포 보호 작용 (Protective Effect of Betula Platyphylla on Ultraviolet B-irradiated HaCaT Keratinocytes)

  • 최학순;김현주;이학송;백승원;김지은;송용선
    • 대한한의학회지
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    • 제44권2호
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    • pp.119-131
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    • 2023
  • Objectives: Betula Platyphylla(BP) has been used as a analgesic, anti-microbial, anti-oxidant drug in Eastern Asia. However, it is still unknown whether BP ethanol extract could exhibit the inhibitory activities against ultraviolet B(UVB)-induced skin injury on human keratinocytes, HaCaT cells. This study was aimed to investigate the protective activity of BP ethanol extract on UVB-irradiated skin injury in HaCaT cells. Methods: The skin injury model of HaCaT cells was established under UVB stimulation. HaCaT keratinocyte cells were pre-treated with BP ethanol extract for 1 h, and then stimulated with UVB. Then, the cells were harvested to measure the cell viability, production of reactive oxygen species(ROS), pro-inflammatory cytokines such as interleukin(IL) 1-beta, IL-6, and tumor necrosis factor(TNF)-𝛼, hyaluronidase, type 1 collagen, matrix metalloproteinase(MMP)s. In addition, we examined the mitogen activated protein kinases(MAPKs) and inhibitory kappa B alpha(I𝜅;-B𝛼) as inhibitory mechanisms of BP ethanol extract. Results: The treatment of BP ethanol extract inhibited the UVBinduced cell death and ROS production in HaCaT cells. BP ethanol extract treatment inhibited the UVB-induced increase of IL-1beta, IL-6, and TNF-𝛼. BP ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. BP ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of BP ethanol extract could inhibit the UVB-induced skin injury via deactivation of MAPKs and nuclear factor kappa B(NF-𝜅B) in HaCaT cells. This study could suggest that BP ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

식도암 치료용 $^{166}Ho$-Stent 개발 (Development of $^{166}Ho$-Stent for the Treatment of Esophageal Cancer)

  • 박경배;김영미;김경화;신병철;박응우;한광희;정영주;최상무;이종두
    • 대한핵의학회지
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    • 제34권1호
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    • pp.62-73
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    • 2000
  • 목적: 식도암은 종양자체 혹은 주위조직의 침범으로 인한 식도 내강의 협착으로 음식물 섭취가 곤란하고 이에 따른 영양결핍, 면역력 약화등으로 생존율이 매우 낮은 것으로 보고되고 있다. 본 연구에서는 좁아진 식도 내강을 넓혀줄 뿐만 아니라 종양에 방사선 치료도 병행할 수 있는 새로운 형태의 식도암 치료용 방사성 stent를 개발하고자 한다. 대상 및 방법: ${\ulcorner}$하나로${\lrcorner}$ 연구로를 이용하여 금속 stent 외부를 $^{166}Ho$ 동위원소가 함유된 원통형의 방사성슬리브로 덮어 씌운 방사성 stent 어셈블리($^{166}Ho$-SA)를 전 방사능화법과 후 방사능화법에 의하여 제조하였다. 결과: 폴리우레탄 :매트릭스 내에 함유되어 있는 $^{165}Ho(NO_3)_3$$^{166}Ho(NO_3)_3$의 분포도를 전자현미경 사진과 자가방사기록법으로 확인한 결과 이들 화합물이 균일하게 분포되어 있음을 알 수 있었다. 식도의 구조적 특성을 고려한 전산용 기하학적인 모델을 개발하여 식도벽에 전달되는 흡수선량을 평가하였다. 본 연구에서 개발된 방사성 stent를 황견을 대상으로 식도부위에 삽입한 결과 육안적으로 점막층의 함몰이 일어나 식도내강이 넓어짐을 확인할 수 있었다. 결론: 금속 stent 외부에 $^{166}Ho$ 동위원소가 함유된 얇은 원통형 sleeve를 덮어씌워 균일한 방사선을 방출할 수 있는 방사성 stent를 개발하였으며, 이를 좁아진 식도부위에 삽입하면 물리적 압력에 의한 식도 내강의 확장과 함께 서서히 방사선 효과에 의해 종양괴사를 유도함으로 시간이 지남에 따라 종양 크기의 증대에 의한 이차적 폐쇄를 현저히 감소시킬 수 있을 것으로 기대된다.

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유방암 환자에서 종양조직내 Collagenase 활성도와 골스캔과의 비교 (Comparison of Bone Scan Findings with Collagenase Activities in Patients with Breast Cancer)

  • 김현정;김창근;김선구;임형근;최시성;노병석
    • 대한핵의학회지
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    • 제30권3호
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    • pp.332-337
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    • 1996
  • 기저막 성분인 type IV collagen을 분해하는 type IV collagenase의 농도와 종양의 전이사이에 상관관계가 있다는 동물 실험보고가 있다. 저자들은 유방암환자의 종양조직내 type IV collagenase의 농도와 골스캔상 골전이 소견과 비교하여 그 의의를 알아보고자 하였다. 원발성 및 전이성 유방암 환자의 종양조직에서 92kDa 및 72kDa type IV collagenase에 대한 면역조직화학염색을 각각 57명, 56명 환자에서 시행하여 각 효소 농도를 평가하고 골스캔상 골전이 소견을 관찰하고 등급을 부여하였다. 면역조직화학적으로 평가한 각 효소의 농도는 원발성 유방암과 전이성 유방암 환자 사이에 큰 차이가 있었으며, 골스캔 소견과 효소농도를 상호 비교한 결과 각 효소의 농도가 170이하일 경우에는 골스캔상 활동적인 골전이 소견을 볼 수 없었으나 효소의 농도가 200이상일 경우 골스캔 소견은 정상에서 골전이 소견까지 매우 다양하게 분포하였다. 결론적으로, 면역 조직화학적으로 측정한 92kDa 및 72kDa collagenase의 농도가 170이하일 때는 골스캔상 대부분 정상소견을 보여 골전이의 확률이 낮았다. 반면에 각 효소치의 농도가 200이상일 경우에는 골전이의 확진과 병소의 위치를 확인하고 추적검사를 위해서는 골스캔이 필요하다고 사료된다.

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재관류가 허혈 심근세포의 미세구조에 미치는 영향 : 재관류 손상에 관한 연구 (Effect of Reperfusion after 20 min Ligation of the Left Coronary Artery in Open-chest Bovine Heart: An Ultrastructural Study)

  • 이종욱;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • 제31권8호
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    • pp.739-748
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    • 1998
  • 연구배경: 재관류 없이 허혈 심근세포의 기능이나 형태학적 변화를 원래의 상태로 회복시킬 수 없음은 주 지의 사실이나 재관류가 반드시 유익하지만은 않다는 실험결과들이 있으므로 국소적으로 일과성 허혈을 유도하여 심근세포에서 일어나는 형태학적 변화를 관찰하고 재관류가 허혈심근에 미치는 영향을 알아보고자 하였다. 재료 및 방법: 생후 12개월 내외의 홀슈타인종 소를 사용하여 정맥 마취하에서 흉부를 열고 왼쪽 관상동맥 의 전하방 가지를 20분 동안 결찰하여 국소허혈을 유도하고 결찰을 풀어 재관류를 유도하였다. 위험부위의 심근조직 을 재관류 직후, 재관류후 1, 2, 3, 6, 12시간 및 재관류 12시간후 1시간동안 보조호흡과 수액공급만을 한 후 각각 생검하여 통상적인 방법으로 처리하여 투과전자현미경으로 관찰하였다. 결과: 20분 동안의 국소허혈로 심근세포는 경도에서 중등도에 이르는 미세구조적 변화들이 나타났는데 특히 세포막하, 핵, 사립체, 심근원섬유 등의 소기관에서 많은 변화들이 관찰되었다. 그러나 재관류를 시작하여 1시간이 지나면 허혈심근세포에서는 회복을 시사하는 소견들이 나타나기 시작하였으며 미세혈관 내에서 혈전형성이나 내강의 협착 등이 관찰되었으나 재관류가 계속됨에 따라 심근세포의 미세구조적 변화들은 서서히 회복되어 가는 양상을 나 타내었다. 그러나 시간이 경과함에 따라 심내막하 심근세포의 일부에서는 재관류 손상으로 추측되는 미세구조적 변 화들이 관찰되었다. 결론: 이상의 결과로 미루어 미세혈관은 허혈에 대한 저항력이 심근세포보다 강하며 허혈 심근세포는 재관류 없이는 회복될 수 없고, 회복에는 비교적 장시간이 요구되며, 따라서 혈관폐쇄로 인한 허혈시 혈관성형술이나 혈전 용해를 촉진하는 물질을 이용한 치료는 타당성이 있는 것으로 생각되나 재관류 유발성 세포손상에 대한 주의가 요망 된다.

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Glass Dissolution Rates From MCC-1 and Flow-Through Tests

  • Jeong, Seung-Young
    • 한국방사성폐기물학회:학술대회논문집
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    • 한국방사성폐기물학회 2004년도 학술논문집
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    • pp.257-258
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    • 2004
  • The dose from radionuclides released from high-level radioactive waste (HLW) glasses as they corrode must be taken into account when assessing the performance of a disposal system. In the performance assessment (PA) calculations conducted for the proposed Yucca Mountain, Nevada, disposal system, the release of radionuclides is conservatively assumed to occur at the same rate the glass matrix dissolves. A simple model was developed to calculate the glass dissolution rate of HLW glasses in these PA calculations [1]. For the PA calculations that were conducted for Site Recommendation, it was necessary to identify ranges of parameter values that bounded the dissolution rates of the wide range of HLW glass compositions that will be disposed. The values and ranges of the model parameters for the pH and temperature dependencies were extracted from the results of SPFT, static leach tests, and Soxhlet tests available in the literature. Static leach tests were conducted with a range of glass compositions to measure values for the glass composition parameter. The glass dissolution rate depends on temperature, pH, and the compositions of the glass and solution, The dissolution rate is calculated using Eq. 1: $rate{\;}={\;}k_{o}10^{(ph){\eta})}{\cdot}e^{(-Ea/RT)}{\cdot}(1-Q/K){\;}+{\;}k_{long}$ where $k_{0},\;{\eta}$ and Eaare the parameters for glass composition, pH, $\eta$ and temperature dependence, respectively, and R is the gas constant. The term (1-Q/K) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_{0},\;{\eta}\;and\;E_{a}$ are the parameters for glass composition, pH, and temperature dependence, respectively, and R is the gas constant. The term (1-Q/C) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_0$, and Ea are determined under test conditions where the value of Q is maintained near zero, so that the value of the affinity term remains near 1. The dissolution rate under conditions in which the value of the affinity term is near 1 is referred to as the forward rate. This is the highest dissolution rate that can occur at a particular pH and temperature. The value of the parameter K is determined from experiments in which the value of the ion activity product approaches the value of K. This results in a decrease in the value of the affinity term and the dissolution rate. The highly dilute solutions required to measure the forward rate and extract values for $k_0$, $\eta$, and Ea can be maintained by conducting dynamic tests in which the test solution is removed from the reaction cell and replaced with fresh solution. In the single-pass flow-through (PFT) test method, this is done by continuously pumping the test solution through the reaction cell. Alternatively, static tests can be conducted with sufficient solution volume that the solution concentrations of dissolved glass components do not increase significantly during the test. Both the SPFT and static tests can ve conducted for a wide range of pH values and temperatures. Both static and SPFt tests have short-comings. the SPFT test requires analysis of several solutions (typically 6-10) at each of several flow rates to determine the glass dissolution rate at each pH and temperature. As will be shown, the rate measured in an SPFt test depends on the solution flow rate. The solutions in static tests will eventually become concentrated enough to affect the dissolution rate. In both the SPFt and static test methods. a compromise is required between the need to minimize the effects of dissolved components on the dissolution rate and the need to attain solution concentrations that are high enough to analyze. In the paper, we compare the results of static leach tests and SPFT tests conducted with simple 5-component glass to confirm the equivalence of SPFT tests and static tests conducted with pH buffer solutions. Tests were conducted over the range pH values that are most relevant for waste glass disssolution in a disposal system. The glass and temperature used in the tests were selected to allow direct comparison with SPFT tests conducted previously. The ability to measure parameter values with more than one test method and an understanding of how the rate measured in each test is affected by various test parameters provides added confidence to the measured values. The dissolution rate of a simple 5-component glass was measured at pH values of 6.2, 8.3, and 9.6 and $70^{\circ}C$ using static tests and single-pass flow-through (SPFT) tests. Similar rates were measured with the two methods. However, the measured rates are about 10X higher than the rates measured previously for a glass having the same composition using an SPFT test method. Differences are attributed to effects of the solution flow rate on the glass dissolution reate and how the specific surface area of crushed glass is estimated. This comparison indicates the need to standardize the SPFT test procedure.

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