• 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.

• Journal of agricultural medicine and community health
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• v.47 no.3
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• pp.181-188
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• 2022

Objectives: The prevalence of diabetes mellitus was approximately 16% in populations of over age 30 years, and deaths from diabetes mellitus became the sixth most prevalent cause of death by disease. To assess the relationship between HbA1c and heavy metal level in blood and urine, targeted residents were evaluated in a vast steel industrial complex. Methods: We selected 414 subjects for analysis after applying the following exclusion criterion: 18 persons with diabetes mellitus. They took part in a questionnaire survey and underwent blood and urinary assessments. HbA1c and lead (Pb) level were measured in blood and, cadmium (Cd), inorganic arsenic (iAs) and mercury (Hg) were evaluated in urine. Two subgroups were divided by HbA1c 6.5%. Each subgroup was divided by 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th and 90th percentile levels of biological exposure index of the heavy metals for logistic regression. Results: Odd ratios have a tendency to increase as they go from the 90th to the 10th percentile of cadmium. However, lead, arsenic and mercury did not have significant relationships with HbA1c. In correction of age, region, gender and smoking history, a higher distribution in the subgroup with cadmium above 0.8318 ㎍/g creatinine (30th percentile) was demonstrated in the subgroup with HbA1c levels above the 6.5%, with an odds ratio of 5.26 (95% C.I. ; 1.44~19.17). Conclusion: This study found a significant correlation between urinary levels of cadmium and HbA1c in correction of several factors. It is meaningful that this outcome may be used as a basis for a study to establish the acceptable limit of urinary cadmium in Korea.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.3
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• pp.227-232
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• 2017

Although water is an essential component of the human body and is involved in many physiological processes, the effect of a steady and sufficient water intake on blood components has not well elucidated. Therefore, we investigated the changes in hematological parameters, high-sensitivity C-reactive protein (hs-CRP), and immunoglobulin G (IgG) after water intake in 13 healthy adults. They were divided into two groups: The control group (N=4), which consumed water ad libitum, and the experimental group (N=9), which consumed 2 L of water per day. Two weeks later, blood cell counts, hematocrit, and hemoglobin content had increased in the experimental group, although not significantly (p>0.05); however, there was a significant increase in the mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (p<0.05; and p<0.01, respectively), and a significant decrease in the mean platelet volume (MPV) (p<0.05). Of the immunologic parameters, a non-significant decrease in the concentration of hs-CRP, an indicator of cardiovascular disease risk, was observed (p>0.05). However, there was a dramatic and significant increase in the concentration of IgG (p<0.05). In conclusion, a steady and sufficient water intake may contribute to alleviate anemia by increasing hemoglobin. Additionally, it may decrease the risk of cardiovascular disease by decreasing platelet activation and concentration of hs-CRP. Furthermore, a steady intake of water may improve immune function by increasing the concentration of the components of humoral immunity.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.87-100
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• 2003

It is important to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of our planet as well as human health. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. Research continues to support the theory of endocrine disruption. However, endocrine disruption researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of tonicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis (2D/E) and MALDI-TOF mass spectrometry (MS) sr protein chip array and SELDI-TOF MS. Proteomics have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease. Proteomics can also play an imfortant role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to notions of endocrine disruptors. Understanding the need for the proteomics and possessing knowledge of the developing biomakers used to abbess endocrine activity potential will he essential components relevant to the topic of endocrine disruptors.

• Journal of the korean academy of Pediatric Dentistry
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• v.40 no.3
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• pp.185-193
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• 2013

Mineral trioxide aggregate (MTA) has recently been used as a pulpotomy medicament for primary molars. The aim of this study was to evaluate and compare the proliferation and differentiation potential of dental pulp stromal cells of permanent teeth and deciduous teeth cultured on MTA-coated surface. Human dental pulp stromal cells were obtained from human permanent premolars and deciduous teeth and cultured on MTA-coated culture plates. The cells were subjected to proliferation assay and cell cycle analysis. Their differentiation potential was evaluated by analysing changes in the mRNA expressions of runt-related transcriptional factor 2 (Runx2) and alkaline phosphatase (ALP). Morphological changes of cells in direct contact with MTA were observed using scanning electron microscopy (SEM). The proliferation rates, distribution of cell cycles and mRNA expression patterns of Runx2 and ALP were similar in both types of pulpal cells. SEM observations revealed that both types changed into more dendrite-like cells. On the surface of MTA, human dental pulp stromal cells from deciduous and permanent teeth were able to both proliferate and differentiate into cells that induce mineralization. MTA is suitable as a biocompatible pulpotomy medicament for primary teeth.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.133-152
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• 2005

1. 목적 Prostaglandin은 치주질환과 관련된 국소적 골 대사에 중요한 역할을 한다. ${\Delta}^{12}PGJ_2$는 생체 내에서 혈장의 존재 하에 형성되는 천연 $PGD_2$ 대사산물이며 peroxisome- proliferator에 의해 활성화되는 감마 수용체 (PPAR ${\Gamma}$)에 대해 높은 친화성을 갖는 리간드로서 핵 수용체군에 속하는 전사조절인자이다. 이 연구의 목적은 골화 과정에서 ${\Delta}^{12}PGJ_2$의 역할을 규명하기 위해, 조골세포주의 증식과 분화에 미치는 영향과 그에 관련된 세포기전을 조사하는 데에 있다. 2. 방법 인간 골육종세포주인 Saos-2 (ATCC.HTB 85)와 쥐의 조골세포주 (MC3T3-E1)를 배양한 후 실험군에 농도가 각각 $10^{-5}$, $10^{-6}$, $10^{-7}$, $10^{-8}$, $10^{-9}$ 몰인 ${\Delta}^{12}PGJ_2$와 ciglitazone (합성 PPAR 감마 길항체)를 첨가하였다. 조골세포에서 PPAR 감마의 발현을 관찰하기 위해 역전사효소-중합효소연쇄반응(RT-PCR)을 특정한 primer를 이용하여 시행하였다. 세포 증식은 1일, 2일, 3 일째에 MIT 분석법으로 측정하였고, 2 일째에 알칼리성 인산효소 (ALPase) 생산을 측정하였다. 위의 결과에서 얻은 적정한 농도에서 다양한 조골세포 분화의 표지자들-제 1 형 교원질, 알칼리성 인산효소, osteopontin 및 bone sialoprotein-에 대한 간이 정량적 역전사효소-중합효소연쇄반응 (semiquantitative RT-PCR)을 실시하였으며 골결절 형성에 대한 효과를 알아보고자 석회화 분석도 시행하였다. 3. 결과 ${\Delta}^{12}PGJ_2$와 ciglitazone 모두 Saos-2 세포주의 증식을 촉진시켰다 .$10^{-8}$ 몰의 ${\Delta}^{12}PGJ_2$와 $10^{-6}$몰의 ciglitazone을 첨가한 실험군을 대조군과 비교했을 때, 시간에 비례하여 세포 증식률이 증가되었다. 알칼리성 인산효소의 활성화 검사에서도 증식률에서와 유사한 결과를 보여주었다. 간이 정량적 RT-PCR에서는 ${\Delta}^{12}PGJ_2$로 처리한 군의 경우 제 1 형 교원질, 알칼리성 인산효소, osteopontin, 그리고 bone sialoprotein의 상대적 mRNA 수준이 유의하게 높았다. 석회화 분석에서는 MC3T3-E1 세포를 $10^{-6}$ 몰의 ${\Delta}^{12}PGJ_2$로 처리한 군과 $10^{-5}$ 몰의 ciglitazone으로 처리한 군에서 현저한 골결절 형성을 보였다. 이러한 결과들은 ${\Delta}^{12}PGJ_2$가 유용한 골 유도물질이 될 수 있으며 또한 그 작용기전이 PPAR 감마-의존형 경로와 연관되어 있음을 보여준다.

• Korean Journal of Psychosomatic Medicine
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• v.25 no.2
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• pp.153-165
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• 2017

Objectives : Recent neuroimaging studies focus on dysfunctions in connectivity between cognitive circuits and emotional circuits: anterior cingulate cortex that connects dorsolateral orbitofrontal cortex and prefrontal cortex to limbic system. Previous studies on pediatric depression using DTI have reported decreased neural connectivity in several brain regions, including the amygdala, anterior cingulate cortex, superior longitudinal fasciculus. We compared the neural connectivity of psychotropic drug naïve adolescent patients with a first onset of major depressive episode with healthy controls using DTI. Methods : Adolescent psychotropic drug naïve patients(n=26, 10 men, 16 women; age range, 13-18 years) who visited the Korea University Guro Hospital and were diagnosed with first onset major depressive disorder were registered. Healthy controls(n=27, 5 males, 22 females; age range, 12-17 years) were recruited. Psychiatric interviews, complete psychometrics including IQ and HAM-D, MRI including diffusion weighted image acquisition were conducted prior to antidepressant administration to the patients. Fractional anisotropy(FA), radial, mean, and axial diffusivity were estimated using DTI. FMRIB Software Library-Tract Based Spatial Statistics was used for statistical analysis. Results : We did not observe any significant difference in whole brain analysis. However, ROI analysis on right superior longitudinal fasciculus resulted in 3 clusters with significant decrease of FA in patients group. Conclusions : The patients with adolescent major depressive disorder showed statistically significant FA decrease in the DTI-based structure compared with healthy control. Therefore we suppose DTI can be used as a bio-marker in psychotropic drug-naïve adolescent patients with first onset major depressive disorder.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.132-139
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• 2015

Recently, $p16^{INK4a}$/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the $p16^{INK4a}$/Ki-67 dual immunostaining using a CINtec$^{(R)}$ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of $p16^{INK4a}$ and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, $p16^{INK4a}$ and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of $p16^{INK4a}$/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the $p16^{INK4a}$/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.