• Title/Summary/Keyword: Receptor methods

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Radioligands for Imaging Dopamine and Serotonin Receptors and Transporters (도파민과 세로토닌 운반체 및 수용체 영상을 위한 방사성리간드)

  • Chi, Dae-Yoon
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.3
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    • pp.159-168
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    • 2000
  • In the 1980s, techniques to image the human subjects in a three-dimensional direction were developed. Two major techniques are SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) which allow the detector to detect a single photon or annihilation photons emitted from the subjects injected with radiopharmaceuticals. Since the latter two techniques can measure the density of receptors, enzymes and transporters in living human, it may be very important project to develop selective methods of labeling with radionuclides and to develop new radiopharmaceuticals. There has been a considerable interest in developing new compounds which specifically bind to dopamine and serotonin receptor and transporters, and it will be thus very useful to label those compounds with radionuclides in order to gain a better understanding in biochemical and pharmacological interactions in living human. This review mentions the characteristics of radioligands for the imaging of dopamine and serotonin receptors and transporters. Although significant progress has been achieved in the development of new PET and SPECT ligands for in vivo imaging of those receptors and transporters, there are continuous needs of new diagnostic radioligands.

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Calcium Sensing Receptor Modulation for Cancer Therapy

  • Sarkar, Puja;Kumar, Sudhir
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3561-3568
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    • 2012
  • The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.

Modeling of Positive Selection for the Development of a Computer Immune System and a Self-Recognition Algorithm

  • Sim, Kwee-Bo;Lee, Dong-Wook
    • International Journal of Control, Automation, and Systems
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    • v.1 no.4
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    • pp.453-458
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    • 2003
  • The anomaly-detection algorithm based on negative selection of T cells is representative model among self-recognition methods and it has been applied to computer immune systems in recent years. In immune systems, T cells are produced through both positive and negative selection. Positive selection is the process used to determine a MHC receptor that recognizes self-molecules. Negative selection is the process used to determine an antigen receptor that recognizes antigen, or the nonself cell. In this paper, we propose a novel self-recognition algorithm based on the positive selection of T cells. We indicate the effectiveness of the proposed algorithm by change-detection simulation of some infected data obtained from cell changes and string changes in the self-file. We also compare the self-recognition algorithm based on positive selection with the anomaly-detection algorithm.

Lack of Association Between the Dopamine $D_3$ Receptor Gene and Korean Schizophrenic Patients (한국인 정신분열증 환자와 도파민 $D_3$ 수용체 유전자의 연합)

  • Han, Moon-Cyun;Lee, Min-Soo;Lee, Dae-Hie
    • Korean Journal of Biological Psychiatry
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    • v.2 no.2
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    • pp.237-247
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    • 1995
  • The finding of contrasting results regarding an association between schizophrenia and the Mlul polymorphism site in the dopamine $D_3$ receptor gene prompted us to study the distribution of this palymorphism in Korean schizophrenic patients and controls. The author's approach was case-control study. Schizophrenic patients (n=66) and controls (n=76) were examined by case-control study for distribution of the Mlul polymorphism of the dopamine $D_3$ receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. The frequency of the allele 1 in schizophrenic patients and controls was 0.66 and 0.76, respectively. There was no significant differencies in the frequency of the allele 1 between schizophrenic patients and controls ($x^2$=3.07, p>.05), and between positive and negative schizophrenic patients ($x^2$=1.02, p>.05). We present here the evidence of a lack of alleic association between the Mlul polymorphism of the dopamine $D_3$ receptor gene and Korean schizophrenic patients and also report no increased homozygosity for the Mlul polymorphism. The assumption that the dopamine $D_3$ receptor gene has a predisposing role in schizophrenia was not supported by this case-control study. Although, the possibility that this gene has a minor gene effects in the etiology of schizophrenia cannot be excluded because of the intrinsic limitations of the methods of analysis and number of subjects in our study.

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Synergic induction of human periodontal ligament fibroblast cell death by nitric oxide and N-methyl-D-aspartic acid receptor antagonist

  • Seo, Tae-Gun;Cha, Se-Ho;Woo, Kyung-Mi;Park, Yun-Soo;Cho, Yun-Mi;Lee, Jeong-Soon;Kim, Tae-Il
    • Journal of Periodontal and Implant Science
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    • v.41 no.1
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    • pp.17-22
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    • 2011
  • Purpose: Nitric oxide (NO) has been known as an important regulator of osteoblasts and periodontal ligament cell activity. This study was performed to investigate the relationship between NO-mediated cell death of human periodontal ligament fibroblasts (PDLFs) and N-methyl-D-aspartic acid (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK801). Methods: Human PDLFs were treated with various concentrations (0 to 4 mM) of sodium nitroprusside (SNP) with or without $200\;{\mu}M$ MK801 in culture media for 16 hours and the cell medium was then removed and replaced by fresh medium containing MTS reagent for cell proliferation assay. Western blot analysis was performed to investigate the effects of SNP on the expression of Bax, cytochrome c, and caspase-3 proteins. The differences for each value among the sample groups were compared using analysis of variance with 95% confidence intervals. Results: In the case of SNP treatment, as a NO donor, cell viability was significantly decreased in a concentration-dependent manner. In addition, a synergistic effect was shown when both SNP and NMDA receptor antagonist was added to the medium. SNP treated PDLFs exhibited a round shape in culture conditions and were dramatically reduced in cell number. SNP treatment also increased levels of apoptotic marker protein, such as Bax and cytochrome c, and reduced caspase-3 in PDLFs. Mitogen-activated protein kinase signaling was activated by treatment of SNP and NMDA receptor antagonist. Conclusions: These results suggest that excessive production of NO may induce apoptosis and that NMDA receptor may modulate NO-induced apoptosis in PDLFs.

Mechanism of Hyperalgesia Following Cutaneous Inflammation by Complete Freund Adjuvant (Complete Freund Adjuvant에 의한 피부염증에서 통각과민현상의 기전)

  • Jeong, Yong;Leem, Joong-Woo;Chung, Seung-Soo;Kim, Yun-Suk;Yoon, Duck-Mi;Nam, Taick-Sang;Paik, Kwang-Se
    • The Korean Journal of Pain
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    • v.13 no.2
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    • pp.164-174
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    • 2000
  • Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.

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Effect of Hormone Therapy on Long-term Outcomes of Patients with Human Epidermal Growth Factor Receptor 2-and Hormone Receptor-Positive Metastatic Breast Cancer: Real World Experience in China

  • Du, Feng;Yuan, Peng;Wang, Jia-Yu;Ma, Fei;Fan, Ying;Luo, Yang;Xu, Bing-He
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.903-907
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    • 2015
  • Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer.

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle

  • Jecminkova, Katerina;Muller, Uwe;Kyselova, Jitka;Sztankoova, Zuzana;Zavadilova, Ludmila;Stipkova, Miloslava;Majzlik, Ivan
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.11
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    • pp.1721-1728
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    • 2018
  • Objective: The use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of leptin (LEP), toll-like receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle. Methods: Phenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along with information from the 1st three parities. To determine genotype, the polymerase chain reaction-restriction fragment length polymorphism method was used. Results: Except for LEP g.-963C>T, all studied genotype frequencies of single nucleotide polymorphisms (SNPs) were distributed according to the Hardy-Weinberg equilibrium. Two LEP SNPs (g.-963C>T and c.357C>T) were associated with the age at the 1st calving, days open (DO), pregnancy rate after 1st service (PR), and calving interval (CLI). In LEP g.-963C>T the TT genotype heifers firstly calved 24 days earlier than CC genotype and the CT genotype cow showed a tendency for shorter DO and higher PR. In LEP c.357C>T we observed longer CLI and DO period in TT cows. In general, we can propose the TT genotype of g.-963C>T as favorable and the TT genotype of c.357C>T as unfavorable for a cow's fertility. Heterozygotes in TLR4 c.-226C>G were significantly associated with shorter CLI, and presented a nonsignificant tendency to be associated with higher PR. In CXCR1 c.777 C>G, we did not observe any relationship of this SNP with reproduction. Conclusion: Overall, the results showed that LEP could be an effective marker for improving reproduction in Czech Fleckvieh cattle. This study also provides novel insights into the relationship between TLR4 and CXCR1 SNPs and reproduction in dual-purpose cattle.

A Study on Patients Dose and Image Quality according to Source to Image receptor Distance in Abdomen Radiography: comparison of ESD measured and DRLs in other countries (복부일반촬영시 선원과 검출기간의 거리변화에 따른 영상 화질 및 피폭선량에 관한 연구)

  • Jang, Ji-Sung;Choi, Weon-Keun;Jung, Jae-Yon;Lee, Kwan-Sub;Ha, Dong-Yoon
    • Korean Journal of Digital Imaging in Medicine
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    • v.14 no.2
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    • pp.39-46
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    • 2012
  • Purpose : The purpose of this study was to reduce Entrance Surface Dose and maintain image quality by changing Source to Image receptor Distance. And we'd like to compare ESD on this study to DRLs in other contries. Materials and Methods : We used indirect DR system(Definium 8000, General Electric, USA)and phantom(ART-200X, Flukebiomedical, USA),glass dosimeters(GD-352M, Asahi Techno Glass, Japan)for this study. The imagies were obtained throuh 80kVp fixed, and different tube currents using AEC mode in $16{\times}16$(inch) field size and changing Source to Image receptor Distance from 100 cm to 130 cm per 10 cm unit. The phantom with attaching 5 glass dosimeters on abdomonal skin was set at supine and erect position as a anterioposterial projection on detector For measuring Entrance Surface Dose. Image analysis was conducted by histograms of Image J(1.46r) which was given from National Institutes of Health(NIH). Results : Due to inverse square law of distance, the tube currents were increasing 42.6 % in supine position and 32.6 % in erect position according to the change of Source to Image receptor Distance. While Entrance Surface Doses were rapidly decreasing 14.2 % in supine position and 29.4 % in erect position according to the change of Source to Image receptor Distance. As the results of histogram using Image J, pixel mean values from 100 cm to 110 cm, 120 cm and 130 cm were decreasing each 1.4%, 2.5%, 2.7%, 4.5%, 2.2 %, 5.8 % in supine, erect position. While standard deviations from 100 cm to 110 cm, 120 cm and 130 cm were increasing each 1.4 %, 2.5 %, 2.5 %, 4.0 %, 2.0 %, 4.9 % Consequently, there are no significant differences in abdomen images taken. Conclusion: As the results described above, we strongly recommend using long Sourceto Image receptor Distance than 100cm that we have been using. So, we should deliver less Entrance Surface Dose to the patients while maintaining image quality in abdomen radiography.

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Gintonin-mediated release of astrocytic vascular endothelial growth factor protects cortical astrocytes from hypoxia-induced cell damages

  • Choi, Sun-Hye;Kim, Hyeon-Joong;Cho, Hee-Jung;Park, Sang-Deuk;Lee, Na-Eun;Hwang, Sung-Hee;Rhim, Hyewon;Kim, Hyoung-Chun;Cho, Ik-Hyun;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.305-311
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    • 2019
  • Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5- triphosphate receptor antagonist, 2-APB; and intracellular $Ca^{2+}$ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor-VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system.