• Title/Summary/Keyword: $AT_1$ receptor

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Radioimmunoassay Reagent Survey and Evaluation (검사별 radioimmunoassay시약 조사 및 비교실험)

  • Kim, Ji-Na;An, Jae-seok;Jeon, Young-woo;Yoon, Sang-hyuk;Kim, Yoon-cheol
    • The Korean Journal of Nuclear Medicine Technology
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    • v.25 no.1
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    • pp.34-40
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    • 2021
  • Purpose If a new test is introduced or reagents are changed in the laboratory of a medical institution, the characteristics of the test should be analyzed according to the procedure and the assessment of reagents should be made. However, several necessary conditions must be met to perform all required comparative evaluations, first enough samples should be prepared for each test, and secondly, various reagents applicable to the comparative evaluations must be supplied. Even if enough comparative evaluations have been done, there is a limit to the fact that the data variation for the new reagent represents the overall patient data variation, The fact puts a burden on the laboratory to the change the reagent. Due to these various difficulties, reagent changes in the laboratory are limited. In order to introduce a competitive bid, the institute conducted a full investigation of Radioimmunoassay(RIA) reagents for each test and established the range of reagents available in the laboratory through comparative evaluations. We wanted to share this process. Materials and Methods There are 20 items of tests conducted in our laboratory except for consignment tests. For each test, RIA reagents that can be used were fully investigated with the reference to external quality control report. and the manuals for each reagent were obtained. Each reagent was checked for the manual to check the test method, Incubation time, sample volume needed for the test. After that, the primary selection was made according to whether it was available in this laboratory. The primary selected reagents were supplied with 2kits based on 100tests, and the data correlation test, sensitivity measurement, recovery rate measurement, and dilution test were conducted. The secondary selection was performed according to the results of the comparative evaluation. The reagents that passed the primary and secondary selections were submitted to the competitive bidding list. In the case of reagent is designated as a singular, we submitted a explanatory statement with the data obtained during the primary and secondary selection processes. Results Excluded from the primary selection was the case where TAT was expected to be delayed at the moment, and it was impossible to apply to our equipment due to the large volume of reagents used during the test. In the primary selection, there were five items which only one reagent was available.(squamous cell carcinoma Ag(SCC Ag), β-human chorionic gonadotropin(β-HCG), vitamin B12, folate, free testosterone), two reagents were available(CA19-9, CA125, CA72-4, ferritin, thyroglobulin antibody(TG Ab), microsomal antibody(Mic Ab), thyroid stimulating hormone-receptor-antibody(TSH-R-Ab), calcitonin), three reagents were available (triiodothyronine(T3), Tree T3, Free T4, TSH, intact parathyroid hormone(intact PTH)) and four reagents were available are carcinoembryonic antigen(CEA), TG. In the secondary selection, there were eight items which only one reagent was available.(ferritin, TG, CA19-9, SCC, β-HCG, vitaminB12, folate, free testosterone), two reagents were available(TG Ab, Mic Ab, TSH-R-Ab, CA125, CA72-4, intact PTH, calcitonin), three reagents were available(T3, Tree T3, Free T4, TSH, CEA). Reasons excluded from the secondary selection were the lack of reagent supply for comparative evaluations, the problems with data reproducibility, and the inability to accept data variations. The most problematic part of comparative evaluations was sample collection. It didn't matter if the number of samples requested was large and the capacity needed for the test was small. It was difficult to collect various concentration samples in the case of a small number of tests(100 cases per month or less), and it was difficult to conduct a recovery rate test in the case of a relatively large volume of samples required for a single test(more than 100 uL). In addition, the lack of dilution solution or standard zero material for sensitivity measurement or dilution tests was one of the problems. Conclusion Comparative evaluation for changing test reagents require appropriate preparation time to collect diverse and sufficient samples. In addition, setting the total sample volume and reagent volume range required for comparative evaluations, depending on the sample volume and reagent volume required for one test, will reduce the burden of sample collection and planning for each comparative evaluation.

Effects of Locus Coeruleus/Subcoeruleus Stimulation on the Tail Flick Reflex and Efflux of Noradrenaline into the Spinal Cord Superfusates (청반핵 자극으로 인한 노르아드레날린의 유리가 동통의 조절에 미치는 영향)

  • Park, Kyung-Pyo;Kim, Jong-Sung;Suh, Dae-Chul;Park, Hyoung-Sup
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.29-37
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    • 1994
  • Inhibition of the nociceptive Tail Flick Reflex (TFR) was observed with electrical stimulation of the locus coeruleus/subcoeruleus (LC/SC) in the male Sprague - Dawley rats under light anesthesia, and the involved neurotransmitter (s) were characterized. Electrical stimulation of LC/SC induced the analgesia with the stimulation threshold (intensity of the current, given for 100 usec and in 100 Hz frequency, which caused the TF latency longer than 6.5 sec) around 55 uA. Intrathecal administrations of ${\alpha}_2$ antagonist, yohimbine (30 ug) or opioid antagonist, naloxone (20 ug) increased the stimulation threshold by 147% and 123% respectively (from 55 uA to 135 uA,9 and from 54 uA to 123 uA;P0.01, n=5, each). The basal TF latency without stimulation (3.1 sec) was reduced by the antagonists (to 2.5 sec by yohimbine, p<0.05, n=5; to 2.6 sec by naloxone, p<0.1, n=5), vehicle only did not show any effect. Noradrenaline(NA) in the spinal cord superfusates measured with HPLC was increased by the LC/SC stimulation, from 4.18 ng/ml before to 7.74 ng/ml after stimulation (P<0.05, n=10). The result suggest that analgesia induced by LC/SC stimulation is mediated, at least in part, by the noradrenergic system in which ${\alpha}_2$ receptor is involved, as well as the opioid system.

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Renal Effects of Intracerebroventricular Bromocriptine in the Rabbit (가토에 있어서 측뇌실내 Bromocriptine의 신장작용)

  • Kook, Young-Johng;Kim, Kyung-Keun;Kim, Jae-Pil;Kim, Kyung-Ho
    • The Korean Journal of Pharmacology
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    • v.21 no.1
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    • pp.49-61
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    • 1985
  • In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.

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Expression of Estrogen and Progesterone Receptors in Non-small-cell Lung Cancer Tissue Using Tissue Microarray Method (조직 미세배열법을 이용한 비소세포 폐암 조직에서 에스트로겐과 프로게스테론 수용체 발현)

  • Han, Hye-Seung;Kim, Min-Ji;Cho, Jae-Hwa;Yoon, Yong-Han;Kwak, Seung-Min;Lee, Hong-Lyeol;Kim, Kwang-Ho;Ryu, Jeong-Seon
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.1
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    • pp.54-58
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    • 2005
  • Background : To evaluate the role of estrogen and progesterone in the carcinogenesis of NSCLC, IHC studies for the expression of the receptors of estrogen and progesterone have been performed with inconsistent results. Recently the TMA method has been developed and has become recognized as a useful and rapid method for extensively analysing molecular markers at the gene and protein level. We have investigated their expressions in the tissue from NSCLC using the microarray method. Methods : The TMA construction was made with 70 formalinfixed, paraffin-embedded tissues of NSCLC. After heat-induced epitope retrieval, IHC staining on primary tissues of NSCLC was performed with the monoclonal antibodies, ER1D5 and PR1A6. Results : Our sample of 70 consisted of 74% men and 26% women. Of the patients, 49% were current smokers, 27% were non-smokers and 24% were former smokers. By histologic classification, 34 patients had squamous cell carcinoma, 24 had adenocarcinoma, 9 had adenosquamous cell carcinoma, and 3 had other carcinomas. No cancer cells were immunostained with these monoclonal antibodies in any primary tissues of NSCLC. Conclusions : No expression of neither of the two receptors was found in any of the lung cancer tissues. This suggests that adequate genetic variants for IHC staining need to be developed for NSCLC.

Immunohistochemical Study on the Activation of Cell mediated immunity in Murine Lymph node on Allergic Contact Dermatitis by DNCB -Based on the change of T lymphocytes and Il-2 receptors- (알러지성 접촉피부염 유발 피부 주변 림프절에서의 세포성 면역 활성에 관한 면역조직화학적 연구 - T 림프구와 IL-2 수용기의 분포 변화를 중심으로 -)

  • kim, Jin-Taek;Ahn, Sang-Hyun;Park, In-Sick;Chung, Jae-Man;Kim, Ho-Hyun
    • The Journal of Dong Guk Oriental Medicine
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    • v.7 no.1
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    • pp.33-41
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    • 1998
  • Lymph node tissues of BALB/C mouse treated with DNCB were immunohistochemically observed to investigate the activation of cell mediated immunity in lymph node of murine with allergic contact dermatitis. The inguinal region of BALB/C mice were sensitized by one application of $25{\mu}l$ of 5% 2,4-dinitrochlorobenzene(DNCB) onto an abdominal skin and 2 weeks later, the mice were challenged with $4{\mu}l$ of 2.5% DNCB. The inguinal lymph node were obtained at hour 24, 48, and 72 after 2nd DNCB treatment and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25). The distribution of helper T lymphocytes, cytotoxic T lymphocytes and IL-2 receptors began to increase at hour 24 after after 2nd DNCB treatment and these increase appeared in paracortical area and medullary sinius. These increase were greatest at hour 48. These results indicated that the IL-2 secretion began to increase by activation of helper T lymphocytes in lymph node of DNCB re-exposure area and subsequently to activate suppress T lymphocytes.

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Effects of Non-Steroidal Anti-Inflammatory Drugs on the FMLP-Induced Migration of Neutrophil (비스테로이드성 항염증제가 FMLP에 의한 사람 중성구의 이동에 미치는 영향)

  • Kim, Woo-Mi;Kang, Koo-Il
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.137-143
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    • 1994
  • Enhancement or diminution of leukocyte migration to the specific site might be important factors for the development of inflammatory diseases. To investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on chemotaxis of neutrophil, we obtained neutrophils by Hypaque-Ficoll step gradient centrifugation and tested the effects of seven drugs on the n-formyl-leucyl-phenylalanine (FMLP)-induced migration of neutrophil using a 48-well micro chemotaxis assembly. Oxyphenbutazone, phenylbutazone, sulindac, zomepirac, and ibuprofen suppressed the migration of neutrophil at the therapeutic concentrations, however, indomethacin showed stimulation effect. IC50s for inhibition of neutrophil migration by these drugs are less than 100uM. When drugs were preincubated with FMLP, no inhibition on migration of neutrophil was observed. These results indicated that inhibitory effects of these drugs on migration of neutrophil might be related to the receptor sites of neutrophil rather than molecular inactivation of chemoattractant (FMLP). In conclusion, we suggested that the property of inhibition effects on neutrophil migration of several NSAIDs might be another mode of pharmacological action for anti-iflammatory effect, which showed significant effects at concentrations below therapeutic levels, in addition to cyclooxygenase inhibition.

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Effects of Head-Down Tilt$(-6^{\circ})$ on Hemodynamics and Plasma Catecholamine Levels (도립$(-6^{\circ})$이 혈장 Catecholamine 및 심장혈관계에 미치는 영향)

  • Song, Dae-Kyu;Bae, Jae-Hoon;Park, Won-Kyun;Chae, E-Up
    • The Korean Journal of Physiology
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    • v.21 no.2
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    • pp.211-223
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    • 1987
  • Head-down tilt (HDT) at $-6^{\circ}$ has been commonly used as the experimental model in both man and animals to induce the blood shift toward the head or central protion of the body, demonstrating similar physiological effect encountered in the weightlessness in the orbital flight. There are few reports about the physiological response upon the cardiovascular regulatory system or the tolerance to the $(-6^{\circ})$ HDT within a relatively short period less than 1 hour. Therefore, the purpose of this study way to observe the effects of $-6^{\circ}$ HDT on cardiovascular system within 30 minutes and to evaluate early regulatory mechanism for simulated hypogravity. Ten mongrel dogs weighing 8-12 kg were anesthetized with the infusion of 1% ${\alpha}-chloralose$ (100 mg/kg) intravenously, and the postural changes were performed from the supine to the $-6^{\circ}$ head-down Position, then from the head-down to the supine (SUP), and each posture was maintained for 30 minutes. Blood flow $({\dot{Q}})$ through common carotid and femoral arteries were determined by the electromagnetic flowmeter. Mean arterial pressure (MAP), heart rate (HR), respiratory rate , and pH, $P_{O_2}$, $P_{CO_2}$ and hematocrit (Hct) of arterial and venous blood were also measured. The peripheral vascular resistance was calculated by dividing respective MAP values by ${\dot{Q}}$ through both sides of common carotid or femoral arteries. The concentration of plasma epinephrine and norepinephrine was determined by Peuler & Johnson's radioenzymatic method. The results are summarized as follows: In the initial 5 minutes in $-6^{\circ}$ HDT, HR was significantly (p<0.05) increased and MAP slightly decreased. Although ${\dot{Q}}$ and carotid peripheral artery resistance were not significantly changed, ${\dot{Q}}$ through femoral artery was diminished and femoral peripheral artery resistance was elevated. In the SUP, the initial changes of MAP and HR were increased (p<0.05), but those of ${\dot{Q}}$ and peripheral vascular resistance through both common carotid and femoral arteries were not significant. After 10 minutes of each postural change in both HDT and SUP, MAP was maintained almost equal to that of the level of pretilting control. During 60 minutes of both postural changes of HDT and SUP, $P_{O_2}$ and Hct were not changed significantly. However pH tended to increase slowly and $P_{CO_2}$ was gradually decreased. The pH and $P_{CO_2}$ seemed to be related to the increased respiratory rate. Plasma epinephrine concentration was not changed significantly and plasma norepinephrine concentration was slightly decreased in the course of HDT and also at 10 minutes of SUP. However these concentration changes were statistically insignificant. From these results, it may be concluded that the effect of $-6^{\circ}$ HDT for 30 minutes on the cardiovascular system and plasma catecholamine levels of the dog is minimum and it is suggestive that the cardiovascular regulatory mechanism, possibly mediated by so called gravity receptors including baroreceptor and volume receptor, has been properly and adequately operated.

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Attenuation of the Corticosterone-induced Antiproliferative Effect on Human Neuroblastoma SH-SY5Y Cells Using Hot-water Extract from Liriope muscari (Corticosterone에 의해 유도된 인간의 신경모세포종 SH-SY5Y 세포 증식 억제를 완화시키는 맥문동 열수 추출물의 효과에 관한 연구)

  • Lee, Jong Kyu;Kim, Sang-Bo;Seo, Yong Bae;Kim, Gun-Do
    • Journal of Life Science
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    • v.28 no.5
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    • pp.517-523
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    • 2018
  • Elevated levels of cortisol caused by chronic stress may lead to neuron damage in the hippocampus by activating the glucocorticoid receptors (GRs). In cortisol-deficient animals, corticosterone is known to function as a stress hormone. In humans however, corticosterone is considered a precursor of aldosterone and a glucocorticoid with similar properties to cortisol. Recently, many studies have been conducted on the role of cortisol and other synthetic glucocorticoids like dexamethasone in humans, but the exact function of corticosterone is unknown. This study examined the viability of human neuroblastoma SH-SY5Y cells treated with various concentrations of corticosterone for 24 and 48 hr via MTT assay. The MTT-assay results showed that corticosterone had an antiproliferation effect on SH-SY5Y cells at higher concentrations (500 and $1,000{\mu}M$), while in lower concentrations ($100{\mu}M$), it showed no antiproliferation effect. Cytotoxicity analysis of extracts from three medicinal crops (Liriope muscari, Schisandra chinensis, and Wolfiporia extensa) revealed that they all possessed deleterious effects on SH-SY5Y cells depending on dosage. However, it was observed that, at a concentration of $500{\mu}g/ml$, Liriope muscari attenuated the corticosterone-induced antiproliferation on SY-SH5Y cells and restored cell growth after 48 hours of treatment. The study examined the synergistic effect of six mixtures each containing $500{\mu}g/ml$ of Liriope and various concentrations of Schisandra (50 or $100{\mu}g/ml$) and Wolfiporia (10, 30, and $50{\mu}g/ml$). The results showed minor growth-restoration activity but less than that of Liriope muscari only, suggesting that Schisandra and Wolfiporia had no additive or synergistic effects.

Smoking-Induced Dopamine Release Studied with $[^{11}C]Raclopride$ PET ($[^{11}C]Raclopride$ PET을 이용한 흡연에 의한 도파민 유리 영상 연구)

  • Kim, Yu-Kyeong;Cho, Sang-Soo;Lee, Do-Hoon;Ryu, Hye-Jung;Lee, Eun-Ju;Ryu, Chang-Hung;Jeong, In-Soon;Hong, Soo-Kyung;Lee, Jae-Sung;Seo, Hong-Gwan;Jeong, Jae-Min;Lee, Won-Woo;Kim, Sang-Eun
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.6
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    • pp.421-429
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    • 2005
  • Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.

Craniofacial morphologic alteration induced by bone-targeted mutants of FGFR2 causing Apert and Crouzon syndrome (어퍼트 및 크루즌 증후군을 유발하는 골조직 특이성 FGFR2 돌연변이에 의한 두개안면 형태의 변화)

  • Lee, Kee-Joon;Nah, Hyun-Duck;Tjoa, Stephen T. J.;Park, Young-Chel;Baik, Hyoung-Seon;Yun, Tae-Min;Song, Jin-Wook
    • The korean journal of orthodontics
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    • v.36 no.4
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    • pp.284-294
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    • 2006
  • Objective: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. Methods: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. Results: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. Conclusion: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.