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The Expression of MUC1 and CD44s in Non-small Cell Lung Cancer (비소세포폐암에서 MUC1과 CD44s의 발현)

  • Park, Hye-Kyung;Lee, Ji-Seok;Lee, Jun-Hee;Lee, Jung-Wook;Kim, Yun-Seong;Lee, Min-Ki;Kim, Young-Dae;Lee, Hyung-Ryu;Kim, Kun-Il;Lee, Chang-Hun;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.2
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    • pp.117-127
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    • 2002
  • Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

Detection of Pyrazinamide Resistance in Mycobacterium Tuberculosis by Sequencing of pncA Gene (pncA 유전자의 염기 서열 결정에 의한 결핵균의 Pyrazinamide 내성 진단)

  • Hwang, Jee-Yoon;Kwak, Kyung-Rok;Park, Hye-Kyung;Lee, Ji-Seok;Park, Sam-Seok;Kim, Yun-Seong;Lee, Jung-Yoo;Chang, Chul-Hun;Lee, Min-Ki;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.94-105
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    • 2001
  • Background : Examining the biological susceptibility of Mycobacterium tuberculosis to pyrazinamide (PZA) in vitro is very difficult as PZA is inactive under normal culture conditions. The biological susceptibility test, an enzyme assay for Pzase activity, and a genetic test for pncA gene mutations, were performed in order to predict PZA resistance. Methods : 28 cultured clinical isolates of Mycobacterium tuberculosis were tested. The biological susceptibility was performed by the absolute concentration method using Lowenstein-Jensen media. The PZase activity was tested by means of Wayne's method. A 710-bp region includes the entire open reading frame of pncA was amplified and sequenced. Results : All six strains with positive PZase activity exhibited no pncA mutations with one strain showing a false resistance in the biological susceptibility test. Among the 22 strains with no PZase activity, 21 exhibited showed pncA mutations. In the biological susceptibility test, 20 strains were resistant, and one was susceptible, and the other flied to test. The mutation types varied with ten missense, one silent and one nonsense mutation 1 slipped-strand mispairing, and 6 frameshift mutations. Three strains had an adenine to guanine mutation at position -11 upstream of the start codon. Conclusion : The mutation at the pncA promotor region is frequent at -11 upstream position. Automatic sequencing of pncA is a useful tool for rapid and accurate detection of PZA resistant M. tuberculosis, and for demonstrating the epidemiological relatedness of the PZA resistant M. tuberculosis strains.

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Effects of Immunostimulatory CpG-Oligodeoxynucleotides on Bronchial Asthma in Rat (백서 천식에서 면역 증강성 CpG 올리고 뉴클레오티드 투여의 효과)

  • Lee, Sin-Hyung;Kim, Je-Hyeong;Jeong, Hye-Cheol;Kim, Kyung-Kyu;Jung, Ki-Hwan;Kim, Byung-Gyu;Lee, Seung-Heon;Park, Sang-Myun;Sin, Cheol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.12-28
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    • 2001
  • Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

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Adenosine Deaminase Activity in Bronchoalveolar Lavage Fluid in Patients with Pulmonary Tuberculosis (폐결핵 환자의 기관지폐포세척액에서 Adenosine Deaminase 활성도에 관한 연구)

  • Cheon, Seon-Hee;Cho, Chul-Ho;Kim, Byung-Il;Jang, Sang-Ho;Chang, Joon;Kim, Sung-Kyu;Hahn, Jee-Sook;Lee, Won-Young;Kwon, Oh-Hun
    • Tuberculosis and Respiratory Diseases
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    • v.38 no.1
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    • pp.16-24
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    • 1991
  • Adenosine deaminase (ADA) is an enzyme which is essential for the differentiation of lymphoid cells, especially T-cells and ADA plays a role in the maturation of monocyte to macrophage. Therefore ADA levels are related to stimulation of cellular immunity. We have investigated the measurement of ADA activity in bronchoalveolar lavage fluid of the patients with active and inactive pulmonary tuberculosis and control group. The results obtained are as follows: 1) The ADA activity and corrected ADA activity from the BAL fluid in active tuberculosis group (Total Lavage ADA; $18.4{\pm}22.5\;mU$, Total Lavage ADA/Albumin; $2.45{\pm}1.61\;mU/mg$) were increased when compared with those in inactive tuberculosis (TL-ADA; $5.8{\pm}2.5\;mU$, TL-ADA/Alb; $1.83{\pm}O.53\;mU/mg$) and control (TL-ADA; $6.6{\pm}4.3\;mU$, TL-ADA/Alb; $1.62{\pm}0.60\;mU/mg$) groups. 2) The ADA activity and lavage ADA/serum ADA activity ratio in BAL fluid from the lesion site (TL-ADA; $42.9{\pm}42.3\;mU$, L-ADA/S-ADA; $0.53{\pm}0.32$) were increased when compared with those from the non-lesion site (TL-ADA; $12.5{\pm}11.2\;mU$, L-ADA/S-ADA; $0.29{\pm}0.12$)and normal side (TL-ADA; $12.7{\pm}11.0\;mU$, L-ADA/S-ADA; $0.34{\pm}0.27$) in active tuberculosis group. 3) The ADA activity in BAL fluid from far advanced group (TL-ADA; $62.5{\pm}30.3\;mU$) was increased when compared with those from the mild group (TL-ADA; $10.5{\pm}7.5\;mU$) and moderate advanced group (TL-ADA; $13.2{\pm}11.7\;mU$) in active tuberculosis. 4) The albumin level from the BAL fluid was correlated with the ADA activity (R=0.89). 5) The ADA activity recovered from the BAL fluid was correlated with the recovered lymphocyte percentage (R=0.60). In conclusion, the ADA activity from the BAL fluid in active tuberculosis group was increased when compared with that in inactive tuberculosis and control groups, especially from the lesion site. To evaluated the specificity of ADA determination for diagnosis of active tuberculosis, BAL must be done at lesion site of the diseased lung and the proper correcting material other than albumin must be chosen to correct the dilution factor of lavage fluid.

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Spontaneous and Stimulated Release of the TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 of Alveolar Macrophages in the Patients with Pulmonary Tuberculosis (폐결핵 환자의 폐포 대식세포에서 TNF-$\alpha$, IL-1$\beta$, IL-6 및 IL-8의 분비에 관한 연구)

  • Cheon, Seon-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.942-952
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    • 1998
  • The aim of this study was to evaluate spontaneous and LPS stimulated proinflammatory cytokines and chemokine release of alveolar macrophages in the patients with pulmonary tuberculosis and healthy individuals, as a control. Alveolar macrophages recovered from bronchoalveolar lavage fluids were cultured with or without LPS 0.1, 1, or 10 ${\mu}g/ml$ for 24 and 48 hours in 37C, 5% CO2. TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 amount were evaluated using ELISA kit from the supernatants. There were a significant increase in the spontaneous 24 hours release of TNF-$\alpha$ and IL-6 from the involved segments of tuberculosis patients compared with uninvolved segments and normal control There were also increasing trends of release of them after LPS stimulation in involved segments, but not significant. IL-1$\beta$ and IL-8 were not evaluated from the involved segments of tubeculosis and there were not significant differences of them between uninvolved segments of tuberculosis and normal control. It is concluded that cytokine release of alveolar macrophages in the pulmonary tuberculosis was markedly increased, and it was localized to the alveolar macrophages from the involved segments.

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Clinical Feature of Submersion Injury in Adults (성인 익수 손상의 임상적 특성)

  • Jung, Chi Young;Cha, Sung Ick;Jang, Sang Soo;Lee, Sin Yeob;Lee, Jae Hee;Son, Ji Woong;Park, Jae Yong;Jung, Tae Hoon;Kim, Chang Ho
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.3
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    • pp.287-296
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    • 2003
  • Background : Drowning represents the third most common cause of all accidental deaths worldwide. Although few studies of submersion injury were done in Korea, the subjects were mainly pediatric patients. The purpose of this study is to describe the clinical feature of submersion injury in adults. Methods : The medical records of 31 patients with submersion injury who were >15 years of age and admitted to Kyungpook National University Hospital from July 1990 to March 2003 were retrospectively examined. Results : The most common age-group, cause, and site of submersion accidents in adults were 15-24 years of age, inability to swim, and river followed by more than 65 years of age, drinking, and public bath respectively. The initial chest radiographics showed bilaterally and centrally predominant distribution of pulmonary edema at lung base in about 90% of patients with pulmonary edema represented by submersion injury but at only upper lung zone in 10%. Eventually, 25 patients (80.6%) survived without any neurologic deficit and 2 patients (6.5%) with significant neurologic deficit, and 4 patients (12.9%) died. Age, arterial gas oxygenation, and mental status among baseline variables showed significant difference for prognosis. Conclusions : More than 65 year of age, drinking, and occurrence in public bath were relatively important in submersion injury of adults, and the successful survival of 80.6% of patients suggests that cardiopulmonary resuscitation should be intensively done in even adults.

Gene Expression of Surfactant Protein A mRNA of the Lung in Endotoxin and Thiourea Treated Rats (폐장에서 내독소 및 Thiourea 투여 후 Surfactant Protein A mRNA발현의 비교)

  • Lee, Jae Young;Kim, Mi Ok;Sohn, Jang Won;Yoon, Ho Joo;Shin, Dong Ho;Kim, Tae Wha;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.3
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    • pp.257-266
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    • 2003
  • Background : The surfactant protein A(SP-A) is important in the regulation of surfactant secretion, synthesis and recycling. Since the acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury casued by a variety of insults and since abnormalities in surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-A. Methods : Sprague-Dawley rats were given 5 mg/kg intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and sacrified at different time periods. Results : 1) SP-A mRNA was significantly increased 67.0% in 6 hours and 73.4% in 24 hours after 5 mg/kg endotoxin treatment respectively(P<0.005, P<0.005). 2) SP-A mRNA significantly decreased 32.9% in 24 hours after 3.5 mg/kg thiourea treatment(P<0.05). Conclusions : These results indicate that the differential regulation of surfactant protein A in vivo is evident and suggest that surfactant protein A might be differentially regulated during different kind of insults of lung injury at different time periods without altering lung wet to dry ratios.

Application of Noninvasive Positive Pressure Ventilation in Patients with Respiratory Failure (호흡부전 환자에서 비침습적 양압환기법의 적용)

  • Seol, Young Mi;Park, Young Eun;Kim, Seo Rin;Lee, Jae Hyung;Lee, Su Jin;Kim, Ki Uk;Cho, Jin Hoon;Park, Hye Kyung;Kim, Yun Seong;Lee, Min Ki;Park, Soon Kew;Kim, Young Dae
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.1
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    • pp.26-33
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    • 2006
  • Background: Noninvasive positive pressure ventilation(NPPV) has been increasingly used over the past decade in the management of acute or chronic respiratory failure and weaning of mechanical ventilation. We performed this clinical study to evaluate the usefulness of NPPV in patients who developed acute respiratory failure or post-extubation respiratory failure. Methods: We analysed thirty four patients(sixteen males and eighteen females, mean ages 58 years) who applied NPPV(BIPAP S/T, Respironics co., USA) for respiratory failure or weaning difficulty at medical intensive care unit(MICU), emergency room and general ward of a tertiary hospital. We evaluated the underlying causes of respiratory failure, duration of treatment, the degree of adaptation, complication and predictive parameters of successful outcome. Results: The overall success rate of NPPV was seventy-one percent. The duration of NPPV applying time, baseline blood pressure, pulse rate, respiration rate, $PaO_2$, $PaCO_2$, $SaO_2$ were not different between success group and failure group. But, the baseline pH was higher in the success group. Predictors of success were higher baseline pH, patients with underlying disease of COPD, improvement of vital sign and arterial blood gas value after NPPV application. The success rate in patients with post-extubation respiratory failure was eighty percent. There were no serious complication on applying NPPV except minor complications such as facial skin erythema, abdominal distension & dry mouth. Conclusion: NPPV may be effective treatment in patients with acute respiratory failure or post-extubation respiratory failure in selected cases.

The Clinical Manifestation of Pulmonary Infection in AIDS Patients (국내 일개 대학병원에서 경험한 AIDS 환자의 폐 감염성 질환의 임상적 특성)

  • Jung, Jae Woo;Chung, Jin Won;Song, Ju Han;Jeon, Eun Ju;Lee, Young Woo;Choi, Jae Cheol;Shin, Jong Wook;Park, In Whon;Choi, Byoung Whui;Kim, Jae Yeol
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.6
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    • pp.554-561
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    • 2006
  • Background: In AIDS patients, the respiratory tract is one of the most frequently involved site of by an opportunistic infection, and an even common, casual pulmonary infection manifests in a peculiar ways in AIDS patients. In Korea, because of the low prevalence of AIDS, there is insufficient data compared with other Southeast Asian counties. However, considering the sexual behavior of the younger generation, it is expected that it will not be long before AIDS becomes a major public health issue in Korea. This study examined the clinical manifestation of HIV positive people and AIDS patients. The pulmonary manifestion of HIV-positive was evaluated. This study focused on the differences in the clinical manifestation between AIDS patients with pulmonary disease and simple HIV positive people. The characteristics of common pulmonary infections in AIDS patients were also analyzed. Method: The medical records of 28 HIV positive patients who visited the hospital of ChungAng University Hospital from January, 2001 to February, 2006 were analyzed retrospectively. Result: Twenty-seven patients out of 28 HIV positive patients were male and the average age was 40.6(23-65). Patients in their thirties were most commonly affected. Elven patients had pulmonary diseases. Pulmonary tuberculosis (4 cases) and pneumocystis pneumonia (4 cases) were the most common respiratory infection. One patient showed a peculiar type of systemic cryptococcus. which was accompanied by lung and pleural dissemination. The CD4+lymphocyte count of patients with a pulmonary infection was significantly lower in patients with a pulmonary manifestation than those with only a HIV infection ($79.5/mm^3$ vs $400/mm^3$, respectively)(p<.05). Patients with pulmonary disease were in a more severe immunosuppressive state. There were 4 patients with pulmonary tuberculosis, 4 with pneumocystis pneumonia, 4 with secondary syphilis, 2 with primary syphilis, and 2 with HZV infection. The average CD4 lymphocyte counts was $56/mm^3$ in those with pulmonary tuberculosis, $42/mm^3$ in those with pneumocystis pneumonia, and $455/mm^3$ in those with secondary syphilis. Conclusion: This study examined the clinical manifestation of HIV positive patients, particularly AIDS patients with pulmonary disease, A more severe immunosuppressive status was observed in HIV-related pulmonary compared with those with HIV-related extrapulmonary disease, and the frequency of pulmonary tuberculosis in pulmonary disease was higher than expected. Respiratory infection in AIDS manifest in uncommon ways e.g. disseminated cryptococcosis involving the lung and pleura. Evidently, AIDS patients with a respiratory infection have a more severe form of immunosuppression than those with a simple HIV infection. As expected, patients with a pulmonary infection were in a more severe immunosuppressed state than those with a simple HIV infection. Opportunistic infections can show peculiar clinical presentations in AIDS patients.

A STUDY ON THE MEASUREMENT OF THE IMPLANT STABILITY USING RESONANCE FREQUENCY ANALYSIS (공진 주파수 분석법에 의한 임플랜트의 안정성 측정에 관한 연구)

  • Park Cheol;Lim Ju-Hwan;Cho In-Ho;Lim Heon-Song
    • The Journal of Korean Academy of Prosthodontics
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    • v.41 no.2
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    • pp.182-206
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    • 2003
  • Statement of problem : Successful osseointegration of endosseous threaded implants is dependent on many factors. These may include the surface characteristics and gross geometry of implants, the quality and quantity of bone where implants are placed, and the magnitude and direction of stress in functional occlusion. Therefore clinical quantitative measurement of primary stability at placement and functional state of implant may play a role in prediction of possible clinical symptoms and the renovation of implant geometry, types and surface characteristic according to each patients conditions. Ultimately, it may increase success rate of implants. Purpose : Many available non-invasive techniques used for the clinical measurement of implant stability and osseointegration include percussion, radiography, the $Periotest^{(R)}$, Dental Fine $Tester^{(R)}$ and so on. There is, however, relatively little research undertaken to standardize quantitative measurement of stability of implant and osseointegration due to the various clinical applications performed by each individual operator. Therefore, in order to develop non-invasive experimental method to measure stability of implant quantitatively, the resonance frequency analyzer to measure the natural frequency of specific substance was developed in the procedure of this study. Material & method : To test the stability of the resonance frequency analyzer developed in this study, following methods and materials were used : 1) In-vitro study: the implant was placed in both epoxy resin of which physical properties are similar to the bone stiffness of human and fresh cow rib bone specimen. Then the resonance frequency values of them were measured and analyzed. In an attempt to test the reliability of the data gathered with the resonance frequency analyzer, comparative analysis with the data from the Periotest was conducted. 2) In-vivo study: the implants were inserted into the tibiae of 10 New Zealand rabbits and the resonance frequency value of them with connected abutments at healing time are measured immediately after insertion and gauged every 4 weeks for 16 weeks. Results : Results from these studies were such as follows : The same length implants placed in Hot Melt showed the repetitive resonance frequency values. As the length of abutment increased, the resonance frequency value changed significantly (p<0.01). As the thickness of transducer increased in order of 0.5, 1.0 and 2.0 mm, the resonance frequency value significantly increased (p<0.05). The implants placed in PL-2 and epoxy resin with different exposure degree resulted in the increase of resonance frequency value as the exposure degree of implants and the length of abutment decreased. In comparative experiment based on physical properties, as the thickness of transducer increased, the resonance frequency value increased significantly(p<0.01). As the stiffness of substances where implants were placed increased, and the effective length of implants decreased, the resonance frequencies value increased significantly (p<0.05). In the experiment with cow rib bone specimen, the increase of the length of abutment resulted in significant difference between the results from resonance frequency analyzer and the $Periotest^{(R)}$. There was no difference with significant meaning in the comparison based on the direction of measurement between the resonance frequency value and the $Periotest^{(R)}$ value (p<0.05). In-vivo experiment resulted in repetitive patternes of resonance frequency. As the time elapsed, the resonance frequency value increased significantly with the exception of 4th and 8th week (p<0.05). Conclusion : The development of resonance frequency analyzer is an attempt to standardize the quantitative measurement of stability of implant and osseointegration and compensate for the reliability of data from other non-invasive measuring devices It is considered that further research is needed to improve the efficiency of clinical application of resonance frequency analyzer. In addition, further investigation is warranted on the standardized quantitative analysis of the stability of implant.