Kim, Sangkyu;Park, Insoo;Park, Seung Gu;Cho, Seulki;Kim, Jin Hong;S.Ipper, Nagesh;Choi, Sun Shim;Lee, Eung Suk;Hong, Hyo Jeong
Molecules and Cells
/
제40권9호
/
pp.655-666
/
2017
We constructed a large $na{\ddot{i}}ve$ human Fab library ($3{\times}10^{10}$ colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and ${\kappa}$ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 pyrosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries. The frequency of somatic hypermutations (SHMs) in heavy-chain complementarity determining region (HCDR)1 and HCDR2 are higher compared with the natural IgM repertoire. Analysis of position-specific SHMs in CDRs indicates that asparagine, threonine, arginine, aspartate and phenylalanine are the most frequent non-germline residues on the antibody-antigen interface and are converted mostly from the germline residues, which are highly represented in germline SHM hotspots. The amino acid composition and length-dependent changes in amino acid frequencies of HCDR3 are similar to those in previous reports, except that frequencies of aspartate and phenylalanine are a little higher in our repertoire. Taken together, the results show that this antibody library shares common features of natural antibody repertoires and also has unique features. The antibody library will be useful in the generation of human antibodies against diverse antigens, and the information about the diversity of natural antibody repertoires will be valuable in the future design of synthetic human antibody libraries with high functional diversity.
Gillani, Munazza;Akhtar, Farhan;Ali, Zafar;Naz, Irum;Atique, Muhammad;Khadim, Muhammad Tahir
Asian Pacific Journal of Cancer Prevention
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제13권8호
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pp.3611-3615
/
2012
Objective: The objective of this study was to establish the diagnostic accuracy, specificity and sensitivity of fine needle aspiration cytology(FNAC) for intra-oral tumors, comparing with histopathology as the gold standard. Materials and methods: Forty cases of FNA cytology from intraoral tumors was performed in AFID along with the demographic data and clinical information and then diagnosed at AFIP, Rawalpindi. Then the cytology results obtained per FNAC were compared with the histopathological biopsy results of the same lesions. The following variables were recorded for each patient: Age, gender, site of biopsy, diagnosis. The data were entered and analyzed using Open-epi version 2.0. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Cohen Kappa was further applied to compare the agreement between the biopsy and FNAC diagnoses. A p-value of < 0.05 was considered as statistically significant. Results: Among the total patients included in the study there were 24 males and 16 females, with a ratio of 1.5:1. Age of the patients ranged from 24 to 80 years with a mean of 52 years. A total of six sites were aspirated from the oral cavity with maximum (11) aspirates taken from alveolar ridge. The results of FNAC revealed that there were 32 malignant and 8 benign aspirates. Confirmation through histopathological analysis came for 31/32 malignant cases while one was falsely given positive for malignancy on FNAC. Among a total of 40 cases, 31(77%) cases diagnosed were found to be malignant and remaining 9(23%) were benign. The FNAC results revealed 32 malignant and 8 benign lesions. Histopathology of the subsequent surgically excised specimen showed malignant lesions in 31(77%) and benign in 9(23%) patients. As a whole, it was found that the absolute sensitivity for introral FNAC was 100% and specificity 89% with positive predictive value of 97% and negative predictive value of 100%. Conclusion: Cytological diagnosis was almost corroborative with final histopathological diagnosis in all cases, with very few exceptions, exhibiting high diagnostic accuracy.
This study evaluated the reproducibility and validity of the self-administered semiquantitative food frequency questionnaire used in a large prospective cohort study(Korean Cancer Research Survey) in middle-aged men. The questionnaire was administered twice at an interval of approximately two years(December, 1992-January, 1995), and four or five 24-hour recalls for each subject were collected at intervals of approximately three months. The results were as follows; 1) Although the distributions of the data estimated by the questionnaire were somewhat wider, the mean nutrient intakes of group estimated by our questionnaires and the multiple 24-hour recalls were roughly comparable. 2) The reproducibility determined by correlation of absolute(unadjusted nutrient intake) and calorie adjusted nutrient intakes from two semiquantitative food frequency questionnaires were more than 0.5, and the weighted kappa values were more than 0.4. 3) The Pearson correlation coefficients between unadjusted nutrient intakes values were average 0.40 on the average(Ca, 0.13-Carbohydrate, 0.58) at the first questionnaire vs. 24-hour recalls, and 0.28 at the second questionnaire vs. 24-hour recalls. The spearman rank order correlation coefficients were similar. When energy intake was adjusted, there was a slight reduction : 0.28 at the second questionnaire, 0.25 average on the second. In order to correct the measurement error of 24-hour recall data, the deattenuated correlation coefficient was calculated. It averaged 0.53 on the first questionnaire, 0.37 on the second questionnaire for unadjusted nutrient intake. for calorie-adjusted nutrient intake, it averaged 0.44 on the first questionnaire, 0.37 on the second questionnarie. 4) There was lower agreement(k<0.4) between the questionnaries and the 24-hour recalls. And the subjects classified in the same quartile by 24-hour recalls and first questionnaire were average 37$\%$(energy-adjusted values) and 40$\%$(unadjusted values) on the average. More than k10$\%$(average) of subjects were in the extreme quartile of the questionnarie and 24-hour recall method. But 8.2$\%$(average) of subjects classified in the lowest quartile of unadjusted nutrient intake level by the 24-hour recalls were in the highest quartile by the first questionnaire. These data indicate that our self-administered semiquantitative food frequency questionnarie is reproducible. Correlation coefficients comparing nutrient intakes measured by two different dietary assessment methods were less than 0.5. The validity of our questionnarie is not high enough.
Background: The risk of malignancy index (RMI) for the evaluation of adnexal masses is a sensitive tool in certain populations. The best cut off value for RMI 1, 2 and 3 is 200. The cut off value of RMI-4 to differentiate benign from malignant lesions is 450. Our aim was to evaluate the efficiency of four different malignancy indexes (RMI1-4) in a homogeneous population. Materials and Methods: We evaluated a total of 153 non-pregnant women with adnexal masses who did not have a history of malignancy and who were above 18 years of age. Results: A cut-off value of 250 for RMI-1 provided 95.9% inter-observer agreement, yielding 95.9% specificity, 93.5% negative predictive value, 75.0% sensitivity and 82.8% positive predictive value. A cut-off value of 250 for RMI-1 showed high performance in preoperative diagnosis of invasive malignant lesions than cut-off value of 200 in our population. A cut-off value of 350 for RMI-2 provided 94.5% inter-observed agreement, yielding 94.2% specificity, 93.4% negative predictive value, 75.0% sensitivity and 77.4% positive predictive value. RMI-2 showed the higher performance when the cut-off value was set at 350 in our population. A cut-off value of 250 provided 95.2% inter-observer agreement, yielding 95.0% specificity, 93.2% negative predictive value, 75.0% sensitivity, and 88.0% positive predictive value. RMI-3 showed the highest performance to diagnose malignant adnexal masses when the cut-off value was set at 250. In our study, RMI-4 showed similar statistical performance when the cut-off value was set at 400 [(Kappa: 0.684/p=0.000), yielding 93.8% inter-observer agreement, 93.4% specificity, 93.4% negative predictive value, 75.0% sensitivity, and 75.0% negative predictive value]. Conclusions: We showed successful utilization of RMIs in preoperative differentiation of benign from malignant masses. Many studies conducted in Asian and Pacific countries have reported different cut-off values as was the case in our study. We think that it is difficult to determine universally accepted cut-off values for RMIs for common use around the globe.
Background: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. Materials and Methods: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). Results: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. Conclusions: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection.
증가하고 있는 심혈관질환을 예방하기 위한 연구와 함께 심혈관질환 위험도를 예측할 수 있는 평가도구에 대한 연구도 꾸준히 진행되고 있다. 가장 널리 알려져 있는 Framingham risk score (FRS)는 여러 선행 연구에서 그 타당성이 검증되었다. 본 연구에서는 연구 대상자들의 LDL 콜레스테롤과 총 콜레스테롤의 적용에 따른 FRS의 점수 차이를 살펴보고, 두 변수의 선택 적용에 따른 10년 내 심혈관질환 발생 위험도의 판정에 대한 일치도를 평가해 보고자 하였다. 2011 국민건강영양조사 데이터 중 심혈관질환 진단을 받은 자를 제외한 1,530명(남성 755명, 여성 775명)의 자료를 이용하였다. LDL 콜레스테롤 또는 총 콜레스테롤 중에 어떤 항목을 적용하느냐에 따라 FRS와 심혈관질환의 10년 예측위험도는 차이가 있었다. 남녀 모두 FRS는 LDL 콜레스테롤 적용 점수 보다 총콜레스테롤 적용 점수가 더 높았다. 위험도 10% 미만의 저위험군, 10~19%의 중등도 위험군, 20% 이상의 고위험군 분류에서 남성 106명, 여성 26명의 판정이 일치하지 않았다. 코헨의 카파 계수는 남성의 경우 0.718, 여성의 경우 0.884로 나타나 여성의 경우 더 높은 일치성을 보였다. 심혈관질환의 10년 예측위험도와의 관련성에서도 LDL 콜레스테롤을 포함한 회귀식 보다 총 콜레스테롤을 포함한 회귀식에서 남녀 모두 설명력이 더 높아 총 콜레스테롤을 반영한 FRS 산출과 10년 예측 위험도의 평가가 더 상관성이 더 높고, 더불어 남성 보다는 여성에서 더 일치하는 결과가 나타남을 알 수 있었다.
Purpose: to evaluate the usefulness of the panoramic radiography, generally used in dental clinic, for the detection of the maxillary sinus pathosis due to the inflammation and tumor, through the comparison with CT findings as the absolute standard. Materials & Methods: 150 maxillary sinuses of 75 patients with or without particular signs and symptoms and showing soft tissue lesions or destruction of maxillary sinus walls in at least one sinus in CT, were selected as subject samples, and the panoramic radiography of the same patients were interpretated by 3 dental radiologists and 3 non dental radiologist given no previous informations. Using the CT findings as the absolute standard, the diagnostic ability of panoraimc radiography in the mucosal thickening, maxillary sinus haziness, inferior wall destruction, medial wall destruction, posterolateral wall destruction and the superior wall destruction was evaluated using the ROC curve and the difference between dental radiologist group and non dental radiologist group was also evaluated. Results: 1. When dental radiologist group interpretated the destruction of inferior wall and posterolateral wall, the kappa value which shows interobserver's coincidence was above 0.75. 2. The diagnostic ability according to site of interpretation was the highest when the inferior wall was interpretated in both observer groups and there was a statistically significant difference between the dental radiologist group and non dental radiologist group in interpretating the mucosal thickening, haziness, destruction of the inferior and medial wall(p<0.05). 3. The diagnostic ability in detecting the destruction of the sinus walls was better than in soft tissue lesions in both groups and between the groups there was a statistically significant difference(p<0.05). Conclusion: When detecting the destruction of inferior and posterolateral wall of the maxillary sinus there was coincident with that of CT findings, and so it is considered that diagnostic ability of panoramic radiography is high in this point. But in interpretating the destruction of medial wall and soft tissue lesions, diagnostic ability of the panoramic radiography was relatively low and there was a significant difference between the dental radiologist group and non dental radiologist group. Therefore CT or other auxiliary diagnostic method will be necessary when evaluating thorough pathosis of maxillary sinus objectively.
Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.
Background: Chong-Myung-Tang (CMT) extract is widely used in Korea as a traditional herbal tonic for increasing memory capacity in high-school students and also for numerous body ailments since centuries. The use of CMT to improve the learning capacity has been attributed to various plant constituents, especially black ginseng, in it. Therefore, in this study, we have first investigated whether black ginseng-enriched CMT extracts affected spatial learning using the Morris water maze (MWM) test. Their molecular mechanism of action underlying improvement of learning and memory was examined in vitro. Methods: We used two types of black ginseng-enriched CMT extracts, designated as CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning behavior and their anti-inflammatory effects in BV2 microglial cells. Results: Our results show that both black ginseng-enriched CMT extracts improved the learning behavior in scopolamine-induced impairment in the water maze test. Moreover, these extracts also inhibited nitric oxide production in BV2 cells, with significant suppression of expression of proinflammatory cytokines, especially inducible nitric oxide synthase, cyclooxygenase-2, and $interleukin-1{\beta}$. The protein expression of mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ pathway factors was also diminished by black ginseng-enriched CMT extracts, indicating that it not only improves the memory impairment, but also acts a potent anti-inflammatory agent for neuroinflammatory diseases. Conclusion: Our research for the first time provides the scientific evidence that consumption of black ginseng-enriched CMT extract as a brain tonic improves memory impairment. Thus, our study results can be taken as a reference for future neurobehavioral studies.
Statement of problem. The intial stability for osseointegration of implant has been an interesting factor. Especially, in the case of poor bone quality or immediately loaded implant, various strategies have been developed focusing on the surface of materials to improve implant fixation to bone. The microscopic properties of implant surfaces play a major role in the osseous healing of dental implants. Purpose. The aims of this study are to perform a histologic and histomorphometric comparison of the healing characteristics of three different surfaces and the comparison of resonance frequency analysis (RFA) values measured by $Osstell^{TM}$ and perio-test values (PTV) measured by Periotest. Material and methods. A total of 24 screw titanium implants (Dentium Co., Seoul, Korea) with 6mm in length and 3.4mm in diameter, were placed in the mandible of 4 beagle dogs. Implants were divided into three groups following the surface treatment methods: Group I is machined(control group). Group II is anodically oxidized. Group III is coated 500nm in thickness with hydroxyapatite(HA) by ion beam assisted deposition(IBAD) on the anodized oxidization. Bone blocks from 2 dogs were caught after 3 weeks of covered healing and another blocks from 2 dogs after 6 weeks. RFA values and PTV were measured right after insertion and at 3 and 6weeks. Histomorphometric analysis was made with Kappa Image Base System to calculate bone-to-implant contact (BIC) and bone area inside the threads. Pearson's correlation analyses were performed to evaluate the correlation between RFA and PTV, BIC and bone area ratio of three different surfaces at 3 and 6 weeks. Results. 1) In all surface treatment methods, the RFA values decreased and the PTV values increased until 6 weeks in comparison to initial values. 2) At 3 weeks, no significant difference was found from bone-to-implant contact ratio and bone area ratio of three different surface treatment methods(P>0.05). However, at 6 weeks, different surface treatment methods showed significantly different bone-toimplant contact ratio and bone area ratio(P<0.05). 3) In the implants with the IBAD on the anodic oxidization, significant difference was found between the 3 weeks and the 6 weeks bone area ratio(P<0.05). 4) Correlation was found between the RFA values and the bone area ratio at 3 and 6 weeks with significant difference(P<0.05). Conclusions. These results indicate that the implants with the IBAD on the anodic oxidization may have a high influence on the initial stability of implant.
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