Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.
Background: MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Materials and Methods: Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Results: The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. Conclusions: The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables.
Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations. Materials and Methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.
Sequence type 410 (ST410) of Escherichia coli is an extraintestinal pathogen associated with multi drug resistance. In this study, we aimed to investigate the horizontal propagation pathway of a high-risk clone of E. coli ST410 that produces Klebsiella pneumoniae carbapenemase (KPC). blaKPC-encoding E. coli and K. pneumoniae isolates were evaluated, and complete sequencing and comparative analysis of blaKPC-encoding plasmids from E. coli and K. pneumoniae, antimicrobial susceptibility tests, polymerase chain reaction, multilocus sequence typing, and conjugal transfer of plasmids were performed. Whole-genome sequencing was performed for plasmids mediating KPC-2 production in E. coli and K. pneumoniae clinical isolates. Strains E. coli CPEc171209 and K. pneumoniae CPKp171210 were identified as ST410 and ST307, respectively. CPEc171209 harbored five plasmids belonging to serotype O8:H21, which is in the antimicrobial-resistant clade C4/H24. The CPKp171210 isolate harbored three plasmids. Both strains harbored various additional antimicrobial resistance genes. The IncX3 plasmid pECBHS_9_5 harbored blaKPC-2 within a truncated Tn4401a transposon, which also contains blaSHV-182 with duplicated conjugative elements. This plasmid displayed 100% identity with the IncX3 plasmid pKPBHS_10_3 from the K. pneumoniae CPKp171210 ST307 strain. The genes responsible for the conjugal transfer of the IncX3 plasmid included tra/trb clusters and pil genes coding the type IV pilus. ST410 can be transmitted between patients, posing an elevated risk in clinical settings. The emergence of a KPC-producing E. coli strain (ST410) is concerning because the blaKPC-2-bearing plasmids may carry treatment resistance across species barriers. Transgenic translocation occurs among carbapenem-resistant bacteria, which may spread rapidly via horizontal migration.
Choi, Eun Ju;Jang, In Sil;Hwang, Ji Hyeon;Kang, Young-Ah;Kim, Sung Reul;Nho, Ju-Hee;Kim, Jeong Hye
Journal of Korean Clinical Nursing Research
/
v.21
no.3
/
pp.335-346
/
2015
Purpose: The purpose of this study was to identify patient satisfaction about nursing care provided by Advanced Practice Nurses (APN) using the La Monica-Oberst Patient Satisfaction Scale (LOPSS). Methods: The investigation was conducted including 263 patients who experienced care provided by 41 APNs at a tertiary hospital in Korea. Patient satisfaction with nursing care was measured using 41-item LOPSS. We analyzed the data using descriptive statistics, independent t-test and one-way ANOVA. Results: Overall patient satisfaction with APN care was high. The LOPSS scores for APNs were 52.26 for good impression, 61.75 for interpersonal support, 81.32 for dissatisfaction and 195.93 for total score. "APNs talk down to me" was a reverse coding item which demonstrated the highest score for patient satisfaction. Among patients' characteristics, age and type of main caregiver were independent factors related to patients's satisfaction. Among APN's characteristics, work experience was significantly related to patients' satisfaction. Conclusion: This study identified patient satisfaction regarding nursing care provided by APNs. High patient satisfaction in APN services demonstrated APNs' contribution to quality improvement in health care services. It is recommended that various outcome research about APN service needs to be performed.
Wright, Eric J.;Khosla, Rohit K.;Howell, Lori;Lee, Gordon K.
Archives of Plastic Surgery
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v.43
no.5
/
pp.451-456
/
2016
Background Comprehensive aesthetic surgery training continues to be a challenge for residency programs. Our residency program developed a rhinoplasty-based objective structured clinical examination (OSCE) based upon validated methods as part of the residency education curriculum. We report our experience with the rhinoplasty-based OSCE and offer guidance to its incorporation within residency programs. Methods The encounter involved resident evaluation and operative planning for a standardized patient desiring a rhinoplasty procedure. Validated OSCE methods currently used at our medical school were implemented. Residents were evaluated on appropriate history taking, physical examination, and explanation to the patient of treatment options. Examination results were evaluated using analysis of variance (statistical significance P<0.05). Results Twelve residents completed the rhinoplasty OSCE. Medical knowledge assessment showed increasing performance with clinical year, 50% versus 84% for postgraduate year 3 and 6, respectively (P<0.005). Systems-based practice scores showed that all residents incorrectly submitted forms for billing and operative scheduling. All residents confirmed that the OSCE realistically represents an actual patient encounter. All faculty confirmed the utility of evaluating resident performance during the OSCE as a useful assessment tool for determining the Next Accreditation System Milestone level. Conclusions Aesthetic surgery training for residents will require innovative methods for education. Our examination showed a program-educational weakness in billing/coding, an area that will be improved upon by topic-specific lectures. A thoroughly developed OSCE can provide a realistic educational opportunity to improve residents' performance on the nonoperative aspects of rhinoplasty and should be considered as an adjunct to resident education.
Background: Although identifying cases in large administrative databases may aid future research studies, previous reports demonstrated that the use of the International Classification of Diseases, Tenth Revision (ICD-10) code alone for diagnosis leads to disease misclassification. Purpose: We aimed to assess the value of the ICD-10 diagnostic code for identifying potential children with biliary atresia. Methods: Patients aged <18 years assigned the ICD-10 code of biliary atresia (Q44.2) between January 1996 and December 2016 at a quaternary care teaching hospital were identified. We also reviewed patients with other diagnoses of code-defined cirrhosis to identify more potential cases of biliary atresia. A proposed diagnostic algorithm was used to define ICD-10 code accuracy, sensitivity, and specificity. Results: We reviewed the medical records of 155 patients with ICD-10 code Q44.2 and 69 patients with other codes for biliary cirrhosis (K74.4, K74.5, K74.6). The accuracy for identifying definite/probable/possible biliary atresia cases was 80%, while the sensitivity was 88% (95% confidence interval [CI], 82%-93%). Three independent predictors were associated with algorithm-defined definite/probable/possible cases of biliary atresia: ICD-10 code Q44.2 (odds ratio [OR], 2.90; 95% CI, 1.09-7.71), history of pale stool (OR, 2.78; 95% CI, 1.18-6.60), and a presumed diagnosis of biliary atresia prior to referral to our hospital (OR, 17.49; 95% CI, 7.01-43.64). A significant interaction was noted between ICD-10 code Q44.2 and a history of pale stool (P<0.05). The area under the curve was 0.87 (95% CI, 0.84-0.89). Conclusion: ICD-10 code Q44.2 has an acceptable value for diagnosing biliary atresia. Incorporating clinical data improves the case identification. The use of this proposed diagnostic algorithm to examine data from administrative databases may facilitate appropriate health care allocation and aid future research investigations.
Cho, Min-Chul;Kim, Jin Hyun;Jung, Myeong Hee;Cho, In Ae;Jo, Hyen Chul;Shin, Jeong Kyu;Lee, Soon Ae;Choi, Won Jun;Lee, Jong Hak
Clinical and Experimental Reproductive Medicine
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v.46
no.3
/
pp.132-139
/
2019
Objective: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis. Methods: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two single-nucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs. Results: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups. Conclusion: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.
Sung Hyun Kang;Do-Eun Lee;Junghyun Choi;Gwang Woo Kim;Yeoung Su Lyu;Hyung Won Kang;Moon Joo Cheong
Journal of Oriental Neuropsychiatry
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v.34
no.3
/
pp.319-334
/
2023
Objectives: The purpose of this study was to identify the doctor-patient relationship perceived by doctors in clinical settings and the effect of doctor-patient relationships on treatment schemes. A qualitative case study was conducted for this purpose. Methods: In-depth interviews were conducted with five oriental medicine doctors and doctors working in clinical settings using a semi-structured questionnaire. Transcription and coding were performed to analyze the data. By analyzing each case individually through within-case analysis, we attempted to find themes that emerged from the research subjects' experiences with establishing relationships with patients. Afterward, a cross-case analysis was conducted to identify the meaning of the experiences through commonalities and differences. Results: Within-case analysis confirmed the thoughts and emotions of the research participants in recognizing, defining, and participating in doctor-patient relationships while delivering treatments. Case-to-case analysis derived two themes, seven categories, and 20 meaningful units for doctor-patient relationships. Conclusions: The study found that a doctor-patient relationship regarding patient treatment could be established based on the doctor's 'professional qualifications' and 'human qualities'. In the future, it is necessary to present an educational model for relationship-based intervention techniques and personality maturity. Follow-up research should be conducted to enable the establishment of therapeutic relationships between doctors and patients.
Park, Gye-Young;Hwang, You-Jin;Lim, Young-Hee;An, Chang-Hyeok;Park, Jeong-Woong;Jeong, Seong-Hwan
Tuberculosis and Respiratory Diseases
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v.52
no.5
/
pp.497-505
/
2002
Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.
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