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1.
Sensors (Basel) ; 24(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38894137

RESUMO

The advent of digital twins facilitates the generation of high-fidelity replicas of actual systems or assets, thereby enhancing the design's performance and feasibility. When developing digital twins, precise measurement data is essential to ensure alignment between the actual and digital models. However, inherent uncertainties in sensors and models lead to disparities between observed and predicted (simulated) behaviors. To mitigate these uncertainties, this study originally proposes a multi-objective optimization strategy utilizing a Gaussian process regression surrogate model, which integrates various uncertain parameters, such as load angle, bucket cylinder stroke, arm cylinder stroke, and boom cylinder stroke. This optimization employs a genetic algorithm to indicate the Pareto frontiers regarding the pressure exerted on the boom, arm, and bucket cylinders. Subsequently, TOPSIS is applied to ascertain the optimal candidate among the identified Pareto optima. The findings reveal a substantial congruence between the experimental and numerical outcomes of the devised virtual model, in conjunction with the TOPSIS-derived optimal parameter configuration.

2.
Clin Lab ; 69(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36912312

RESUMO

BACKGROUND: We established reference intervals for research parameters of complete blood cell count and examined their usefulness for diagnosing certain diseases. METHODS: Reference intervals for 26 basic and 38 research parameters were established for 3,457 and 1,325 men and 2,742 and 830 women aged 20 - 59 and ≥ 60 years, respectively. Research parameter values for patients with iron deficiency anemia (IDA), appendicitis, sepsis, and myelodysplastic syndromes (MDS) were compared against gender- and age-matched reference values. RESULTS: Seven basic and 10 research parameters among men and one research parameter among women required partitioning by age. No partitioning by gender was required. Further, 67% patients with IDA showed micro red blood cell ratio values above the upper reference limits of their corresponding age and gender subgroups; 3% and 5% patients with appendicitis showed immature granulocyte percentages and counts above the upper reference limits, respectively; 12% - 42% of patients with sepsis showed numerous values exceeded their reference limits, and 67% and 100% patients with MDS showed neutrophil cell complexity and structural dispersion values outside their reference ranges, respectively. CONCLUSIONS: Overall, < 60% of research parameter values were outside their reference ranges among most patients, indicating their limited diagnostic usefulness.


Assuntos
Anemia Ferropriva , Apendicite , Hematologia , Síndromes Mielodisplásicas , Masculino , Humanos , Feminino , Contagem de Células Sanguíneas , Granulócitos , Valores de Referência
3.
Endocr J ; 67(12): 1187-1192, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-32713865

RESUMO

The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.


Assuntos
Anticorpos Heterófilos , Imunoterapia , Células Matadoras Naturais , Recidiva Local de Neoplasia/terapia , Neoplasias da Glândula Tireoide/terapia , Transferência Adotiva , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Hormônio Paratireóideo/sangue , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue
4.
Clin Chem Lab Med ; 57(8): 1218-1228, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30964746

RESUMO

Background Bile acids (BAs) have been demonstrated to exert a variety of metabolic effects and alterations in BAs have been reported in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it is unclear which metabolic condition is the main contributor to alterations in BAs. In this study, we investigate the associations between different BA profiles with glycemia, obesity or IR status. Methods Fasting serum concentrations of 15 BA species were determined in a total of 241 individuals (71 drug-naïve patients with T2DM, 95 patients with impaired fasting glucose [IFG], and 75 healthy controls. Results A comparison of the mean values of the BAs revealed no significant differences between normoglycemic controls and patients with IFG or T2DM. However, when the entire cohort was divided according to the presence of IR as determined by a homeostasis model assessment of insulin resistance (HOMA-IR) value >2.5, the levels of total BA and most species of BAs were significantly higher in patients with IR than in patients without. In the correlation analysis, most species of BAs, as well as total BA, were significantly associated with HOMA-IR levels. Furthermore, when the subjects were divided into four groups according to IR and diabetic status, subjects with IR had significantly higher total BAs than participants without IR both in diabetic and non-diabetic groups. Ultimately, multiple linear regression analysis identified HOMA-IR as the only significant contributor to most serum BA species. Conclusions Our findings support the essential role of IR in regulating BA metabolism and that this effect is independent of diabetic status.


Assuntos
Ácidos e Sais Biliares/sangue , Análise Química do Sangue , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Adulto , Ácidos e Sais Biliares/metabolismo , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Jejum/metabolismo , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Análise de Regressão
5.
Vaccines (Basel) ; 11(3)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36992169

RESUMO

The coronavirus disease (COVID-19) outbreak affected the utilization and management of blood products in hospitals. Blood shortages occurred owing to social distancing policies and reduction in blood donors. However, only a few studies examined whether these changes affected blood usage and transfusion patterns. We retrospectively reviewed blood component usage according to hospital departments and phases of surgery in transfused patients admitted between 1 March 2019 and 28 February 2021, in a single center in Anyang, Korea. We also analyzed the length of hospital stay and mortality to determine prognosis. In 2020, 32,050 blood components were transfused to 2877 patients, corresponding to 15.8% and 11.8% less than the rates in 2019, respectively. Postoperative usage of blood products significantly decreased in 2020 (3.87 ± 6.50) compared to 2019 (7.12 ± 21.71) (p = 0.047). The length of hospital stay of the patients who underwent postoperative transfusion in 2019 (n = 197) was 13.97 ± 11.95 days, which was not significantly different from that in 2020 (n = 167), i.e., 16.44 ± 17.90 days (p = 0.118). Further, 9 of 197 postoperative transfusion patients died in 2019, while 8 of 167 patients died in 2020 (p = 0.920). The COVID-19 pandemic resulted in limited blood supply and reduced postoperative transfusions; however, patient prognosis was not affected.

6.
Ann Clin Lab Sci ; 52(5): 846-849, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36261189

RESUMO

Granular acute lymphoblastic leukemia (ALL) is defined by the presence of intracytoplasmic granules in lymphoblastic blasts, mimicking acute myeloblastic leukemia. The disease is extremely rare in adults, and hence, the characteristics thereof are poorly understood. We report a case of a 70-year-old man diagnosed with granular ALL. Bone marrow examination showed blasts with azurophilic granules in the cytoplasm, but immunophenotyping showed B-ALL with aberrant expression of myeloid antigens CD13 and CD33. Karyotyping revealed monosomy 7, and targeted NGS showed DNMT3A mutation, which suggested poor prognosis. Despite conventional chemotherapy treatment, the patient did not achieve complete remission. He declined further chemotherapy treatment and was maintained on only supportive care. This is the first report of adult granular ALL with DNMT3A mutation and monosomy 7.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Adulto , Humanos , Idoso , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Deleção Cromossômica , Leucemia Mieloide Aguda/genética , Indução de Remissão , Imunofenotipagem
7.
Lab Med ; 53(3): 326-329, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34725711

RESUMO

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia characterized by predominating abnormal promyelocytes with a PML-RARA rearrangement or a variant thereof. BCR-ABL1 rearrangement is an oncogenic event that is usually associated with chronic myeloid leukemia but also occurs in both acute lymphoblastic and acute myeloid leukemias and in healthy individuals. However, APL with concurrent PML-RARA and BCR-ABL1 rearrangements has rarely been reported. Herein, we describe a patient with APL exhibiting a BCR-ABL1 rearrangement in a minor clone and discuss the importance of evaluating this genetic alteration in terms of pathogenesis and treatment.


Assuntos
Leucemia Promielocítica Aguda , Aberrações Cromossômicas , Células Clonais/patologia , Rearranjo Gênico , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Mutação , Translocação Genética
8.
J Clin Med ; 11(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35566415

RESUMO

Thalassemia is the most common form of hereditary anemia. Here, we aimed to investigate the 13-year trend of the epidemiologic profiles and risk of comorbidities in thalassemia using a nationwide population-based registry in Korea. Diagnosis of thalassemia, the comorbidities and transfusion events in patients with thalassemia were identified in the Korean National Health Insurance database, which includes the entire population. The prevalence of thalassemia increased from 0.74/100,000 in 2006 to 2.76/100,000 in 2018. Notably, the incidence rate has nearly doubled in the last 2 years from 0.22/100,000 in 2016 to 0.41/100,000 in 2018. The annual transfusion rate gradually decreased from 34.7% in 2006 to 20.6% in 2018. Transfusion events in patients with thalassemia were significantly associated with the risk of comorbidities (diabetes: odds ratio [OR] = 3.68, 95% confidence interval [CI] = 2.59-5.22; hypertension: OR = 3.06, 95% CI = 2.35-4.00; dyslipidemia: OR = 1.72, 95% CI = 1.22-2.43; atrial fibrillation: OR = 3.52, 95% CI = 1.69-7.32; myocardial infarction: OR = 3.02, 95% CI = 1.09-8.38; stroke: OR = 3.32, 95% CI = 2.05-5.36; congestive heart failure: OR = 2.83, 95% CI = 1.62-4.97; end-stage renal disease: OR = 3.25, 95% CI = 1.96-5.37). Early detection of comorbidities and timely intervention are required for the management of thalassemia.

9.
Front Med (Lausanne) ; 9: 1021936, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530922

RESUMO

Background: We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR). Materials and methods: We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation. Results: We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, -0.592 for male, -0.484 for female) or CC (r, -0.646 for male, -0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication. Conclusion: We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.

10.
J Appl Lab Med ; 6(2): 367-377, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005941

RESUMO

BACKGROUND: The Alinity i system (Abbott), a recently developed automated immunoassay analyzer, has a compact footprint and a throughput of 200 tests per hour. Here, we present the first performance evaluation of thyroid function test (TFT) on the Alinity i system. METHODS: We performed precision, linearity, comparison, functional sensitivity, carryover, and reference interval verification of 4 hormones (Thyroid Stimulation Hormone; TSH, total T3, free T4, and total T4) using the reagents provided by the manufacturer following the guidelines of the Clinical Laboratory Standards Institute. The performance of Alinity i was compared to that of the Architect i2000 immunoassay analyzer (Abbott, US). RESULTS: The within-laboratory coefficients of variation for all the hormones were 1.6-3.6%. Linearity was observed for all the hormones over the entire tested analytical range (R2 ≥ 0.99). The results for all the evaluated hormones using Alinity i system strongly correlated (r ≥ 0.978) with those from Architect i2000. Functional sensitivity was lower than the lower limit of the analytical measurement range. Sample carryover was less than 1.0%. CONCLUSIONS: TFTs on the Alinity i system showed acceptable performance in terms of precision, linearity, comparison, functional sensitivity, and carryover. Therefore, this system could be a useful laboratory tool for performing TFTs.


Assuntos
Testes Imunológicos , Testes de Função Tireóidea , Humanos , Imunoensaio , Valores de Referência , Reprodutibilidade dos Testes
11.
Ann Lab Med ; 41(4): 419-423, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33536362

RESUMO

Procalcitonin (PCT) is a useful bacterial infection biomarker with the potential for guiding antibiotic therapy. We evaluated the concordance of three automated PCT immunoassays: Kryptor (BRAHMS GmbH, Hennigsdorf, Germany), Atellica IM 1600 (Siemens Healthcare Diagnostics, Munich, Germany), and Cobas e801 (Roche Diagnostics, Mannheim, Germany). In 119 serum samples with a PCT concentration <5.00 µg/L, Kryptor (reference assay) was compared with the other two immunoassays by Spearman's rank correlation, regression analysis, and concordance at two antibiotic stewardship medical decision points: 0.25 and 0.50 µg/L. The Atellica IM 1600 and Cobas e801 results showed high correlations with those of Kryptor, with correlation coefficient (ρ) values of 0.97 and 0.99, respectively. However, negative biases were observed in both immunoassays (slope/y-intercept: 0.75/-0.00 for Atellica IM 1600; 0.88/-0.01 for Cobas e801). Atellica IM 1600 and Cobas e801 demonstrated excellent concordance with Kryptor at both medical decision points, with linearly weighted κ values of 0.90 and 0.92, respectively, despite discrepancies, which were more prominent at the 0.25 µg/L medical decision point. Based on these biases and discrepancies, the alternate use of different PCT immunoassays in repeat examinations is inadvisable. Standardization is required before comparing the results of different PCT immunoassays.


Assuntos
Imunoensaio , Infecções Bacterianas , Biomarcadores , Humanos , Pró-Calcitonina , Análise de Regressão
12.
J Microbiol Immunol Infect ; 54(2): 253-260, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31262511

RESUMO

BACKGROUND/PURPOSE: Transplant recipients are vulnerable to life-threatening community-acquired respiratory viruses (CA-RVs) infection (CA-RVI). Even if non-transplant critically ill patients in intensive care unit (ICU) have serious CA-RVI, comparison between these groups remains unclear. We aimed to evaluate clinical characteristics and mortality of CA-RVI except seasonal influenza A/B in transplant recipients and non-transplant critically ill patients in ICU. METHODS: We collected 37,777 CA-RVs multiplex real-time reverse transcription-polymerase chain reaction test results of individuals aged ≥18 years from November 2012 to November 2017. The CA-RVs tests included adenovirus, coronavirus 229E/NL63/OC43, human bocavirus, human metapneumovirus, parainfluenza virus 1/2/3, rhinovirus, and respiratory syncytial virus A/B. RESULTS: We found 286 CA-RVI cases, including 85 solid organ transplantation recipients (G1), 61 hematopoietic stem cell transplantation recipients (G2), and 140 non-transplant critically ill patients in ICU (G3), excluding those with repeated isolation within 30 days. Adenovirus positive rate and infection cases were most prominent in G2 (p < 0.001). The median time interval between transplantation and CA-RVI was 30 and 20 months in G1 and G2, respectively. All-cause in-hospital mortality was significantly higher in G3 than in G1 or G2 (51.4% vs. 28.2% or 39.3%, p = 0.002, respectively). The mechanical ventilation (MV) was the independent risk factor associated with all-cause in-hospital mortality in all three groups (hazard ratio, 3.37, 95% confidence interval, 2.04-5.56, p < 0.001). CONCLUSIONS: This study highlights the importance of CA-RVs diagnosis in transplant recipients even in long-term posttransplant period, and in non-transplant critically ill patients in ICU with MV.


Assuntos
Infecções Comunitárias Adquiridas/etiologia , Infecções Respiratórias/etiologia , Transplantados , Adulto , Idoso , Estudos de Coortes , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/virologia , Estado Terminal , Suscetibilidade a Doenças , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , República da Coreia/epidemiologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco
13.
Sci Rep ; 10(1): 3825, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123207

RESUMO

Although tuberculosis (TB) is a severe health problem worldwide, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used in the study of infectious diseases. We performed metabolome profiling to identify potential biomarkers in patients with active TB. Serum samples from 21 patients with active pulmonary TB, 20 subjects with latent TB infection (LTBI), and 28 healthy controls were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by multivariate and univariate analyses. Metabolic profiles indicated higher serum levels of glutamate, sulfoxy methionine, and aspartate and lower serum levels of glutamine, methionine, and asparagine in active TB patients than in LTBI subjects or healthy controls. The ratios between metabolically related partners (glutamate/glutamine, sulfoxy methionine/methionine, and aspartate/asparagine) were also elevated in the active TB group. There was no significant difference in the serum concentration of these metabolites according to the disease extent or risk of relapse in active TB patients. Novel serum biomarkers such as glutamate, sulfoxy methionine, aspartate, glutamine, methionine, and asparagine are potentially useful for adjunctive, rapid, and noninvasive pulmonary TB diagnosis.


Assuntos
Metabolômica , Tuberculose Pulmonar/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tuberculose Pulmonar/metabolismo , Adulto Jovem
14.
Endocrinol Metab (Seoul) ; 35(4): 960-964, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33212546

RESUMO

Appropriate reference intervals of serum insulin-like growth factor I (IGF-I) is important for diagnosing and monitoring patients with growth hormone-related diseases. To establish reference intervals, adult individuals (n=1,334, 680 men and 654 women) were divided into six age groups (20-29, 30-39, 40-49, 50-59, 60-69, ≥70). Serum IGF-I was measured by chemiluminescence immunoassay (Liaison). Concordance of patient classification based on reference intervals, manufacturer's intervals, and standard deviation score (SDS) was evaluated. New reference intervals had higher upper and lower limits than those specified by the manufacturer. The agreement between classification using new reference interval and the manufacturer's reference interval, and that using new reference interval and SDS was 75.0% (weighted kappa, 0.17), 91.9% (weighted kappa, 0.51) in men and 91.0% (weighted kappa, 0.41), 92.5% (weighted kappa, 0.53) in women, respectively. Reference intervals should be established not only based on age and sex, but also on ethnicity and assay method.


Assuntos
Biomarcadores/sangue , Fator de Crescimento Insulin-Like I/análise , Adulto , Idoso , Feminino , Transtornos do Crescimento/sangue , Voluntários Saudáveis , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Valores de Referência , República da Coreia , Adulto Jovem
16.
Ann Lab Med ; 35(6): 586-94, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26354346

RESUMO

BACKGROUND: We aimed to determine the major contributing component of metabolic syndrome (MetS) that results in an elevated small dense LDL cholesterol (sdLDL-C) concentration and sdLDL-C/LDL-C ratio. METHODS: Four hundred and forty-seven subjects (225 men; 222 women) with MetS were randomly selected from the Korean Metabolic Syndrome Research Initiatives-Seoul cohort study. Age- and sex-matched healthy controls (181 men; 179 women) were also randomly selected from the same cohort. RESULTS: A comparison of the median values of the sdLDL-C concentration between subgroups, divided according to whether subjects met or did not meet the criteria for each MetS component in patients with MetS, revealed a significant difference in the sdLDL-C concentration only between subgroups divided according to whether subjects met or did not meet the triglyceride (TG) criteria (P<0.05 for each gender). The TG level showed a good correlation with sdLDL-C concentration (correlation coefficients [r]=0.543 for men; 0.653 for women) and the sdLDL-C/LDL-C ratio (r=0.789 for men; 0.745 for women). Multiple linear regression analyses conducted for the MetS group concordantly identified TG as one of the most significant contributors to sdLDL-C concentration (ß=0.1747±0.0105, P<0.0001) and the sdLDL-C/LDL-C ratio (ß=6.9518±0.3011, P<0.0001). CONCLUSIONS: Among five MetS components, only the abnormal TG level was a differentiating factor for sdLDL-C concentration and sdLDL-C/LDL-C ratio. These results were reproducible in both genders, with or without MetS.


Assuntos
LDL-Colesterol/sangue , Hipertrigliceridemia/complicações , Síndrome Metabólica/complicações , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Hipertrigliceridemia/diagnóstico , Modelos Lineares , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue
17.
J Microbiol Biotechnol ; 25(2): 280-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25394603

RESUMO

Current influenza vaccines are produced in embryonated chicken eggs. However, egg-based vaccines have various problems. To address these problems, recombinant protein vaccines have been developed as new vaccine candidates. Unfortunately, recombinant proteins frequently encounter aggregation and low stability during their biogenesis. It has been previously demonstrated that recombinantly expressed proteins can be greatly stabilized with high solubility by fusing stabilizing peptide (SP) derived from the C-terminal acidic tail of human synuclein (ATS). To investigate whether SP fusion proteins can induce protective immunity in mice, we produced influenza HA and SP fusion protein using a baculovirus expression system. In in vitro tests, SP-fused recombinant HA1 (SP-rHA1) was shown to be more stable than recombinant HA1 (rHA1). Mice were immunized intramuscularly with baculovirus-expressed rHA1 protein or SP-rHA1 protein (2 µg/mouse) formulated with aluminum hydroxide. Antibody responses were determined by ELISA and hemagglutination inhibition assay. We observed that SP-rHA1 immunization elicited HA-specific antibody responses that were comparable to rHA1 immunization. These results indicate that fusion of SP to rHA1 does not negatively affect the immunogenicity of the vaccine candidate. Therefore, it is possible to apply SP fusion technology to develop stable recombinant protein vaccines with high solubility.


Assuntos
Anticorpos Antivirais/imunologia , Baculoviridae/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Imunidade Humoral , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/imunologia , Sinucleínas/genética , Vacinação , Vacinas de Subunidades Antigênicas/imunologia
18.
Ann Lab Med ; 33(3): 212-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23667851

RESUMO

Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.


Assuntos
Neoplasias da Mama/diagnóstico , Síndrome de Li-Fraumeni/diagnóstico , Adolescente , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Terapia Combinada , Éxons , Feminino , Genótipo , Heterozigoto , Humanos , Síndrome de Li-Fraumeni/complicações , Síndrome de Li-Fraumeni/terapia , Pessoa de Meia-Idade , Imagem Multimodal , Mutação de Sentido Incorreto , Linhagem , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Adulto Jovem
19.
Clin Chim Acta ; 413(21-22): 1731-6, 2012 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-22759977

RESUMO

BACKGROUND: We compared the diagnostic utilities of procalcitonin (PCT) and C-reactive protein (CRP) for predicting bacteremia diagnosed by blood cultures. PCT was also evaluated as a parameter for differentiating true bacteremia from culture contamination. METHODS: We analyzed a total of 3343 patients in which PCT, CRP, and blood cultures were concurrently requested for detecting bacteremia from January 2010 to December 2011. PCT concentrations were measured by the VIDAS® Brahms PCT assay, and CRP concentrations were determined by a turbidimetric assay using CA-400 analyzer. RESULTS: The PCT concentrations of bacteremia cases (n=331) were significantly higher than those of non-bacteremia (n=2856) (median: 3.2 ng/ml vs. 0.4 ng/ml, P<0.0001). The correlation coefficient between the PCT and CRP concentrations was 0.51. The areas under the receiver operating characteristic curves (ROC-AUCs) of PCT and CRP for discriminating bacteremia from non-bacteremia were 0.76 and 0.64, respectively. The ROC-AUC of PCT for differentiating true bacteremia from contamination was 0.86, while that of CRP was 0.65. CONCLUSIONS: PCT concentration by single testing was more useful for predicting bacteremia than CRP. PCT also exhibited diagnostic utility for ruling out blood culture contamination. Thus, PCT could be helpful in the accurate diagnosis of bacteremia.


Assuntos
Bacteriemia/sangue , Proteína C-Reativa/análise , Calcitonina/sangue , Precursores de Proteínas/sangue , Idoso , Área Sob a Curva , Bacteriemia/diagnóstico , Técnicas Bacteriológicas , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos
20.
Am J Clin Pathol ; 137(5): 770-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22523216

RESUMO

We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/diagnóstico , Patologia Clínica/métodos , Biomarcadores/sangue , Hepatite B/imunologia , Hepatite B/virologia , Humanos
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