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1.
São Paulo; s.n; s.n; 2021. 97 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396743

ABSTRACT

Os polissacarídeos não amido constituem importante parcela das fibras dietéticas, e podem ser considerados modificadores de resposta biológica (MRBs), uma vez que são capazes de interagir com o sistema imune, e suas características estruturais estão atreladas aos efeitos biológicos gerados. O potencial imunomodulador dos polissacarídeos do chuchu já foi demonstrado, entretanto, informações sobre suas características estruturais e sua relação com o perfil imunológico são limitadas a ensaios in vitro, não havendo, até o momento, estudos in vivo. Assim, o objetivo do estudo foi avaliar, in vitro e in vivo, o perfil imunomodulador de frações isoladas do polissacarídeo do chuchu. Por meio da filtração tangencial foram obtidas as frações de estudo, SeRI<50 e SeSE<50, respectivamente as frações isoladas do polissacarídeo do chuchu extraídas do resíduo insolúvel e do sobrenadante pós-tratamento enzimático para retirada do amido com peso molecular menor que 50 kDa. A caracterização por meio da determinação da composição monossacarídica e da análise de ligação apontou que ambas as frações são formadas por galacturonanos, arabinanos, arabinogalactanos e glicomananos. A SeRI<50 é menos ramificada e, provavelmente, composta por galactanos, enquanto SeSE<50 é mais ramificada e, provavelmente, composta por galactuglucomananos. Essas frações foram capazes de estimular os macrófagos murinos RAW 264.7 e as células mononucleares do baço, do sangue e do intestino delgado de camundongos Balb/c, sugerindo um perfil de ação mais pró-inflamatório, com base nos efeitos produzidos pelas espécies reativas de oxigênio, citocinas e pelos marcadores de ativação de linfócitos. Ambas as amostras, SeRI<50 e SeSE<50, mostraram ser eficientes em ativar a cascata imunológica, não sendo citotóxicas mesmo com a maior concentração testada no ensaio in vitro


Non-starch polysaccharides are important components of dietary fibers, and they may be considered biological response modifiers (MRBs), as they may interact with the immune system, depending on their structural characteristics. The immunomodulatory potential of chayote polysaccharides has already been demonstrated, however, information on their structural characteristics and their relationship with the immunological profile are limited to in vitro assays, with no reports on in vivo studies. Thus, the objective of the study was to evaluate, in vitro and in vivo, the immunomodulatory profile of polysaccharide from chayote. Through tangential filtration two fractions, SeRI <50 and SeSE <50, were obtained, respectively the fraction isolated from the chayote polysaccharide extracted from the insoluble residue and the fraction from the enzymatic post-treatment supernatant to remove starch, both under molecular weight 50 kDa. The monosaccharide composition and linkage analysis showed that both fractions are formed by galacturonans, arabinans, arabinogalactans and glycomanans. SeRI <50 is less branched and probably composed of galactans, while SeSE <50 is more branched and probably composed of galactuglucomannans. These fractions were able to stimulate murine macrophages RAW 264.7 and mononuclear cells of the spleen, blood and small intestine of Balb / c mice, suggesting a more proinflammatory action profile, based on the reactive oxygen species production, cytokines and lymphocyte activation markers. Both samples, SeRI <50 and SeSE <50, were able to efficiently activate the immunological cascade, not being cytotoxic even at the highest concentration tested in the in vitro assay


Subject(s)
Starch/adverse effects , Vegetables/classification , In Vitro Techniques/instrumentation , Lymphocyte Activation , Lymphocytes/classification , Cytokines/agonists , Immunomodulation , Immunologic Factors , Macrophages/classification
2.
Article in English | WPRIM | ID: wpr-922382

ABSTRACT

OBJECTIVES@#To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex.@*METHODS@#A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes.@*RESULTS@#Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils (@*CONCLUSIONS@#Sex has no significant effect on the proportion of lymphocyte subsets in 3-month-old full-term infants, but feeding patterns are associated with the proportion of CD28


Subject(s)
Breast Feeding , CD8-Positive T-Lymphocytes , Female , HLA-DR Antigens , Humans , Infant , Lymphocyte Activation , Male , Prospective Studies
3.
Article in English | WPRIM | ID: wpr-880368

ABSTRACT

BACKGROUND@#Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8@*METHODS@#For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8@*RESULTS@#IL-15 addition partially reversed the decrease in CD3@*CONCLUSION@#These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.


Subject(s)
Asbestos/adverse effects , CD8-Positive T-Lymphocytes/metabolism , Humans , Interleukin-15/pharmacology , Lymphocyte Activation/immunology , T-Lymphocytes, Cytotoxic/metabolism
4.
Article in Chinese | WPRIM | ID: wpr-880131

ABSTRACT

OBJECTIVE@#To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ.@*METHODS@#The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3@*RESULTS@#A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated.@*CONCLUSION@#The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.


Subject(s)
Humans , Leukocytes, Mononuclear , Lymphocyte Activation , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Up-Regulation
5.
Rio de Janeiro; s.n; ilus; 2020. 173 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1252813

ABSTRACT

As leishmanioses são causadas por cerca de 20 espécies de Leishmania e se apresentam em diversas formas clínicas, que podem variar de branda a muito grave. Elas afetam milhões de pessoas e até então não existem medidas de controle eficazes. Assim, a imunização da população seria uma alternativa eficiente de controle. Evidências sugerem que a resposta imune que se estabelece após a cura clínica de leishmanioses deva constituir um padrão de resposta imunológica associado à proteção, e que uma preparação vacinal deveria estimulá-la preferencialmente. Nosso grupo demonstrou que antígenos de L. (Viannia) naiffi (espécie considerada benigna) conseguem induzir respostas bem moduladas, e que soros de voluntários curados de leishmaniose tegumentar cutânea reconheceram frações desse antígeno consideradas imunodominantes. Experimentos anteriores demonstraram em hamster que a imunização intranasal com antígenos totais dessa espécie são capazes de induzir uma imunidade protetora contra L. (V.) braziliensis. O mesmo grupo já havia obtido a mesma resposta protetora utilizando o antígeno total de L. (L.) amazonensis. No entanto, sabe-se que nem todos os componentes presentes nesses antígenos estão associados à proteção e que a identificação de proteínas que sejam imunogênicas é uma etapa indispensável na formulação de uma vacina.


O objetivo deste trabalho foi identificar as proteínas imunodominantes presentes nas frações solúveis de L. (L.) amazonensis (LaAg(s)) e L.(V.) naiffi (LnAg(s)), que sejam conservadas dentro do gênero Leishmania, para formular uma vacina pan específica para o controle das leishmanioses. Primeiramente, os antígenos LnAg(s) e LaAg(s) foram subfracionados em gel de poliacrilamida e as bandas com peso molecular entre 35 e 100KDa foram extraídas e submetidas à análise por espectrometria de massa para análise proteômica. Desta análise, foram obtidas as sequências de aminoácidos, o tamanho das sequências, e a abundância das proteínas. As proteínas mais abundantes foram submetidas à análise de similaridade com proteínas de hospedeiros. As proteínas de LnAg(s) e LaAg(s) com baixa similaridade (<30%) às proteínas humanas foram analisadas por preditores de epítopos reconhecidos por linfócitos B.


Em paralelo, a predição de epítopos presentes em LnAg(s) e LaAg(s), capazes de se ligar com alta afinidade a moléculas HLA classes I e II, assim como a promiscuidade de ligação a alelos de HLA para cada proteína, foram avaliados dentre aquelas que apresentaram maior abundância e baixa similaridade. Por fim, após a análise de homologia das proteínas entre as espécies de Leishmania, foram identificadas 11 proteínas com mais homólogos. Elas apresentaram potencial de reconhecimento por linfócitos B, assim como também por componentes da resposta imune celular (como predito para a apresentação por HLA classes I e II). O potencial de ativação de linfócitos T pelos epítopos presentes nas 11 proteínas foi incrementado pela ampla capacidade de apresentação antigênica na população humana, devido à alta promiscuidade quanto à capacidade de ligação destes epítopos a alelos de HLA. Esses resultados contribuem para a identificação de antígenos com potencial de compor um protótipo vacinal capaz de induzir uma resposta imune protetora pan específica em humanos, com características imunodominantes e indutoras de resposta humoral e celular, para serem empregados no controle das leishmanioses. (AU)


Subject(s)
Humans , Leishmania mexicana , Lymphocyte Activation , Leishmaniasis , Immunization , Epitopes, T-Lymphocyte
6.
Article in Chinese | WPRIM | ID: wpr-772044

ABSTRACT

OBJECTIVE@#To investigate the effect of sputum ubiquitin ligase (Cbl-b) gene known-down on the cytotoxicity of H9 T lymphocytes against human laryngeal squamous cancer Hep-2 cells and explore the underlying mechanism.@*METHODS@#CD4 T lymphocytes isolated from 12 patients with laryngeal squamous carcinoma and 12 healthy individuals were examined for Cbl-b mRNA expressions using RT-PCR. H9 T lymphocytes cultured in 96-well plates were transfected with Cbl-b siRNA via liposomes followed by treatment with an anti-IL-2 monoclonal antibody, with H9 T lymphocytes transfected with a scrambled sequence as the negative control. The expressions of Cbl-b mRNA and protein in the cells were detected using real-time fluorescent quantitative PCR and Western blotting, respectively. The killing effect of the treated T lymphocytes against Hep-2 cells was assessed using the cell counting kit (CCK-8). The positive expression rates of CD69 and CD25 on the surface of H9 T lymphocytes were determined using flow cytometry, and the levels of interleukin-2 (IL-2) and interferon-gamma (INF-γ) in the culture supernatants of H9 T lymphocytes were detected with ELISA.@*RESULTS@#The CD4 T lymphocytes from patients with laryngeal squamous carcinoma showed significantly increased Cbl-b mRNA level compared with those from healthy individuals ( < 0.05). Transfection of H9 T lymphocytes with Cbl-b siRNA significantly reduced the expression levels of Cbl-b mRNA and protein ( < 0.05), which were not significantly affected by subsequent treatment of the cells with the anti-IL-2 antibody (>0.05). At different target-effector ratios, the Cbl-b siRNA-transfected cells showed significantly higher Hep-2 cell killing rates and higher positivity rates of CD69 and CD25 expressions than the blank and negative control cells and the cells with both Cbl-b siRNA transfection and anti-IL-2 treatment ( < 0.05). Cbl-b silencing in H9 T lymphocytes resulted in significantly increased levels of IL-2 and INF-γ in the supernatant as compared with those in the blank and negative control groups ( < 0.05).@*CONCLUSIONS@#Cbl-b gene silencing effectively enhances the killing effect of H9 T lymphocytes against Hep-2 cells probably as the result of enhanced IL-2 secretion and T lymphocyte activation.


Subject(s)
Carcinoma, Squamous Cell , Genetics , Therapeutics , Gene Silencing , Humans , Laryngeal Neoplasms , Genetics , Therapeutics , Lymphocyte Activation , RNA, Small Interfering , T-Lymphocytes
7.
Frontiers of Medicine ; (4): 69-82, 2019.
Article in English | WPRIM | ID: wpr-771259

ABSTRACT

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-γ and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.


Subject(s)
Cell Line, Tumor , Cytokines , Metabolism , Cytotoxicity, Immunologic , Genetic Engineering , HLA-A2 Antigen , Metabolism , Humans , Immunotherapy, Adoptive , Methods , Lymphocyte Activation , Receptors, Antigen, T-Cell , Genetics , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology
8.
Article in English | WPRIM | ID: wpr-761933

ABSTRACT

Antiepileptic drugs (AEDs) can induce severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. We performed HLA genotyping and lymphocyte activation tests (LATs) for five AED-induced SCAR patients (three males and two females; aged 40–66 years old). Three patients were treated with carbamazepine (CBZ) for pain control, one was treated with phenytoin (PHT) for seizure prevention, and one was treated with valproic acid (VPA) for seizure prevention. One patient was diagnosed with CBZ-induced DRESS syndrome and the remaining patients were diagnosed with SJS. All patients recovered from SCARs after stopping suspicious drugs and supportive care. LATs were conducted to confirm the culprit drug responsible for inducing SCARs; and LAT results were positive for the suspected culprit drugs, in all except in one case. HLA-A,


Subject(s)
Alleles , Anticonvulsants , Carbamazepine , Cicatrix , Drug Hypersensitivity Syndrome , Female , HLA-A Antigens , Humans , Long-Acting Thyroid Stimulator , Lymphocyte Activation , Lymphocytes , Male , Methods , Phenytoin , Seizures , Stevens-Johnson Syndrome , Valproic Acid
9.
Article in English | WPRIM | ID: wpr-772938

ABSTRACT

The activation mechanism of chimeric antigen receptor (CAR)-engineered T cells may differ substantially from T cells carrying native T cell receptor, but this difference remains poorly understood. We present the first comprehensive portrait of single-cell level transcriptional and cytokine signatures of anti-CD19/4-1BB/CD28/CD3ζ CAR-T cells upon antigen-specific stimulation. Both CD4 helper T (T) cells and CD8 cytotoxic CAR-T cells are equally effective in directly killing target tumor cells and their cytotoxic activity is associated with the elevation of a range of T1 and T2 signature cytokines, e.g., interferon γ, tumor necrotic factor α, interleukin 5 (IL5), and IL13, as confirmed by the expression of master transcription factor genes TBX21 and GATA3. However, rather than conforming to stringent T1 or T2 subtypes, single-cell analysis reveals that the predominant response is a highly mixed T1/T2 function in the same cell. The regulatory T cell activity, although observed in a small fraction of activated cells, emerges from this hybrid T1/T2 population. Granulocyte-macrophage colony stimulating factor (GM-CSF) is produced from the majority of cells regardless of the polarization states, further contrasting CAR-T to classic T cells. Surprisingly, the cytokine response is minimally associated with differentiation status, although all major differentiation subsets such as naïve, central memory, effector memory, and effector are detected. All these suggest that the activation of CAR-engineered T cells is a canonical process that leads to a highly mixed response combining both type 1 and type 2 cytokines together with GM-CSF, supporting the notion that polyfunctional CAR-T cells correlate with objective response of patients in clinical trials. This work provides new insights into the mechanism of CAR activation and implies the necessity for cellular function assays to characterize the quality of CAR-T infusion products and monitor therapeutic responses in patients.


Subject(s)
Antigens , Metabolism , CTLA-4 Antigen , Metabolism , Cell Differentiation , Cell Line , Cytokines , Metabolism , Cytotoxicity, Immunologic , Granulocyte-Macrophage Colony-Stimulating Factor , Pharmacology , Humans , Lymphocyte Activation , Allergy and Immunology , Lymphocyte Subsets , Metabolism , Phenotype , Proteomics , Receptors, Chimeric Antigen , Metabolism , Single-Cell Analysis , Methods , T-Lymphocytes, Regulatory , Metabolism , Th1 Cells , Cell Biology , Th2 Cells , Cell Biology , Transcription, Genetic , Up-Regulation
10.
Protein & Cell ; (12): 121-129, 2018.
Article in English | WPRIM | ID: wpr-756967

ABSTRACT

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.


Subject(s)
Animals , Antibodies, Bispecific , Allergy and Immunology , Antibodies, Monoclonal , Allergy and Immunology , Pharmacokinetics , CD3 Complex , Metabolism , Cell Line, Tumor , Cytotoxicity, Immunologic , ErbB Receptors , Metabolism , Female , Humans , Lymphocyte Activation , Allergy and Immunology , Mice, SCID , Neoplasms , Allergy and Immunology , Pathology , Rats, Sprague-Dawley , T-Lymphocytes, Cytotoxic , Allergy and Immunology
11.
Journal of Experimental Hematology ; (6): 1765-1771, 2018.
Article in Chinese | WPRIM | ID: wpr-774388

ABSTRACT

OBJECTIVE@#To investigate the effects of different stimultors (PHA, PMA and IL-2) and culture systems (PBMC and whole blood) on the proliferation of human peripheral blood lymphocyte subsets, so as to provide the experimental basis for selecting the appropriate system according to the experimental purposes.@*METHODS@#A total of 10 ml serum samples were collected from healthy volunteers (n=6). The 300 μl whole blood was directly used to detect lymphocyte subsets by flow cytometry. The 400 μl whole blood were inoculated respectively with 3 different stimulators at 37℃ and 5% CO2 for 60 h; Three different stimulators were also added to the PBMC which were isolated from 2 ml whole blood. Then the proliferation ability of lymphocyte subsets was analyzed by flow cytometry.@*RESULTS@#After the PBMC were stimulated with PHA, CD4CD8CD3 lymphocytes were the most subset; The proportion of CD3CD4 T lymphocytes and CD3CD19 B lymphocytes decreased after being stimulated by PMA (P<0.01, P<0.05); the lymphocyte subset ratio had no significant change after being stimulated by IL-2. After the whole blood system was stimulated with PHA, the CD4/CD8 T lymphoblasts were main subsets, the counts of B lymphocytes and NK cells were reduced; after being stimulated with PMA, the number of CD8CD3 T lymphoblast and CD4CD8T lymphocytes increased, the B/NK cells were not distinguished with the surface markers; after the whole blood system was stimulated with IL-2, the proportion of NK cells significantly increased (P<0.05).@*CONCLUSION@#Lymphocyte proliferation stimulated by PMA is the fastest, while the effect of IL-2 on the lymphocyte subset proportion stimulated by IL-2 is the minimal. After being stimulated by PHA the division cycles of lymphocyte are the most.


Subject(s)
Cell Proliferation , Flow Cytometry , Humans , Killer Cells, Natural , Lymphocyte Activation , Lymphocyte Count , Lymphocyte Subsets
12.
Article in English | WPRIM | ID: wpr-715546

ABSTRACT

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.


Subject(s)
Blood Cells , Colorectal Neoplasms , CTLA-4 Antigen , Diagnosis , Early Detection of Cancer , Flow Cytometry , Hematology , Humans , Immunologic Factors , Leukocytes , Logistic Models , Lymphocyte Activation , Lymphocytes , Methods , Neutrophils , Prospective Studies , Retrospective Studies , Sensitivity and Specificity , T-Lymphocytes , T-Lymphocytes, Regulatory
13.
Asia Pacific Allergy ; (4): e26-2018.
Article in English | WPRIM | ID: wpr-750150

ABSTRACT

Both immediate and nonimmediate type hypersensitivity reactions (HRs) with a single dose of quinolone in the same patient have not been previously reported. A 47-year-old female patient referred to us because of the history of a nonimmediate type HR to radio contrast agent and immediate type HR to clarithromycin. She experienced anaphylaxis in minutes after the second dose of 50 mg when she was provocated with moxifloxacin. She was treated immediately with epinephrine, fluid replacement and methylprednisole and pheniramine. On the following day she came with macular eruptions, and she was treated with methylprednisolone. The positive patch test performed with moxifloxacin as well as the lymphocyte transformation test proved the T-cell mediated HR. In order to prove the immediate type HR, basophil activation test was performed but was found negative. This case report presents for the first time the 2 different types of HRs in a patient with a test dose of quinolone.


Subject(s)
Anaphylaxis , Basophils , Clarithromycin , Epinephrine , Female , Humans , Hypersensitivity , Lymphocyte Activation , Methylprednisolone , Middle Aged , Patch Tests , Pheniramine , T-Lymphocytes
14.
Intestinal Research ; : 273-281, 2018.
Article in English | WPRIM | ID: wpr-714183

ABSTRACT

BACKGROUND/AIMS: Mesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy. METHODS: Patients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017. RESULTS: The DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE− group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE− group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE− group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE− group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively. CONCLUSIONS: The DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine.


Subject(s)
Colitis, Ulcerative , Diagnosis , Humans , Hypersensitivity , Lymphocyte Activation , Lymphocytes , Mesalamine , Sensitivity and Specificity
16.
Ann. hepatol ; 16(2): 308-311, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-887237

ABSTRACT

ABSTRACT A 75-year old male patient had been regularly visiting our hospital for the management of his type 2 diabetes mellitus since he was diagnosed at age 64 years. When he developed hypoglycemic episodes with sulfonylurea, ipragliflozin (50 mg/day) was started to replace the sulfonylurea therapy. However, 49 days after starting ipragliflozin, his AST increased from 13 to 622 U/L, ALT increased from 9 to 266 U/L, ALP increased from 239 to 752 U/L, and γ-GTP increased from 19 to 176 U/L. ZTT was 3.5 U, TTT was 0.4 U, and total bilirubin was 0.7 mg/dL. IgM hepatitis A antibody, hepatitis B antigen, hepatitis C virus antibody, IgM CMV antibody, and IgM EB VCA antibody were negative, whereas a lymphocyte transformation test for ipragliflozin was positive. Abdominal CT scan showed mild fatty liver but no sign of nodular lesions. Following admission to our hospital, he received liver supportive therapy with the discontinuation of ipragliflozin therapy. He was discharged from the hospital 18 days later with AST and ALT levels reduced to 20 U/L and 13 U/L, respectively. Based on the clinical presentation of this patient, it is highly important to monitor liver function along with other possible clinical complications (e.g., dehydration, ketosis, and urinary tract infection) associated with SGLT2 inhibitor therapy.


Subject(s)
Humans , Male , Aged , Lymphocyte Activation/drug effects , Diabetes Mellitus, Type 2/drug therapy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/immunology , Glucosides/adverse effects , Hypoglycemic Agents/adverse effects , Thiophenes/adverse effects , Predictive Value of Tests , Risk Factors , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Chemical and Drug Induced Liver Injury/therapy , Liver Function Tests
17.
Article in English | WPRIM | ID: wpr-226321

ABSTRACT

BACKGROUND: Traditional medicines have been leveraged for the treatment and prevention of obesity, one of the fastest growing diseases in the world. However, the exact mechanisms underlying the effects of traditional medicine on obesity are not yet fully understood. METHODS: We produced the transcriptomes of epididymal white adipose tissue (eWAT), liver, muscle, and hypothalamus harvested from mice fed a normal diet, high-fat-diet alone, high-fat-diet together with green tea, or a high-fat-diet together with Taeumjowitang, a traditional Korean medicine. RESULTS: We found tissue-specific gene expression patterns as follows: (i) the eWAT transcriptome was more significantly altered by Taeumjowitang than by green tea, (ii) the liver transcriptome was similarly altered by Taeumjowitang and green tea, and (iii) both the muscle and hypothalamus transcriptomes were more significantly altered by green tea than Taeumjowitang. We then applied integrated network analyses, which revealed that functional networks associated with lymphocyte activation were more effectively regulated by Taeumjowitang than by green tea in the eWAT. In contrast, green tea was a more effective regulator of functional networks associated with glucose metabolic processes in the eWAT. CONCLUSIONS: Taeumjowitang and green tea have a differential tissue-specific and pathway-specific therapeutic effect on obesity.


Subject(s)
Adipose Tissue, White , Animals , Diet , Gene Expression , Gene Regulatory Networks , Glucose , Hypothalamus , Liver , Lymphocyte Activation , Medicine, Traditional , Metabolism , Mice , Obesity , Sequence Analysis, RNA , Tea , Transcriptome
18.
Article in English | WPRIM | ID: wpr-49038

ABSTRACT

Allergy to antibiotics is an important worldwide problem, with an estimated prevalence of up to 10% of the population. Reaction patterns for different antibiotics have changed in accordance with consumption trends. Most of the allergic reactions to antibiotics have been reported for betalactams, followed by quinolones and macrolides and, to a lesser extent, to others, such as metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a detailed clinical history, which is not always possible and can be unreliable. This is usually followed by in vivo, skin, and drug provocation tests. These are not recommended for severe, potentially lifethreaten reactions or for drugs that are known to produce a high rate of false positive results. Given the limitations of in vivo tests, in vitro test can be helpful for diagnosis, despite having suboptimal sensitivity. The most highly employed techniques for diagnosing immediate reactions to antibiotics are immunoassays and basophil activation tests, while lymphocyte transformation tests are more commonly used to diagnose non-immediate reactions. In this review, we describe different in vitro techniques employed to diagnose antibiotic allergy.


Subject(s)
Anti-Bacterial Agents , Basophils , Clindamycin , Diagnosis , Diagnostic Tests, Routine , Drug Hypersensitivity , Hypersensitivity , Immunoassay , In Vitro Techniques , Lymphocyte Activation , Macrolides , Metronidazole , Prevalence , Quinolones , Skin , Sulfonamides
19.
Article in English | WPRIM | ID: wpr-49031

ABSTRACT

PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. METHODS: We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.


Subject(s)
Basophils , Ciprofloxacin , Diagnosis , Diagnostic Tests, Routine , Humans , Hypersensitivity , In Vitro Techniques , Levofloxacin , Lymphocyte Activation , Ofloxacin , Quinolones , Skin Tests , Urticaria
20.
Protein & Cell ; (12): 573-589, 2017.
Article in English | WPRIM | ID: wpr-756986

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal-curing cancer with high safety, high efficacy, and low cost.


Subject(s)
Cell Movement , Allergy and Immunology , Cell Proliferation , Gene Expression , Genetic Vectors , Chemistry , Metabolism , Humans , Immunotherapy, Adoptive , Methods , Lymphocyte Activation , Lymphocytes, Tumor-Infiltrating , Cell Biology , Allergy and Immunology , Transplantation , Neoplasms , Genetics , Allergy and Immunology , Pathology , Therapeutics , Patient Safety , Receptors, Antigen, T-Cell , Chemistry , Genetics , Allergy and Immunology , Recombinant Fusion Proteins , Chemistry , Genetics , Allergy and Immunology , Signal Transduction , Single-Chain Antibodies , Chemistry , Genetics , T-Lymphocytes , Cell Biology , Allergy and Immunology , Transplantation , Treatment Outcome
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