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1.
J Clin Periodontol ; 49(7): 706-716, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35569027

RESUMO

AIM: Mucosal-associated invariant T (MAIT) cells are known to be resident in oral mucosal tissue, but their roles in periodontitis are unknown. This study aimed to examine the level and function of MAIT cells in periodontitis patients. MATERIALS AND METHODS: Frequency, activation, and function of MAIT cells from 28 periodontitis patients and 28 healthy controls (HCs) were measured by flow cytometry. RESULTS: Circulating MAIT cells were numerically reduced in periodontitis patients. Moreover, they exhibited higher expression of CD69 and annexin V, together with more increased production of interleukin (IL)-17 and tumour necrosis factor (TNF)-α, in periodontitis patients than in HCs. Interestingly, periodontitis patients had higher frequencies of MAIT cells in gingival tissue than in peripheral blood. In addition, circulating MAIT cells had elevated expression of tissue-homing chemokine receptors such as CCR6 and CXCR6, and the corresponding chemokines (i.e., CCL20 and CXCL16) were more strongly expressed in inflamed gingiva than in healthy gingiva. CONCLUSIONS: This study demonstrates that circulating MAIT cells are numerically deficient with an activated profile toward the production of IL-17 and TNF-α in periodontitis patients. Furthermore, circulating MAIT cells have the potential to migrate to inflamed gingival tissues.


Assuntos
Interleucina-17/biossíntese , Células T Invariantes Associadas à Mucosa , Periodontite , Fator de Necrose Tumoral alfa/biossíntese , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Ativação Linfocitária , Células T Invariantes Associadas à Mucosa/metabolismo , Periodontite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Thorax ; 77(9): 865-872, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35086913

RESUMO

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that are engaged in a number of diseases, but their roles in acute respiratory distress syndrome (ARDS) are not fully examined yet. This study aimed to examine levels and functions of MAIT cells in patients with ARDS. METHODS: Peripheral blood samples from patients with ARDS (n=50) and healthy controls (HCs, n=50) were collected. Levels of MAIT cells, cytokines, CD69, programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) were measured by flow cytometry. RESULTS: Circulating MAIT cell levels were significantly reduced in patients with ARDS than in HCs. MAIT cell levels were inversely correlated with disease severity and mortality. Cytokine production profiles in MAIT cells showed that percentages of interleukin (IL)-17 producing MAIT cell were significantly higher in patients with ARDS than in HCs. Patients with ARDS exhibited higher expression levels of CD69, PD-1 and LAG-3 in circulating MAIT cells. Moreover, levels of MAIT cells and expression levels of CD69, PD-1 and IL-17 in MAIT cells were higher in bronchoalveolar lavage fluid samples than in peripheral blood samples. Our in vitro experiments showed that MAIT cells triggered macrophages to produce proinflammatory cytokines such as tumour necrosis factor-α, IL-1ß and IL-8. CONCLUSIONS: This study demonstrates that circulating MAIT cells are numerically deficient in patients with ARDS. In addition, MAIT cells were found to be activated, migrate into lung, secrete IL-17 and then stimulate macrophages. These findings suggest that MAIT cells contribute to the worsening of inflammation in the lung of patients with ARDS.


Assuntos
Células T Invariantes Associadas à Mucosa , Síndrome do Desconforto Respiratório , Citocinas/metabolismo , Humanos , Interleucina-17/metabolismo , Ativação Linfocitária , Células T Invariantes Associadas à Mucosa/metabolismo , Receptor de Morte Celular Programada 1/metabolismo
3.
Int J Surg Case Rep ; 86: 106301, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34392019

RESUMO

INTRODUCTION AND IMPORTANCE: Perivascular epithelioid cell tumor (PEComa), especially angiomyolipoma (AML) is a rare mesenchymal tumor in wide array of anatomic locations such as the kidney, lung, uterus, and gastrointestinal tract. AML is commonly found in the kidneys and classified as a classic AML or epithelioid AML. We report a case of epithelioid AML diagnosed in the rectum, treated by robot assisted low anterior resection. PRESENTATION OF CASE: A 45-year-old woman was referred to our hospital because when an intramural rectal mass was detected on a colonoscopic examination performed during a regular health checkup. Colonoscopic examination revealed an intramural mass, 2 cm in diameter, bulging in the rectal wall, 6 cm from the anal verge. Based on abdominal and pelvic computed tomography images and magnetic resonance imaging findings, the patient was suspected of having gastrointestinal stromal tumor of the rectum. The patient was treated by robot assisted low anterior resection under the diagnosis of GIST. The patient improved without any postoperative complication and was diagnosed as epithelioid AML, a type of PEComa. DISCUSSION: AML diagnosed in gastrointestinal tract is very rare and among them, epithelioid AML has possibility of malignancy. However, confirmed diagnosis before surgical resection is difficult because PEComa shows nonspecific imaging characteristics. Treatment of choice of epithelioid angiomyolipoma is surgical resection. CONCLUSION: Because epithelioid AML has the potential for malignancy, clinicians must be aware of the knowledge of the characteristics and natural history of epithelioid AML.

4.
Front Immunol ; 12: 700755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276693

RESUMO

Background: Dendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients. Methods: The study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry. Results: Circulating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α. Conclusions: This study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.


Assuntos
Células Dendríticas/imunologia , Tifo por Ácaros/imunologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Arthritis Res Ther ; 23(1): 182, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233727

RESUMO

BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Estudos Prospectivos , Tacrolimo/efeitos adversos , Resultado do Tratamento , Fator de Necrose Tumoral alfa
6.
J Innate Immun ; 11(6): 506-515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31085907

RESUMO

Mucosal-associated invariant T (MAIT) cells rapidly produce proinflammatory cytokines in an innate-like manner and play an important role in controlling the host immune response. This study examined the function of MAIT cells in trauma patients. The expression of cytokines in peripheral blood MAIT cells was measured by flow cytometry. MAIT cells in trauma patients displayed impaired tumor necrosis factor (TNF)-α production, together with elevated CD69 expression. The expression of CD69 was negatively correlated with MAIT cell frequency. These patients had higher plasma levels of interleukin (IL)-12 and IL-18. In particular, CD69 expression of MAIT cells was increased by stimulation with IL-18 in synergy with other proinflammatory cytokines or plasma of trauma patients. The production of TNF-α by MAIT cells was characterized by an initial burst and rapid decline, in contrast to delayed and sustained production of interferon (IFN)-γ. Activated MAIT cells showed a functional defect in the production of TNF-α upon restimulation. This study demonstrates that circulating MAIT cells are activated and functionally impaired in TNF-α production in patients with trauma. The activation and dysfunction of MAIT cells was mediated by proinflammatory cytokines. These findings provide important information underlying the innate immune response of patients with trauma.


Assuntos
Células T Invariantes Associadas à Mucosa/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Ferimentos e Lesões/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Células Cultivadas , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunidade Inata , Mediadores da Inflamação/metabolismo , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade
7.
Int J Rheum Dis ; 22(5): 913-920, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30809965

RESUMO

AIM: The aim of this study was to define clinical, histopathologic, and prognostic differences according to the presence of anti-ribosomal P antibody (anti-P) in Korean patients with biopsy-proven lupus nephritis (LN). METHODS: We studied 79 patients who underwent kidney biopsies prior to the start of induction treatment, and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than 6 months. Anti-P was measured by immunoblot analysis at the time of renal biopsy. RESULTS: Of all patients, 35.4% were anti-P-positive. Such patients exhibited earlier LN onset, a higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and a higher estimated glomerular filtration rate at the time of renal biopsy, than did those without antibodies. Upon renal histopathological analysis, patients with anti-P exhibited less interstitial inflammation in terms of the activity index, less glomerular sclerosis, less tubular atrophy, and less interstitial fibrosis in terms of the chronicity index. Furthermore, anti-P was associated with lower chronicity scores. At a median follow-up time of 47 months, renal function was preserved in 27 of 28 patients who had anti-P, but only 38 of 51 patients without such antibodies did not progress to chronic renal disease. After multivariate logistic regression, we found that anti-P positivity was associated with a reduced rate of progression to chronic kidney disease after adjusting for gender, baseline creatinine, activity and chronicity score, and treatment response (odds ratio = 0.196, 95% CI: 0.039-0.989, P = 0.048). CONCLUSION: Anti-P was associated with better histological findings, and anti-P-positive patients had better renal outcomes than those without anti-P.


Assuntos
Autoanticorpos/sangue , Rim/imunologia , Nefrite Lúpica/imunologia , Proteínas Ribossômicas/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/imunologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Int J Rheum Dis ; 21(4): 804-812, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27126923

RESUMO

AIM: Cardiac autonomic dysfunction (CAD) is frequently found in patients with fibromyalgia (FM). Thus, we evaluated whether heart rate variability (HRV) is superior to the Ewing tests in detecting CAD in FM patients. METHODS: We studied 35 females with FM and 25 age-matched healthy females. In Ewing tests, results were added to yield an overall score. An abnormal result on deep breathing, the Valsalva maneuver, or orthostatic standing was counted as 1 point. A change in systolic blood pressure (SBP) of > 10 mmHg while standing counted as 1 point, and a change of > 20 mmHg as 2 points. A score of 0 was regarded as no CAD, a score of ≥ 2 as severe CAD and a score of 1 as mild CAD. HRV was measured in two ways: by R-R intervals (time-domain analysis) and by spectral analysis of a series of successive R-R intervals (frequency-domain analysis). RESULTS: FM patients had significantly lower expiratory/inspiratory (E/I) ratios, lower Valsalva ratios and higher SBP values than healthy controls (P < 0.05, P < 0.05, P < 0.01, respectively). In the frequency domain, very low-frequency and low-frequency bands were also lower in FM patients than controls (both P < 0.05). Based on the discriminant analysis of the Ewing tests, 54.4% of cases were correctly classified. The addition of HRV parameters did not improve the reclassification. CONCLUSION: HRV does not improve detection of CAD in FM patients over classic autonomic testing.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Eletrocardiografia , Cardiopatias/diagnóstico , Frequência Cardíaca , Coração/inervação , Leiomioma/complicações , Exame Neurológico , Adulto , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Leiomioma/diagnóstico , Leiomioma/fisiopatologia , Pessoa de Meia-Idade , Posicionamento do Paciente , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Respiração , Fatores de Tempo , Manobra de Valsalva , Adulto Jovem
9.
J Korean Med Sci ; 32(5): 750-756, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28378547

RESUMO

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.


Assuntos
Células T Invariantes Associadas à Mucosa/citologia , Traumatismo Múltiplo/patologia , Células T Matadoras Naturais/citologia , Adulto , Idoso , Plaquetas/citologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Hemoglobinas/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/imunologia , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/imunologia , Células T Matadoras Naturais/imunologia , Índice de Gravidade de Doença
10.
Clin Exp Rheumatol ; 35(2): 234-240, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27782867

RESUMO

OBJECTIVES: To investigate whether CCL21 and CXCL13 expression levels in the minor salivary gland are associated with the laboratory and clinical manifestations of Sjögren's syndrome (SS). METHODS: Sociodemographic data on 106 SS patients were obtained and the glandular and extraglandular manifestations of the disease were documented. In addition, minor salivary gland biopsies were performed and the patients' laboratory findings were analysed. European League Against Rheumatism SS disease activity index (ESSDAI) values of SS disease activity at the time of biopsy and the SS disease damage index (SSDDI) values were also recorded. An immunohistochemical approach was used to semiquantitatively measure the CCL21 and CXCL13 expression in the minor salivary glands. RESULTS: The minor salivary glands of SS patients stained positively for CCL21 and CXCL13 in 46.2% (49/106) and 70.7% (75/106) of all cases, respectively. Higher-level expression of CCL21 and CXCL13 was associated with increases in ESR, IgG and rheumatoid factor levels, as well as anti-SS-A and -SS-B titers. A higher focus score and ESSDAI value at the time of biopsy were also associated with these chemokines. In patients with extraglandular manifestations of SS, the prevalence of lymphadenopathy increased with increasing CCL21 levels. CONCLUSIONS: The expression levels of CCL21 and CXCL13 within the lymphocytic infiltrates of SS patients were associated with several laboratory features of the disease as well as lymphadenopathy and the extent of clinical disease activity. CCL21 and CXCL13 levels can therefore serve as useful markers to predict the disease activity and prognosis of patients with SS.


Assuntos
Quimiocina CCL21/análise , Quimiocina CXCL13/análise , Glândulas Salivares Menores/química , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/metabolismo , Adulto , Biomarcadores/análise , Biópsia , Sedimentação Sanguínea , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Regulação para Cima
11.
Head Neck Pathol ; 11(2): 162-167, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27550513

RESUMO

Anaplastic transformation of papillary thyroid carcinoma (PTC) at distant metastatic sites is extremely rare, and there have been fewer than 20 reported cases in the literature. A 61-year-old woman presented with 1-week history of dyspnea. Her past medical history was remarkable because, 19 years ago, she underwent nearly total thyroidectomy and radical neck dissection due to PTC. Computed tomography of the chest revealed a 1.7 cm nodule in the lung and diffuse pleural thickening. Gun biopsy of the lung nodule revealed metastatic PTC with typical histology. However, the pleural biopsy predominantly showed anaplastic pleomorphic and spindle sarcomatoid carcinoma with microscopic focus of PTC. Immunohistochemical results showed both anaplastic sarcomatoid and PTC components positive for TTF-1, galectin-3 and PAX-8, thus supporting anaplastic transformation of PTC at the metastatic site. Subsequently the patient received 1 cycle of cisplatin-based chemotherapy but died from the disease 4 months after diagnosis. Although it is rare, anaplastic transformation of PTC should be considered during differential diagnosis of patients who present with exclusive sarcomatoid morphology at metastatic sites and have a history of PTC. We report another case of anaplastic transformation of PTC, found at pleural metastasis, together with the immunohistochemical profile and a literature review.


Assuntos
Carcinoma Papilar/secundário , Transformação Celular Neoplásica/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pleurais/secundário , Neoplasias da Glândula Tireoide/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide
12.
J Infect ; 74(3): 281-293, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27871809

RESUMO

OBJECTIVE: We aimed to determine whether combinations of multiplex cytokine responses could differentiate Mycobacterium tuberculosis (Mtb) infection states. METHODS: Mtb-specific antigen-induced and unstimulated cytokines were measured by Luminex assay in supernatants of QuantiFERON® Gold In-Tube assay (QFT) in 48 active pulmonary TB patients (TB), 15 latent TB infection subjects (LTBI), and 13 healthy controls (HCs). RESULTS: Among the 29 cytokines, eight Mtb antigen-specific biomarkers (GM-CSF, IFN-γ, IL-1RA, IL-2, IL-3, IL-13, IP-10, and MIP-1ß) in the Mtb-infected group were significantly different from those of the HCs. Five Mtb-specific biomarkers (EGF, GM-CSF, IL-5, IL-10, and VEGF), two unstimulated biomarkers (TNF-α[Nil] and VEGF[Nil]), and one Mtb-specific biomarker ratio (IL-2/IFN-γ) showed significant differences between active TB and LTBI. Three unstimulated biomarkers (IL-8[Nil], IL-13[Nil], and VEGF[Nil]) and 5 Mtb-specific biomarkers (IFN-γ, IL-2, IL-3, IP-10, and VEGF) were significantly different between active TB and non-active TB groups. Combinations of three cytokine biomarkers resulted in the accurate prediction of 92.1-93.7% of Mtb-infected cases and 92.3-100% of HCs, respectively. Moreover, combinations of five biomarkers accurately predicted 90.9-100% of active TB cases and 80-100% of LTBI subjects, respectively. In discriminating between active TB and non-active TB regardless of QFT results, combinations of six biomarkers predicted 79.2-95.8% of active TB cases and 67.9-89.3% of non-active TB subjects. CONCLUSIONS: Taken together, our data suggest that combinations of whole blood Mtb antigen-dependent cytokines could serve as biomarkers to determine TB disease states. Especially, VEGF is highlighted as a key biomarker for reflecting active TB, irrespective of stimulation.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Tuberculose Latente/diagnóstico , Tuberculose/diagnóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Tuberculose/sangue , Tuberculose/microbiologia , Adulto Jovem
13.
Oncotarget ; 7(46): 76274-76290, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27517754

RESUMO

Mucosal-associated invariant T (MAIT) cells are an antimicrobial MR1-restricted T cell subset and play an important role in immune defense response to bacteria. However, little is known about the role of MAIT cells in cancer. The aims of this study were to examine the level and function of MAIT cells in cancer patients and to evaluate the clinical relevance of MAIT cell levels. Ninety-nine patients with cancer and 20 healthy controls were included in this study. Circulating MAIT cell levels were significantly reduced in patients with mucosal-associated cancers (MACs), such as gastric, colon and lung cancers, but their capacities for IFN-γ, IL-17, or TNF-α production were preserved. This MAIT cell deficiency was significantly correlated with N staging and carcinoembryonic antigen level. Percentages of MAIT cells were significantly higher in cancer tissue than in peripheral blood and immunofluorescent labeling showed MAIT cell infiltration into colon cancer tissues. Circulating MAIT cells exhibited high levels of CCR6 and CXCR6, and their corresponding chemokines, such as CCL20 and CXCL16, were strongly expressed in colon cancer tissues. Activated MAIT cells not only had lymphokine-activated killer activity, but they also had direct cytotoxicity on K562 cells via degranulation of granzyme B and perforin. This study primarily demonstrates that circulating MAIT cells are reduced in MAC patients due to migration to mucosal cancer tissues and they have the potential to kill cancer cells. In addition, this circulating MAIT cell deficiency is related to the degree of cancer progression in mucosal tissues.


Assuntos
Carcinoma/imunologia , Carcinoma/patologia , Contagem de Linfócitos , Células T Invariantes Associadas à Mucosa/imunologia , Idoso , Carcinoma/metabolismo , Movimento Celular , Citocinas/metabolismo , Citotoxicidade Imunológica , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/metabolismo , Mucosa/imunologia , Mucosa/metabolismo , Mucosa/patologia , Estadiamento de Neoplasias , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Carga Tumoral
14.
PLoS Negl Trop Dis ; 10(7): e0004832, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27463223

RESUMO

BACKGROUND: Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression. CONCLUSIONS: This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.


Assuntos
Ativação Linfocitária/imunologia , Células T Invariantes Associadas à Mucosa/fisiologia , Tifo por Ácaros/patologia , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tifo por Ácaros/metabolismo , Fator de Necrose Tumoral alfa/genética
15.
J Korean Med Sci ; 31(2): 190-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26839471

RESUMO

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjögren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.


Assuntos
Centro Germinativo/patologia , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/patologia , Adulto , Autoanticorpos/sangue , Proteína C-Reativa/análise , Demografia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores de Complemento 3d/metabolismo , Estudos Retrospectivos , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo
16.
Am J Sports Med ; 44(4): 1011-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26786901

RESUMO

BACKGROUND: Chronic ankle instability with generalized joint hypermobility (GJH) is considered a contraindication for the modified Broström procedure. The most widely accepted definition of GJH is a Beighton score of ≥4 on a 9-point scale. However, it is not clear whether this criterion can be applied to determine the GJH that would lead to a poor outcome after a modified Broström procedure. Some of the previous studies that report unfavorable outcomes do not specify the tests or cutoff scores used to determine the GJH, and, in fact, some of the patients with GJH in these studies had good outcomes. HYPOTHESIS: The modified Broström procedure results in satisfactory outcomes in patients who have chronic ankle instability with GJH if the contralateral uninjured ankle shows a normal varus talar tilt and anterior talar translation during stress tests. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Modified Broström procedure was performed in 32 patients with chronic ankle instability with GJH if the contralateral uninjured ankle showed a normal varus talar tilt and anterior talar translation on stress tests. The mean patient age at surgery was 21.7 years, and the mean follow-up duration was 27.4 months. RESULTS: The Karlsson-Peterson ankle score significantly improved from a mean ± SD of 63.6 ± 7.1 preoperatively to 90.4 ± 6.7 at the final postoperative follow-up (P < .001). Sixteen patients were very satisfied with the results, 10 patients were satisfied, 3 patients rated their satisfaction as fair, and 1 patient was dissatisfied with the results. Nine patients sustained ankle sprains after the surgery, 6 of which were mild sprains. Although 3 of these 9 patients had a mechanically unstable ankle on stress radiographs, they were satisfied with the postoperative results. None of the patients required a reoperation. CONCLUSION: GJH was not a contraindication for the modified Broström procedure if the contralateral uninjured ankle showed a normal varus talar tilt and a normal anterior talar translation on stress tests. Further studies are needed to better define GJH affecting the ankle.


Assuntos
Articulação do Tornozelo/cirurgia , Instabilidade Articular/cirurgia , Ligamentos Articulares/cirurgia , Procedimentos Ortopédicos/métodos , Adulto , Feminino , Humanos , Masculino , Satisfação do Paciente , Adulto Jovem
17.
Rheumatology (Oxford) ; 55(3): 495-503, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26467750

RESUMO

OBJECTIVE: The relationship between OA and osteoporosis has exhibited contradictory features over the past four decades. The aim of this study was to determine using separate analysis of the radiographic features of OA whether various radiographic features of OA were associated differently with BMD in the Korean elderly. METHODS: Data were derived from the Dong-gu cohort; 2354 subjects were enrolled in the present cross-sectional study. Baseline characteristics, the BMDs of the lumbar spine and femoral neck measured by DXA, and X-rays of knees and hands were collected. A semi-quantitative grading system was used to estimate the severities of individual radiographic features. We adjusted for confounders using multiple linear regression modelling to analyse the relationships. RESULTS: After adjustment for confounders, hand and knee OA total scores were negatively associated with the BMDs of the lumbar spine and femoral neck, except for the total knee OA score and lumbar spine BMD. In detail, hand osteophytes and sclerosis exhibited positive relationships with the BMDs of the lumbar spine and femoral neck, except for hand osteophytes and femoral neck BMD. On the contrary, however, knee joint space narrowing (JSN), hand JSN, and hand subchondral cysts were negatively associated with the BMD of the lumbar spine and femoral neck. Knee JSN and hand subchondral cysts exerted the greatest effects on BMD. CONCLUSION: Separate analysis of the radiographic features of OA better reveals associations of OA with the BMD of the lumbar spine and femoral neck.


Assuntos
Densidade Óssea/fisiologia , Colo do Fêmur/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Absorciometria de Fóton/métodos , Idoso , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Colo do Fêmur/fisiopatologia , Avaliação Geriátrica , Articulação da Mão/fisiopatologia , Humanos , Modelos Lineares , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Prognóstico , República da Coreia , Índice de Gravidade de Doença
18.
Int J Rheum Dis ; 19(5): 459-64, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26013056

RESUMO

AIM: Despite its shortcomings, the Fibromyalgia Impact Questionnaire (FIQ) is widely used to assess clinical symptoms and measure therapeutic changes in patients with fibromyalgia (FM). Recently, the revised version of the FIQ (FIQR) was released. In this study, we validated the Korean version of the FIQR and evaluated whether the revised version is superior to the original version in reflecting the physical function and quality of life of these patients. METHODS: Seventy-nine patients with FM were invited to complete a questionnaire that included the original FIQ, FIQR, Multidimensional Health Assessment Questionnaire (MDHAQ), Rheumatology Attitudes Index (RAI), and Medical Outcome Study Short-Form 36 (SF-36). RESULTS: The test-retest reliability was assessed in 55 patients after 1 week, and the Spearman coefficients were 0.604-0.825 and Cronbach's alpha was 0.948 (95% confidence interval 0.930-0.964). The FIQR was significantly correlated with the pain visual analogue scale (VAS), fatigue VAS, RAI, MDHAQ, and physical and mental component summary scores of the SF-36. The FIQR was more strongly associated with the MDHAQ and SF-36 scores than with the original FIQ. CONCLUSION: Our study showed that the FIQR is a reliable, valid instrument for assessing patients with FM and performs better in the prediction of physical function and health status than the original version.


Assuntos
Povo Asiático/psicologia , Características Culturais , Fibromialgia/diagnóstico , Nível de Saúde , Qualidade de Vida , Inquéritos e Questionários , Adulto , Feminino , Fibromialgia/etnologia , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , República da Coreia , Índice de Gravidade de Doença
19.
Clin Exp Otorhinolaryngol ; 8(4): 396-401, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26622961

RESUMO

OBJECTIVES: Argon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors. METHODS: Twenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal. RESULTS: The median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P<0.001). The median American Thoracic Society dyspnea grade (3 [IQR, 1 to 4] vs. 1 [IQR, 0 to 1], P<0.001) and forced expiratory volume in one second (1.03 L [IQR, 0.52 to 1.36 L] vs. 1.98 L [IQR, 1.57 to 2.64 L], P=0.004) were significantly improved after intervention. There were no procedure-related acute complications and deaths. CONCLUSION: Rigid bronchoscopy with APC is an effective and safe procedure to alleviate central airway obstruction caused by tumors.

20.
Environ Toxicol Pharmacol ; 40(3): 924-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26509733

RESUMO

Obese individuals show increased susceptibility to infection, low vaccine efficacy, and worse pathophysiology. However, it is unclear how obesity affects these events. The aim of this study was to investigate the effect of obesity-triggered chronic inflammation on immune cells after influenza virus infection. Control and lipopolysaccharide mice, in which an osmotic pump continually released Tween saline or lipopolysaccharide, were prepared and 3 weeks later were infected with pandemic H1N1 2009 influenza A virus. In lipopolysaccharide mice, we found a reduction in macrophage activation markers in the steady state, and reduced production of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1ß, and interleukin-6, in restimulated peritoneal macrophages. Interestingly, lipopolysaccharide-triggered chronic inflammation exacerbated the severity of pathological symptoms in the lungs after challenge with influenza virus. Taken together, the increased severity of virus-induced symptoms in obese individuals with chronic inflammation may be, at least partially, caused by macrophage dysfunction.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Lipopolissacarídeos/efeitos adversos , Macrófagos Peritoneais/efeitos dos fármacos , Obesidade/complicações , Infecções por Orthomyxoviridae/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Vacinas contra Influenza/imunologia , Ativação de Macrófagos , Macrófagos Peritoneais/patologia , Camundongos , Obesidade/induzido quimicamente , Obesidade/imunologia , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia
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