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1.
Eur Radiol ; 33(1): 720-729, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35760909

RESUMO

OBJECTIVES: Ultrasound often corroborates clinical diagnosis of Achilles tendinopathy (AT). Traditional measures assess macromorphological features or use qualitative grading scales, primarily focused within the free tendon. Shear wave imaging can non-invasively quantify tendon elasticity, yet it is unknown if proximal structures are affected by tendon pathology. The purpose of the study was to determine the characteristics of both traditional sonographic measures and regional shear wave speed (SWS) between limbs in patients with AT. METHODS: Twenty patients with chronic AT were recruited. Traditional sonographic measures of tendon structure were measured. Regional SWS was collected in a resting ankle position along the entire length of the tendon bilaterally. SWS measures were extracted and interpolated across evenly distributed points corresponding to the free tendon (FT), soleus aponeurosis (SA), and gastrocnemius aponeurosis (GA). Comparisons were made between limbs in both traditional sonographic measures and regional SWS. RESULTS: Symptomatic tendons were thicker (10.2 (1.9) vs. 6.8 (1.8) mm; p < 0.001) and had more hyperemia (p = 0.001) and hypoechogenicity (p = 0.002) than the contralateral tendon. Regional SWS in the FT was lower in the symptomatic limb compared to the contralateral limb (11.53 [10.99, 12.07] vs. 10.97 [10.43, 11.51]; p = 0.03). No differences between limbs were found for the SA (p = 0.13) or GA (p = 0.99). CONCLUSIONS: Lower SWS was only observed in the FT in AT patients, indicating that alterations in tendon elasticity associated with AT were localized to the FT and did not involve the proximal passive tendon structures. KEY POINTS: • Baseline characteristics of a pilot sample of 20 subjects suffering from chronic Achilles tendinopathy showed differences in conventional sonographic measures of tendon thickness, qualitatively assessed hypoechogenicity, hyperemia, and quantitative measures of shear wave speed. • Regional shear wave speeds were lower in the free tendon but not in the proximal regions of the soleus or gastrocnemius aponeuroses in Achilles tendinopathy patients. • Using shear wave imaging to estimate tendon stiffness may prove beneficial for clinical validation studies to address important topics such as return to activity and the effectiveness of rehabilitation protocols.


Assuntos
Tendão do Calcâneo , Técnicas de Imagem por Elasticidade , Hiperemia , Tendinopatia , Humanos , Tendão do Calcâneo/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Tendinopatia/diagnóstico por imagem , Elasticidade , Ultrassonografia/métodos
2.
Clin J Sport Med ; 32(3): 318-321, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852433

RESUMO

OBJECTIVE: Sport-related concussion (SRC) is a known risk of contact sports and strategies to minimize risk have been used. We aimed to determine if an independent medical spotter (IMS) identified more SRCs than would otherwise be detected by trained sideline medical staff (SMS). DESIGN: Prospective review of SRCs during competition in the 2019 season and retrospective review of SRCs in the 2015 to 2018 seasons, which also used an IMS. SETTING: Division I football games (home and away) of a Big 10 Conference institution. PARTICIPANTS: All football team members who participated in competition. INDEPENDENT VARIABLES: Occurrence of SRC during competition and whether the IMS or SMS directly visualized the injury. MAIN OUTCOME MEASURES: The total number of SRCs that occurred during competition in the 2015 to 2019 football seasons and whom observed the SRC-SMS or IMS-or if a student athlete reported symptoms after competition. RESULTS: Over the 5-year study period, 24 SRCs occurred during competition. Of those, 19 (79.2%) were observed by SMS, 2 (8.3%) by the IMS, and 3 (12.5%) were reported to SMS after competition ended. CONCLUSIONS: Most SRCs are accurately identified by SMS, but a small number were apparent only to the IMS who seemed to add sensitivity in detecting a SRC. Instances remain in which SRC recognition and diagnosis were delayed despite trained SMS and IMS. CLINICAL RELEVANCE: An IMS allows for a small-added player protection benefit using different vantage points to identify potential SRCs during competition.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Traumatismos Craniocerebrais , Futebol Americano , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/epidemiologia , Futebol Americano/lesões , Humanos , Incidência , Estudos Prospectivos
3.
Exp Dermatol ; 28(9): 1091-1093, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31323149

RESUMO

2-deoxy D-glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T-cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell-mediated autoimmune mouse disease, alopecia areata.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Desoxiglucose/uso terapêutico , Animais , Desoxiglucose/administração & dosagem , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Folículo Piloso/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Transplante de Pele , Falha de Tratamento
4.
J Magn Reson Imaging ; 46(5): 1441-1447, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28263448

RESUMO

PURPOSE: To compare bicomponent ultrashort echo time (UTE) T2* parameters of patellar tendon between healthy volunteers and patients with patellar tendinopathy. MATERIALS AND METHODS: This study was performed with Institutional Review Board approval and with all subjects signing informed consent. A UTE- T2* mapping sequence was performed at 3.0T on the knees of 10 healthy volunteers and in 11 patients with patellar tendinopathy. The UTE- T2* relaxation times of the fast relaxing macromolecular bound water component ( T2*F) and the slow relaxing bulk water component ( T2*S) and the fraction of the fast relaxing macromolecular bound water component (FF ) of patellar tendon were measured in all subjects. Wilcoxon rank-sum tests were used to compare UTE- T2* parameters between healthy volunteers and patients with patellar tendinopathy. RESULTS: Mean T2*F, T2*S, and FF of the patellar tendon was 1.5 msec, 23.1 msec, and 79.5%, respectively, for healthy volunteers and 1.9 msec, 22.3 msec, and 75.5%, respectively, for patients with patellar tendinopathy. There were statistically significant differences between groups of subjects for T2*F (P = 0.01) and FF (P = 0.007) but not T2*S (P = 0.10) of the patellar tendon. CONCLUSION: Patients with patellar tendinopathy had significantly higher T2*F and significantly lower FF of patellar tendon than healthy volunteers, which suggests that bicomponent UTE- T2* parameters can detect changes in the composition and microstructure of degenerative tendon. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1441-1447.


Assuntos
Imageamento por Ressonância Magnética , Patela/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Adulto , Cartilagem Articular , Feminino , Voluntários Saudáveis , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Masculino , Patela/fisiopatologia , Reprodutibilidade dos Testes , Tendinopatia/fisiopatologia , Adulto Jovem
5.
Radiology ; 277(2): 477-88, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26024307

RESUMO

PURPOSE: To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. MATERIALS AND METHODS: This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2(Single)), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (F(F)) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. RESULTS: Higher cartilage T2(Single) (P < .001), lower cartilage F(F) (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2(Single) and F(F) remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with F(F) than with T2(Single) for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. CONCLUSION: Patients with osteoarthritis of the knee had significantly higher cartilage T2(Single) and significantly lower cartilage F(F) than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that F(F) may allow greater diagnostic performance than that with T2(Single) for distinguishing between normal and degenerative cartilage.


Assuntos
Cartilagem Articular/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
6.
J Magn Reson Imaging ; 42(5): 1321-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25847733

RESUMO

PURPOSE: To compare multicomponent T2 parameters of menisci measured using Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and osteoarthritis (OA) patients with intact and torn menisci. MATERIALS AND METHODS: The prospective study was performed with Institutional Review Board approval and with all subjects signing written informed consent. mcDESPOT was performed on the knee joint of 12 asymptomatic volunteers and 14 patients with knee OA. Single-component T2 relaxation time (T2Single ), T2 relaxation time of the fast relaxing water component (T2F ), and the slow relaxing water component (T2S ), and fraction of the fast relaxing water component (FF ) of the medial and lateral menisci were measured. Multivariate linear regression models were used to compare mcDESPOT parameters between normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients with adjustment for differences in age between subjects. RESULTS: The mean mcDESPOT parameters for normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients were respectively 16.1 msec, 18.8 msec, and 22.7 msec for T2Single ; 9.0 msec, 10.0 msec, and 11.1 msec for T2F ; 24.4 msec, 27.7 msec, and 31.4 msec for T2S ; and 34%, 32%, 27% for FF . There were significant differences (P < 0.05) in T2Single , T2F , T2S , and FF between the three groups of menisci. CONCLUSION: The menisci of OA patients had significantly higher T2Single , T2F , and T2S and significantly lower FF than normal menisci in asymptomatic volunteers with greater changes in multicomponent T2 parameters noted in torn than intact menisci in OA patients.


Assuntos
Cartilagem Articular/patologia , Traumatismos do Joelho/patologia , Imageamento por Ressonância Magnética , Meniscos Tibiais/patologia , Osteoartrite do Joelho/patologia , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
7.
Am Fam Physician ; 89(1): 27-34, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24444505

RESUMO

Hip pain is a common and disabling condition that affects patients of all ages. The differential diagnosis of hip pain is broad, presenting a diagnostic challenge. Patients often express that their hip pain is localized to one of three anatomic regions: the anterior hip and groin, the posterior hip and buttock, or the lateral hip. Anterior hip and groin pain is commonly associated with intra-articular pathology, such as osteoarthritis and hip labral tears. Posterior hip pain is associated with piriformis syndrome, sacroiliac joint dysfunction, lumbar radiculopathy, and less commonly ischiofemoral impingement and vascular claudication. Lateral hip pain occurs with greater trochanteric pain syndrome. Clinical examination tests, although helpful, are not highly sensitive or specific for most diagnoses; however, a rational approach to the hip examination can be used. Radiography should be performed if acute fracture, dislocations, or stress fractures are suspected. Initial plain radiography of the hip should include an anteroposterior view of the pelvis and frog-leg lateral view of the symptomatic hip. Magnetic resonance imaging should be performed if the history and plain radiograph results are not diagnostic. Magnetic resonance imaging is valuable for the detection of occult traumatic fractures, stress fractures, and osteonecrosis of the femoral head. Magnetic resonance arthrography is the diagnostic test of choice for labral tears.


Assuntos
Artralgia/diagnóstico , Artralgia/tratamento farmacológico , Quadril , Manejo da Dor/métodos , Atenção Primária à Saúde/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/normas , Guias de Prática Clínica como Assunto
8.
STAR Protoc ; 5(2): 102971, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38536814

RESUMO

Efficient metabolism, or the means by which cells produce energy resources, is critical for proper effector function. Here, we present a protocol for examining the bioenergetics and mitochondrial fuel utilization of primary murine autoreactive immunocytes using cellular metabolism-modulating drugs. We describe steps for plate calibration, isolation of primary immunocytes, and Seahorse assay plate preparation. We then detail procedures for performing the XF Cell Mito Stress Test followed by bioenergetics calculations and statistics. For complete details on the use and execution of this protocol, please refer to Wilson et al.1.


Assuntos
Metabolismo Energético , Mitocôndrias , Animais , Camundongos , Metabolismo Energético/fisiologia , Mitocôndrias/metabolismo
9.
Cancer Immunol Res ; 12(7): 822-839, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38739030

RESUMO

Cytotoxic T lymphocytes (CTL) are pivotal in combating cancer, yet their efficacy is often hindered by the immunosuppressive tumor microenvironment, resulting in CTL exhaustion. This study investigates the role of interleukin-3 (IL3) in orchestrating antitumor immunity through CTL modulation. We found that intratumoral CTLs exhibited a progressive decline in IL3 production, which was correlated with impaired cytotoxic function. Augmenting IL3 supplementation, through intraperitoneal administration of recombinant IL3, IL3-expressing tumor cells, or IL3-engineered CD8+ T cells, conferred protection against tumor progression, concomitant with increased CTL activity. CTLs were critical for this therapeutic efficacy as IL3 demonstrated no impact on tumor growth in Rag1 knockout mice or following CD8+ T-cell depletion. Rather than acting directly, CTL-derived IL3 exerted its influence on basophils, concomitantly amplifying antitumor immunity within CTLs. Introducing IL3-activated basophils retarded tumor progression, whereas basophil depletion diminished the effectiveness of IL3 supplementation. Furthermore, IL3 prompted basophils to produce IL4, which subsequently elevated CTL IFNγ production and viability. Further, the importance of basophil-derived IL4 was evident from the absence of benefits of IL3 supplementation in IL4 knockout tumor-bearing mice. Overall, this research has unveiled a role for IL3-mediated CTL-basophil cross-talk in regulating antitumor immunity and suggests harnessing IL3 sustenance as a promising approach for optimizing and enhancing cancer immunotherapy. See related Spotlight, p. 798.


Assuntos
Interleucina-3 , Camundongos Knockout , Linfócitos T Citotóxicos , Animais , Camundongos , Linfócitos T Citotóxicos/imunologia , Interleucina-3/metabolismo , Interleucina-3/imunologia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Comunicação Celular/imunologia , Humanos
10.
PLoS One ; 19(3): e0299595, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451972

RESUMO

OBJECTIVE: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. METHODS: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. RESULTS: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.


Assuntos
Desoxiglucose , Epilepsia , Camundongos , Animais , Desoxiglucose/farmacologia , Desoxiglucose/metabolismo , Camundongos Endogâmicos C57BL , Glucose/metabolismo , Perfilação da Expressão Gênica
11.
iScience ; 26(9): 107487, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37636066

RESUMO

Aberrant metabolic demand is observed in immune/inflammatory disorders, yet the role in pathogenesis remains unclear. Here, we discover that in lupus, activated B cells, including germinal center B (GCB) cells, have remarkably high glycolytic requirement for survival over T cell populations, as demonstrated by increased metabolic activity in lupus-activated B cells compared to immunization-induced cells. The augmented reliance on glucose oxidation makes GCB cells vulnerable to mitochondrial ROS-induced oxidative stress and apoptosis. Short-term glycolysis inhibition selectively reduces pathogenic activated B in lupus-prone mice, extending their lifespan, without affecting T follicular helper cells. Particularly, BCMA-expressing GCB cells rely heavily on glucose oxidation. Depleting BCMA-expressing activated B cells with APRIL-based CAR-T cells significantly prolongs the lifespan of mice with severe autoimmune disease. These results reveal that glycolysis-dependent activated B and GCB cells, especially those expressing BCMA, are potentially key lupus mediators, and could be targeted to improve disease outcomes.

12.
bioRxiv ; 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37162857

RESUMO

OBJECTIVE: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. METHODS: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. RESULTS: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

13.
PLoS One ; 18(10): e0293218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883475

RESUMO

The Lamc2jeb junctional epidermolysis bullosa (EB) mouse model has been used to demonstrate that significant genetic modification of EB symptoms is possible, identifying as modifiers Col17a1 and six other quantitative trait loci, several with strong candidate genes including dystonin (Dst/Bpag1). Here, CRISPR/Cas9 was used to alter exon 23 in mouse skin specific isoform Dst-e (Ensembl GRCm38 transcript name Dst-213, transcript ID ENSMUST00000183302.5, protein size 2639AA) and validate a proposed arginine/glutamine difference at amino acid p1226 in B6 versus 129 mice as a modifier of EB. Frame shift deletions (FSD) in mouse Dst-e exon 23 (Dst-eFSD/FSD) were also identified that cause mice carrying wild-type Lamc2 to develop a phenotype similar to human EB simplex without dystonia musculorum. When combined, Dst-eFSD/FSD modifies Lamc2jeb/jeb (FSD+jeb) induced disease in unexpected ways implicating an altered balance between DST-e (BPAG1e) and a rarely reported rodless DST-eS (BPAG1eS) in epithelium as a possible mechanism. Further, FSD+jeb mice with pinnae removed are found to provide a test bed for studying internal epithelium EB disease and treatment without severe skin disease as a limiting factor while also revealing and accelerating significant nasopharynx symptoms present but not previously noted in Lamc2jeb/jeb mice.


Assuntos
Distonia , Distúrbios Distônicos , Epidermólise Bolhosa Simples , Epidermólise Bolhosa Juncional , Epidermólise Bolhosa , Animais , Camundongos , Distonia/genética , Distonia/metabolismo , Distúrbios Distônicos/metabolismo , Distonina/metabolismo , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Simples/diagnóstico , Epidermólise Bolhosa Simples/genética , Epidermólise Bolhosa Simples/metabolismo , Epidermólise Bolhosa Juncional/genética , Epidermólise Bolhosa Juncional/diagnóstico , Epidermólise Bolhosa Juncional/metabolismo , Pele/metabolismo
14.
WMJ ; 111(1): 21-7; quiz 28, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22533212

RESUMO

Concussion is a common medical problem with significant morbidity and sometimes devastating consequences. Awareness of this injury has increased dramatically in recent years, and our understanding of its pathophysiology and treatment is rapidly evolving. This article reviews the current concepts of concussion pathophysiology and epidemiology, and will provide an overview of proper diagnosis and management. Complications and risk reduction also will be reviewed. By understanding the essentials of concussion medicine, health care professionals will be equipped to manage this injury, including common complications.


Assuntos
Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Concussão Encefálica/fisiopatologia , Diagnóstico por Imagem , Humanos , Testes Neuropsicológicos , Exame Físico , Comportamento de Redução do Risco
15.
Front Immunol ; 13: 864949, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493515

RESUMO

T follicular helper (Tfh) cells provide support to B cells upon arrival in the germinal center, and thus are critical for the generation of a robust adaptive immune response. Tfh express specific transcription factors and cellular receptors including Bcl6, CXCR5, PD-1, and ICOS, which are critical for homing and overall function. Generally, the induction of an immune response is tightly regulated. However, deviation during this process can result in harmful autoimmunity or the inability to successfully clear pathogens. Recently, it has been shown that Tfh differentiation, activation, and proliferation may be linked with the cellular metabolic state. In this review we will highlight recent discoveries in Tfh differentiation and explore how these cells contribute to functional immunity in disease, including autoimmune-related disorders, cancer, and of particular emphasis, during infection.


Assuntos
Células T Auxiliares Foliculares , Linfócitos T Auxiliares-Indutores , Diferenciação Celular , Centro Germinativo , Receptores CXCR5/metabolismo
16.
Radiology ; 259(1): 203-12, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21330563

RESUMO

PURPOSE: To determine whether preoperative magnetic resonance (MR) imaging could help identify factors associated with poor clinical outcome after arthroscopic partial meniscectomy (APM) in middle-aged and elderly patients with meniscal tears. MATERIALS AND METHODS: The prospective, institutional review board-approved, HIPAA-compliant study was performed with informed consent in 53 men and 47 women (average ages, 54.5 and 56.6 years, respectively). Patients underwent knee MR imaging before APM; clinical symptoms were evaluated preoperatively and 1 year postoperatively with International Knee Documentation Committee (IKDC) questionnaire. Overall severity of knee joint degeneration and severity of each feature of joint degeneration were assessed with Boston Leads Osteoarthritis Knee (BLOK) scoring system. Tear length was measured, and type of meniscal tear was classified. Spearman correlation coefficients and relative risks showed the relationship between clinical outcome after APM (difference between preoperative and postoperative IKDC scores) and severity of joint degeneration. RESULTS: Seventy-four patients with isolated medial APM had a significant (P < .05) inverse correlation between clinical outcome and severity of cartilage loss and bone marrow edema in the medial femoral condyle and medial tibial plateau. Fifteen patients with isolated lateral APM had a significant (P < .05) inverse correlation between clinical outcome and severity of cartilage loss in the lateral femoral condyle and lateral tibial plateau and bone marrow edema in the lateral femoral condyle. One hundred patients with APM had a significant (P < .05) inverse correlation between clinical outcome and severity of meniscal extrusion, total BLOK score, and meniscal tear length. A significantly (P < .05) increased relative risk that a patient would not definitely improve after APM was observed if a meniscal root tear was present. CONCLUSION: Poorer clinical outcome after APM was associated with greater severity of cartilage loss and bone marrow edema in the same compartment as the meniscal tear, greater severity of meniscal extrusion, greater overall severity of joint degeneration, a meniscal root tear, and a longer meniscal tear at preoperative MR imaging.


Assuntos
Artroscopia/métodos , Traumatismos do Joelho/diagnóstico , Traumatismos do Joelho/cirurgia , Imageamento por Ressonância Magnética/métodos , Meniscos Tibiais/cirurgia , Recuperação de Função Fisiológica , Lesões do Menisco Tibial , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Meniscos Tibiais/patologia , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
17.
AJR Am J Roentgenol ; 196(3): 628-36, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21343507

RESUMO

OBJECTIVE: The purpose of this article is to detail the biology of platelet-rich plasma (PRP), critically review the existing literature, and discuss future research applications needed to adopt PRP as a mainstay treatment method for common musculoskeletal injuries. CONCLUSION: Any promising minimally invasive therapy such as PRP deserves further investigation to avoid surgery. Diagnostic imaging outcome assessments, including ultrasound-guided needle precision, should be included in future investigations.


Assuntos
Diagnóstico por Imagem , Sistema Musculoesquelético/lesões , Plasma Rico em Plaquetas , Ferimentos e Lesões/terapia , Animais , Humanos , Ferimentos e Lesões/diagnóstico
18.
Curr Sports Med Rep ; 8(2): 65-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19276905

RESUMO

Vocal cord dysfunction (VCD) is defined by paradoxical vocal fold closure during inhalation, and rarely upon exhalation. The precise etiology of VCD is unknown; however, a variety of potential causes may include laryngeal hyperresponsiveness, laryngeal irritants, psychogenic causes, and rarely neurologic diseases. VCD can occur in athletes, particularly females, and the sports medicine professional likely is to care for patients with acute respiratory difficulties caused by this condition. Given its complex nature, a multidisciplinary approach to VCD evaluation and management is necessary and results in optimal outcomes.


Assuntos
Paralisia das Pregas Vocais/diagnóstico , Paralisia das Pregas Vocais/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Laringe/anatomia & histologia , Laringe/fisiologia , Masculino , Esportes/fisiologia , Medicina Esportiva , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/fisiopatologia , Prega Vocal/fisiopatologia , Adulto Jovem
19.
Cancer Biol Ther ; 20(2): 169-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183475

RESUMO

Targeting the early steps of the glycolysis pathway in cancers is a well-established therapeutic strategy; however, the doses required to elicit a therapeutic effect on the cancer can be toxic to the patient. Consequently, numerous preclinical and clinical studies have combined glycolytic blockade with other therapies. However, most of these other therapies do not specifically target cancer cells, and thus adversely affect normal tissue. Here we first show that a diverse number of cancer models - spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells - can be efficiently targeted by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor. Next, we tested the cancer-cell specificity of a therapeutic compound using the MEC1 cell line, a chronic lymphocytic leukemia (CLL) cell line that expresses activation induced cytidine deaminase (AID). We show that MEC1 cells, are susceptible to 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), a specific RAD51 inhibitor. We then combine 2DG and DIDS, each at a lower dose and demonstrate that this combination is more efficacious than fludarabine, the current standard- of- care treatment for CLL. This suggests that the therapeutic blockade of glycolysis together with the therapeutic inhibition of RAD51-dependent homologous recombination can be a potentially beneficial combination for targeting AID positive cancer cells with minimal adverse effects on normal tissue. Implications: Combination therapy targeting glycolysis and specific RAD51 function shows increased efficacy as compared to standard of care treatments in leukemias.


Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxiglucose/farmacologia , Neoplasias/tratamento farmacológico , Rad51 Recombinase/antagonistas & inibidores , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/administração & dosagem , Animais , Linhagem Celular Tumoral , Desoxiglucose/administração & dosagem , Sinergismo Farmacológico , Feminino , Glicólise/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Neoplasias/metabolismo , Rad51 Recombinase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(5): 3553-4, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26260175

RESUMO

We have sequenced and characterized the complete mitochondrial genome of the soft-shell clam, Mya arenaria, an important organism for environmental toxicology and aquaculture. Mya arenaria is located in the taxonomic order Myoida, which lacks any member with a completely annotated mitogenome. The M. arenaria mitochondrial genome is 17 947 bp in length. Like most marine bivalves, the circular mitogenome codes entirely on the heavy strand, with no introns. As with other bivalves, the gene order of the mitochondrion is highly rearranged. The mitogenome contains 12 protein-coding genes but ATP8 is missing, consistent with about half of all bivalve genera. Twenty-three tRNAs were identified. Phylogenetic analysis shows that M. arenaria is related most closely with the bivalves Sinonovacula constricta, and Moerella iridescens, of the infraclass Euheterodonta (unassigned). This, along with the close grouping of the phylogenetic trees, confirms a close tie between Myoida and Euheterodonta (unassigned).


Assuntos
Genoma Mitocondrial , Mitocôndrias/genética , Mya/genética , Análise de Sequência de DNA/métodos , Animais , Composição de Bases , Ordem dos Genes , Genes de RNAr , Tamanho do Genoma , Filogenia , RNA de Transferência/genética
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