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INTRODUCTION: At-home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population-based outreach approaches, we conducted qualitative research on current processes and barriers to at-home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. METHODS: We conducted 53 semi-structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT-DNA (i.e., Cologuard) workflows, referral for a follow-up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub-themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. RESULTS: Each site's process for stool-based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. CONCLUSION: Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs.
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Neoplasias Colorrectales , Centros Comunitarios de Salud , Detección Precoz del Cáncer , Área sin Atención Médica , Humanos , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Femenino , Masculino , Colonoscopía , Massachusetts , Sangre Oculta , Persona de Mediana Edad , California , South Dakota , Investigación Cualitativa , Anciano , Tamizaje Masivo/métodos , Navegación de PacientesRESUMEN
PURPOSE: Little is known about serious illness conversations (SIC) conducted during telemedicine visits and their impact on end-of-life (EOL) outcomes for patients with advanced cancer. PATIENTS AND METHODS: We conducted a retrospective analysis telemedicine visits for patients with metastatic lung cancer conducted during the first surge of the COVID-19 pandemic (October 3, 2020-October 6, 2020). We used natural language processing (NLP) to characterize documentation of SIC domains (ie, goals of care [GOC], limitation of life-sustaining treatment [LLST], prognostic awareness [PA], palliative care [PC], and hospice). We used unadjusted logistic regression to evaluate factors associated with SIC documentation and the relationship between SIC documentation and EOL outcomes. RESULTS: The study included 634 telemedicine visits across 360 patients. Documentation of at least one SIC domain was present in 188 (29.7%) visits with GOC and PA being the most discussed domains. Family presence (odds ratio [OR], 1.66; Pâ =â .004), progressive or newly diagnosed disease (OR, 5.42; Pâ <â .000), ageâ ≥â 70 (OR, 1.80; Pâ =â .009), and male sex (OR, 2.23; Pâ <â .000) were associated with a greater likelihood of discussingâ ≥â 1 SIC domain. Of the 61 patients who died within 12 months of the study period, havingâ ≥â 1 SIC domain discussed was associated with a lower likelihood of hospitalization in the last 30 days of life (OR, 0.27; Pâ =â .020). CONCLUSION: In this study of telehealth visits, we identified important factors associated with an increased likelihood of having documentation of an SIC and demonstrated that SIC documentation correlated with lower likelihood of hospitalization at EOL.
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INTRODUCTION: To evaluate the impact of the updated United States Preventive Services Task Force colorectal cancer (CRC) screening recommendations on screening rates in a large health system. METHODS: We reviewed Massachusetts General Brigham electronic health record data for individuals eligible for CRC screening between January 3, 2020, and January 5, 2023, and calculated whether age-eligible individuals were up-to-date with CRC screening. RESULTS: There were large declines in the percentage of individuals who were up-to-date with CRC screening for all racial/ethnic groups, with non-Hispanic Asians being largest (-13.5%). DISCUSSION: Health systems should implement culturally tailored strategies to reach and screen newly eligible individuals for CRC screening to prevent worsening disparities in CRC.
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INTRODUCTION: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings. METHODS: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment. RESULTS: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings. CONCLUSIONS: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities. TRIAL REGISTRATION: NCT05714644.
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Objective: Disparities in colorectal cancer (CRC) screening prevalence across United States neighborhoods may reflect social inequities that create barriers to accessing and completing preventive health services. Our objective was to identify whether neighborhood social vulnerability was associated with a change in CRC screening prevalence in Boston neighborhoods during the COVID-19 pandemic. Methods: Adults ages 50-74 years due for CRC screening who received primary care at one of 35 primary care practices affiliated with Massachusetts General Hospital or Brigham and Women's Hospital (Boston, MA), 3/1/2020 to 3/1/2022. The Social Vulnerability Index (SVI) is an aggregate measure of neighborhood social factors often used by public health authorities to examine neighborhood susceptibility to many health outcomes. Results: In 2020, 74.9 % of eligible individuals were up to date with CRC screening and this fell to 67.4 % in 2022 (p < 0.001). In 2020, 36.2 % of eligible patients lived in a neighborhood above the 80th percentile of SVI, consistent with high social vulnerability, while the same value was 35.1 % in 2022. There was no association between the change in screening prevalence and SVI: a decrease of 5.5 % screened in neighborhoods with SVI ≤ 80 compared to a decrease of 3.6 % in neighborhoods with SVI > 80 (p = 0.79). Conclusions: The COVID-19 pandemic equalized the prevalence of CRC screening across Boston-area neighborhoods despite pre-existing geographic disparities in screening prevalence and SVI. Strategies to ensure equitable participation in CRC screening to promote health equity should be considered to promote equitable pandemic recovery.
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Orbital lesions in the pediatric population vary from adults in terms of their presentation, unique pathology, and imaging characteristics. The prompt and accurate diagnosis of these lesions is imperative to prevent serious consequences in terms of visual impairment and disfigurement. Along with dedicated ophthalmologic examination, imaging is instrumental in characterizing these lesions, both for accurate diagnosis and subsequent management. In our pictorial essay, we provide a basic review of orbital embryology, anatomy, and congenital orbital pathologies, with emphasis on radiological findings.
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Órbita/anatomía & histología , Enfermedades Orbitales/congénito , Enfermedades Orbitales/diagnóstico por imagen , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Órbita/anomalías , Tomografía Computarizada por Rayos XRESUMEN
Autoimmune hypophysitis is a rare complication of immune checkpoint inhibitors. Immune checkpoint inhibitors have been used for advanced stages of melanoma, renal cell carcinoma, and lung cancer. Multiple endocrinopathies, among them hypophysitis, could result as a reverse event from this therapy. MRI is the imaging modality of choice and usually demonstrates pituitary gland hypertrophy, irregular thickening of the pituitary infundibulum, and diffuse enhancement. We present a case of stage IV metastatic renal cell carcinoma complicated with hypophysitis secondary to combined nivolumab and ipilimumab therapy.
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Carcinoma de Células Renales/tratamiento farmacológico , Hipofisitis/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ipilimumab/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Nivolumab/efectos adversos , Carcinoma de Células Renales/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ipilimumab/uso terapéutico , Neoplasias Renales/patología , Neoplasias Pulmonares/secundario , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nivolumab/uso terapéuticoRESUMEN
A 64-year-old man with history of renal stones and prostate cancer presented for evaluation of osseous metastatic disease due to elevated prostate-specific antigen (13.7 ng/mL). A Tc-labeled bone scan demonstrated unusual linear uptake projecting over the lower pelvis extending into the scrotum. Follow-up CT confirmed a rare case of inguinoscrotal extraperitoneal herniation of the ureter associated with a partially duplicated left renal collecting system. The left-sided inguinoscrotal uptake was within the herniated ureter, potentially mimicking disease within the pelvis.
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Huesos/diagnóstico por imagen , Hernia/diagnóstico por imagen , Uréter/diagnóstico por imagen , Hernia/patología , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder that predisposes patients to cutaneous tumors, pulmonary cysts with recurrent spontaneous pneumothoraces, and a variety of renal neoplasms including hybrid oncocytic and chromophobe renal cell carcinomas. There has been much debate regarding the genetic link with the occurrence of colorectal cancer and other colonic anomalies. Associations between BHD and intestinal adenomatous polyposis and sigmoid diverticulosis have been described in the literature, but there have been no prior reports of appendiceal diverticulosis in patients with BHD. Here, we present a 40-year-old female patient with a known family history of BHD, who was found to have diverticulosis of the appendix and pulmonary blebs on computed tomography upon routine screening for renal and pulmonary abnormalities, suggesting additional focus be given to the gastrointestinal tract (including the appendix) at the time of CT assessment.
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Adrenal myelolipoma is a benign tumor of the adrenal cortex composed predominantly of fat and hematopoietic tissue. These lesions are usually asymptomatic, and most often incidentally detected on imaging. Uncommonly, they present with retroperitoneal hemorrhage, and these have been traditionally treated with emergent surgery. Although, transarterial embolization has been effectively and safely used in patients presenting with active hemorrhage from acute traumatic and nontraumatic causes, literature specifically pertaining to adrenal artery embolization is scant, perhaps due to smaller size and variability of adrenal arteries. With recent advances in endovascular techniques and imaging, there are emerging case reports and series of adrenal artery embolization in acute and nonacute settings. We report a case of spontaneous hemorrhage within an adrenal myelolipoma in a 43-year-old male patient, successfully treated with transarterial embolization, thereby avoiding major surgery. Our report adds to the growing body of literature pertaining to adrenal artery embolization.
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COVID-19 (Corona Virus Disease-19) is a zoonotic illness first reported in the city of Wuhan, China in December 2019, and is now officially a global pandemic as declared by the World Health Organization. The infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 infected patients can be asymptomatic carriers or present with mild-to-severe respiratory symptoms. Imaging, including computed tomography is not recommended to screen/diagnose COVID-19 infections, but plays an important role in management of these patients, and to rule out alternative diagnoses or coexistent diseases. In our multicenter case series, we outline the clinical presentations and illustrate the most common imaging manifestations in patients hospitalized with COVID-19.
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Betacoronavirus , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Adulto , Anciano , COVID-19 , Infecciones por Coronavirus/terapia , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/terapia , Radiografía Torácica , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Primary appendiceal cancers are rare, and they generally present with liver and/or peritoneal metastases. Currently there are no guidelines to treat metastatic appendiceal cancer, and hence they are treated as metastatic colorectal cancer. Combining Yttrium 90 (Y-90) radioembolization (RE) with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival. Based on this data, a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer. CASE SUMMARY: A 76-year-old male presented to the emergency room with progressive right lower quadrant pain. A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation. Urgent laparoscopic appendectomy was then followed by histological analysis, which was significant for appendiceal adenocarcinoma. After complete workup he underwent right hemicolectomy and lymph node dissection. He received adjuvant chemotherapy as the local lymph nodes were positive. Follow-up imaging was significant for liver metastasis. Due to rapid growth of the liver lesions and new peritoneal nodules, the patient was treated with a combination of Y-90 RE and folinic acid, fluorouracil, and irinotecan with bevacizumab and not microwave ablation as previously planned. Follow up imaging demonstrated complete response of the liver lesions. At 12-mo follow-up, the patient continued to enjoy good quality of life with no recurrent disease. CONCLUSION: Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.
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In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE.
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Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/prevención & control , Fluoxetina/uso terapéutico , Animales , Apoptosis , Antígeno CD11b/metabolismo , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Femenino , Adyuvante de Freund/efectos adversos , Adyuvante de Freund/inmunología , Macrófagos/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Transgénicos , Proteína Básica de Mielina/genética , Proteína Proteolipídica de la Mielina/efectos adversos , Proteína Proteolipídica de la Mielina/inmunología , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/patología , Receptor fas/metabolismoRESUMEN
Using an integrated antigen microarray approach, we observed epitope-spreading of autoantibody responses to a variety of antigenic structures in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and in the serum of mice with experimental autoimmune encephalomyelitis (EAE). These included previously described protein- and lipid-based antigenic targets and newly discovered autoimmunogenic sugar moieties, notably, autoantibodies specific for the oligomannoses in both MS patient CSF and the sera of mice with EAE. These glycans are often masked by other sugar moieties and belong to a class of cryptic autoantigens. We further determined that these targets are highly expressed on multiple cell types in MS and EAE lesions. Co-immunization of SJL/J mice with a Man9-KLH conjugate at the time of EAE induction elicited highly significant levels of anti-Man9-cluster autoantibodies. Nevertheless, this anti-glycan autoantibody response was associated with a significantly reduced clinical severity of EAE. The potential of these cryptic glycan markers and targeting antibodies for diagnostic and therapeutic interventions of neurological disorders has yet to be explored.
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Autoanticuerpos/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Esclerosis Múltiple/inmunología , Polisacáridos/inmunología , Adulto , Animales , Antígenos/inmunología , Encéfalo/inmunología , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Masculino , Manosidasas/inmunología , Ratones , Análisis por Micromatrices , Persona de Mediana Edad , Médula Espinal/inmunología , Adulto JovenRESUMEN
Four questions were posed about multiple sclerosis (MS) at the 2011 Charcot Lecture, Oct. 22, 2011. 1. The Male/Female Disparity: Why are women developing MS so much more frequently than men? 2. Neuronal and Glial Protection: Are there guardian molecules that protect the nervous system in MS? 3. Predictive Medicine: With all the approved drugs, how can we rationally decide which one to use? 4. The Precise Scalpel vs. the Big Hammer for Therapy: Is antigen-specific therapy for demyelinating disease possible? To emphasize how our views on the pathogenesis and treatment of MS are evolving, and given the location of the talk in Amsterdam, Piet Mondrian's progressive interpretations of trees serve as a heuristic.
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Esclerosis Múltiple , HumanosRESUMEN
Peroxisome proliferator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-gamma(+)IL-17A(-) and IFN-gamma(+)IL-17A(+) CD4(+) cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constellation of immune system aberrations that included higher CD4(+) cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for the control of autoimmune inflammation.
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Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , PPAR delta/metabolismo , Linfocitos T Colaboradores-Inductores/patología , Animales , Encéfalo/inmunología , Encéfalo/patología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/trasplante , Proliferación Celular , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Expresión Génica/inmunología , Glicoproteínas/inmunología , Proteínas de Homeodominio/genética , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/farmacología , Activación de Linfocitos/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Glicoproteína Mielina-Oligodendrócito , Células Mieloides/efectos de los fármacos , Células Mieloides/inmunología , Células Mieloides/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , PPAR delta/antagonistas & inhibidores , Fragmentos de Péptidos/inmunología , Médula Espinal/inmunología , Médula Espinal/patología , Proteínas de Dominio T Box/genética , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/trasplante , Células TH1/inmunología , Células TH1/metabolismo , Tiazoles/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Interferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-beta was effective in reducing EAE symptoms induced by T helper type 1 (T(H)1) cells but exacerbated disease induced by T(H)17 cells. Effective treatment in T(H)1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In T(H)17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-beta treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-gamma. In the absence of IFN-gamma signaling, IFN-beta therapy was ineffective in EAE. In RRMS patients, IFN-beta nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta.
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Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Subgrupos de Linfocitos T/fisiología , Linfocitos T Colaboradores-Inductores/fisiología , Células TH1/fisiología , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/fisiología , Encefalomielitis Autoinmune Experimental/inmunología , Humanos , Factor 3 de Genes Estimulados por el Interferón/efectos de los fármacos , Factor 3 de Genes Estimulados por el Interferón/fisiología , Interferón gamma/fisiología , Interleucina-10/fisiología , Interleucina-17/inmunología , Interleucina-17/fisiología , Ratones , Esclerosis Múltiple Recurrente-Remitente/inmunología , Transducción de Señal/efectos de los fármacos , Bazo/citología , Bazo/inmunología , Bazo/fisiopatología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Células TH1/inmunologíaRESUMEN
GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.
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Encefalomielitis Autoinmune Experimental/inmunología , Inflamación/inmunología , Esclerosis Múltiple/inmunología , Ácido gamma-Aminobutírico/inmunología , 4-Aminobutirato Transaminasa/genética , 4-Aminobutirato Transaminasa/metabolismo , Animales , Células Presentadoras de Antígenos/citología , Células Presentadoras de Antígenos/metabolismo , Células Presentadoras de Antígenos/fisiología , Western Blotting , Células Cultivadas , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/prevención & control , GABAérgicos/farmacología , Proteínas Transportadoras de GABA en la Membrana Plasmática/genética , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Inflamación/metabolismo , Inflamación/prevención & control , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Macrófagos/fisiología , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Esclerosis Múltiple/metabolismo , Proteínas de la Mielina , Glicoproteína Asociada a Mielina/inmunología , Glicoproteína Mielina-Oligodendrócito , Técnicas de Placa-Clamp , Receptores de GABA/genética , Receptores de GABA/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
The immune system has two major components, an innate arm and an adaptive arm. Certain autoimmune diseases of the brain represent examples of disorders where one of these constituents plays a major role. Some rare autoimmune diseases involve activation of the innate arm and include chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. In contrast, adaptive immunity is prominent in multiple sclerosis, neuromyelitis optica, and the paraneoplastic syndromes where highly specific T cell responses and antibodies mediate these diseases. Studies of autoimmune brain disorders have aided in the elucidation of distinct neuronal roles played by key molecules already well known to immunologists (e.g., complement and components of the major histocompatibility complex). In parallel, molecules known to neurobiology and sensory physiology, including toll-like receptors, gamma amino butyric acid and the lens protein alpha B crystallin, have intriguing and distinct functions in the immune system, where they modulate autoimmunity directed to the brain.