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1.
N C Med J ; 81(5): 293-299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32900887

RESUMO

BACKGROUND Mailed at-home stool testing offers a promising strategy for overcoming barriers to colorectal cancer (CRC) screening in vulnerable populations. This paper evaluates the facilitators and barriers of successful implementation of a mailed fecal testing program among Medicaid populations within a health department setting.METHOD Interviews were conducted with key informants involved in intervention start-up and implementation tasks. The Consolidated Framework for Implementation Research (CFIR) was used to design the interview guide and structure the analysis. Axial coding was used to connect the themes to each other under the major categories of facilitators and barriers.RESULTS Overall, the process evaluation suggests that with strong partnerships, effective champions, and existing infrastructure, a large county health department can successfully implement a mailed fecal testing program targeted at Medicaid beneficiaries. The identified facilitators and challenges to implementation provide important information for similar emerging programs.LIMITATIONS The sample size of this evaluation is small. Additionally, we are unable to discern whether participating stakeholders' responses represent the feelings of non-interviewed staff, program implementers, or participants. We were not able to collect data on patient perspectives of the intervention. The nursing staff and interns were not able to be included in the process evaluation. Lastly, the information taken from this process evaluation may not be applicable to organizations and systems with different attributes.CONCLUSION The process evaluation suggests strong partnerships, effective champions, and elegant program designs were key contributors to successful implementation of a CRC screening program targeted at Medicaid beneficiaries in a large county health department.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Acessibilidade aos Serviços de Saúde , Fezes , Humanos , Medicaid , Serviços Postais , Avaliação de Programas e Projetos de Saúde , Estados Unidos
2.
Cancer ; 124(16): 3346-3354, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30004577

RESUMO

BACKGROUND: Colorectal cancer (CRC) screening is effective but underused. Screening rates are lower among Medicaid beneficiaries versus other insured populations. No studies have examined mailed fecal immunochemical testing (FIT)-based outreach programs for Medicaid beneficiaries. METHODS: In a patient-level randomized controlled trial, a mailed CRC screening reminder plus FIT, sent from an urban health department to Medicaid beneficiaries, was compared with the same reminder without FIT. The reminder group could request FIT. Completed FIT kits were processed by the health department laboratory. Respondents were notified of normal results by mail. Abnormal results were given via phone by a patient navigator who provided counselling and assistance with follow-up care. The primary outcome was FIT return. RESULTS: In all, 2144 beneficiaries at average CRC risk were identified, and there was no evidence of screening with Medicaid claims data. To the reminder+FIT group, 1071 were randomized, and 1073 were randomized to the reminder group; 307 (28.7%) in the reminder+FIT group and 347 (32.3%) in the reminder group were unreachable or ineligible (previous screening). The FIT return rate was significantly higher in the reminder+FIT group than the reminder group (21.1% vs 12.3%; difference, 8.8%; 95% confidence interval, 3.7%-13.9%; P < .01). Eighteen individuals (7.2%) who completed FIT tests had abnormal results, and 15 were eligible for follow-up colonoscopy; 66.7% (n = 10) completed follow-up colonoscopy. CONCLUSIONS: A health department-based, mailed FIT program targeting Medicaid beneficiaries was feasible. Including a FIT kit resulted in greater screening completion than a reminder letter alone. Further research is needed to understand the comparative cost-effectiveness of these interventions.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Fezes , Idoso , Colonoscopia , Neoplasias Colorretais/economia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Imunoquímica/métodos , Masculino , Medicaid , Pessoa de Meia-Idade , Serviços Postais , Estados Unidos
3.
Dialogues Health ; 5: 100187, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39282217

RESUMO

Under the collective weight of growing test volume, staffing constraints, and Medicare reimbursements cuts, an enhancement-based, alternative payment structure focused on rewarding the laboratory's care delivery efforts via benchmarking is appealing. However, achieving a value-based payment model requires the development of an inclusive laboratory care delivery model (LCDM) framework. Today, a holistic, practical LCDM framework for laboratory medicine does not exist. However, such creation is essential for establishing unifying tenants of practice for value-tracing by which standardized key performance and population health indicators can be derived. LAB-CARES is the first step in formulating an LCDM with the primary objective of defining and streamlining the processes and strategies necessary to deliver and articulate the value of diagnostic excellence across the healthcare system. The goal of LAB-CARES is to maximize efficiencies, enhance quality, disseminate clinical expertise, increase patient safety, and promote integrative practice. LAB-CARES is designed to improve an individual patient's quality of life (longitudinal laboratory results - beyond one test) and their surrounding communities (e.g., through surveillance and prevention - beyond one patient). Further professional conversation and efforts are paramount to integrate LAB-CARES as a formalized structure within the healthcare landscape.

5.
Ambio ; 51(10): 2169-2181, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35384617

RESUMO

Climate change will likely intensify hurricane activity in coastal regions. A thorough understanding of hurricane impacts to marine fauna is necessary to prepare for and mitigate potential impacts to social systems dependent upon adjacent fauna. Yet, research attention, conservation funding, and policy all can be biased toward taxa of societal interest, potentially favoring a limited understanding of hurricane impacts. Here, we analyzed the frequency of mentions of taxa in newspaper articles in relation to hurricane activity at three coastal US locations coupled with analysis of long-term fisheries-independent data. While economically important taxa dominate media discourse, we observed long-term hurricane-related abundance declines in ecologically important taxa having little direct human utility. We conclude that there is a potential for research and policy biases related to hurricane impacts. Preparation and mitigation efforts will benefit from researchers and managers making directed efforts to identify and incorporate hurricane sensitive taxa into their work.


Assuntos
Tempestades Ciclônicas , Mudança Climática , Ecossistema , Pesqueiros , Humanos
6.
Lab Med ; 52(4): e115-e124, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33942859

RESUMO

OBJECTIVE: To explore the experiences of medical laboratory professionals (MLPs) and their perceptions of the needs of clinical laboratories in response to COVID-19. METHODS: We surveyed laboratory professionals working in United States clinical laboratories during the initial months of the pandemic. RESULTS: Overall clinical laboratory testing and overtime work for laboratorians decreased during the first months of the pandemic. Laboratory professionals reported better or unchanged job satisfaction, feelings toward their work, and morale in their workplace, which were related to healthcare facility and laboratory leadership response. They reported receiving in-kind gifts, but no hazard pay, for their essential work. Important supply needs included reagents and personal protective equipment (PPE). CONCLUSION: The response by healthcare facilities and laboratory leadership can influence MLPs job satisfaction, feelings toward their work, and laboratory morale during a pandemic. Current COVID-19 laboratory testing management, in the absence of sufficient reagents and supplies, cannot fully address the needs of clinical laboratories.


Assuntos
COVID-19 , Laboratórios , Pessoal de Laboratório Médico/estatística & dados numéricos , Saúde Ocupacional , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Laboratórios/organização & administração , Laboratórios/estatística & dados numéricos , Laboratórios/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Equipamento de Proteção Individual/provisão & distribuição , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos , Carga de Trabalho/estatística & dados numéricos , Adulto Jovem
7.
Bioanalysis ; 11(15): 1405-1418, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31401845

RESUMO

Background: Neurofilament light (NfL) chain is an established cerebrospinal fluid (CSF) biomarker for neuroaxonal injury. The highly sensitive Quanterix Simoa™ platform is evaluated for NfL measurement in both CSF and blood. There is a need to link historical ELISA data that use bovine NfL to that of Simoa using a recombinant human (rhuman) NfL standard. Results/Methodology: The Simoa NF-light® Advantage Kit was validated for CSF and qualified for serum and plasma, using both rhuman and bovine NfL calibrators. Matched CSF, serum and plasma samples from 112 multiple sclerosis patients were analyzed using both calibrators. Conclusion: In multiple sclerosis, there is a good correlation between blood and CSF NfL levels. A conversion factor of approximately 5:1 was established between bovine and rhuman NfL calibrators.


Assuntos
Análise Química do Sangue/métodos , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Animais , Análise Química do Sangue/normas , Calibragem , Bovinos , Humanos , Limite de Detecção , Proteínas de Neurofilamentos/química , Recidiva , Padrões de Referência
8.
AAPS J ; 20(1): 10, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196830

RESUMO

An in-depth evaluation of the Quanterix© Simoa™ platform was undertaken by scientists from the AAPS Emerging Technologies Focus Group to determine the overall performance of the technology as well as provide guidance to future users. In order to test the platform in a non-GLP bioanalytical setting, a cross-site evaluation of the Quanterix IL-6 biomarker kit was performed. Parameters tested during this evaluation included sensitivity, accuracy and precision, and parallelism in human serum from normal individuals. The results demonstrated improved sensitivity compared to the claimed sensitivity of other commercially available IL-6 kits and showed excellent site-to-site reproducibility. Observed issues included difficulties with system reliability and a lack of parallelism and specificity in a subset of samples. Overall, these results demonstrate that while there are challenges to the Simoa platform this technology offers automation capabilities and excellent sensitivity that enhance bioanalysis especially of low-abundance analytes.


Assuntos
Interleucina-6/sangue , Kit de Reagentes para Diagnóstico , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Brain Behav ; 7(10): e00828, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29075574

RESUMO

INTRODUCTION: The role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western-type diet (high in fat and branched-chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A). METHODS: Mouse dams were fed one of four diets (high-fat/high BCAA, low-fat/high BCAA, high-fat, and low-fat) prior to mating and throughout gestation and lactation. Postpartum behavioral assessments were conducted, and plasma and brain tissues assayed. To evaluate potential clinical utility, we conducted preliminary human studies using data from an extant sample of 17 primiparous women with high GWG, comparing across self-reported postpartum mood symptoms using the Edinburgh Postnatal Depression Scale (EPDS) for percent GWG and plasma amino acid levels. RESULTS: Mouse dams fed the high-fat/high BCAA diet gained more weight per kcal consumed, and BCAA-supplemented dams lost weight more slowly postpartum. Dams on BCAA-supplemented diets exhibited increased PPD/A-like behavior, decreased dopaminergic function, and decreased plasma tyrosine and histidine levels when assessed on postnatal day (P)8. Preliminary human data showed that GWG accounted for 29% of the variance in EPDS scores. Histidine was also lower in women with higher EPDS scores. CONCLUSIONS: These findings highlight the role of perinatal diet and excess GWG in the development of postpartum mood disorders.


Assuntos
Ansiedade , Depressão , Dieta Ocidental/psicologia , Período Pós-Parto , Transtornos Puerperais , Aumento de Peso/fisiologia , Adulto , Animais , Ansiedade/sangue , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/sangue , Depressão/diagnóstico , Depressão/etiologia , Feminino , Histidina/sangue , Humanos , Camundongos , Período Pós-Parto/sangue , Período Pós-Parto/psicologia , Gravidez , Escalas de Graduação Psiquiátrica , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/etiologia , Transtornos Puerperais/prevenção & controle , Estatística como Assunto , Tirosina/sangue
10.
AAPS J ; 18(1): 115-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26340860

RESUMO

Omalizumab (Xolair®) is a recombinant humanized monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab is used to treat IgE-mediated diseases such as chronic idiopathic urticaria (CIU) and moderate to severe allergic asthma. In pre-marketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3,507 (0.1%) patients. In post-marketing spontaneous reports, the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. To better understand the risk of anaphylaxis in patients with allergic asthma receiving omalizumab, a post-marketing pharmacosurveillance study was initiated in 2009. As part of this study, an assay was developed to detect antibodies of IgE isotype to omalizumab. Serum samples from patients in the study were evaluated using this assay. Our results indicated that there was no observable correlation between either anaphylaxis or skin test reactivity and the presence of antibodies of IgE isotype to omalizumab. Here, we discuss the development of this assay as well as the results of the immunogenicity assessment.


Assuntos
Anafilaxia/epidemiologia , Antialérgicos/imunologia , Anticorpos/análise , Imunoglobulina E/análise , Omalizumab/imunologia , Adulto , Anafilaxia/etiologia , Antialérgicos/efeitos adversos , Anticorpos/genética , Asma/tratamento farmacológico , Humanos , Imunoglobulina E/genética , Omalizumab/efeitos adversos , Vigilância de Produtos Comercializados , Testes Cutâneos
11.
Curr Med Res Opin ; 30(5): 913-22, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24354863

RESUMO

BACKGROUND: The anti-IgE monoclonal antibody, omalizumab, is approved in the US as add-on therapy for patients ≥12 years of age with moderate-to-severe persistent allergic asthma. Omalizumab is administered according to the US Food and Drug Administration approved dosing table included in the prescribing information. The dosing table was developed using Genentech's free IgE assay and is designed to achieve free serum IgE levels of <50 ng/mL, known to be associated with clinical benefit. Lack of clinical benefit in a subset of patients on omalizumab has prompted demand for commercial free IgE assays to guide omalizumab dosing. To date, two commercial free IgE assays marketed by ViraCor-IBT (no longer offered) and BioTeZ have been available to physicians. OBJECTIVE: This study compares the results generated from the two commercial free IgE assays with the free IgE levels generated by the Genentech assay. METHODS: Two serum sample sets were prepared using 20 samples from patients with a wide range of IgE and omalizumab from an omalizumab clinical trial and 36 samples from omalizumab-naïve patients. Different amounts of omalizumab were added to the 36 omalizumab naïve samples based on measured total IgE levels to ensure that a good range of IgE and omalizumab was represented in the study samples. Samples were randomized for blinded analysis of free IgE levels using the Genentech, ViraCor-IBT and BioTeZ free serum IgE assays. Analysis of samples in the ViraCor-IBT assay were conducted by ViraCor-IBT and the analysis of samples using the Genentech and BioTeZ assay methods were conducted by a third party contract research organization. RESULTS: The ViraCor-IBT and BioTeZ free IgE assays demonstrated significantly higher free IgE levels than the Genentech free IgE assay. Twenty-nine of 56 samples tested <50 ng/mL in the Genentech assay; of these, 12/29 (41%) and 20/29 (69%) tested >50 ng/mL in the BioTeZ and ViraCor-IBT assays, respectively. In the BioTeZ free IgE evaluations, 11/20 samples that were re-tested had inter-assay differences ranging from 40-190%. CONCLUSIONS: Free ligand (such as IgE) measurements are challenging and dependent on the method and reagents used. The Viracor-IBT and BioTeZ methods tend to over-estimate free serum IgE levels compared with the Genentech free IgE assay. Using these assays to monitor therapy and adjust omalizumab doses post treatment is considered off-label use and could lead to a potential risk for unnecessary treatment and/or risk to patient safety.


Assuntos
Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Asma/sangue , Asma/tratamento farmacológico , Imunoensaio/métodos , Imunoglobulina E/sangue , Antiasmáticos/administração & dosagem , Humanos , Omalizumab
12.
AAPS J ; 16(4): 625-33, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24752719

RESUMO

Data generated using various immunoassay methods are an integral part of the development of protein therapeutics. These assays are used in clinical and preclinical studies to establish the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics as well as to assess the immunogenicity properties of a therapeutic. PK assays measure therapeutic levels post-administration which is essential for understanding the effective dose and dose regimen for a therapeutic. Anti-OX40L is a fully humanized monoclonal antibody designed for the potential treatment of an autoimmune disease. The anti-OX40L human PK assay is required to be sensitive, robust, and precise. To address challenges due to assay sensitivity and reproducibility, as well as assay technology limitations, during development of the anti-OX40L human PK assay, three different assays, including an MSD-based electrochemiluminescence assay (ECLA), a fluorometric enzyme-linked immunosorbent assay (ELISA), and a colorimetric ELISA, were evaluated. The MSD-based assay was the most sensitive but posed risk of inter-well signal crosstalk. The fluorescence ELISA fell short on reproducibility. The colorimetric ELISA was ultimately chosen for supporting sample analysis. This paper presents characterization data obtained from each of these assay formats, challenges that were encountered in the development of the assay, and the rationale for selecting the ultimate assay format.


Assuntos
Química Farmacêutica/métodos , Farmacocinética , Anticorpos/análise , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/farmacocinética , Colorimetria , Ensaio de Imunoadsorção Enzimática , Fluorescência , Humanos , Luminescência , Ligante OX40/análise , Ligante OX40/farmacocinética , Reprodutibilidade dos Testes
13.
Cancer Res ; 73(19): 6080-93, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23959857

RESUMO

Obesity is one of the most important preventable causes of cancer and the most significant risk factor for breast cancer in postmenopausal women. Compared with lean women, obese women are more likely to be diagnosed with a larger, higher grade tumor, an increased incidence of lymph node metastases, and elevated risk of distant recurrence. However, the mechanisms connecting obesity to the pathogenesis of breast cancer are poorly defined. Here, we show that during obesity, adipocytes within human and mouse breast tissues recruit and activate macrophages through a previously uncharacterized CCL2/IL-1ß/CXCL12 signaling pathway. Activated macrophages in turn promote stromal vascularization and angiogenesis even before the formation of cancer. Recapitulating these changes using a novel humanized breast cancer model was sufficient to promote angiogenesis and prime the microenvironment prior to neoplastic transformation for accelerated breast oncogenesis. These findings provide a mechanistic role for adipocytes and macrophages before carcinogenesis that may be critical for prevention and treatment of obesity-related cancer.


Assuntos
Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Quimiocina CCL2/metabolismo , Macrófagos/patologia , Neovascularização Patológica , Obesidade/complicações , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Apoptose , Western Blotting , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Bovinos , Diferenciação Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CXCL12/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Obesidade/metabolismo , Obesidade/patologia , Retina/citologia , Retina/metabolismo , Microambiente Tumoral
14.
MAbs ; 4(6): 724-31, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23778267

RESUMO

Modulating the binding affinities to IgE or changing the FcγR binding properties of anti-IgE antibodies offers an opportunity to enhance the therapeutic potential of anti-IgE antibodies, but the influence of increased affinity to IgE or reduced Fc effector function on the pharmacological properties of anti-IgE therapies remains unclear. Our studies were designed to characterize the pharmacokinetics, pharmacodynamics and immune-complex distribution of two high-affinity anti-IgE monoclonal antibodies, high-affinity anti-IgE antibody (HAE) 1 and 2, in mice and monkeys. HAE1, also known as PRO98498, is structurally similar to omalizumab (Xolair®), a humanized anti-IgE IgG1 marketed for the treatment of asthma, but differs by 9 amino acid changes in the complementarity-determining region resulting in a 23-fold improvement in affinity. HAE2 is similar to HAE1, but its Fc region was altered to reduce binding to Fcγ receptors. As expected given the decreased binding to Fcγ receptors, systemic exposure to pre-formed HAE2:IgE complexes in mice was greater (six-fold) and distribution to the liver lower (four-fold) compared with HAE1:IgE complexes. In monkeys, systemic exposure to HAE1 was similar to that previously observed for omalizumab in this species, but required comparatively lower serum drug concentrations to suppress free IgE levels. HAE2 treatment resulted in greater exposure and greater increase of total IgE, relative to HAE1, because of decreased clearance of HAE2:IgE complexes. Overall, these data suggest that increased binding affinity to IgE may provide a more effective therapeutic for asthma patients, and that retaining FcγR binding of the anti-IgE antibody is important for elimination of anti-IgE:IgE complexes.


Assuntos
Anticorpos Monoclonais/farmacocinética , Afinidade de Anticorpos , Asma/terapia , Receptores Fc/metabolismo , Animais , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Afinidade de Anticorpos/genética , Afinidade de Anticorpos/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Asma/imunologia , Haplorrinos , Humanos , Imunoglobulina E/imunologia , Taxa de Depuração Metabólica , Camundongos , Omalizumab , Ligação Proteica/genética , Receptores Fc/genética
16.
J Pharmacol Exp Ther ; 302(3): 1023-30, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12183659

RESUMO

N-Methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors that play putative roles in learning, memory, and excitotoxicity. NMDA receptor-mediated calcium entry can activate the calcium-dependent protease calpain, leading to substrate degradation. The major NMDA receptor 2 (NR2) subunits of the receptor are in vitro substrates for calpain at selected sites in the C-terminal region. In the present study, we assessed the ability of calpain-mediated proteolysis to modulate the NR1a/2A subtype in a heterologous expression system. Human embryonic kidney (HEK293t) cells, which endogenously express calpain, were cotransfected with NR1a/2A in addition to the calpain inhibitor calpastatin or empty vector as control. Receptor activation by glutamate and glycine as co-agonists led to calpain activation as measured by succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosyl-aminomethyl coumarin (Suc-LLVY-AMC). Calpain activation also resulted in the degradation of NR2A and decreased binding of (125)I-MK-801 ((125)I-dizocilpine) to NR1a/2A receptors. No stable N-terminal fragment of the NMDA receptor was formed after calpain activation, suggesting calpain regulation of NMDA receptor levels in ways distinct from that previously observed with in vitro cleavage. NR2 subunit constructs lacking the final 420 amino acids were not degraded by calpain. Agonist-stimulated NR1a/2A-transfected cells also had decreased calcium uptake and produced lower changes in agonist-stimulated intracellular calcium compared with cells cotransfected with calpastatin. Calpastatin had no effect on either calcium uptake or intracellular calcium levels when the NR2A subunit lacked the final 420 amino acids. These studies demonstrate that NR2A is a substrate for calpain in situ and that this proteolytic event can modulate NMDA receptor levels.


Assuntos
Calpaína/metabolismo , Peptídeo Hidrolases/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Western Blotting , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Cisteína Proteinase/genética , Inibidores de Cisteína Proteinase/metabolismo , DNA Complementar/biossíntese , DNA Complementar/genética , Maleato de Dizocilpina/metabolismo , Antagonistas de Aminoácidos Excitatórios/metabolismo , Humanos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/genética , Transfecção
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