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1.
Lancet ; 397(10288): 1992-2011, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-33965066

RESUMO

Approximately 13% of the total UK workforce is employed in the health and care sector. Despite substantial workforce planning efforts, the effectiveness of this planning has been criticised. Education, training, and workforce plans have typically considered each health-care profession in isolation and have not adequately responded to changing health and care needs. The results are persistent vacancies, poor morale, and low retention. Areas of particular concern highlighted in this Health Policy paper include primary care, mental health, nursing, clinical and non-clinical support, and social care. Responses to workforce shortfalls have included a high reliance on foreign and temporary staff, small-scale changes in skill mix, and enhanced recruitment drives. Impending challenges for the UK health and care workforce include growing multimorbidity, an increasing shortfall in the supply of unpaid carers, and the relative decline of the attractiveness of the National Health Service (NHS) as an employer internationally. We argue that to secure a sustainable and fit-for-purpose health and care workforce, integrated workforce approaches need to be developed alongside reforms to education and training that reflect changes in roles and skill mix, as well as the trend towards multidisciplinary working. Enhancing career development opportunities, promoting staff wellbeing, and tackling discrimination in the NHS are all needed to improve recruitment, retention, and morale of staff. An urgent priority is to offer sufficient aftercare and support to staff who have been exposed to high-risk situations and traumatic experiences during the COVID-19 pandemic. In response to growing calls to recognise and reward health and care staff, growth in pay must at least keep pace with projected rises in average earnings, which in turn will require linking future NHS funding allocations to rises in pay. Through illustrative projections, we show that, to sustain annual growth in the workforce at approximately 2·4%, increases in NHS expenditure of 4% annually in real terms will be required. Above all, a radical long-term strategic vision is needed to ensure that the future NHS workforce is fit for purpose.


Assuntos
Política de Saúde , Mão de Obra em Saúde/estatística & dados numéricos , Medicina Estatal/estatística & dados numéricos , COVID-19/psicologia , Ocupações em Saúde/economia , Ocupações em Saúde/educação , Mão de Obra em Saúde/economia , Humanos , Estresse Ocupacional , Seleção de Pessoal , Medicina Estatal/economia , Reino Unido
2.
J Community Health ; 46(1): 1-12, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32170531

RESUMO

Living in a low-income neighborhood with low access to healthy food retailers is associated with increased risk for chronic disease. The U.S. Healthy Food Financing Initiative (HFFI) provides resources to support the development of infrastructure to improve neighborhood food environments. This natural experiment examined a HFFI funded food hub that was designed to be implemented by a community development corporation in an urban neighborhood in Cleveland, Ohio. It was intended to increase access to affordable, local, and healthy foods; establish programs to increase social connections and support for healthy eating; and create job opportunities for residents. We used a quasi-experimental, longitudinal design to externally evaluate food hub implementation and its impact on changes to the built and social environment and dietary patterns among residents living in the intervention neighborhood (n = 179) versus those in a comparison (n = 150) neighborhood. Overall, many of the food hub components were not implemented fully, and dose and reach of the executed food hub components was low. There were statistically significant improvements in observed availability of healthy foods in the intervention neighborhood versus the comparison neighborhood. There were no changes over time in diet quality scores, total caloric intake, or fruit and vegetable intake in the intervention neighborhood. In conclusion, low dose implementation of a food hub led to small improvements in availability of healthy foods but not in dietary patterns. Findings highlight challenges to implementing a food hub in neighborhoods with low access to healthy food retailers.


Assuntos
Dieta Saudável/estatística & dados numéricos , Dieta/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Comportamento Alimentar , Frutas , Humanos , Ohio , Pobreza/estatística & dados numéricos , Meio Social , Verduras
3.
Am J Community Psychol ; 68(3-4): 455-470, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34333787

RESUMO

Access to fresh and healthy food within a neighborhood has been identified as a social mechanism contributing to community health. Grounded in the understanding that challenges related to equity within a food system are both structural and systemic, our research demonstrates how systems thinking can further understandings of food system complexity. Within systems thinking, we provide an illustration of how system archetypes offer an analytic tool for examining complex community issues. We map semi-structured interview data from community stakeholders (N = 22) to the "Fixes that Fail" system archetype to illuminate systemic challenges, such as incarceration and poverty, that structure food system inequity in urban communities. Within our research, the "Fixes that Fail" archetype provided a narrative interpretive tool for unveiling complexity within the food system and interdependencies with racialized systems such as criminal justice and labor markets. This system archetype provided an accessible approach for generating narratives about systemic complexity, the production of inequity through racialized forces, and opportunities for transformation.


Assuntos
Pobreza , Humanos
4.
Matern Child Health J ; 24(Suppl 2): 191-199, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31981063

RESUMO

INTRODUCTION: Programs supporting adolescent parents have been shown to increase socio-economic opportunities and promote healthy child development for young families, but retaining young parents is challenging. The Massachusetts Pregnant and Parenting Teen Initiative (MPPTI) offers case management and linkages to community and clinical services to young families. We examine engagement strategies identified by MPPTI participants and staff members in relation to participant retention by program site to identify potential strategies for increasing program engagement. METHODS: We employed a mixed-methods approach incorporating quantitative data on program participant characteristics and program retention by site with qualitative data from staff and participant interviews and focus groups. RESULTS: Key program engagement strategies identified by both MPPTI staff and youth participants were social-emotional supports, staffing model, and concrete supports. We found significant differences in program retention by site; the two sites with the highest levels of program retention offered all engagement strategies identified. DISCUSSION: Quantitative data on program retention coupled with qualitative data from staff and youth interviews suggests that in our program, there may be an association between the engagement strategies identified and levels of program retention.


Assuntos
Poder Familiar/psicologia , Participação do Paciente/psicologia , Apoio Social , Adolescente , Análise de Variância , Feminino , Grupos Focais/métodos , Humanos , Masculino , Massachusetts , Participação do Paciente/métodos , Gravidez , Gravidez na Adolescência/psicologia , Avaliação de Programas e Projetos de Saúde/métodos , Pesquisa Qualitativa , Adulto Jovem
5.
Ann Emerg Med ; 71(3): 369-377.e1, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29033296

RESUMO

STUDY OBJECTIVE: Intravenous subdissociative-dose ketamine has been shown to be effective for pain management, but has not been specifically studied for headaches in the emergency department (ED). For this reason, we designed a study to compare standard treatment (prochlorperazine) with ketamine in patients with benign headaches in the ED. METHODS: This study was a multicenter, double-blind, randomized, controlled trial with a convenience sample of patients presenting to the ED with benign headaches. Patients were randomized to receive either prochlorperazine and diphenhydramine or ketamine and ondansetron. Patients' headache severity was measured on a 100-mm visual analog scale (VAS) at 0, 15, 30, 45, and 60 minutes. Nausea, vomiting, anxiety, and the need for rescue medications were also tracked. Patients were contacted at 24 to 48 hours posttreatment to rate their satisfaction and to determine whether they were still experiencing a headache. RESULTS: There were a total of 54 subjects enrolled. Two patients in the ketamine group and one in the prochlorperazine group withdrew because of adverse effects of the medications. In regard to the primary outcome, at 60 minutes, the prochlorperazine group had a mean improvement in VAS pain scores of 63.5 mm compared with 43.5 mm in the ketamine group, corresponding to a between-groups difference of 20.0 mm (95% confidence interval [CI] 2.8 to 37.2 mm) and a P value of .026. At 45 minutes, the prochlorperazine group had a mean improvement in pain scores of 56.1 mm compared with 38.0 mm in the ketamine group, a difference of 18.1 mm (95% CI 1.0 to 35.2 mm). At 24- to 48-hour follow-up, the mean satisfaction score was 8.3 of 10 for prochlorperazine and 4.9 of 10 for ketamine, a difference of 3.4 (95% CI 1.2 to 5.6). There was not a statistically significant difference in the percentage of patients who had a headache at follow-up or in other secondary outcomes. CONCLUSION: Prochlorperazine appears to be superior to ketamine for the treatment of benign headaches in the ED.


Assuntos
Serviço Hospitalar de Emergência , Cefaleia/tratamento farmacológico , Ketamina/administração & dosagem , Proclorperazina/administração & dosagem , Adolescente , Adulto , Idoso , Anestésicos Dissociativos/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Cefaleia/diagnóstico , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
8.
J Interprof Care ; 29(1): 34-40, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25006869

RESUMO

The potential of interprofessional education (IPE) to influence the perceptions and attitudes of health and social care professionals towards their colleagues in other disciplines is well recognized. However, empirical evidence for the positive impact of IPE on stereotypical beliefs has been limited. We report the findings of a pioneering, large scale study designed to assess the influence of IPE on these beliefs. A pre-test, post-test, quasi experimental design compared students' stereotypical views at the beginning and end of undergraduate studies. 580 students from 10 health and social care professional groups undertook assessed IPE modules over 3 years (the intervention group). Baseline and post-course stereotype ratings were compared with those of 672 students in a comparison group, not exposed to IPE modules. Baseline stereotype profiles showed clear variations in the way different professions were perceived, indicating stereotypical beliefs about the characteristics of each profession. Rating patterns were similar for intervention and comparison groups. At graduation, only minor changes were observed in the overall rating patterns for both groups. However, more ratings had decreased in the intervention group than the comparison group, suggesting that IPE may play a role in moderating more extreme stereotyping of colleagues in other professions.


Assuntos
Relações Interprofissionais , Assistentes Sociais/educação , Assistentes Sociais/psicologia , Estereotipagem , Estudantes de Ciências da Saúde/psicologia , Adulto , Atitude do Pessoal de Saúde , Competência Clínica , Estudos de Coortes , Comportamento Cooperativo , Feminino , Humanos , Relações Interpessoais , Liderança , Aprendizagem , Masculino , Equipe de Assistência ao Paciente/organização & administração , Autoeficácia
9.
MMWR Morb Mortal Wkly Rep ; 63(3): 59-62, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24452134

RESUMO

In 2006, Massachusetts passed legislation that broadened access to health insurance for its residents. The percentage of the state population that had health insurance (obtained through either private insurance or publicly funded programs) subsequently increased, reaching 97% in 2011, leaving only 3% uninsured, compared with approximately 9%-20% uninsured among nonelderly residents in 2006. Given such high rates of insurance coverage, questions arise about the need for categorical public health programs designed to serve clients without health insurance. This report describes trends in the percentage of uninsured clients seen at community-based organizations in Massachusetts that received federal funding for one such program, the Title X family planning program. Title X program data from 2005-2012 indicate that client volume remained high throughout the period, and that the percentage of clients who were uninsured declined, from 59% in 2005 to 36% in 2012. Across years, young adults aged 20-29 years and persons whose incomes were 101%-250% of the federal poverty level were more likely to be uninsured than were persons in other age and income groups. After health-care reform, publicly funded family planning services in Massachusetts saw continued demand from uninsured and insured clients. Family planning services in other states implementing health-care reform might have a similar experience, and public health agencies are encouraged to track such trends to monitor the demand for such services and inform budget planning and resource allocation.


Assuntos
Serviços de Planejamento Familiar/economia , Serviços de Planejamento Familiar/estatística & dados numéricos , Financiamento Governamental/estatística & dados numéricos , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Adulto , Reforma dos Serviços de Saúde , Humanos , Massachusetts , Adulto Jovem
10.
J Health Polit Policy Law ; 38(2): 393-419, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23262763

RESUMO

We investigated the impact of Massachusetts health care reform on low-income women's experiences accessing insurance and health services, specifically reproductive health services such as contraception. Our findings suggest that concentrated efforts are needed to make sure that health services are available and accessible to populations who fall through the cracks of health care reform, including immigrants, minors and young adults, and women living outside urban areas. In addition, systems changes are needed to ensure that women going through common life transitions, such as pregnancy, marriage, moving, or graduating from school, have continuous access to insurance, and therefore health services, as their lives change. These groups face barriers enrolling in and maintaining their insurance coverage as well as obtaining timely health care benefits they are eligible for through their insurance benefits or public health programs. Without intervention, many in these groups may delay or avoid seeking health care altogether, which may increase health care disparities in the long term. Family planning providers in Massachusetts have played a critical role in mitigating barriers to insurance and health care. However, recent threats to defund family planning providers call into question the ability of these providers to continue providing much-needed services.


Assuntos
Reforma dos Serviços de Saúde/organização & administração , Avaliação das Necessidades , Pobreza , Anticoncepção , Feminino , Reforma dos Serviços de Saúde/legislação & jurisprudência , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Humanos , Cobertura do Seguro/legislação & jurisprudência , Massachusetts , Serviços de Saúde Reprodutiva/legislação & jurisprudência
11.
Br J Psychother ; 29(2): 182-201, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-24748706

RESUMO

Despite evidence that nurses may play a crucial part in the wellbeing and recovery of cancer patients by facilitating their expression of feelings, research is lacking into the emotional content of nurse-patient talk and patients' use of language in emotion disclosure. In this study, 23 participating nurses in a variety of cancer care settings were asked to tape-record their conversations with patients during daily care. A data set of 60 nurse-patient conversations was collected. Individual expression of emotion by patients was identified through interpretive literary analysis within a framework of psychodynamic theory. Overall the picture of emotion disclosure was intense. In particular, patients' use of metaphor and figurative language to express their distress was powerful and pervasive. Participating nurses demonstrated responsive skills but their responses to figurative expression were often problematic. The study provides evidence of unconscious processes in nurses' work and advocates career-long psychoanalytically informed supervision for nurses to better support them in challenging dialogue with cancer patients. Research is needed to evaluate the impact of supervision on communications with cancer patients to ensure patients have access to appropriate emotional supportive and care.

13.
Anat Sci Educ ; 15(1): 127-142, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33369254

RESUMO

While integrated delivery of anatomy and radiology can support undergraduate anatomical education, the interpretation of complex three-dimensional spatial relationships in cross-sectional and radiological images is likely to be demanding for novices. Due to the value of technology-enhanced and multimodal strategies, it was hypothesized that simultaneous digital and physical learning could enhance student understanding of cross-sectional anatomy. A novel learning approach introduced at a United Kingdom university medical school combined visualization table-based thoracic cross-sections and digital models with a three-dimensional printed heart. A mixed-method experimental and survey approach investigated student perceptions of challenging anatomical areas and compared the multimodal intervention to a two-dimensional cross-section control. Analysis of seven-point Likert-type responses of new medical students (n = 319) found that clinical imaging (mean 5.64 SD ± 1.20) was significantly more challenging (P < 0.001) than surface anatomy (4.19 ± 1.31) and gross anatomy (4.92 ± 1.22). Pre-post testing of students who used the intervention during their first anatomy class at medical school (n = 229), identified significant increases (P < 0.001) in thoracic cross-sectional anatomy interpretation performance (mean 31.4% ± 15.3) when compared to the subsequent abdominal control activity (24.1% ± 17.6). Student test scores were independent of mental-rotation ability. As depicted on a seven-point Likert-type scale, the intervention may have contributed to students considering cross-sectional interpretation of thoracic images (4.2 ± 1.23) as significantly less challenging (P < 0.001) than comparable abdominal images (5.59 ± 1.14). These findings could have implications for how multimodal cross-sectional anatomy learning approaches are implemented within medical curricula.


Assuntos
Anatomia , Estudantes de Medicina , Anatomia/educação , Anatomia Transversal/educação , Currículo , Humanos , Imageamento Tridimensional
14.
Am J Clin Nutr ; 115(4): 1027-1038, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34792095

RESUMO

BACKGROUND: The food system is a social determinant of health and a leverage point for reducing diet-related racial inequities. Yet, food system interventions have not resulted in sustained improvement in dietary outcomes for underrepresented minorities living in neighborhoods with a history of disinvestment. Research is needed to illuminate the dynamics structuring food systems in racialized neighborhoods to inform intervention development. OBJECTIVES: To conduct participatory research examining the complexity and inequity of food systems in historically redlined neighborhoods to identify feedback mechanisms to leverage in efforts to transform system outcomes for racial equity. METHODS: We conducted a mixed-methods study in Cleveland, Ohio, USA from 2018 to 2021 using participatory system dynamic modeling with 30 academic and community partners, in-depth qualitative interviews with 22 key stakeholders, and public convenings with 250 local food policy council affiliates. Data were synthesized into causal loop diagrams depicting feedback mechanisms reinforcing or balancing neighborhood-level food system dynamics. RESULTS: We identified 10 feedback mechanisms structuring nutrition equity, which was identified as a meta-goal for food systems in racialized neighborhoods. Feedback mechanisms were organized in 3 domains: 1) meeting basic food needs with dignity (i.e., side hustle, government benefits, emergency food assistance, stigma, and stereotypes); 2) local food supply and demand dynamics (i.e., healthy food retail, job security, food culture, and norms); and 3) community empowerment and food sovereignty (i.e., community power, urban agriculture, risk of gentrification). Five exogenous factors moderate feedback dynamics: neighborhood crisis, neighborhood investments, household costs, government benefit funding, and voter participation. CONCLUSIONS: We identified nutrition equity as an overarching goal for local food systems, which reflects a state of having freedom, agency, and dignity in food traditions resulting in people and communities healthy in body, mind, and spirit. It is a transformative goal designed to spur system-level interventions that further racial equity through improved local food system dynamics.


Assuntos
Assistência Alimentar , Abastecimento de Alimentos , Dieta , Alimentos , Humanos , Estado Nutricional
15.
J Biol Chem ; 285(18): 13542-9, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20177054

RESUMO

In pulmonary arterial smooth muscle, Ca(2+) release from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) may induce constriction and dilation in a manner that is not mutually exclusive. We show here that the targeting of different sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases (SERCA) and RyR subtypes to discrete SR regions explains this paradox. Western blots identified protein bands for SERCA2a and SERCA2b, whereas immunofluorescence labeling of isolated pulmonary arterial smooth muscle cells revealed striking differences in the spatial distribution of SERCA2a and SERCA2b and RyR1, RyR2, and RyR3, respectively. Almost all SERCA2a and RyR3 labeling was restricted to a region within 1.5 microm of the nucleus. In marked contrast, SERCA2b labeling was primarily found within 1.5 microm of the plasma membrane, where labeling for RyR1 was maximal. The majority of labeling for RyR2 lay in between these two regions of the cell. Application of the vasoconstrictor endothelin-1 induced global Ca(2+) waves in pulmonary arterial smooth muscle cells, which were markedly attenuated upon depletion of SR Ca(2+) stores by preincubation of cells with the SERCA inhibitor thapsigargin but remained unaffected after preincubation of cells with a second SERCA antagonist, cyclopiazonic acid. We conclude that functionally segregated SR Ca(2+) stores exist within pulmonary arterial smooth muscle cells. One sits proximal to the plasma membrane, receives Ca(2+) via SERCA2b, and likely releases Ca(2+) via RyR1 to mediate vasodilation. The other is located centrally, receives Ca(2+) via SERCA2a, and likely releases Ca(2+) via RyR3 and RyR2 to initiate vasoconstriction.


Assuntos
Cálcio/metabolismo , Músculo Liso Vascular/metabolismo , Artéria Pulmonar/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Membrana Celular/metabolismo , Endotelina-1/farmacologia , Masculino , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/citologia , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
16.
Agric Human Values ; 38(1): 175-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32904580

RESUMO

Dominant food systems, based on industrial methods and corporate control, are in a state of flux. To enable the transition towards more sustainable and just food systems, food movements are claiming new roles in governance. These movements, and the initiatives they spearhead, are associated with a range of labels (e.g., food sovereignty, food justice, and community food security) and use a variety of strategies to enact change. In this paper, we use the concept of relational fields to conduct a post-hoc analysis of nine cases, examining how social movement organizations and other actors actively create new deliberative governance spaces. We argue that successes are related to the "power to convene," a process-oriented approach that increases movements' capacity to mobilize; leverage different types of power; and integrate, coordinate, and build a systems-oriented vision. The power to convene and create deliberative spaces is demonstrated in a variety of contexts and often results in outcomes that further movement aims, including policy change and repositioning food movement actors vis-à-vis others in the field. Our findings suggest that success is not only measured as policy outcomes, but as an advantageous repositioning of social movement actors that enables them to be part of governance processes beyond simple policy advocacy.

17.
Health Place ; 69: 102564, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33894655

RESUMO

Using a relational approach, this study investigates whether shopping close to home moderates the relationship between the proximate food environment and diet. To address this question, we develop the proximate food retail quality (PFRQ) score, an inverse-distance weighted measure of all food retailers within a resident's neighborhood that incorporates audit data of each food retailer. This study relies on data collected through 24-h dietary recalls and psychosocial surveys administered to 449 adults in two socioeconomically matched neighborhoods. Food retailer audits collected data on the availability, price, and quality of healthful foods. Seventy-one percent of study participants report conducting at least 50% of their food shopping within approximately one mile of their home. Household income and education are associated with likelihood to shop close to home, while access to a personal vehicle is not. Finally, results suggest that, for residents who shop primarily close to home, a one unit increase in proximate food retail environment score is associated with a 17.2-point increase in HEI-2010 score, a measure of overall diet quality that ranges from zero to 100. This study suggests that the food environment matters for those who use it and that a low-quality proximate food environment can amplify individual disadvantage.


Assuntos
Comércio , Abastecimento de Alimentos , Adulto , Dieta , Alimentos , Humanos , Características de Residência
18.
Appl Econ Perspect Policy ; 43(1): 169-184, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33173572

RESUMO

As lockdown and school closure policies were implemented in response to the coronavirus, the federal government provided funding and relaxed its rules to support emergency food provision, but not guidance on best practices for effectiveness. Accordingly, cities developed a diverse patchwork of emergency feeding programs. This article uses qualitative data to provide insight into emergency food provision developed in five cities to serve children and families. Based on our qualitative analysis, we find that the effectiveness of local approaches appears to depend on: (i) cross-sector collaboration, (ii) supply chains, and (iii) addressing gaps in service to increased risk populations.

19.
Clin Endocrinol (Oxf) ; 73(3): 404-12, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20550534

RESUMO

OBJECTIVE: Patients who appear to have both stimulating and blocking TSHR autoantibodies in their sera have been described, but the two activities have not been separated and analysed. We now describe the isolation and detailed characterization of a blocking type TSHR monoclonal autoantibody and a stimulating type TSHR monoclonal autoantibody from a single sample of peripheral blood lymphocytes. DESIGN, PATIENTS AND MEASUREMENTS: Two heterohybridoma cell lines secreting TSHR autoantibodies were isolated using standard techniques from the lymphocytes of a patient with hypothyroidism and high levels of TSHR autoantibodies (160 units/l by inhibition of TSH binding). The ability of the two new monoclonal antibodies (MAbs; K1-18 and K1-70) to bind to the TSHR and compete with TSH or TSHR antibody binding was analysed. Furthermore, the effects of K1-18 and K1-70 on cyclic AMP production in Chinese hamster ovary cells (CHO) cells expressing the TSHR were investigated. RESULTS: One MAb (K1-18) was a strong stimulator of cyclic AMP production in TSHR-transfected CHO cells and the other (K1-70) blocked stimulation of the TSHR by TSH, K1-18, other thyroid-stimulating MAbs and patient serum stimulating type TSHR autoantibodies. Both K1-18 (IgG1 kappa) and K1-70 (IgG1 lambda) bound to the TSHR with high affinity (0.7 x 10(10) l/mol and 4 x 10(10) l/mol, respectively), and this binding was inhibited by unlabelled K1-18 and K1-70, other thyroid-stimulating MAbs and patient serum TSHR autoantibodies with stimulating or blocking activities. V region gene analysis indicated that K1-18 and K1-70 heavy chains used the same V region germline gene but different D and J germline genes as well as having different light chains. Consequently, the two antibodies have evolved separately from different B cell clones. CONCLUSIONS: This study provides proof that a patient can produce a mixture of blocking and stimulating TSHR autoantibodies at the same time.


Assuntos
Anticorpos Monoclonais/imunologia , Autoanticorpos/imunologia , Hipotireoidismo/imunologia , Receptores da Tireotropina/imunologia , Monofosfato de Adenosina/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacologia , Autoanticorpos/metabolismo , Autoanticorpos/farmacologia , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/imunologia , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Feminino , Humanos , Hibridomas , Hipotireoidismo/sangue , Região de Junção de Imunoglobulinas/imunologia , Região de Junção de Imunoglobulinas/metabolismo , Cadeias Leves de Imunoglobulina/imunologia , Cadeias Leves de Imunoglobulina/metabolismo , Região Variável de Imunoglobulina/imunologia , Região Variável de Imunoglobulina/metabolismo , Radioisótopos do Iodo , Pessoa de Meia-Idade , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/imunologia , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismo , Tireotropina/metabolismo
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