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1.
J Card Fail ; 30(5): 722-727, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38584015

RESUMO

Financial considerations continue to impact access to heart transplantation. Transplant recipients face various costs, including, but not limited to, the index hospitalization, immunosuppressive medications, and lodging and travel to appointments. In this study, we sought to describe the state of crowdfunding for individuals being evaluated for heart transplantation. Using the search term heart transplant, 1000 GoFundMe campaigns were reviewed. After exclusions, 634 (63.4%) campaigns were included. Most campaigns were in support of white individuals (57.8%), males (63.1%) and adults (76.7%). Approximately 15% of campaigns had not raised any funds. The remaining campaigns fundraised a median of $53.24 dollars per day. Of the patients, 44% were admitted at the time of the fundraising. Within the campaigns in the United States, the greatest proportions were in the Southeast United States in non-Medicaid expansion states. These findings highlight the significant financial toxicities associated with heart transplantation and the need for advocacy at the governmental and payer levels to improve equitable access and coverage for all.


Assuntos
Obtenção de Fundos , Transplante de Coração , Humanos , Transplante de Coração/economia , Estados Unidos , Masculino , Feminino , Crowdsourcing/economia , Crowdsourcing/métodos , Adulto , Acessibilidade aos Serviços de Saúde/economia , Pessoa de Meia-Idade
2.
Nurs Res ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38498869

RESUMO

BACKGROUND: Oropharyngeal cancer survivorship is a nursing priority because patients are living longer while significant short-term and long-term treatment complications that require nursing care are increasing. Hospital readmission is costly and reflects the quality of care patients receive. OBJECTIVES: This secondary analysis aimed to determine the prevalence of treatment complications resulting in hospital admissions among persons with OPC and examine the relationship between treatment complications resulting in hospital admission among persons with oropharyngeal cancer and all other persons with head and neck cancer. METHODS: Using the National Inpatient Survey 2008-2019 database, we identified persons with relevant head and neck cancer diagnoses using specific International Classification of Disease (ICD) ICD-9 and ICD-10 codes. Complications were operationalized by diagnosis-related codes; persons with codes for major elective surgery were excluded as our focus was post-treatment symptoms requiring hospitalization. Descriptive statistics were used to characterize persons with OPC hospitalized between 2008 and 2019. Binary logistic regression was used to assess complications using crude comparisons. The Elixhauser Comorbidity Index was used for controlling for comorbidities. RESULTS: The final analysis samples included 751,533: 164,770 persons with oropharyngeal cancer and 586,763 with other head and cancers. The most prevalent diagnoses observed in those with oropharyngeal cancer were esophagitis, nutrition disorder, hematological disorder, and renal failure; the least common diagnoses were sepsis, respiratory tract infection, and pneumonia. Binary regression revealed that persons with oropharyngeal cancer experienced significantly more esophagitis, nutrition disorders, hematological disorders, and renal failure compared to persons with other head and neck cancers. DISCUSSION: Treatment of survivors of oropharyngeal cancer requires more intensive monitoring for early symptoms associated with treatment, including esophagitis, nutrition disorders, bleeding disorders, and renal failure, than persons with other head and neck cancers. Monitoring laboratory values and clinical manifestations of these conditions is imperative. Nurses may encounter persons with oropharyngeal cancer in emergency departments, outpatient radiology, or inpatient general medicine floors to manage swallowing difficulties, dehydration, malnutrition, and bleeding. Delayed or ineffective treatment of these conditions contributes to readmission, financial burden, and impairment of patient's quality of life. Future research should investigate the relationship between targeted treatment for expected complications and readmission rates in persons with oropharyngeal cancer.

3.
Echocardiography ; 41(1): e15719, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38126261

RESUMO

AIM: To test the feasibility and accuracy of a new attention-based deep learning (DL) method for right ventricular (RV) quantification using 2D echocardiography (2DE) with cardiac magnetic resonance imaging (CMR) as reference. METHODS AND RESULTS: We retrospectively analyzed images from 50 adult patients (median age 51, interquartile range 32-62 42% women) who had undergone CMR within 1 month of 2DE. RV planimetry of the myocardial border was performed in end-diastole (ED) and end-systole (ES) for eight standardized 2DE RV views with calculation of areas. The DL model comprised a Feature Tokenizer module and a stack of Transformer layers. Age, gender and calculated areas were used as inputs, and the output was RV volume in ED/ES. The dataset was randomly split into training, validation and testing subsets (35, 5 and 10 patients respectively). Mean RVEDV, RVESV and RV ejection fraction (EF) were 163 ± 70 mL, 82 ± 42 mL and 51% ± 8% respectively without differences among the subsets. The proposed method achieved good prediction of RV volumes (R2  = .953, absolute percentage error [APE] = 9.75% ± 6.23%) and RVEF (APE = 7.24% ± 4.55%). Per CMR, there was one patient with RV dilatation and three with RV dysfunction in the testing dataset. The DL model detected RV dilatation in 1/1 case and RV dysfunction in 4/3 cases. CONCLUSIONS: An attention-based DL method for 2DE RV quantification showed feasibility and promising accuracy. The method requires validation in larger cohorts with wider range of RV size and function. Further research will focus on the reduction of the number of required 2DE to make the method clinically applicable.


Assuntos
Aprendizado Profundo , Disfunção Ventricular Direita , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ecocardiografia , Estudos de Viabilidade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Direita
4.
Clin J Oncol Nurs ; 27(4): 355, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37677780

RESUMO

Limited English proficiency (LEP) is challenging for oncology nursing because language barriers affect access to health services and patient outcomes. Strategies to mitigate this problem may differ based on the region of the.


Assuntos
Proficiência Limitada em Inglês , Humanos , Enfermagem Oncológica , Pacientes
5.
Br J Haematol ; 200(5): 541-542, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36352551

RESUMO

The article by Moser et al. details the outcomes of 11 patients with inflammatory bowel disease (IBD) as the main manifestation of their immune deficiency syndrome who are treated with allogeneic transplantation. The authors report low rates of complications (including graft-versus-host disease) and resolution of symptoms. Here we outline whether allogeneic transplantation should be considered more broadly for IBD. Commentary on: Moser et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2023;200:595-607.


Assuntos
Doença de Crohn , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/etiologia , Doença de Crohn/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Inflamatórias Intestinais/complicações , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/complicações
6.
J Holist Nurs ; 36(1): 15-22, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27872340

RESUMO

PURPOSE: To describe the unmet needs of adult patients living with solid tumor cancer. DESIGN: Survey design. METHOD: Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. FINDINGS: There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. CONCLUSION: Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.


Assuntos
Ansiedade/etiologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Neoplasias/complicações , Psicometria/instrumentação , Psicometria/métodos , Grupos Raciais/psicologia , Grupos Raciais/estatística & dados numéricos , Apoio Social , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Inquéritos e Questionários
7.
Clin J Oncol Nurs ; 21(1): 30-33, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28107328

RESUMO

Cognition, psychological well-being, stress, functional status, and pain are all priority outcomes of interest to oncology nurses. However, it can be challenging to choose an instrument for clinical assessment or for use in research projects that assess these constructs. The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function was created for measuring emotional health and cognitive, motor, and sensory function. The toolbox can be a potentially useful resource for clinicians and nurse researchers.


Assuntos
Adaptação Psicológica , National Institutes of Health (U.S.)/normas , Neoplasias/psicologia , Testes Neuropsicológicos/normas , Autoeficácia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Função Executiva , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Psicometria , Desempenho Psicomotor , Estresse Psicológico , Estados Unidos , Adulto Jovem
8.
Kidney Int ; 91(2): 477-492, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27988211

RESUMO

Chronic antibody-mediated rejection, a common cause of renal transplant failure, has a variable clinical phenotype. Understanding why some with chronic antibody-mediated rejection progress slowly may help develop more effective therapies. B lymphocytes act as antigen-presenting cells for in vitro indirect antidonor interferon-γ production in chronic antibody-mediated rejection, but many patients retain the ability to regulate these responses. Here we test whether particular patterns of T and B cell antidonor response associate with the variability of graft dysfunction in chronic antibody-mediated rejection. Our results confirm that dynamic changes in indirect antidonor CD4+ T-cell responses correlate with changes in estimated glomerular filtration rates, independent of other factors. Graft dysfunction progressed rapidly in patients who developed unregulated B-cell-driven interferon-γ production. However, conversion to a regulated or nonreactive pattern, which could be achieved by optimization of immunosuppression, associated with stabilization of graft function. Functional regulation by B cells appeared to activate an interleukin-10 autocrine pathway in CD4+ T cells that, in turn, impacted on antigen-specific responses. Thus, our data significantly enhance the understanding of graft dysfunction associated with chronic antibody-mediated rejection and provide the foundation for strategies to prolong renal allograft survival, based on regulation of interferon-γ production.


Assuntos
Comunicação Autócrina , Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Interferon gama/imunologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Rim/imunologia , Células Th1/imunologia , Adulto , Área Sob a Curva , Comunicação Autócrina/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Biópsia , Distribuição de Qui-Quadrado , Doença Crônica , Progressão da Doença , ELISPOT , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto , Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Interferon gama/metabolismo , Testes de Liberação de Interferon-gama , Interleucina-10/imunologia , Interleucina-10/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Transdução de Sinais , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Fatores de Tempo , Resultado do Tratamento
9.
Lasers Surg Med ; 48(1): 14-22, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26581783

RESUMO

BACKGROUND AND OBJECTIVES: Cellulite and lipodystrophy are often found together, especially in areas of the buttocks and thighs, causing skin surface irregularities. Each of these conditions is currently treated independently as two separate surgical procedures. In our practice, we developed a novel combined approach for the simultaneous treatment of cellulite and lipodystrophy, as a single stage procedure in the same anatomic area. For the treatment of cellulite, we used the Nd:YAG laser at a wavelength of 1,440-nm, along with an innovative 1,000-micron directional side-firing fiber optic laser system. For the treatment of lipodystrophy, the Nd:YAG laser with a 1,440 nm wavelength, along with a fiber optic laser system was used. The objective of this study is to determine the efficacy and safety of a combined approach for the simultaneous treatment of cellulite and lipodystrophy. STUDY DESIGN, PATIENTS AND METHODS: In 2012, 16 subjects with noticeable cellulite, Grade II and Grade III, accompanied by mild-to-moderate lipodystrophy of the lower body received single treatments of the Nd:YAG laser at a wavelength of 1,440-nm along with the 1,000-micron side-firing fiber optic laser system for simultaneous treatments of both cellulite and lipodystrophy. Patients were assessed at baseline and 3-6 months post-treatment by a modified Nurnberger-Muller scale utilized to quantify the cellulite severity. Additionally, patient satisfaction and a global aesthetic improvement scale were used to measure the improvement in lipodystrophy. RESULTS: Blinded reviewers identified the correct baseline photographs 97% of the time when presented with a set of photographs. The median modified Nurnberger-Muller scale score at baseline was 4.75 ± 1.2 and the average improvement was 2.0 ± 1.2. Global aesthetic improvement scores ranged from 1 to 3 with an average of 1.58 indicating a much-improved overall appearance. Satisfaction was high for both physicians and patients with scores corresponding to extremely satisfied/satisfied. CONCLUSION: Precise, effective delivery of laser energy to the dermal-adipose tissue, as well as the deep adipose lipodystrophy is feasible as a safe modality for the simultaneous treatment of cellulite and lipodystrophy in the buttocks and thighs, as a single stage procedure.


Assuntos
Celulite/cirurgia , Técnicas Cosméticas , Lasers de Estado Sólido/uso terapêutico , Lipectomia/métodos , Adulto , Nádegas , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coxa da Perna
10.
Kidney Int ; 88(3): 560-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25830760

RESUMO

We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell-dependent allo-specific reactivity was shown by depletion of CD25(+) cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19(+) cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.


Assuntos
Linfócitos B/imunologia , Comunicação Celular , Rejeição de Enxerto/imunologia , Imunidade Humoral , Transplante de Rim/efeitos adversos , Rim/imunologia , Linfócitos T/imunologia , Linfócitos B/metabolismo , Biópsia , Células Cultivadas , Doença Crônica , ELISPOT , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Humanos , Imunofenotipagem , Interferon gama/imunologia , Interferon gama/metabolismo , Testes de Liberação de Interferon-gama , Isoanticorpos/imunologia , Isoanticorpos/metabolismo , Isoantígenos/imunologia , Ativação Linfocitária , Fenótipo , Linfócitos T/metabolismo , Resultado do Tratamento
12.
Oncol Nurs Forum ; 41(3): E194-202, 2014 05.
Artigo em Inglês | MEDLINE | ID: mdl-24769602

RESUMO

PROBLEM IDENTIFICATION: To understand how taste impairment caused by head and neck cancer treatment changes over time or varies with treatment site or type. LITERATURE SEARCH: Ovid MEDLINE® database was searched for reports of health-related quality of life (HRQOL) in head and neck cancer treatment survivors (HNCTS), which included taste function in a HRQOL instrument from 1946-2013. Eligible studies compared taste scores from baseline to post-treatment, using two treatment types or two cancer sites. DATA EVALUATION: 247 reports were identified; 19 were suitable for meta-analysis. DATA ANALYSIS: A series of dichotomous meta-analyses were conducted using comprehensive meta-analysis software .PRESENTATION OF FINDINGS: Taste scores were statistically significantly worse after treatment; the summary effect for the standard measure difference between pretreatment and post-treatment taste scores was 0.353 (p < 0.001). Patients treated with radiation therapy (RT) reported statistically significant worse taste function post-treatment than those who received no RT; the summary effect for the standard mean differences in taste scores was 0.77 (p = 0.001). Differences in tumor site were not significant. IMPLICATIONS FOR NURSING: Taste dysfunction is a long-term complication for HNCTS, and nurses should screen survivors for this sensory dysfunction.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia/efeitos adversos , Sobreviventes , Distúrbios do Paladar/etiologia , Percepção Gustatória/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sobreviventes/psicologia , Distúrbios do Paladar/psicologia
13.
14.
Oncol Nurs Forum ; 40(1): E4-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23269780

RESUMO

PURPOSE/OBJECTIVES: To describe the prevalence of issues with taste function in survivors of head and neck cancer. DESIGN: Exploratory, cross-sectional. SETTING: Outpatients from Saint Louis University Cancer Center in Missouri. SAMPLE: 92 adult head and neck cancer survivors, heterogeneous in cancer site, treatment type, and time post-treatment, ranging from three months to more than 28 years after completion of therapy. METHODS: Taste discrimination was assessed using high, medium, and low concentrations of sweet, salty, sour, and bitter tasting solutions. MAIN RESEARCH VARIABLES: Taste, percentage of weight change, tumor site and stage, treatment type, and time since completion of therapy. FINDINGS: Eighty-five of 92 participants had some measurable taste dysfunction. Confusion between bitter and sour and the inability to discriminate among the different concentrations of the sweet solutions were common. Statistically significant weight loss was associated with dysgeusia. CONCLUSIONS: Taste dysfunction was a persistent problem across all categories of head and neck cancer treatments, sites, and stages. Participants who reported the loss of one or more specific taste modality performed poorly on the taste test. However, participants could not accurately predict which taste was most severely impaired. IMPLICATIONS FOR NURSING: Taste dysfunction is a long-term treatment-related side effect for head and neck cancer survivors. Assessing for taste changes and dysgeusia are important nursing considerations, as taste loss is distressing and associated with decreased appetite. Future studies are needed to identify interventions to help patients better manage and adapt to this long-term complication of cancer therapy. KNOWLEDGE TRANSLATION: Flavors are recognized by taste, texture, aroma, thermal quality, and visual cues. A disruption of one or more of those sensory experiences alters flavor recognition. Having intact taste sense but impaired flavor recognition is possible. Finally, taste is not accurately self-reported because it is commonly confused with flavor recognition.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/enfermagem , Enfermagem Oncológica/métodos , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/enfermagem , Idoso , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/enfermagem , Prevalência , Lesões por Radiação/epidemiologia , Lesões por Radiação/enfermagem , Sobreviventes/estatística & dados numéricos , Percepção Gustatória
15.
Clin J Oncol Nurs ; 16(2): 171-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22459526

RESUMO

Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.


Assuntos
Neoplasias/complicações , Distúrbios do Paladar/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Educação Continuada em Enfermagem , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Valor Nutritivo , Paladar/fisiologia , Distúrbios do Paladar/enfermagem , Língua/anatomia & histologia , Língua/fisiopatologia
16.
FEMS Microbiol Rev ; 36(3): 600-15, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22335190

RESUMO

Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time and pose significant public-health problems. Multidrug-resistant S. enterica serovar Typhi (S. Typhi) and nontyphoidal Salmonella (NTS) are on the increase and are often associated with HIV infection. Chronically infected hosts are often asymptomatic and transmit disease to naïve hosts via fecal shedding of bacteria, thereby serving as a critical reservoir for disease. Salmonella utilizes multiple ways to evade and modulate host innate and adaptive immune responses in order to persist in the presence of a robust immune response. Survival in macrophages and modulation of immune cells migration allow Salmonella to evade various immune responses. The ability of Salmonella to persist depends on a balance between immune responses that lead to the clearance of the pathogen and avoidance of damage to host tissues.


Assuntos
Portador Sadio/imunologia , Portador Sadio/microbiologia , Interações Hospedeiro-Patógeno , Salmonelose Animal/microbiologia , Infecções por Salmonella/microbiologia , Salmonella enterica/imunologia , Salmonella enterica/patogenicidade , Animais , Doenças Assintomáticas , Doença Crônica , Humanos , Evasão da Resposta Imune , Macrófagos/imunologia , Macrófagos/microbiologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/patologia , Salmonelose Animal/imunologia , Salmonelose Animal/patologia
17.
Cell ; 144(5): 675-88, 2011 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-21376231

RESUMO

Toll-like receptors (TLRs) contribute to host resistance to microbial pathogens and can drive the evolution of virulence mechanisms. We have examined the relationship between host resistance and pathogen virulence using mice with a functional allele of the nramp-1 gene and lacking combinations of TLRs. Mice deficient in both TLR2 and TLR4 were highly susceptible to the intracellular bacterial pathogen Salmonella typhimurium, consistent with reduced innate immune function. However, mice lacking additional TLRs involved in S. typhimurium recognition were less susceptible to infection. In these TLR-deficient cells, bacteria failed to upregulate Salmonella pathogenicity island 2 (SPI-2) genes and did not form a replicative compartment. We demonstrate that TLR signaling enhances the rate of acidification of the Salmonella-containing phagosome, and inhibition of this acidification prevents SPI-2 induction. Our results indicate that S. typhimurium requires cues from the innate immune system to regulate virulence genes necessary for intracellular survival, growth, and systemic infection.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Inata , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Transdução de Sinais , Receptores Toll-Like/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Receptores Toll-Like/imunologia
18.
PLoS Pathog ; 5(11): e1000671, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19956712

RESUMO

Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time despite the presence of a robust immune response. Chronically infected hosts are asymptomatic and transmit disease to naïve hosts via fecal shedding of bacteria, thereby serving as a critical reservoir for disease. We show that the bacterial effector protein SseI (also called SrfH), which is translocated into host cells by the Salmonella Pathogenicity Island 2 (SPI2) type III secretion system (T3SS), is required for Salmonella typhimurium to maintain a long-term chronic systemic infection in mice. SseI inhibits normal cell migration of primary macrophages and dendritic cells (DC) in vitro, and such inhibition requires the host factor IQ motif containing GTPase activating protein 1 (IQGAP1), an important regulator of cell migration. SseI binds directly to IQGAP1 and co-localizes with this factor at the cell periphery. The C-terminal domain of SseI is similar to PMT/ToxA, a bacterial toxin that contains a cysteine residue (C1165) that is critical for activity. Mutation of the corresponding residue in SseI (C178A) eliminates SseI function in vitro and in vivo, but not binding to IQGAP1. In addition, infection with wild-type (WT) S. typhimurium suppressed DC migration to the spleen in vivo in an SseI-dependent manner. Correspondingly, examination of spleens from mice infected with WT S. typhimurium revealed fewer DC and CD4(+) T lymphocytes compared to mice infected with Delta sseI S. typhimurium. Taken together, our results demonstrate that SseI inhibits normal host cell migration, which ultimately counteracts the ability of the host to clear systemic bacteria.


Assuntos
Proteínas de Bactérias/fisiologia , Movimento Celular , Interações Hospedeiro-Patógeno , Proteínas de Membrana/fisiologia , Infecções por Salmonella/etiologia , Salmonella enterica/patogenicidade , Animais , Células Dendríticas/microbiologia , Células Dendríticas/fisiologia , Macrófagos/microbiologia , Macrófagos/fisiologia , Camundongos , Baço/imunologia , Fatores de Tempo
19.
Vaccine ; 24(21): 4630-9, 2006 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-16157426

RESUMO

Although the recent clinical trial of the ABeta42 peptide vaccine against Alzheimer's Disease (AD) has been halted due to adverse events, the apparent clinical utility of this approach underscores the need to further improve the safety of the vaccine, as well as to understand the potential immunological basis for complications. In this study, we examine both humoral and cellular immune responses elicited by immunization with peptide or DNA encoding wild-type and the Flemish and Dutch mutations of ABeta42 (i.e. the beta amyloid peptide spanning amino acids 1-42) in mice of different immune haplotypes as well as HLA Class II transgenic mice. The Flemish and Dutch mutations have been associated with cerebrovascular hemorrhages in affected individuals. These data allow determination of potential immunological responses that could mediate pathology observed with mutant forms of amyloid beta, as well as lead to the generation of safer vaccine preparations. Following peptide or plasmid immunization, antibody responses were measured against the different ABeta42 peptides in an ELISA assay, while T cell epitopes were analyzed through interferon gamma ELISPOT and lymphocyte proliferation assays. B cell mapping studies indicated that sera from all of the haplotype mice vaccinated with any of the ABeta42 peptides reacted specifically to the first 10 amino acids of ABeta42 with the ABeta42 mutants eliciting higher immune responses. ELISPOT analysis, which accessed cellular immune responses indicated that mice expressed differences in Class I epitopes dependent on the different immune haplotypes. These results may have implications for the design of future ABeta42 based vaccines against Alzheimer's Disease.


Assuntos
Peptídeos beta-Amiloides/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe II/imunologia , Peptídeos/administração & dosagem , Plasmídeos , Sequência de Aminoácidos , Animais , Formação de Anticorpos , Linfócitos T CD8-Positivos/citologia , Clonagem Molecular , DNA/administração & dosagem , DNA/genética , Ensaio de Imunoadsorção Enzimática , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
20.
Cancer Res ; 65(14): 6097-104, 2005 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16024610

RESUMO

When nitric oxide (NO) is produced at micromolar concentrations, as during inflammation, exposure to surrounding cells is potentially cytotoxic. The NO-dependent signaling pathways that initiate cell death are thought to involve the tumor suppressor protein p53, but the degree to which this factor contributes to NO-induced cell death is less clear. Various reports either confirm or negate a role for p53 depending on the cell type and NO donor used. In this study, we have used several pairs of cell lines whose only differences are the presence or absence of p53, and we have treated these cell lines with the same NO donor, spermineNONOate (SPER/NO). Treatment with SPER/NO induced such apoptotic markers as DNA fragmentation, nuclear condensation, poly(ADP-ribose) polymerase cleavage, cytochrome c release, and Annexin V staining. p53 was required for at least 50% of SPER/NO-induced apoptotic cell death in human lymphoblastoid cells and for almost all in primary and E1A-tranformed mouse embryonic fibroblasts, which highlights the possible importance of DNA damage for apoptotic signaling in fibroblasts. In contrast, p53 did not play a significant role in NO-induced necrosis. NO treatment also induced the phosphorylation of p53 at Ser15; pretreatment with phosphoinositide-3 kinase (PI3K) family inhibitors, wortmannin, LY294002, and caffeine, blocked such phosphorylation, but the p38 mitogen-activated protein kinase inhibitor, SB203580, did not. Pretreatment with the PI3K family inhibitors also led to a switch from NO-induced apoptosis to necrosis, which implicates a PI3K-related kinase such as ataxia telangiectasia mutated (ATM) or ATR (ATM and Rad3 related) in p53-dependent NO-induced apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Fibroblastos/citologia , Linfócitos/citologia , Óxido Nítrico/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Humanos , Imidazóis/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfócitos/fisiologia , Camundongos , Necrose , Doadores de Óxido Nítrico/farmacologia , Óxidos de Nitrogênio , Fosforilação , Piridinas/farmacologia , Espermina/análogos & derivados , Espermina/farmacologia , Transcrição Gênica , Proteína Supressora de Tumor p53/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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