Defective selection of thymic regulatory T cells accompanies autoimmunity and pulmonary infiltrates in Tcra-deficient mice double transgenic for human La/Sjögren's syndrome-B and human La-specific TCR.

A human La/Sjögren's syndrome-B (hLa)-specific TCR/hLa neo-self-Ag double-transgenic (Tg) mouse model was developed and used to investigate cellular tolerance and autoimmunity to the ubiquitous RNA-binding La Ag often targeted in systemic lupus erythematosus and Sjögren's syndrome. Extensive thymic clonal deletion of CD4(+) T cells occurred in H-2(k/k) double-Tg mice presenting high levels of the I-E(k)-restricted hLa T cell epitope. In contrast, deletion was less extensive in H-2(k/b) double-Tg mice presenting lower levels of the epitope, and some surviving thymocytes were positively selected as thymic regulatory T cells (tTreg). These mice remained serologically tolerant to hLa and healthy. H-2(k/b) double-Tg mice deficient of all endogenous Tcra genes, a deficiency known to impair Treg development and function, produced IgG anti-hLa autoantibodies and displayed defective tTreg development. These autoimmune mice had interstitial lung disease characterized by lymphocytic aggregates containing Tg T cells with an activated, effector memory phenotype. Salivary gland infiltrates were notably absent. Thus, expression of nuclear hLa Ag induces thymic clonal deletion and tTreg selection, and lymphocytic infiltration of the lung is a consequence of La-specific CD4(+) T cell autoimmunity.

Toll-like receptor 7 (TLR7) modulates anti-nucleosomal autoantibody isotype and renal complement deposition in mice exposed to syngeneic late apoptotic cells.

OBJECTIVES: The objectives of this study were to determine whether late apoptotic cell material directly induces autoantibodies characteristic of systemic lupus erythematosus (SLE) and to investigate the innate recognition pathways involved. METHODS: B6, B6.MyD88(-/-), B6.TLR7(-/-) and B6.TLR9(-/-) mice were subcutaneously injected with B6 syngeneic late apoptotic thymocytes (SLATs) without adjuvant on days 0, 10, 24 and 37. Sera were tested for IgG antibodies to histones and double-stranded DNA (dsDNA) by ELISA and Crithidia luciliae indirect immunofluorescence. IgG and C3 deposition in kidney glomeruli was assessed by immunostaining and fluorescence microscopy. RESULTS: SLAT injections induced anti-dsDNA and anti-histone antibodies of the IgG1 and IgG2b isotypes in B6 but not MyD88(-/-) mice. TLR7(-/-) and TLR9(-/-) mice injected with SLATs produced delayed or slightly more robust responses, respectively. SLAT injections induced IgG deposits in renal glomeruli of B6, TLR7(-/-) and TLR9(-/-) mice that were absent in MyD88(-/-) mice. Unlike B6 and TLR9(-/-) animals, TLR7(-/-) mice failed to exhibit IgG colocalised glomerular C3 deposits and demonstrated autoantibodies of primarily the IgG2a isotype. CONCLUSIONS: Late apoptotic cell-induced anti-histone and anti-dsDNA antibodies require MyD88 but not Toll-like receptor (TLR)9. Moreover, TLR7 promotes glomerular C3 deposition, possibly through a mechanism of altered antibody isotype switching.

Telemonitoring of heart failure patients and their caregivers: a pilot randomized controlled trial.

Heart failure (HF) is the leading cause of rehospitalization in older adults. The purpose of this pilot study was to examine whether telemonitoring by an advanced practice nurse reduced subsequent hospital readmissions, emergency department visits, costs, and risk of hospital readmission for patients with HF. One hundred two patient/caregiver dyads were randomized into 2 groups postdischarge; 84 dyads completed the study. Hospital readmissions, emergency department visits, costs, and days to readmission were abstracted from medical records. Participants were interviewed soon after discharge and 3 months later about effects of telemonitoring on depressive symptoms, quality of life, and caregiver mastery. There were no significant differences due to telemonitoring for any outcomes. Caregiver mastery, informal social support, and electronic home monitoring were not significant predictors for risk of hospital readmission. Further studies should address the interaction between the advanced practice nurse and follow-up intervention with telemonitoring of patients with HF to better target those who are most likely to benefit.

Reglamentación de la Ley 1178 en cuanto al uso y redistribución de bienes y servicios

Menciona que en la administración pública boliviana no existe una normativa eficaz, eficiente y económica que norme la disposición de los bienes y obras usados o en desuso que reportan las instituciones públicas

T cell epitopes of the La/SSB autoantigen in humanized transgenic mice expressing the HLA class II haplotype DRB1*0301/DQB1*0201.

OBJECTIVE: T cells are implicated in the production of anti-La/SSB and anti-Ro/SSA autoantibodies commonly associated with the DR3/DQ2 haplotype in systemic lupus erythematosus and Sjögren's syndrome. This study was undertaken to investigate the DR3/DQ2-restricted T cell response to wild-type human La (hLa) and a truncated form of mutant La. METHODS: Humanized transgenic mice expressing HLA-DRB1*0301/DQB1*0201 (DR3/DQ2) were immunized with recombinant antigen and examined for development of autoantibodies and T cell proliferation against overlapping peptides spanning the La autoantigen. HLA restriction and peptide binding of identified T cell epitopes to DR3 or DQ2 were determined using blocking monoclonal antibodies and a direct binding assay. RESULTS: DR3/DQ2-transgenic mice generated an unusually rapid class-switched humoral response to hLa with characteristic spreading to Ro 52 and Ro 60 proteins following hLa protein immunization. Seven T cell determinants in hLa were restricted to the HLA-DR3/DQ2 haplotype. Six epitopes tested were restricted to HLA-DR and bound DR3 with semiconserved DR3 binding motifs. No DQ restriction of these epitopes was demonstrable despite efficient DQ binding activity in some cases. No neo-T cell epitopes were identified in mutant La; however, T cells primed with mutant La exhibited a striking increase in proliferation to the epitope hLa(151-168) compared with T cells primed with hLa. CONCLUSION: Multiple DR3-restricted epitopes of hLa have been identified. These findings suggest that truncation of La produced by somatic mutation or possibly granzyme B-mediated cleavage alters the immunodominance hierarchy of T cell responsiveness to hLa and may be a factor in the initiation or maintenance of anti-La autoimmunity.

The relationship of medication regimen to hospital readmissions for older adults with heart failure.

The purpose of this part of a longitudinal study was to examine whether medication therapy for older adults with heart failure predicted days to readmission post-hospital discharge. Using a prospective, predictive design, a convenience sample included 127 older adults with heart failure who had been recently discharged from two hospitals in northeastern Ohio. One hundred five patients were prescribed diuretics, 49 angiotensin-converting enzyme inhibitors, 23 b blockers, and 47 digoxin. There were no significant differences between readmitted and non-readmitted patients with regard to the use of the specific classes of cardiac medications. None of the specific classes of cardiac medications predicted the number of days between the initial hospital discharge and readmission 3 months later. The use of a small, non-probability sample and exclusion of variables limit the results of the study. Effective case management with teaching about heart failure must address changes involved with heart failure and the use of medication therapy. More research is needed about treatment protocols in various regions of the United States.

Measurement of cardiac functioning in older adults with heart failure after exercise.

Although the length of a hospital stay is very limited for patients with heart failure, many patients attempt to resume some activities of daily living soon after arrival at home. Home care nurses routinely assess symptoms indicative of recurrent heart failure and the need for hospital readmission. The purpose of this comparative study was to determine whether there was a significant difference in diastolic blood pressure and oxygen saturation after walking for 6 min. Twenty adults with heart failure in an outpatient cardiology clinic were evaluated after the 6-min walk test. Although diastolic blood pressure and oxygen saturation were not significantly different after walking for 6 min, functional status was significantly related to oxygen saturation. Further study with home care clients is needed to evaluate the relation between activity and oxygen saturation.

Identification of factors predictive of hospital readmissions for patients with heart failure.

OBJECTIVE: The objective was to evaluate whether severity of cardiac illness, cognitive functioning, and functional health of older adults with heart failure (HF) and psychosocial factors related to caregiving are predictive of hospital readmissions for those with HF. DESIGN: A prospective, descriptive, predictive design was used. SETTING: The study took place in 2 community hospitals in northeastern Ohio. SAMPLE: Originally 156 patient-caregiver dyads were interviewed within 7 to 10 days of hospital discharge, but only 128 dyads completed the study. Subjects had HF and their mean age was 77.3 years. Their caregivers were mostly women with a mean age of 64.8 years. RESULTS: Fourty-four percent of the patients were readmitted to the hospital within 3 months. Among patients, severity of illness was moderate, blood pressure was within normal limits, functional and cognitive status were high. For patients, the interaction of severity of cardiac illness and functional status predicted risk of hospital readmission. Among caregivers, depressive symptoms and perceived stress were low; informal social support and caregiving appraisal were high. The interaction of caregiver stress and depression were significant predictors of risk of hospital readmission. CONCLUSION: Nurses should consistently assess changes in patients' cardiac symptoms in addition to their ability to provide self-care. Since patients with HF are at high risk for readmission, further study is needed to determine whether interventions designed to increase spousal support would decrease hospital readmissions.

An examination of perceived stress in family caregivers of older adults with heart failure.

This investigation evaluates the moderating influence of social support on the negative effects of stress for family caregivers and validates the Perceived Stress Scale as a standard of measurement. Seventy-five family caregivers to older adults with heart failure were interviewed in their homes about perceived stress, depressive symptoms, and social support after hospital discharge. The Perceived Stress Scale demonstrated internal consistency. Social support did not moderate the effects of stress on depressive symptoms. Lack of a significant association between salivary cortisol and the Perceived Stress Scale did not support testing of construct validity. Stress levels, however, frequently vary due to caregiving demands and additional influencing factors.