STAT1-dependent IgG cell-surface expression in a human B cell line derived from a STAT1-deficient patient.

STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expression. Analysis of this point is difficult in humans, as STAT1 deficiency is extremely rare. SD patients die early in childhood from a severe immunodeficiency. Herein, a SD B cell line obtained from a SD patient was compared with a B cell line from a STAT1-proficient subject in search of differences in surface Ig expression. In this SD B cell line, a complete absence of surface IgG was noted. The mRNA encoding the surface form of IgG was detected only in STAT1-proficient B cells; the mRNAs encoding the secreted and the surface forms were detected in SD and STAT1-proficient B cells. Re-expression of STAT1 in SD B cells restored surface IgG expression and a functional BCR. Conversely, shRNA silencing of STAT1 in B cells reduced considerably the expression of the surface IgG. Although limited to one B cell line, these results suggest that STAT1 may play an essential role in surface IgG expression in human B cells. Possible mechanisms involve regulation of mRNA splicing, transcription, or both. These observations extend the role of STAT1 further in adaptive immunity, including the regulation of BCR expression

The development of a scale of the Guttman Type for the assessment of mobility disability in multiple sclerosis

Objective: The aim of the study was to develop a valid and reliable unidimensional scale of the Guttman type for the assessment of mobility disability in multiple sclerosis (MS). Subjects: Sixty-eight subjects with a definite diagnosis of MS participated.They were attending as outpatients at a MS unit at a District General Hospital. Thirty had the primary progressive pattern of disease, and 38 had the relapsing-remitting pattern. Methods: Formal assessments used for neurological disability were inspected, and 14 test items of gross motor function were extracted and ordered according to two criteria. These were that actions progressed from lying, to sitting, to standing and walking tasks, and that they progressed from broader to narrower bases of support. All subjects carried out all test items which were scored as ‘pass’ or ‘fail’. Analysis: Data were tested for internal consistency, reliability, inter item correlation, reproducibility and scalability. On the basis of the results, the items were re-ordered in rank, and reduced to eleven tests. The eleven item scale was re-analysed. Results: Results showed that the scale had an internal consistency of 0.88 (alpha coefficient) and a coefficient of reproducibility (CR) of 0.95 and above for both MS subject groups. The coefficient of scalability (CS) for items was 0.78 for primary progressive subjects and 0.74 for the relapsing-remitting group. Reliability ranged from good (kappa = 0.49) for one item, to perfect for six items. Conclusion: The scale was demonstrated to be a hierarchical scale of the Guttman type exhibiting homogeneous unidimensionality and good reliability. The high CR indicated that scores may be summed, and the very acceptable levels of CS indicated that the cumulative scores are meaningful within the defined concept of hierarchy used in this study

Pacemaker implantation after sutureless or stented valve: results from a controlled randomized trial

OBJECTIVES: Sutureless aortic valves demonstrated non-inferiority to standard stented valves for major cardiovascular and cerebral events at 1 year after aortic valve replacement. We aim to assess the factors correlating with permanent pacemaker implantation (PPI) in both cohorts.METHODS: PERSIST-AVR is a prospective, randomized, open-label trial. Patients undergoing aortic valve replacement were randomized to receive a sutureless aortic valve replacement (Su-AVR) or stented sutured bioprosthesis (SAVR). Multivariable analysis was performed to identify possible independent risk factors associated with PPI. A logistic regression analysis was performed to estimate the risk of PPI associated to different valve size.RESULTS: The 2 groups (Su-AVR; n = 450, SAVR n = 446) were well balanced in terms of preoperative risk factors. Early PPI rates were 10.4% in the Su-AVR group and 3.1% in the SAVR. PPI prevalence correlated with valve size XL (P = 0.0119) and preoperative conduction disturbances (P = 0.0079) in the Su-AVR group. No predictors were found in the SAVR cohort. Logistic regression analysis showed a significantly higher risk for PPI with size XL compared to each individual sutureless valve sizes [odds ratio (OR) 0.272 vs size S (95%confidence interval 0.07-0.95), 0.334 vs size M (95% CI 0,16-0; 68), 0.408 vs size L (95% CI 0,21-0.81)] but equivalent risk of PPI rates for all other combination of valve sizes.CONCLUSIONS: Su-AVR is associated with higher PPI rate as compared to SAVR. However, the increased PPI rate appears to be size-dependent with significant higher rate only for size XL. The combination of preoperative conduction disorder and a size XL can lead to a higher probability of early PPI in Su-AVR