Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study.

Background: Atrophied T2-lesion volume (aT2-LV) is an exploratory imaging marker in multiple sclerosis (MS) reflecting the volume of lesions subsumed into cerebrospinal fluid (CSF).

Objective: To investigate the effect of ocrelizumab (OCR) versus placebo (PBO) over 120 weeks on the accumulation of aT2-LV in a double-blind placebo-controlled (DBP) phase 3, primary-progressive (PP) MS study (ORATORIO; NCT01194570).

Methods: This post-hoc, MRI-blinded analysis evaluated 732 PPMS randomised to OCR (488) or PBO (244).

Site-directed mutagenesis of large DNA palindromes: construction and in vitro characterization of herpes simplex virus type 1 mutants containing point mutations that eliminate the oriL or oriS initiation function.

Technical challenges associated with mutagenesis of the large oriL palindrome have hindered comparisons of the functional roles of the herpes simplex virus type 1 (HSV-1) origins of DNA replication, oriL and oriS, in viral replication and pathogenesis. To address this problem, we have developed a novel PCR-based strategy to introduce site-specific mutations into oriL and other large palindromes. Using this strategy, we generated three plasmids containing mutant forms of oriL, i.

Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit.

Naive peripheral B cells are maintained in sufficient numbers and diversity to mount effective immune responses against infectious agents. However, the size and repertoire of this B cell pool is constantly diminished by normal cell turnover and Ag activation. Homeostatic (Ag-independent) proliferation in response to B cell depletion is one mechanism to compensate for this cell loss.