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Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key mediator in the development of these characteristic lesions, but the molecular mechanisms underlying the pulmonary vascular lesions are largely unknown. We employed a rat model of how-associated PAH, which induced specific pulmonary neointimal lesions. We identified gene expression profiles in rats specifically related to the addition of increased pulmonary blood flow to monocrotaline and the associated occurrence of neointimal lesions. Increased pulmonary blood flow induced the expression of the transcription factors activating transcription factor-3 (ATF3) and early growth response factor-i (EGR-l), for which presence was confirmed in neointimal lesions. Monocrotaline alone induced increased numbers of activated mast cells and their products. We further identified molecular pathways that may be involved in treatment with the prostacyclin analog iloprost, a vasoactive compound with clinically beneficial effects in patients with PAH, which were similar to pathways described in samples from patient studies. These pathways, associated with the development of angioproliferative lesions as well as with the response to therapy in PAH, may provide new therapeutic targets. [ABSTRACT FROM AUTHOR]

Delayed and weak virus neutralizing antibody (nAb) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. Using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. Swapping the glycoproteins (GPs) of lymphocytic choriomeningitis virus (LCMV, naturally persisting, noncytolytic, inefficient nAb inducer) and vesicular stomatitis virus (VSV, nonpersisting, cytolytic, potent nAb inducer) transferred the only target of nAb's from either virus to the other. We analyzed the nAb response to each of the 2 recombinant and parent viruses in infected mice and found that nAb kinetics were solely determined by the viral surface GP and not by the virus backbone. Moreover, the slowly and poorly nAb-triggering LCMV virion was a potent immunogenic matrix for the more antigenic VSV-GP. These findings indicate that the viral GP determines nAb kinetics largely independently of the specific viral infection context. They further suggest that structural features of viral GPs or coevolutionary adaptation of the virus's GP to the host's naive B cell repertoire, or both, may critically limit nAb kinetics and improvement of vaccine efficacy. [ABSTRACT FROM AUTHOR]

Recurrent herpes simplex virus (HSV) encephalitis is a rare disorder with only a few cases reported. We report a case of HSV encephalitis with documented recurrence in the same anatomic location, lending support to the theory of reactivation as the mechanism of disease.