Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons.

Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.

The role of electron microscopy in the diagnosis of pleomorphic sarcomas of soft tissue.

Classification of pleomorphic malignancies is frequently problematic and important with regard to treatment. Their histologic differential diagnosis is extremely wide, including sarcomatoid carcinoma, melanoma, anaplastic lymphoma, and a large number of sarcomas with overlapping light microscopic appearances. Not infrequently, immunohistochemical investigations of such tumors yield conflicting or confusing results. In such cases, electron microscopy remains an invaluable investigative and diagnostic adjunct, revealing certain subcellular features that indicate a specific line of differentiation. Combining ultrastructural and immunohistochemical studies is particularly useful in these tumors. This article focuses on the ultrastructural aspects of certain sarcomas that are predominantly pleomorphic, including high-grade fibrosarcoma, myxofibrosarcoma-malignant fibrous histiocytoma, acral myxoinflammatory fibroblastic sarcoma, pleomorphic liposarcoma, pleomorphic leiomyosarcoma, and pleomorphic rhabdomyosarcoma, as well as certain sarcomas that are occasionally quite pleomorphic, including angiosarcoma, malignant granular cell tumor, alveolar soft part sarcoma, and extraskeletal osteosarcoma. We also briefly comment on the common simulators of pleomorphic sarcomas, including melanoma, carcinoma, and lymphoma.