This is a report of a case of bidirectional tachycardia in a 6-year-old girl with no evidence of any structural abnormality of the heart. The patient had never received digitalis. The arrhythmia appeared to be precipitated by effort and emotional stress, and could be induced by increasing the heart rate by atrial pacing or isoprenaline administration. His bundle electrography showed that the arrhythmia was ventricular in origin. This emphasizes the importance of recording an effort electrocardiogram in all children with unexplained syncopal episodes, even when the resting electrocardiogram is normal.

We report on the ability of single-chain variable fragment (scFv) incorporated into the viral envelope to alter the tropism of herpes simplex virus (HSV) 1716. Using recombinant viruses expressing fusion proteins comprising cellsurface antigen-specific scFvs N terminus linked to amino acids 274-393 of gD, we demonstrated that the tropism of these HSV1716 variants was modified such that infection was mediated by the cognate antigen. Thus, an HSV1716 variant that expressed an anti-CD55 scFv targeting moiety linked to these gD residues was able to infect non-permissive Chinese hamster ovary cells expressing CD55 and this infection was specifically blocked by an anti-CD55 monoclonal antibody. Similarly, the infection efficiency of an HSV1716 variant for semi-permissive human leukaemic, CD38-positive cell lines was greatly improved by an anti-CD38 scFv targeting moiety linked to gD residues 274-393, and this enhanced infectivity was abrogated specifically by an anti-CD38 monoclonal antibody. Finally, intravenous/ intraperitoneal injection of an HSV1716 variant displaying an anti-epidermal growth factor receptor (EGFR) scFv linked to residues 274-393 of gD enhanced destruction of subcutaneous EGFR-positive tumours in nude mice compared to unmodified HSV1716. Therefore, targeting of HSV1716 oncolysis to specific cell types through the display of entry mediating scFv/gD fusion proteins represents an efficient route for systemic delivery.

High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro. Further, pharmacologic inhibition or genetic knock-down of HMGB1 reveals a role for HMGB1 in viral restriction, the ability to modulate bystander cell proliferation, and drug sensitivity in 3T6 cells. These data further support the multifactorial role of HMGB1, and suggest it could be a target for modulating the efficacy of oncolytic virus therapies alone or in combination with other frontline cancer treatments.

No abstract

No abstract