Clinicaltrials.gov registry number: NCT00296829.

The mechanism of anterograde transport of herpes simplex virus was studied in cultured dissociated human and rat dorsal root ganglion neurons. The neurons were infected with HSV-1 to examine the distribution of capsid (VP5), tegument (VP16), and glycoproteins (gC and gB) at 2, 6, 10, 13, 17, and 24 h postinfection (p.i.) with or without nocodazole (a microtubule depolymerizer) or brefeldin A (a Golgi inhibitor). Retrogradely transported VP5 was detected in the cytoplasm of the cell body up to the nuclear membrane at 2 h p.i. It was first detected de novo in the nucleus and cytoplasm at 10 h p.i., the axon hillock at 13 h p.i., and the axon at 15 to 17 h p.i. gC and gB were first detected de novo in the cytoplasm and the axon hillock at 10 h p.i. and then in the axon at 13 h p.i., which was always earlier than the detection of VP5. De novo-synthesized VP16 was first detected in the cytoplasm at 10 to 13 h p.i. and in the axon at 16 to 17 h p.i. Nocodazole inhibited the transport of all antigens, VP5, VP16, and gC or gB. The kinetics of inhibition of VP5 and gC could be dissociated. Brefeldin A inhibited the transport of gC or gB and VP16 but not VP5 into axons. Transmission immunoelectron microscopy confirmed that there were unenveloped nucleocapsids in the axon with or without brefeldin A. These findings demonstrate that glycoproteins and capsids, associated with tegument proteins, are transported by different pathways with slightly differing kinetics from the nucleus to the axon. Furthermore, axonal anterograde transport of the nucleocapsid can proceed despite the loss of most VP16.HSV-1 enters the human body via the mucosa or skin and then the termini of neurons within the epidermis and is retrogradely transported to the cell bodies of neurons in the DRG, where it becomes latent. Reactivation of HSV-1 from latency during a patient's lifetime is very frequent, resulting in symptomatic disease or, more commonly, unrecognized lesions and asymptomatic shedding (10, 43). Latency and other stages of the viral infection cycle have been well studied in experimental animals in vivo. Retrograde transport of HSV in rat DRG neurons was demonstrated to be microtubule associated, and virions travel as unenveloped nucleocapsids (19,23). However, the events following reactivation have not been well characterized. The development of a model of interaction between the outgrowing axons of human fetal DRG and epidermal explants in separate chambers of a two-chamber in vitro system in our laboratory allowed studies of the transport of HSV-1 from the cell bodies of DRG neurons along the principal axon to epidermal cells (17,31,32). The rate of anterograde transport of nucleocapsids and glycoproteins was estimated by immunofluorescence and confocal microscopy at 0.6 mm per s, consistent with rapid microtubule-associated transport (28). TEM of cross sections of axons behind the advancing front of viral antigen showed that only unenveloped nucleocapsids adjacent to microtubules were present. Recent studies using scanning immunoelectro...

Corynebacteria were isolated from breast tissue, pus, or deep wound swabs of 24 women; the most common species isolated was the newly described Corynebacterium kroppenstedtii, followed by Corynebacterium amycolatum and Corynebacterium tuberculostearicum. Gram-positive bacilli were seen in samples sent for culture or in histological specimens for 12 women, and 9 of the 12 women from whom adequate histological specimens were obtained had conditions that met the criteria for granulomatous lobular mastitis, a chronic inflammatory disease of unknown etiology.

Little is known about the mechanisms of transport of neurotropic herpesviruses, such as herpes simplex virus (HSV), varicella-zoster virus, and pseudorabies virus, within neurons. For these viruses, which replicate in the nucleus, anterograde transport from the cell body of dorsal root ganglion (DRG) neurons to the axon terminus occurs over long distances. In the case of HSV, unenveloped nucleocapsids in human DRG neurons cocultured with autologous skin were observed by immunoelectron microscopy to colocalize with conventional ubiquitous kinesin, a microtubule-dependent motor protein, in the cell body and axon during anterograde axonal transport. Subsequently, four candidate kinesin-binding structural HSV proteins were identified (VP5, VP16, VP22, and US11) using oligohistidine-tagged human ubiquitous kinesin heavy chain (uKHC) as bait. Of these viral proteins, a direct interaction between uKHC and US11 was identified. In vitro studies identified residues 867 to 894 as the US11-binding site in uKHC located within the proposed heptad repeat cargo-binding domain of uKHC. In addition, the uKHC-binding site in US11 maps to the C-terminal RNA-binding domain. US11 is consistently cotransported with kinetics similar to those of the capsid protein VP5 into the axons of dissociated rat neurons, unlike the other tegument proteins VP16 and VP22. These observations suggest a major role for the uKHC-US11 interaction in anterograde transport of unenveloped HSV nucleocapsids in axons.

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High-intensity interval training (HIIT) is recognized as a potent stimulus for improving cardiorespiratory fitness (volume of oxygen consumption [VO 2 ] peak) in patients with coronary artery disease (CAD). However, the feasibility, safety, and long-term effects of HIIT in this population are unclear. OBJECTIVE To compare HIIT with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and efficacy of improving VO 2 peak in patients with CAD. DESIGN, SETTING, AND PARTICIPANTS In this single-center randomized clinical trial, participants underwent 4 weeks of supervised training in a private hospital cardiac rehabilitation program, with subsequent home-based training and follow-up over 12 months.A total of 96 participants with angiographically proven CAD aged 18 to 80 years were enrolled, and 93 participants were medically cleared for participation following a cardiopulmonary exercise test.

Australian and New Zealand Clinical Trials Registry (ACTRN12612001178831).