Semen-derived enhancer of viral infection (SEVI) binds bacteria, enhances bacterial phagocytosis by macrophages, and can protect against vaginal infection by a sexually transmitted bacterial pathogen.

The semen-derived enhancer of viral infection (SEVI) is a positively charged amyloid fibril that is derived from a self-assembling proteolytic cleavage fragment of prostatic acid phosphatase (PAP(248-286)). SEVI efficiently facilitates HIV-1 infection in vitro, but its normal physiologic function remains unknown. In light of the fact that other amyloidogenic peptides have been shown to possess direct antibacterial activity, we investigated whether SEVI could inhibit bacterial growth. Neither SEVI fibrils nor the unassembled PAP(248-286) peptide had significant direct antibacterial activity in vitro. However, SEVI fibrils bound to both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Neisseria gonorrhoeae) bacteria, in a charge-dependent fashion. Furthermore, SEVI fibrils but not the monomeric PAP(248-286) peptide promoted bacterial aggregation and enhanced the phagocytosis of bacteria by primary human macrophages. SEVI also enhanced binding of bacteria to macrophages and the subsequent release of bacterially induced proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-1ß). Finally, SEVI fibrils inhibited murine vaginal colonization with Neisseria gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity and that this activity is dependent on both the cationic charge and the fibrillar nature of SEVI.

Diagnostic Performance of Pulmonary Embolism Imaging in Patients with History of Asthma.

Asthma and pulmonary embolism (PE) can present with overlapping symptoms, and distinguishing between these 2 conditions can be challenging. Asthma may limit imaging for PE because of either worsened ventilation defects on ventilation-perfusion scanning (VQ) or increased motion artifacts on CT pulmonary angiography (CTPA). Methods: We identified adults evaluated for PE with VQ or CTPA from 2012 to 2016. Patients with chronic lung disease (other than asthma) were excluded. Studies were classified as negative, positive, or nondiagnostic. Follow-up of negative cases was reviewed to determine the rate of repeat exams (within 1 wk) and the false-negative rate (defined as diagnosis of venous thromboembolism within 90 d). Results: We reviewed 19,412 adults (aged 52 ± 18 y, 70% women) evaluated for PE (60% with VQ, 40% with CTPA); 23% had a history of asthma. Nondiagnostic results were comparable for those with and without asthma for both VQ (asthma, 3.3%; nonasthma, 3.8%; P = 0.223) and CTPA (asthma, 1.6%; nonasthma, 1.5%; P = 0.891). A history of asthma was not associated with a higher rate of repeat exams after negative imaging for VQ (asthma, 1.9%; nonasthma, 2.1%; P = 0.547) or CTPA (asthma, 0.6%; nonasthma, 0.6%; P = 0.796), nor was a history of asthma associated with a higher false-negative rate for VQ (asthma, 0.4%; nonasthma, 0.9%; P = 0.015) or CTPA (asthma, 1.9%; nonasthma 1.5%; P = 0.347). Conclusion: A history of asthma in the preceding 10 y was not associated with impaired diagnostic performance of PE imaging for either VQ or CTPA.

Intracranial metastasis from prostate adenocarcinoma: a case report and literature review.

Intracranial metastasis from prostate adenocarcinoma is rare. A 70-year-old African American male with a history of prostate adenocarcinoma for the last 14 years, presented to our hospital complaining of generalized weakness for the past 2 weeks. He was found to have fever with left ptosis and mild eyelid edema. Brain MRI showed dural metastasis. Two months after the first presentation, he was readmitted with a suspected acute cerebral vascular accident (CVA). CT brain showed vasogenic edema in the right subcortical, likely from intracranial metastasis. His acute neurological symptoms improved with intravenous dexamethasone. This case highlights the possibility of intracranial metastasis from prostate adenocarcinoma. With the advent of novel therapies for prostate cancer, which prolong life expectancy, intracranial metastasis from prostate adenocarcinoma may become an increasingly frequent clinical scenario.

Adenoviral vector driven by a minimal Rad51 promoter is selective for p53-deficient tumor cells.

BACKGROUND: The full length Rad51 promoter is highly active in cancer cells but not in normal cells. We therefore set out to assess whether we could confer this tumor-selectivity to an adenovirus vector. METHODOLOGY/PRINCIPAL FINDINGS: Expression of an adenovirally-vectored luciferase reporter gene from the Rad51 promoter was up to 50 fold higher in cancer cells than in normal cells. Further evaluations of a panel of truncated promoter mutants identified a 447 bp minimal core promoter element that retained the full tumor selectivity and transcriptional activity of the original promoter, in the context of an adenovirus vector. This core Rad51 promoter was highly active in cancer cells that lack functional p53, but less active in normal cells and in cancer cell lines with intact p53 function. Exogenous expression of p53 in a p53 null cell line strongly suppressed activity of the Rad51 core promoter, underscoring the selectivity of this promoter for p53-deficient cells. Follow-up experiments showed that the p53-dependent suppression of the Rad51 core promoter was mediated via an indirect, p300 coactivator dependent mechanism. Finally, transduction of target cells with an adenovirus vector encoding the thymidine kinase gene under transcriptional control of the Rad51 core promoter resulted in efficient killing of p53 defective cancer cells, but not of normal cells, upon addition of ganciclovir. CONCLUSIONS/SIGNIFICANCE: Overall, these experiments demonstrated that a small core domain of the Rad51 promoter can be used to target selective transgene expression from adenoviral vectors to tumor cells lacking functional p53.