Women in Academic Pathology: Pathways to Department Chair.

The Association of Pathology Chairs, an organization of American and Canadian academic pathology departments, has a record percent of women department chairs in its ranks (31%), although still not representative of the percent of women pathology faculty (43%). These women chairs were surveyed to determine what had impeded and what had facilitated their academic advancement before becoming chairs. The 2 most frequently identified impediments to their career advancement were heavy clinical loads and the lack of time, training, and/or funding to pursue research.

Life After Being a Pathology Department Chair III: Reflections on the "Afterlife".

The Association of Pathology Chairs Senior Fellows Group provided reflections on activities that have kept them engaged and inspired after stepping down as chair. They offered advice to current chairs who were considering leaving their positions and also to individuals contemplating becoming pathology chairs. A majority (35/41) responded: 60% maintained teaching/mentoring activities; 43% engaged in hobbies; 40% took other administrative positions including deans, medical center chief executive officers, and residency program directors; 31% continued research; 28% wrote books; 20% performed community service; 14% led professional organizations; 14% developed specialized programs; 11% engaged in clinical service; and 11% performed entrepreneurial activities.

What Advice Current Pathology Chairs Seek From Former Chairs.

The 2018 Association of Pathology Chairs annual meeting included a panel discussion of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) about the type of advice that current (sitting) pathology chairs ask them. To inform the panel discussion, information was obtained from the senior fellows by e-mail and subsequent conference call. Of the 33 respondents, 24 (73%) had provided consultation advice (9, <5; 11, 5-10; 2, 10-20; and 2, >20).

Life After Being a Pathology Department Chair II: Lessons Learned.

The 2016 Association of Pathology Chairs annual meeting featured a discussion group of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) that focused on how they decided to transition from the chair, how they prepared for such transition, and what they did after the transition. At the 2017 annual meeting, the senior fellows (encompassing 481 years of chair service) discussed lessons they learned from service as chair. These lessons included preparation for the chairship, what they would have done differently as chair, critical factors for success as chair, factors associated with failures, stress reduction techniques for themselves and for their faculty and staff, mechanisms for dealing with and avoiding problems, and the satisfaction they derived from their service as chair.

Life After Being a Pathology Department Chair: Issues and Opportunities.

Although there is a considerable literature on transition of faculty members to the position of department chair, there is a dearth of publications about transitioning from the chair to other activities including retirement. The Association of Pathology Chairs senior fellows (all of whom are former chairs of academic departments of pathology) made this topic a focus of discussion at the Association of Pathology Chairs 2016 Annual Meeting. Of the 33 senior fellows engaged in this discussion, following their time as chairs, a small majority (18) transitioned to other administrative posts within or outside the university, while the others either returned to the active faculty (7) or retired (8).

Lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge.

Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule.

Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.

Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability.

Anti-IgE therapy results in decreased myeloid dendritic cells in asthmatic airways.

Anti-IgE treatment of intermittent to mild-persistent asthma in a cohort of seven volunteers resulted in improved allergen-induced airway hyperreactivity and a significant reduction in the number of airway myeloid dendritic cells.

The pathogenesis of acute pulmonary viral and bacterial infections: investigations in animal models.

Acute viral and bacterial infections in the lower respiratory tract are major causes of morbidity and mortality worldwide. The proper study of pulmonary infections requires interdisciplinary collaboration among physicians and biomedical scientists to develop rational hypotheses based on clinical studies and to test these hypotheses in relevant animal models. Animal models for common lung infections are essential to understand pathogenic mechanisms and to clarify general mechanisms for host protection in pulmonary infections, as well as to develop vaccines and therapeutics.

Discriminating virulence mechanisms among Bacillus anthracis strains by using a murine subcutaneous infection model.

Bacillus anthracis strains harboring virulence plasmid pXO1 that encodes the toxin protein protective antigen (PA), lethal factor, and edema factor and virulence plasmid pXO2 that encodes capsule biosynthetic enzymes exhibit different levels of virulence in certain animal models. In the murine model of pulmonary infection, B. anthracis virulence was capsule dependent but toxin independent.

Effect of Bacillus anthracis virulence factors on human dendritic cell activation.

Bacillus anthracis possesses three primary virulence factors: capsule, lethal toxin (LT), and edema toxin (ET). Dendritic cells (DCs) are critical to innate and acquired immunity and represent potential targets for these factors. We examined the ability of B.

Murine innate immune response to virulent toxigenic and nontoxigenic Bacillus anthracis strains.

Effective treatment of anthrax is hampered by our limited understanding of the pathophysiology of Bacillus anthracis infection. We used a genetically complete (pXO1(+) pXO2(+)) virulent B. anthracis strain and four isogenic toxin-null mutants to determine the effects of the anthrax edema toxin (ET; edema factor [EF] plus protective antigen [PA]) and lethal toxin (LT; lethal factor [LF] plus PA) on the host innate response during systemic infection.

Characterization of myeloid and plasmacytoid dendritic cells in human lung.

Dendritic cells (DCs) are bone marrow-derived mononuclear cells that play a central role in the initiation of immune responses. Because human lung DCs have been incompletely characterized, we enumerated and phenotyped mononuclear cell populations from excess lung tissue obtained at surgery. Myeloid DCs (MDCs) were identified as CD1c(+)CD11c(+)CD14(-)HLA-DR(+) cells and comprised approximately 2% of low autofluorescent (LAF) mononuclear cells.

Toxin-deficient mutants of Bacillus anthracis are lethal in a murine model for pulmonary anthrax.

Bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. The capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. We show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to those of the parent strain.

Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility.

Bioweapons are most often designed for delivery to the lung, although this route is not the usual portal of entry for many of the pathogens in the natural environment. Vaccines and therapeutics that are efficacious for natural routes of infection may not be effective against the pulmonary route. Pulmonary models are needed to investigate the importance of specific bacterial genes in virulence, to identify components of the host immune system that are important in providing innate and acquired protection, and for testing diagnostic and therapeutic strategies.

Flt3 ligand preferentially increases the number of functionally active myeloid dendritic cells in the lungs of mice.

In the present study, we investigated the effects of in vivo Flt3L administration on the generation, phenotype, and function of lung dendritic cells (DCs) to evaluate whether Flt3L favors the expansion and maturation of a particular DC subset. Injection of Flt3L into mice resulted in an increased number of CD11c-expressing lung DCs, preferentially in the alveolar septa. FACS analysis allowed us to quantify a 19-fold increase in the absolute numbers of CD11c-positive, CD45R/B220 negative DCs in the lungs of Flt3L-treated mice over vehicle-treated mice.

Complementation of a capsule deficient Cryptococcus neoformans with CAP64 restores virulence in a murine lung infection.

Cryptococcosis is a systemic infection in humans caused by the opportunistic fungal pathogen, Cryptococcus neoformans. The infection usually presents as chronic meningoencephalitis, but infects via the respiratory tract. A polysaccharide capsule is a major virulence factor, which allows the yeast to resist host defenses.

Dendritic cells: immune regulators in health and disease.

Dendritic cells (DCs) are bone marrow-derived cells of both lymphoid and myeloid stem cell origin that populate all lymphoid organs including the thymus, spleen, and lymph nodes, as well as nearly all nonlymphoid tissues and organs. Although DCs are a moderately diverse set of cells, they all have potent antigen-presenting capacity for stimulating naive, memory, and effector T cells. DCs are members of the innate immune system in that they can respond to dangers in the host environment by immediately generating protective cytokines.