Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. Individuals with HPS type 2 (HPS2) lack the cytosolic adaptor protein 3 (AP-3) involved in lysosomal sorting, and are also immunodeficient. Here we characterize an HPS2 mutation and demonstrate that AP-3 deficiency leads to a loss of cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Although the lysosomal protein CD63 was mislocalized to the plasma membrane, perforin and granzymes were correctly localized to the lytic granules in AP-3-deficient CTLs. However, the lytic granules of AP-3-deficient CTLs were enlarged and were unable to move along microtubules and dock within the secretory domain of the immunological synapse. These data show that AP-3 is essential for polarized secretion from CTLs.

Substantial gaps between recommended and current care exist in the management of COPD patients in primary care practice. Undertreatment of patients with severe COPD has potential clinical implications, including loss of autonomy and hospitalization.

There is a worldwide epidemic of chronic obstructive pulmonary disease (COPD) in women. Some large epidemiologic studies suggest that female smokers may have increased susceptibility to COPD. The biological mechanisms to explain these observations are far from certain. However, the susceptibility to the effects of cigarette smoke in women could be due to a greater deposition of toxic substances in the lung, impaired clearance of the toxins that are deposited, and/or an exaggerated biologic response to these toxins. The latter effect could be due to an increased ability to convert certain xenobiotics to more toxic metabolites or to a decreased ability to conjugate and excrete metabolites of these toxins. Female hormones, in particular estrogen, can up-regulate certain cytochrome P450 enzymes without altering detoxifying enzymes, leading to a disturbance in the balance between metabolism and conjugation. This article reviews this and other potential mechanisms that may confer increased susceptibility of COPD to female smokers.

This analysis shows a higher prevalence of AHR and exercise-induced respiratory symptoms in female compared to male athletes, but a similar prevalence of physician-diagnosed asthma. This suggested that the increase in respiratory symptoms in female athletes failed to translate into a higher prevalence of physician-diagnosed asthma.

Mortality in people with COPD has decreased; however, the decrease has been greater in men than in women. Public health interventions and medical care appear to be improving mortality in individuals with COPD but more research is needed to determine if they are benefiting both sexes equally.