Publications

Granzyme A (GzmA) induces a caspase-independent cell death pathway characterized by single-stranded DNA nicks and other features of apoptosis. A GzmA-activated DNase (GAAD) is in an ER associated complex containing pp32 and the GzmA substrates SET, HMG-2, and Ape1. We show that GAAD is NM23-H1, a nucleoside diphosphate kinase implicated in suppression of tumor metastasis, and its specific inhibitor (IGAAD) is SET. NM23-H1 binds to SET and is released from inhibition by GzmA cleavage of SET. After GzmA loading or CTL attack, SET and NM23-H1 translocate to the nucleus and SET is degraded, allowing NM23-H1 to nick chromosomal DNA. GzmA-treated cells with silenced NM23-H1 expression are resistant to GzmA-mediated DNA damage and cytolysis, while cells overexpressing NM23-H1 are more sensitive.

OBJECTIVE

To examine breastfeeding and the risk of hospitalization for lower respiratory tract disease in healthy full-term infants with access to modern medical care.

DATA SOURCES

MEDLINE, personal communication with researchers, the OVID databases, Dissertation Abstracts Online, and BIOSIS.

STUDY SELECTION

The titles, abstracts, and text of studies from developed countries were explored for breastfeeding exposure measures and lower respiratory tract disease hospitalization rates. For summary statistics, we required 3 inclusion criteria: (1) a feeding contrast of a minimum of 2 months of exclusive breastfeeding (no formula supplementation) vs no breastfeeding and (2) study populations that excluded sick, low birth weight or premature infants and (3) reflected affluent regions; 27% of studies met these criteria.

DATA EXTRACTION

We abstracted data from all relevant reports.

DATA SYNTHESIS

Data from all primary material (33 studies) indicated a protective association between breastfeeding and the risk of respiratory disease hospitalization. Nine studies met all inclusion criteria, and 7 cohort studies were pooled. The feeding contrasts in these 7 studies were 4 or more months of exclusive breastfeeding vs no breastfeeding. The summary relative risk (95% confidence interval) was 0.28 (0.14-0.54), using a random-effects model. This effect remained stable and statistically significant after adjusting for the effects of smoking or socioeconomic status.

CONCLUSION

Among generally healthy infants in developed nations, more than a tripling in severe respiratory tract illnesses resulting in hospitalizations was noted for infants who were not breastfed compared with those who were exclusively breastfed for 4 months.

We report the molecular cloning of a KIR3DL1 receptor in the mouse and the rat, between 37.4 and 45.4% identical with primate killer cell Ig-like receptors (KIRs/CD158). Both mouse and rat molecules contain a pair of immunoreceptor tyrosine-based inhibition motifs in their cytoplasmic regions, suggesting an inhibitory function. Southern blot analysis indicated a single KIR gene in the rat, whereas the mouse genome contains more than one KIR-related element. The rat Kir3dl1 locus was mapped to the leukocyte receptor gene complex on chromosome 1, whereas mouse Kir3dl1 was localized to the X chromosome. RT-PCR demonstrated that KIR3DL1 was selectively expressed by NK cells in both rat and mouse. An epitope-tagged expression construct of mouse KIR3DL1 transfected into 293T cells induced expression of a approximately 55-kDa protein. Our data indicate that KIR receptors may contribute to the NK cell receptor repertoire in rodents, alongside the Ly-49 family.