Impact of social support for mothers as caregivers of cerebral palsy children in Japan.

PURPOSE: Social supports are critical to alleviate the psychological and physical burden of primary caregivers of children with disabilities. This study aims to (1) clarify how cerebral palsy in children affects caregiving burden of the mother, and (2) identify the social supports that can effectively reduce that burden. DESIGN AND METHODS: This is a cross-sectional study in which mothers of children with cerebral palsy completed questionnaires and provided data regarding their child's condition, family support, social support usage, degree of satisfaction with supports, and caregiving burden. RESULTS: We analyzed responses from 1190 mothers. Support usage, particularly of home-visit nursing, home care, home-visit rehabilitation, and mobility support, was higher in severely burdened groups. However, the proportion of satisfaction with social support in groups with light or no burden were higher, particularly in home care, home-visit rehabilitation, training/treatment, and short stays. Mothers whose children have an intellectual disability and gross exercise ≥1 in addition to tube feeding or intravenous nutrition especially felt a strong sense of burden. The most effective measure in reducing mother's sense of burden was short stays. CONCLUSIONS: Mothers with children who can move and have an intellectual disability felt more burden compared with mothers of bedridden children. The findings clarify that supports, such as home care and short stays, have a significant impact on reducing the mother's sense of burden. PRACTICE IMPLICATIONS: Due to the large sample size, we believe that the results can inform efforts to increase social support for caregivers.

Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse.

Infection with cagA-positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. Despite these CagA activities that contribute to neoplastic transformation, a causal link between CagA and in vivo oncogenesis remains unknown. Here, we generated transgenic mice expressing wild-type or phosphorylation-resistant CagA throughout the body or predominantly in the stomach. Wild-type CagA transgenic mice showed gastric epithelial hyperplasia and some of the mice developed gastric polyps and adenocarcinomas of the stomach and small intestine. Systemic expression of wild-type CagA further induced leukocytosis with IL-3/GM-CSF hypersensitivity and some mice developed myeloid leukemias and B cell lymphomas, the hematological malignancies also caused by gain-of-function SHP-2 mutations. Such pathological abnormalities were not observed in transgenic mice expressing phosphorylation-resistant CagA. These results provide first direct evidence for the role of CagA as a bacterium-derived oncoprotein (bacterial oncoprotein) that acts in mammals and further indicate the importance of CagA tyrosine phosphorylation, which enables CagA to deregulate SHP-2, in the development of H. pylori-associated neoplasms.

EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells.

Helicobacter pylori contributes to the development of peptic ulcers and atrophic gastritis. Furthermore, H. pylori strains carrying the cagA gene are more virulent than cagA-negative strains and are associated with the development of gastric adenocarcinoma. The cagA gene product, CagA, is translocated into gastric epithelial cells and localizes to the inner surface of the plasma membrane, in which it undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif. Tyrosine-phosphorylated CagA specifically binds to and activates Src homology 2-containing protein-tyrosine phosphatase-2 (SHP-2) at the membrane, thereby inducing an elongated cell shape termed the hummingbird phenotype. Accordingly, membrane tethering of CagA is an essential prerequisite for the pathogenic activity of CagA. We show here that membrane association of CagA requires the EPIYA-containing region but is independent of EPIYA tyrosine phosphorylation. We further show that specific deletion of the EPIYA motif abolishes the ability of CagA to associate with the membrane. Conversely, reintroduction of an EPIYA sequence into a CagA mutant that lacks the EPIYA-containing region restores membrane association of CagA. Thus, the presence of a single EPIYA motif is necessary for the membrane localization of CagA. Our results indicate that the EPIYA motif has a dual function in membrane association and tyrosine phosphorylation, both of which are critically involved in the activity of CagA to deregulate intracellular signaling, and suggest that the EPIYA motif is a crucial therapeutic target of cagA-positive H. pylori infection.