Chaperoning of estrogen receptor and induction of mammary gland proliferation by neuronal protein synuclein gamma.

Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein gamma (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly associated with breast cancer progression. Using transgenic mouse model, we demonstrated a role of SNCG in induction of highly proliferative pregnancy-like phenotype of mammary epithelial cells and branching morphology. SNCG participated in the heat shock protein-based multiprotein chaperone complex for steroid receptor signaling. Expression of SNCG in mammary epithelium resulted in a significant stimulation of ERalpha transcriptional activity. SNCG-induced mammary gland proliferation can be effectively blocked by antiestrogen and ovariectomy, indicating that the induced proliferation is mediated by ERalpha signaling and requires estrogen stimulation. These data indicate the chaperone activity of SNCG on stimulation of steroid receptor signaling in mammary gland and, thus induces extensive mammary gland proliferation and contributes to the hormonal impact on mammary tumorigenesis.

The clinical spectrum of respiratory syncytial virus disease in The Gambia.

BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections in early childhood in industrialized countries, but less is known about RSV infection in developing countries. METHODS: Four outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia, West Africa, were studied. RSV was sought by immunofluorescent staining of nasopharyngeal aspirate samples among young children who presented with respiratory infections at three hospitals in the Western Region of the country. RESULTS: Five hundred seventy-four children with RSV infection were identified. The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months, respectively. Sixty-two percent of children <6 months old were boys. Thirteen children (2.4%) had conditions considered to increase the risk of severe RSV infection. On physical examination crepitations were heard in 80% of the children admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%) children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%) were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2 Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV Subgroup A, respectively. CONCLUSIONS: RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It poses a significant burden on the health system, especially through the demand for supplementary oxygen. The clinical spectrum of RSV disease in The Gambia is similar to that seen in developed countries; concomitant bacterial infections are uncommon.

PIP: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections during early childhood in industrialized countries. The study of 4 RSV infection outbreaks which occurred during 1993-96 in The Gambia led to the identification of RSV infection in 574 children through the immunofluorescent staining of nasopharyngeal aspirate samples among children of median age 3-8 months who presented with respiratory infections at 3 hospitals in the Western region of the country. 13 children had conditions thought to increase the risk of severe RSV infection, with crepitations heard during physical examinations in 80% of children admitted to the hospital and wheezes heard in 39%. 80 children were given oxygen because of hypoxemia. 9 of 255 blood cultures were positive for the following pathogens: 4 Streptococcus pneumoniae, 2 Haemophilus influenzae type b, 2 Staphylococcus aureus, and 1 Enterobacter agglomerans. 13 children died. 90% of isolates typed during year 1 were RSV subgroup A, 25% in the second year of study, 75% in year 3, and 95% in year 4. These findings demonstrate that RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It is most likely cost-effective to prevent RSV infection through vaccination.

Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria.

Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain. Therefore, the effects of supplementary treatment with iron or folic acid, given together with chloroquine or pyrimethamine-sulfadoxine (Fansidar), has been assessed in 600 Gambian children with uncomplicated falciparum malaria. After one month, haematological recovery was significantly better in the group treated with Fansidar than in the chloroquine-treated group (difference in mean haemoglobin level = 0.54 g/dL, P = 0.01). Children who received iron had a significantly better response than those given placebo (differences in mean haemoglobin level after one month and at dry season follow-up = 0.70 g/dL, P = 0.006, and 0.81 g/dL, P = 0.001, respectively). Iron supplementation was not associated with increased prevalence of malaria. Supplementation with folic acid did not improve the haematological response but, among children who received Fansidar, the treatment failure rate was significantly higher among those given folic acid than among those given placebo. Thus, supplementation with iron, but not folic acid, improves haematological recovery without increasing susceptibility to malaria.

Molecular epidemiology of respiratory syncytial virus in The Gambia.

Respiratory syncytial virus (RSV) infection in The Gambia occurs seasonally in association with the rainy season. This study examined the genetic variability of RSV isolates from four consecutive epidemics from 1993-6. Each epidemic was made up of a number of variants which were replaced in subsequent epidemics. Analysis of attachment (G) protein gene sequences showed that isolates were closely related to those observed in the rest of the world. However, many isolates from 1993 and 1994 were unlike other isolates observed in the developed world during this period and were more similar to isolates from 1984 in Europe. In addition, the most commonly observed genotype in the UK in the 1990s was not detected in The Gambia during this period.