Australia's notifiable disease status, 2008: annual report of the National Notifiable Diseases Surveillance System

In 2008, 65 communicable diseases and conditions were nationally notifiable in Australia. States and territories reported a total of 160,508 notifications of communicable diseases to the National Notifiable Diseases Surveillance System, an increase of 9% on the number of notifications in 2007. In 2008, the most frequently notified diseases were sexually transmissible infections (69,459 notifications, 43% of total notifications), vaccine preventable diseases (34,225 notifications, 21% of total notifications) and gastrointestinal diseases (27,308 notifications, 17% of total notifications). There were 18,207 notifications of bloodborne diseases; 8,876 notifications of vectorborne diseases; 1,796 notifications of other bacterial infections; 633 notifications of zoonoses and 4 notifications of quarantinable diseases.     

Canine retinal angioblasts are multipotent

The purpose of this study was to culture and characterize endothelial cells and angioblasts, vascular precursors, from adult and neonatal dog retina and determine if angioblasts are committed to endothelial cell lineage or have the potential to be multipotent, i.e. express phenotypic characteristics of other vascular cell types. Endothelial cells were established from adult dog retina (ADREC) by the technique of Gitlin and D'Amore. For angioblasts, pieces of neonatal day 2 (P2) avascular peripheral retina were placed under coverslips until sufficient cells had explanted. All cells were maintained initially on hyaluronic acid (HA)/fibronectin (FN) substratum. Neonatal canine retinal angioblasts (NCRA) were maintained initially on retinal-derived growth factor with alpha-amino adipic acid to inhibit growth of Muller cells. Cell lines were characterized by enzyme histochemistry [menadione-dependent alpha glycerophosphate dehydrogenase (alphaGPDH), marker for angioblasts] and immunocytochemistry. Once characterized, cells were grown on FN, or collagens I or IV substrata and fed platelet-derived growth factor-BB (PDGF-BB) or fibroblast growth factor-2 (FGF-2). The phenotypic expression of a marker for endothelial cells [acetylated LDL (acLDL) uptake] or a marker for pericytes and smooth muscle cells, production of alpha smooth muscle actin (alphaSMA), was evaluated under those conditions. The canine retinal cell lines that were established had the following characteristics when maintained on serum and a retinal extract. Angioblasts had low expression of vWf and VEGF-R2 (two markers for canine endothelial cells), and very low uptake of acLDL but high expression of alphaGPDH and adenosine A2a receptors (A2aR) (two markers for canine angioblasts in vivo). ADREC had high expression of endothelial cell markers (vWf, VEGF-R2, and acLDL uptake) but minimal expression of alphaGPDH and A2aR. Both angioblasts and endothelial cells expressed CXCR4, a marker for hemangioblasts. Angioblasts grown on any of the substrata in the presence of FGF-2 had high uptake of acLDL and low expression of alphaSMA, while those grown in the presence of PDGF-BB had high expression of alphaSMA and low uptake of acLDL. In conclusion, angioblasts cultured from peripheral vascular retina have low expression of endothelial cell markers and high alphaGPDH and A2aR, markers for canine angioblasts in vivo. Angioblasts will internalize acLDL when maintained on FGF-2 and express alphaSMA when maintained on PDGF-BB, suggesting that they have the potential to become endothelial cells or pericytes, i.e. are multipotent.     

A model of human cytomegalovirus infection in severe combined immunodeficient mice

Animal models for the evaluation of therapies against human cytomegalovirus (HCMV) are limited due to the species-specific replication of CMV. Models utilizing human fetal tissues implanted into SCID mice have been used but tend to be labor intensive and require human tissues. We therefore developed a model using HCMV-infected human foreskin fibroblasts (HFF) seeded onto a biodegradable gelatin matrix (Gelfoam). Infected HFFs are then implanted subcutaneously into SCID mice. We next evaluated two antivirals in this model. Treatment from days 0 to 5 with ganciclovir (GCV) produced a marginally significant reduction in viral titer while treatment from days 0 to 14 resulted in a more significant reduction in viral titers of 1.47 log(10)pfu/ml (P<0.0001). Viral titers were similarly reduced in a group receiving GCV treatment from days 7 to 14 post-implantation (1.50 log(10)pfu/ml, P<0.0001). Cidofovir therapy from days 7 to 14 reduced viral titers by almost 2 log(10)pfu/ml (from 3.51+/-0.31 log(10)pfu/ml in untreated animals to 1.56+/-0.40 log(10)pfu/ml in treated animals, P<0.0001). These results indicate that the Gelfoam-HCMV SCID mouse model is suitable for the in vivo evaluation of new antivirals against HCMV and is simpler and more convenient than previous models.     

Lethal proliferation of erythroid precursors in a neonate with a germline PTPN11 mutation

We report a neonate with hypertrophic cardiomyopathy and lethal myeloproliferative disorder with excessively proliferating immature erythroid precursors infiltrating non-hematopoietic organs. Mutational analysis uncovered a germline mutation in the Noonan syndrome/LEOPARD syndrome (NS/LS) gene PTPN11. In conclusion, this case report suggests that congenital myeloproliferative disorders in association with germline PTPN11 mutations may affect the erythroid lineage.