IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Leishmania identification by PCR of Giemsa-stained lesion imprint slides stored for up to 36 years

This study examined the ability of PCR to amplify Leishmania DNA, stored on Giemsa-stained slides, from American cutaneous leishmaniasis (ACL) patients. In total, 475 slides stored for up to 36 years were obtained from an outpatient clinic in a Brazilian ACL-endemic region, and Leishmania DNA was amplified from 395 (83.2%) of the DNA samples using primers specific for the minicircle kinetoplast DNA. Restriction fragment length polymorphism analysis of these amplicons demonstrated that Leishmania (Viannia) braziliensis was the only species present in these samples. The results demonstrated that archived Giemsa-stained slides can provide a Leishmania DNA source for performing clinical and epidemiological studies of leishmaniasis.     

Role of birds of prey as carriers and spreaders of Cryptococcus neoformans and other zoonotic yeasts.

In the last 20 years, cases of human cryptococcosis, have increased in immunocompromised patients. In several instances, the cases have been associated with the exposure of the patients to bird droppings. In order to investigate birds of prey as potential carriers and spreaders of Cryptococcus neoformans and other yeasts of importance in human infections, 182 swab samples were collected from the cloacae of several species of birds of prey (Group I) and 32 faecal samples from aviaries in which the birds were housed (Group II). Samples were also taken from digestive tract of 60 dead birds (Group III). A total of 454 samples were cultured from which 215 colonies of yeastlike fungi were recovered and identified. Cryptococcusneoformans var. grubii was isolated from three cloacae samples (4.8%) collected from Falco tinnunculus and from one sample (3.1%) obtained from Buteo buteo, as well as from samples collected at the aviaries in which these birds were kept. Overall, 18 samples (9.9%) from Group I, 13 (40.6%) from Group II, 12 crops (20%), three proventriculi (5%) and 12 cloacae (20%) from Group III yielded positive cultures for yeasts. The results indicate that birds of prey and in particular, F. tinnunculus and B. buteo, may act as carriers and spreaders of C. neoformans and other zoonotic yeasts.     

Infectious diseases physicians' preferences for continuing medical education on antimicrobial resistance and other general topics.

A 19-item survey instrument was designed and mailed by the Infectious Diseases Society of America to its membership to determine the media preferred by infectious diseases physicians for continuing medical education on general topics and on antimicrobial resistance. The objective of the survey was to offer the developers of educational programs knowledge on which to base more-effective ways to deliver educational materials to physicians in this specialty.