Aims-To analyse the histopathology of "deep retinal vascular anomalous complex" or "chorioretinal anastomosis". Methods-Six patients with a deep retinal vascular anomalous complex (age range 66-88 years) had fundus photography and fluorescein angiography not more than 14 days before foveal translocation surgery. Four patients were also documented with indocyanine green angiography. The surgical specimens were serially sectioned and stained in a stepped fashion with Masson trichrome, periodic acid SchiV, and phosphotungstic acid haematoxylin, a histochemical stain for fibrin. Results-A subretinal fibrovascular membrane was surrounded by a rim consisting of diVuse drusen (basal laminar deposits), retinal pigment epithelium, and amorphous, fibrinous material interspersed with remains of outer segments in all specimens. In two specimens vascular structures were identified that left the specimen towards the retina. Amorphous material with the remains of outer segments was not found on the retinal side of the fibrovascular tissue itself but in four specimens a small neuroretinal portion (outer nuclear layer) was adherent to the complex. In three specimens a thin fibrocellular membrane was seen at the choroidal side of the diVuse drusen. Conclusion-Deepretinal vascular anomalous complex represents histologically neovascularisation growing out of the neuroretina, into the subretinal space, which mimics choroidal neovascularisation. The term therefore appears rightly chosen.

The presence of transcripts of the recombination activating gene RAG-1 was studied by in situ hybridization on selected populations of murine thymocytes, peripheral lymphocytes and gut intraepithelial lymphocytes (IEL), obtained by cell sorting. RAG-1 mRNA was found in a majority of "double-positive" (DP) thymocytes, but was absent in "single-positive" thymocytes and peripheral T lymphocytes. The only other T lineages in which about 10%-20% of the cells contained RAG-1 mRNA, and in smaller amounts, were "double-negative" (DN), T cell receptor (TcR) gamma delta- cortical thymocytes and gut CD3- IEL. These observations suggest that (a) the high expression of RAG-1 transcripts in DP thymocytes is related to the process of expansion-selection of these cells, probably accompanied by repeated TcR rearrangements, and that (b) in contrast, CD3- IEL from the gut (which are thymus independent) as well as some DN thymocytes undergo limited TcR rearrangement giving rise locally to TcR+ T cells without prior extensive process of local expansion-selection. A small percentage of peripheral B cells also contained RAG-1 mRNA, raising the possibility that this protein may also be involved in immunoglobulin class switching.

The genes for interferon (IFN) alpha, IFN gamma, IL-1 beta, IL-6, and TNF alpha were transcribed at readily detectable levels both in liver biopsies from individuals with normal liver function and in samples of normal viable liver taken for transplantation. These results provided evidence for the concept that such multifunctional cytokines play a role in homeostasis in normal human tissues. In normal human liver, in situ hybridization studies showed that, in the absence of a detectable inflammatory response, both hepatocytes and mononuclear cells exhibited a similar degree of expression of IL-6 mRNA in keeping with the finding that IL-6 is produced by cells of different lineages. The levels of IL-1, IL-6, and TNF mRNA were found to be markedly reduced in extracts of the livers of patients with primary biliary cirrhosis and other forms of autoimmune liver disease at a time when extensive liver lesions were apparent, compared to the levels of expression of these cytokines in the livers of normal individuals. The reduced expression of IL-1, IL-6, and TNF mRNAs appeared to be a specific effect and not due to a general reduction in RNA synthesis as the IFN alpha, IFN gamma and actin mRNAs were expressed at similar levels in both normal and diseased livers. The levels of IL-1 beta, IL-6, and TNF mRNAs were also reduced in samples of liver from a patient with a drug induced fulminant hepatitis suggesting that this specific pattern of altered cytokine gene expression was characteristic of the advanced stage of severe liver disease.

The heterologous antiviral efficiency of bacterially produced human interferon (Hu-IFN alpha 2) in the bovine species was studied, using vaccinia infection as experimental model. In a double blind experiment, young calves were intramuscularly injected daily for seven consecutive days with different doses of Hu-IFN alpha 2 or placebo, the treatment starting 24 h before intradermal inoculation of vaccinia virus. A clear protection by interferon was observed in all the IFN treated animals, although individual variations in the sensitivity to IFN were recorded. The efficiency of treatment varied according to the dose of IFN used: With the highest dose (10(6) IU/kg), complete protection could be obtained. The only side-effect observed was hyperthermia. Circulating antiviral activity appeared quite early after each IFN injection, presented a more or less biphasic kinetics, and was completely cleared after 24 h, justifying the daily treatment schedule. The first evidence of an in vivo antiviral effect of human interferon in the bovine species opens broad perspectives for a future use of interferon in veterinary medicine.