Biomedical subjects
Publications and source records attributed to G Jeffery.
When one eye of a rat is removed at birth an increased projection to the brain is found from the remaining eye. This projection arises from the whole retina and mainly from ganglion cells which project to only one hemisphere of the brain. In the normal course of development many of these cells die and the uncrossed projection diminishes to form the normal adult pattern.
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Adult albino mammals have specific retinal defects, including reduced numbers of rod photoreceptors. To examine when this rod deficit arises and whether it exists in nonmammalian albinos, we have used absorbance spectrophotometry to measure photopigment levels in dark-adapted eyes taken from three groups of pigmented and albino animals: adult rodents (rats and mice), developing rats, and mature Xenopus frogs. Rhodopsin concentrations were consistently and significantly reduced in mammalian albinos compared to their wild-type counterparts from before the time of eye opening, but photopigment levels were similar in frogs of both pigmentation phenotypes. The results strongly suggest that deficits in the rod cell population arise early in development of the mammalian albino retina, but do not generalize to nonmammalian mutants lacking retinal melanin.
In mammals, the major subcortical visual structures receive projections from both eyes, with the uncrossed projection being smaller than the crossed. Each projection is arranged as a separate orderly map of one hemiretina. Although these hemiretinal maps are separate in the nuclei, they are aligned so that the representations of points in the visual field are in register, thus there is a continuity of visual field representation between them. During the early development of the binocular pathways, terminals from the two eyes overlap almost entirely. As development proceeds, terminals arising from each eye segregate to form the adult pattern. In the present study, local retinal lesions were made in ferrets at various stages in development before the separation of the projections from the two eyes. A neuronal tracer was then injected into the damaged eye, defining the pattern of projection from that eye. As reported here, the lesion resulted in a limited interruption in the pattern of terminal label on both sides of the brain, demonstrating that terminals from each eye are arranged in an orderly retinotopic manner at this stage. hence, during later development, as one projection is reduced relative to the other, the two maps must slide in relation to each other.
Sixteen patients with metastatic stage IV melanoma were treated with use of intravenous infusions of dendritic cells (DC) derived by incubation of plastic-adherent peripheral blood mononuclear cells (PBMC) with IL-4 and GM-CSF for 8 days in serumless AIM-V medium, followed by overnight pulsing with peptides. The tyrosinase368-376 (370D) and gp100(209-217 (210M)) peptides restricted to HLA class I A*0201 each differed from wild type by one amino acid modified to increase HLA binding. Median age was 49, with nine men and seven women. All patients, except one, had visceral disease. Patients received escalating doses of peptide-pulsed DCs at 10e7, 3 x 10e7, and 10e8 cells/dose twice at 2 weeks apart, with toxicity and clinical and immune responses as the principal endpoints. The first infusion of DCs was fresh, and frozen DCs were given for the second infusion of each cycle. Mean DC purity by flow cytometry was 49%, with a mean HLA-DR level of 57%, CD86 of 41%, CD58 of 46%, and mean CD14 cells of 0.9%. Toxicity was minimal, with two patients having transient grade III DC-related toxicity. Ten patients received one cycle of treatment and six patients received two cycles of treatment. One patient had a complete remission (CR) of lung and pleural disease after two cycles of DC therapy. Two additional patients had stable disease and two patients had mixed responses. Overall immunity was assessed by recall skin testing with peptides, gamma interferon ELISA assays of peptide specific cytolytic T cell (CTL) stimulated twice with peptide, IL-2, and IL-7 over 24 days, and peptide-specific tetramer assays performed before and after vaccination. Five of 16 patients had an immune response to gp100 or tyrosinase by gamma interferon ELISA assay; four of five were clinically stable or had tumor regression. These data suggest that melanoma antigen peptide-pulsed DC given intravenously are not toxic, and regression or stability of tumor appeared to correlate with the detection of a peptide-specific immune response in the peripheral blood.