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The differentiation of intestinal intraepithelial lymphocytes (IEL) remains controversial, which may be due in part to the phenotypic complexity of these T cells. We have investigated here the development of IEL in mice on the recombination activating gene (RAG)-2(-/-) background which express a T cell antigen receptor (TCR) transgene specific for an H-Y peptide presented by Db (H-Y/Db x RAG-2(-) mice). In contrast to the thymus, the small intestine in female H-Y/Db x RAG-2(-) mice is severely deficient in the number of IEL; TCR transgene+ CD8alphaalpha and CD8alphabeta are virtually absent. This is similar to the number and phenotype of IEL in transgenic mice that do not express the Db class I molecule, and which therefore fail positive selection. Paradoxically, in male mice, the small intestine contains large numbers of TCR+ IEL that express high levels of CD8alphaalpha homodimers. The IEL isolated from male mice are functional, as they respond upon TCR cross-linking, although they are not autoreactive to stimulator cells from male mice. We hypothesize that the H-Y/Db TCR fails to undergo selection in IEL of female mice due to the reduced avidity of the TCR for major histocompatibility complex peptide in conjunction with the CD8alphaalpha homodimers expressed by many cells in this lineage. By contrast, this reduced TCR/CD8alphaalpha avidity may permit positive rather than negative selection of this TCR in male mice. Therefore, the data presented provide conclusive evidence that a TCR which is positively selected in the thymus will not necessarily be selected in IEL, and furthermore, that the expression of a distinct CD8 isoform by IEL may be a critical determinant of the differential pattern of selection of these T cells.

The University of Michigan Regional Nuclear Pharmacy is described. The scope of operation of the nuclear pharmacy includes radiopharmaceutical formulation and dispensing, quality control, inventory control, research and development of new radiopharmaceuticals, and consultation. Also discussed are program objectives, pharmacy location, organizational structure, budget and staff, economic considerations, facilities and equipment, and legal considerations.

Sodium bicarbonate was used to enhance the myocardial concentration of Tl-201 in rabbits and dogs. Organ distribution studies in rabbits and in vivo imaging in dogs showed a 1.5-2 fold increase in myocardial Tl-201 concentration in bicarbonate-treated animals as compared with matched controls. Image improvement was noted, with threefold enhancement of myocardium-to-liver ratios. The results suggest that a similar improvement may be possible for clinical myocardial imaging.

The first synthesis of 131I-19-iodocholesterol had a 10-25% radiochemical impurity that was not iodide ion. This impurity has been identified as 6beta-131I-iodomethyl-19-nor cholest 5(10)-en-3beta-ol (NP-59) and has been synthesized. Tissue distribution studies with 131I-NP-59 in rats and dogs revealed a higher adrenal uptake and adrenal-to-tissue ratios compared to 131I-19-iodocholesterol, probably less in vivo deiodination, and superior adrenal images. A high uptake was seen in the adrenal medulla in addition to that in the cortex. Iodine-131-NP-59 is being evaluated for the early detection of adrenal-cortical disorders and as a potential scanning agent for detecting structural abnormalities of the adrenal medulla.

Carbon-14-diphenylhydantoin (DPH) concentrated maximally in pancreatic islet cells of the toadfish 10 min after its intravenous administration. The islet cell-to-acinar-tissue ratio at this time was 6:1. The islet cell-to-liver ratio was 20:1. Iodine-125-paroiodo-DPH at 10 min in the toadfish showed an islet cell-to-acinar-tissue ratio of 1.7:1 and an islet cell-to-liver ratio of 2.3:1. When 14C-DPH was given to four patients 10-17 min before removal of norma pancreatic tissue and of an insulinoma in three of the patients, the concentration of radioactivity in the insulinoma was never greater than in the pancreas and concentrations in insulinoma and pancreas were always less than in liver in the same individual. Forty-five to 90 min after administration of 131I-DPH, the liver and pancreas were delineated in three patients but the insulinoma was not imaged. Five days after administration of 131I-DPH, the concentration of 131I radioactivity in excised tissue was greater in the insulinomas than in the pancreas of two patient but not sufficient to produce positive images of the insulinoma in the pancreas.

The authors describe a technique for rapid, convenient in vivo labeling of circulating erythrocytes with 99mTc and the application of this technique to the evaluation of abdominal aortic aneurysms. Dynamic perfusion images and equilibrium blood pool images were obtained in 9 patients with documented aneurysm, and 7 of them indicated an aneurysm on the radionuclide study.