The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive ( n ϭ 99) or HIV-1-seronegative ( n ϭ 32) subjects, and correlating these results with the level of circulating CD4 ϩ and CD8 ϩ T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4 ϩ T cell count ( P ϭ 0.02) and a higher percentage and absolute number of circulating naive (CD45RA ϩ CD62L ϩ ) CD4 ϩ T cells ( P Ͻ 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( Յ 39 yr) with CD4 counts in the range 300-500 cells/ l and in older subjects ( Ͼ 40 yr) regardless of CD4 count ( P ϭ 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease. ( J. Clin. Invest. 1998.

SummaryWe have previously postulated that donor cell chimerism in organ transplantation is needed to attain a tolerant state. Here we show that donor cell chimerism can be augmented in organ recipients if they are infused perioperatively with 3 × 10 8 per kg of unmodified donor bone marrow cells and are kept on a conventional immunosuppressive regimen of tacrolimus (FK506) and prednisolone.36 patients took part, of whom the first 18 patients have good transplanted kidney (n = 10), liver (n = 7), and heart (n = 7) function when followed up between 4 and 16 months. All patients are well. We found persistent multilineage leucocyte chimerism in blood of 17 recipients by flow cytometry and PCR techniques to detect donor alleles or Y chromosomes in female recipients of male organs. The use of the 5-antigen HLA matched same sex donor precluded detection of chimerism in one patient.

This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patients had plasma C-peptide greater than 3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparation were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to greater than 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function.

Recent animal and in vitro studies have identified several interrelated metabolic abnormalities in diabetic nerve that are attributable to elevated ambient glucose concentrations. In combination, these metabolic changes may induce a variety of biochemical and biophysical alterations in peripheral nerve that are highly relevant to the pathogenesis of diabetic neuropathy. This article reviews the current status of several of these metabolic defects and describes ways in which their interaction could lead to pathogenetically important changes in nerve metabolism, function, and structure. Areas of related future research are also discussed.