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A study of the histopathological abnormalities in a case of alopecia universalis was accompanied by immunohistochemical analysis of the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (formerly known as endothelial leukocyte adhesion molecule-1) within the skin. ICAM-1 expression on follicular epithelium co-localized with intraepithelial mononuclear cells (MNC) positive for the interleukin-2 receptor alpha-chain (IL-2R) or HLA-DR. Aberrant expression of E-selectin was observed on dermal endothelium. Although restricted to one case, these new observations concerning the expression of E-selectin and IL-2R in alopecia universalis are consistent with the view that extravascular trafficking of MNC into follicular epithelium may play a key role in the pathogenesis of alopecia universalis and that use of agents that interfere with this process may be an effective therapeutic strategy.

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Prednisone was shown to induce hyperglycemia in dogs submitted to total pancreatectomy and pancreatic islet autotransplantation. The hyperglycemia caused by a 10-day course of prednisone, 1 mg/kg/day, starting on the day of operation was reversible within 1 week after steroid discontinuance. Three weeks after prednisone was stopped, there was no detectable adverse effect on glucose homeostasis as judged by fasting blood sugar levels and intravenous glucose tolerance test results. Four months after transplantation, glucose disappearance was delayed in animals previously treated with the prednisone compared with those previously treated with prednisone plus insulin or control animals. This was accompanied by lower insulin values on intravenous glucose tolerance testing and suggests a long-term subtle effect on islet function. The mechanism of the steroid effect is not known. However, this model could be used to test the diabetogenicity of other immunosuppressive agents including cyclosporine, FK 506, and azathioprine.

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FK 506 is a new immunosuppressive agent with a similar molecular action to cyclosporin A. We have investigated immunohistochemical changes in lesional biopsies of seven patients with severe recalcitrant chronic plaque psoriasis receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there was a striking reduction in psoriasis area and severity index (mean reduction 87.4%), accompanied by marked reductions in dermal and epidermal CD4+ and CD8+ cells. Investigation of biopsies obtained 4-8 weeks after start of treatment revealed a significant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease revealed strong expression of CD54 (intercellular adhesion molecule-1, ICAM-1) and E-selectin (previously known as endothelial leukocyte adhesion molecule-1) both on microvascular endothelial cells and of ICAM-1 on infiltrating mononuclear cells; ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood vessels was reduced consistently but nevertheless persisted, even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

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BACKGROUND: Transplantation of untreated rat bone marrow into mouse recipients conditioned by total-body irradiation results in fully xenogeneic chimerism (rat----mouse). The chimerism is stable for up to 10 months, survival is excellent, and there is no evidence for graft-versus-host disease. We recently reported the long-term survival (greater than 180 days) of donor-specific pancreatic islet xenografts in these fully xenogeneic chimeras. METHODS: Chimeras were prepared and typed for chimerism at 6 weeks, and diabetes was induced by streptozocin injection. Donor-specific pancreatic islets were placed under the renal capsule and recipient blood glucose levels were followed biweekly. The aim of this study was to examine whether the transplanted pancreatic islets exhibited normal function in a xenogeneic environment and assess whether the islet xenografts were not only sufficient to support euglycemia but also regulated in function in response to a glucose challenge. RESULTS: We report for the first time that donor-specific rat islet xenografts were capable of producing normal basal and peak levels of insulin and responding to a glucose challenge in a manner similar to that of normal mouse islets. CONCLUSIONS: These data indicate that donor-specific rat islet xenografts are functional and regulated normally in fully xenogeneic (rat----mouse) chimeras.

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Mycotic aneurysm at the site of a Carrel patch arterial anastomosis occurred in four patients who had undergone whole pancreas transplantation 2.5 to 14.5 months previously. In all patients, the graft had been removed, leaving the Carrel patch on the iliac artery. The aneurysms ruptured into the intestine or the extraperitoneal space. The ruptures were sudden and life-threatening in three of four cases. This diagnosis must be suspected in patients with a history of pancreas transplantation in the immediate or distant past if they present with unexplained hypotension, cardiac arrest, or gastrointestinal tract bleeding.

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