Induction of donor-specific transplantation tolerance to skin and cardiac allografts using mixed chimerism in (A + B → A) in rats

Mixed allogeneic chimerism (A + B → A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHC)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts. © 1993

Prevention of graft-versus-host disease following allogeneic bone marrow transplantation in rats using FK506

FK506 and cyclosporine were used for the prevention of acute graft-versus-host disease. Acute GVHD was induced in Lewis rats by total-body irradiation and subsequent reconstitution with allogeneic (ACI) bone marrow and spleen cells (BMTx). GVHD was assessed by both clinical and histologic parameters during the experiment duration of 60 days, and longer for selected animals. All untreated BM recipients died within 26 days from severe acute GVHD. GVHD was prevented with CsA during the period of immunosuppressive therapy, but it appeared within a few days afterward. FK506-treated BM recipients were also protected, but they had a markedly prolonged GVHD-free period after therapy was discontinued. Most such animals eventually developed GVHD but with notable exceptions. Maintenance therapy with doses of FK506 as low as 0.1 mg/kg every other day (1/20 of daily induction dose) was infallible insurance against delayed GVHD. The relevance of these findings to GVHD caused by lymphoid-containing solid organs such as the intestine was discussed. © 1991 by Williams and Wilkins

FK 506 reverses acute graft-versus-host disease after allogeneic bone marrow transplantation in rats

Severe graft-versus-host disease was induced by transplantation of ACI rat bone marrow and spleen cells into irradiated Lewis rat recipients. Treatment with FK 506 or cyclosporine A (CsA) was started after clinical and histologic evidence of acute GVHD was present. A 14-day course of FK 506 at 1.0 mg/kg/day could rescue 100% of the animals suffering from GVHD. In contrast only one half of the animals treated with CsA at a high dose of 25 mg/kg/day recovered. After cessation of immunosuppressive therapy, FK 506-treated animals displayed a marked prolonged disease-free interval as compared to CsA-treated bone marrow recipients. Recurrence of the disease in these animals could be prevented when FK 506 treatment was continued after the induction period with a low maintenance dose of 0.1 mg/kg/day every other day

Efficacy of Liver Transplantation in Patients with Primary Biliary Cirrhosis

No controlled trials have been performed to assess the efficacy of liver transplantation. Because of the marked improvement in survival after liver transplantation since 1981, random assignment of patients to a control group not undergoing transplantation is considered clinically inappropriate. To assess the efficacy of liver transplantation in patients with primary biliary cirrhosis, we compared survival in 161 patients with this diagnosis who had undergone a liver transplantation with survival in patients with the same diagnosis who had been treated conservatively. The comparison was performed with use of a recently developed statistical technique, the Mayo model. All patients had undergone liver transplantation between March 1980 and June 1987 and were followed for a median of 25 months. Three months after liver transplantation, the Kaplan–Meier survival probabilities in the recipients were substantially higher than the Mayo-model “simulated-control” survival probabilities (P<0.001). At two years, the Kaplan–Meier survival probability was 0.74, whereas the mean Mayo-model survival probability was 0.31. The patients who were at low risk according to the Mayo model had the best probability of survival after liver transplantation; however, patients at all risk levels who had undergone liver transplantation had higher probabilities of survival than those who had not. We conclude that liver transplantation is an efficacious treatment in patients with advanced primary biliary cirrhosis. (N Engl J Med 1989; 320:1709–13.), LIVER transplantation has been accepted clinically as a lifesaving treatment in various end-stage liver diseases, including primary biliary cirrhosis.1,2 However, no controlled trials have been performed to evaluate the efficacy of this procedure. Indeed, because there has been a marked improvement since 1981 in survival after transplantation, random assignment of patients with advanced liver disease to a nontransplantation control group is considered to be clinically inappropriate. At the Mayo Clinic, a Cox regression model for predicting the probability of survival in patients with conservatively treated primary biliary cirrhosis has been developed.3 To provide control data for assessing the efficacy of…. © 1989, Massachusetts Medical Society. All rights reserved

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Sociomateriality Implications of Software As a Service Adoption on IT-workers’ Roles and Changes in Organizational Routines of IT Systems Support

This paper aims to deepen our understanding on how sociomateriality practices influence IT workers’ roles and skill set requirements and changes to the organizational routines of IT systems support, when an organization migrates an on-premise IT system to a software as a service (SaaS) model. This conceptual paper is part of an ongoing study investigating organizations that migrated on-premise IT email systems to SaaS business models, such as Google Apps for Education (GAE) and Microsoft Office 365 systems, in New Zealand tertiary institutions. We present initial findings from interpretive case studies. The findings are, firstly, technological artifacts are entangled in sociomaterial practices, which change the way humans respond to the performative aspects of the organizational routines. Human and material agencies are interwoven in ways that reinforce or change existing routines. Secondly, materiality, virtual realm and spirit of the technology provide elementary levels at which human and material agencies entangle. Lastly, the elementary levels at which human and material entangle depends on the capabilities or skills set of an individual