EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Results of Transplanting Developing Third Molars as Part of Orthodontic Space Management

PATIENTS AND METHOD: The aim of the present study was to contribute to a more accurate indication and better integration of developing third molar transplantation into orthodontic space management, using the results gleaned from the authors' own pool of patients. For this purpose, a clinical and radiographic examination of 61 transplanted developing molars in 57 patients was carried out after an average of 3.3 years. RESULTS: The overall success rate was 85%. Failure was due in 10% of cases to impaired periodontal healing (inflammatory root resorption, ankylosis, or increased pocket probing depths) and in 5% of cases to insufficient or arrested postoperative root development accompanied by increased transplant mobility. The incidence of postoperative cessation of further root development was significantly higher (p = 0.011) in transplants at early developmental stages, which also had a negative impact on the final root length, the crown-root ratio and the mobility values of these transplants. CONCLUSIONS: The transplantation of developing third molars should be given stronger consideration in treatment plans for orthodontic space management although it represents a real alternative to orthodontic space closure only in exceptional cases. However, unlike implantological or prosthodontic treatment, it offers an opportunity to replace a missing or non-retainable tooth with a patient's own vital and fully functional tooth, provided the appropriate transplant is selected.     

Mechanical function of intermediate filaments in arteries of different size examined using desmin deficient mice

Protein composition and mechanical function of intermediate filaments were examined in arteries of different sizes using desmin deficient mice (Des−/−) and their wild-type controls (Des+/+). Using SDS-PAGE gels and Western blots we found a gradient in desmin expression in the arterial tree; the desmin content increased from the elastic artery aorta, via the muscular mesenteric artery to the resistance-sized mesenteric microarteries ∼150 μm in diameter in Des+/+ mice. Mechanical experiments were performed on the aorta, the mesenteric artery and resistance-sized arteries using wire myographs. For aorta and mesenteric artery, no differences in passive or active circumference- stress relations were found between Des−/− and Des+/+ mice. In microarteries, both passive and active stress were lower in the Des−/− group. In conclusion, large elastic and muscular arteries contain a relatively low amount of desmin, and the desmin intermediate filaments do not seem to play a major role in the mechanical properties of these larger arterial vessels. In the microarteries, where expression of desmin is high, desmin plays a role in supporting both passive and active tension.     

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Small bowel transplantation in the rat: impact of various immunosuppressive regimens on graft-versus-host reaction.

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.