RESUMEN
We previously reported that vascularized bone allograft using immunosuppressants, such as cyclosporine A (CsA), is one approach for reconstruction of large bone defects in both experimental animals (Microsurgery 15:663; 1994) and clinically in humans (Lancet 347:970, 1996). Because immunosuppressive agents such as CsA induce significant side effects, including bone loss, other therapeutic agents supporting successful vascularized bone allografts have been sought after. We investigated the effects of 22-oxa-1,25-dihydroxyvitamin D(3) (OCT) on vascularized bone allograft, and compared its effects with CsA. Twelve-week-old DA rats with the major histocompatibility antigen (MHC) RT-1(a) were used as donors and age-matched Lewis rats with MHC RT-1(l) used as recipients. Allografted bones in rats treated with vehicle were rejected completely. Soft X-ray examination demonstrated that administration of OCT (0.5 microg/kg per day) for 12 weeks after bone graft induced bone union as effective as treatment for 12 weeks with CsA (10 mg/kg per day). Transplanted bones in OCT-treated rats showed higher bone mineral density than that in CsA-treated rats. Histologically, transplanted bones in OCT-treated rats at 12 weeks were nonvital, but these bones united with recipient vital bones. After cessation of 12 week treatment with OCT, new bone formation occurred around the grafted nonvital bones during a 9 month period. Transplanted bones in CsA-treated rats were vital and formed union with recipient bones, whereas cortical bones became thin when compared with nonvital bones in OCT-treated rats. Urinary deoxypyridinoline levels in rats treated with CsA were significantly higher than levels in rats treated with OCT, suggesting accelerated bone resorption in CsA-treated rats. These results suggest that OCT exerts an anabolic action on bone reconstruction by allogeneic bone transplantation.
Asunto(s)
Antineoplásicos/farmacología , Trasplante Óseo , Calcitriol/farmacología , Supervivencia de Injerto/efectos de los fármacos , Tibia/trasplante , Aminoácidos/orina , Animales , Hilos Ortopédicos , Calcitriol/análogos & derivados , Calcio/sangre , Ciclosporina/farmacología , Peroné/irrigación sanguínea , Peroné/patología , Peroné/trasplante , Inmunosupresores/farmacología , Masculino , Fósforo/sangre , Ratas , Ratas Endogámicas Lew , Tibia/irrigación sanguínea , Tibia/patología , Trasplante HomólogoRESUMEN
3-Methylcrotonyl-CoA carboxylase (MCCase; EC 6.4.1.4) is a mitochondrial biotin enzyme and plays an essential role in the catabolism of leucine and isovalerate in animals, bacterial species, and plants. MCCase consists of two subunits, those that are biotin-containing and non-biotin-containing. The genes responsible for these subunits have been isolated in soybean, Arabidopsis thaliana, and tomatoes, but not in mammals. In humans, MCCase deficiency has been thought to be a rare metabolic disease, but the number of patients with MCCase deficiency appears to be increasing with a wide range of clinical presentations, some that result in a lethal condition and others that are asymptomatic. In this report, we have isolated and carried out chromosomal mapping of the gene for the biotin-containing subunit (A subunit) of the human MCCase gene, MCCA. The cDNA predicts an open reading frame coding for a 725-amino-acid protein with mitochondrial signal peptide, biotin carboxylase, and biotin-carrier domains. The gene is composed of at least 19 exons and covers more than 70 kb of sequence on band q27 of chromosome 3. MCCA was abundantly expressed in mitochondria-rich organs, such as the heart, skeletal muscles, kidney, and liver. In exon 13, we observed a His/Pro polymorphism at codon 464 (an A to C transition at nucleotide position 1391 in the cDNA sequence). Then, we determined the DNA sequences of the 5' untranslated region and entire coding regions in two patients with MCCase deficiency, but no sequence substitution was detected, suggesting that the gene mutations might be in the non-biotin-containing subunit (B subunit) gene, MCCB, in these patients.
Asunto(s)
Biotina , Ligasas de Carbono-Carbono/genética , Cromosomas Humanos Par 3 , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Ligasas de Carbono-Carbono/química , Ligasas de Carbono-Carbono/deficiencia , Bandeo Cromosómico , Mapeo Cromosómico , Análisis Mutacional de ADN , ADN Complementario , Exones , Femenino , Expresión Génica , Genotipo , Humanos , Japón , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo GenéticoRESUMEN
This retrospective study involved Japanese patients with prostheses supported by Brånemark implants following maxillectomy. Questionnaires were sent to 75 institutions, and data on 19 patients were collected from 8 institutions. The mean age of patients at the time of implant placement was 64.2 years (range 22 to 82 years). The mean follow-up time was 27.6 months. Of the 81 implants placed, 16 were lost for an implant survival rate of 80.2%. The effects on implant survival rate of radiotherapy, chemotherapy, hyperbaric oxygen therapy, and the support system of the prosthesis were analyzed, but no significant differences were observed.