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Same Donor (same + donor)
Selected AbstractsAdult thymus transplantation with allogeneic intra-bone marrow,bone marrow transplantation from same donor induces high thymopoiesis, mild graft-versus-host reaction and strong graft-versus-tumour effectsIMMUNOLOGY, Issue 4 2009Takashi Miyake Summary Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow,bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4+ FoxP3+ regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8+ T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR. [source] Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor systemMOLECULAR ORAL MICROBIOLOGY, Issue 1 2003J. Hatakeyama We compared human periodontal ligament fibroblasts with human gingival fibroblasts isolated from the same donor to examine interleukin-8 (IL-8) responses of the cells to Salmonella lipopolysaccharide, a water-soluble peptidoglycan from Staphylococcus epidermidis and the synthetic muramyldipeptide, with special reference to the possible involvement of the CD14/Toll-like receptor (TLR) system of the cells in the responses. Human gingival fibroblasts expressed CD14 on their surfaces and strongly expressed CD14 mRNA, while human periodontal ligament fibroblasts showed considerably lower levels of expression in both respects. Both cells expressed mRNA of TLR-related molecules, i.e. TLR2, TLR4, MD-2 and MyD88, although human periodontal ligament fibroblasts expressed TLR2 more strongly than human gingival fibroblasts. Human gingival fibroblasts exhibited a stronger IL-8 response than human periodontal ligament fibroblasts to lipopolysaccharide, while human periodontal ligament fibroblasts exhibited a response comparable to, or slightly stronger than, that of human gingival fibroblasts to S. epidermidis peptidoglycan and muramyldipeptide. The IL-8 responses of both cells to lipopolysaccharide and S. epidermidis peptidoglycan were completely inhibited by antihuman CD14 monoclonal antibody (MAb). The responses of both cells to lipopolysaccaride were significantly inhibited by antihuman TLR4 MAb, while those to S. epidermidis peptidoglycan were inhibited by antihuman TLR2 MAb. In contrast, muramyldipeptide activated both types of cells in a TLR2- and TLR4-independent manner, although the activities of muramyldipeptide on human gingival fibroblasts, but not human periodontal ligament fibroblasts, were significantly inhibited by anti-CD14 MAb. [source] Correction of enzyme levels with allogeneic hematopoeitic progenitor cell transplantation in Niemann-Pick type BPEDIATRIC BLOOD & CANCER, Issue 7 2007Jennifer Schneiderman MD Abstract Niemann-Pick type B (NP) is an autosomal recessive lysosomal storage disorder with variable phenotypes for which few patients have undergone hematopoietic progenitor cell (HPC) transplantation. We present an 18-month old with NP type B who underwent two allogeneic HPC transplants from her HLA-identical sister. Sphingomyelinase in the peripheral leucocytes and skin fibroblasts was absent at diagnosis. Engraftment failed following initial transplant; therefore a second with the same donor was performed. Engraftment since has been durable; all subsequent sphingomyelinase levels have been normal. Our experience indicates that HPC transplantation for patients with NP type B is feasible and beneficial. Pediatr Blood Cancer 2007;49:987,989. © 2007 Wiley-Liss, Inc. [source] Durable remission following a third allogeneic stem cell transplantation in a patient with repeatedly relapsing SAA.PEDIATRIC TRANSPLANTATION, Issue 3 2007The importance of stroma cells for sustained engraftment? Abstract:, Diagnosis of acquired AATP which finally progressed to SAA was established in an eight-yr-old boy. PBSCT from an HLA-identical unrelated donor using high numbers of CD34+ selected stem cells was performed and resulted in complete remission for almost two yr. However, SAA reoccurred with 100% donor hematopoiesis and was reversed by a second CD 34+ selected PBSCT from the same donor. Declining blood cell counts after an interval of two yr indicated second relapse. Chimerism analysis in PB and BM aspirates revealed a small autologous cell population of 4,12% and 2,11%, respectively. Finally, a third transplantation with unmanipulated BM from the same donor resulted in sustained remission with 100% donor hematopoiesis. The patient is in complete remission for more than five yr following the third SCT. Late graft failure or late graft rejection known to occur after transplantation of highly purified CD34+ cells, or even graft exhaustion caused by stromal dysfunction due to the underlying disease necessitated a third transplantation. Regardless of the cause of relapse, transplantation of unmanipulated BM instead of highly purified PBSCTs led to a permanent and stable engraftment in a third attempt after two previous PBSCTs. [source] Allotransplantation of Cryopreserved Parathyroid Tissue for Severe Hypocalcemia in a Renal Transplant RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010S. M. Flechner We report the successful allotransplantation of cryopreserved parathyroid tissue to reverse hypocalcemia in a kidney transplant recipient. A 36-year-old male received a second deceased donor kidney transplant, and 6 weeks later developed severe bilateral leg numbness and weakness, inability to walk, acute pain in the left knee and wrist tetany. His total calcium was 2.6 mg/dL and parathormone level 5 pg/mL (normal 10,60 pg/mL). He underwent allotransplantation of parathyroid tissue cryopreserved for 8 months into his left brachioradialis muscle. Immunosuppression included tacrolimus (target C0 10,12 ng/mL), mycophenolate mofetil and steroids. Within 2 weeks, the left knee pain, leg weakness and numbness resolved, and by 1 month he could walk normally. After a peak at month 2, his parathyroid hormone (PTH) level fell to <10 pg/mL; therefore at month 3 he received a second parathyroid transplant from the same donor. Eight months later (11 months after initial graft) he has a total calcium of 9.3 mg/dL, PTH level 15 pg/mL and is clinically asymptomatic. The amount of parathyroid tissue needed to render a patient normocalcemic is not known. In our case, the need for second transplant suggests that the amount of tissue transferred for an allograft may need to be substantially greater than for an autograft. [source] Case Report: Fatal Apophysomyces elegans Infection Transmitted by Deceased Donor Renal AllograftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010B. D. Alexander Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near-drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant-related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near-drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near-drowning events. Attention to aseptic technique during organ recovery and processing is re-emphasized. [source] Combined Pancreatic Islet,Lung Transplantation: A Novel Approach to the Treatment of End-Stage Cystic FibrosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010L. Kessler Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. In the present study, we report the long-term follow-up of four end-stage CF patients treated with combined bilateral lung and pancreatic islet transplantation from the same donor. All patients were C-peptide negative (<0.5 ,g/L) and inadequately controlled despite intensive insulin treatment. One patient was transplanted with 4 019 ± 490 islet equivalent/kg injected into the transverse colic vein using a surgical approach. In the remaining three patients, islets were cultured for 3,6 days and transplanted by percutaneous transhepatic catheterization of the portal vein. In all patients, islet allograft recovery was recognized by elevation in the plasma level of C-peptide (>0.5 ,g/L). At 6 months after transplantation, one patient showed multiple episodes of acute lung transplant rejection and a progressive decline in pancreatic islet cell function. Three out of four patients experienced an improved control of glucose levels with a HbA1c of 5.2%, 7% and 6% respectively at 1.5, 2 and 15 years follow-up. Compared with the pretransplant period, there was a 50% reduction in mean daily insulin needs. Pulmonary function remained satisfactory in all patients. In conclusion, our cases series shows that combined bilateral lung and pancreatic islet transplantation may be a viable therapeutic option for patients with end-stage CF and CFRD. [source] Strongyloides Stercoralis Hyperinfection Transmitted by Liver Allograft in a Transplant RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009M. J. Rodriguez-Hernandez We describe a case of Strongyloides stercoralis hyperinfection in a liver allograft recipient 2.5 months after transplantation. The patient lives in Spain, which is not considered an endemic country for strongyloidiasis, and denied prior residence or travel to any known endemic area. The initial symptoms were fever and vomiting, and he subsequently developed a severe respiratory disease. An endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa infiltration by larvae and adult worms, which were also found in respiratory samples. The patient was successfully treated with combined therapy with albendazole and ivermectin. The strongyloides infection was transmitted by the liver allograft. The donor was from Ecuador and, retrospectively, his serum tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas,left kidney allograft recipient from the same donor later developed an intestinal strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the first confirmed case of S. stercoralis infection transmission from the same donor to two solid allograft recipients. [source] Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Petra Hoffmann Abstract The adoptive transfer of CD4+CD25+ natural regulatory T cells (Treg) is a promising strategy for the treatment of autoimmune diseases and the prevention of alloresponses after transplantation. Clinical trials exploring this strategy require efficient in vitro expansion of this rare cell population. Protocols developed thus far rely on high-grade purification of Treg prior to culture initiation, a process still hampered by the lack of Treg cell-specific surface markers. Depletion of CD127+ cells was shown to separate activated conventional T cells from natural Treg cell populations allowing the isolation of highly enriched FOXP3+ cells with all functional and molecular characteristics of natural Treg. Here, we demonstrate that upon in vitro expansion, CpG methylation in a conserved region within the FOXP3 gene locus increased in CD4+CD25+CD127low Treg, correlating with loss of FOXP3 expression and emergence of pro-inflammatory cytokines. Further analysis identified CD45RA,FOXP3+ memory-type Treg as the main source of converting cells, whereas CD45RA+FOXP3+ Treg from the same donors showed no conversion within 3,wk of in vitro expansion. Thus, Treg cell lineage differentiation does not seem to represent a final fate decision, as natural Treg can lose their cell-type-specific characteristics after repetitive TCR stimulation. [source] A randomized comparison of plateletpheresis with the same donors using four blood separators at a single blood center,JOURNAL OF CLINICAL APHERESIS, Issue 4 2002Grace C. Tenorio Abstract At one blood center, each of 20 donors underwent plateletpheresis on four blood cell separators in random order. We compared the CS3000+, Amicus V 2.41, MCS Plus, and Spectra LRS V 7 Turbo regarding platelet (PLT) yield, pre- and post-procedure PLT counts, percent fall in donor PLT count, process time, efficiency, PLT product and donor PLT volume (MPV). Using , 150 × 109 PLTs/L pre-donation counts, a goal was set of 4.5 × 1011 PLTs unit in up to 100 minutes processing time. Results were (mean values) PLT yields of Amicus, Spectra, CS3000+, and MCS Plus: 4.3, 4.6, 4.3, 4.0 × 1011 PLTS, respectively; percent donor PLT fall: 24, 32, 30, 29%, respectively; processing times: 50, 74, 87, 101 minutes, respectively; relative efficiency (RE): 2.2, 1.6, 1.2,1.0, respectively (based on the MCS Plus performance with RE of 1 = 4 × 109 PLTS/min); PLT product MPV: 6.7, 7.4, 6.8,7.1 fL, respectively; pre-procedure donor MPV: 7.7, 7.3, 7.6 and 7.6 fL, respectively; and percent donor MPV change: ,5.2, 0, ,6.6, and ,10%, respectively. Significant changes in the donor MPV were noted (P < 0.05) but could not be related to product MPV. Spectra seemed to collect larger PLTs (higher MPV); the significance remains unknown for both donors and recipients. Importantly, all four separators gave acceptable and comparable PLT yields (P < 0.05) with Spectra trending higher. The short process time and high RE together indicate highly efficient collections particularly by Amicus and Spectra. J. Clin. Apheresis 17:170,176, 2002. © 2002 Wiley-Liss, Inc. [source] In Vitro/in Vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humansBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2001Noriko Hirota Abstract We attempted to predict the in vivo metabolic clearance of alprazolam from in vitro metabolic studies using human liver microsomes and human CYP recombinants. Good correlations were observed between the intrinsic clearance (CLint) for 4-hydroxylation and CYP3A4 content and between the CLint for ,-hydroxylation and CYP3A5 content in ten human liver microsomal samples. Using the recombinant CYP isoforms expressed in insect cells, the CLint for CYP3A4 was about 2-fold higher than the CLint for CYP3A5 in the case of 4-hydroxylation. However, the CLint for CYP3A5 was about 3-fold higher than the CLint for CYP3A4 in the case of ,-hydroxylation. The metabolic rates for 4- and ,-hydroxylation increased as the added amount of cytochrome b5 increased, and their maximum values were 3- to 4-fold higher than those without cytochrome b5. The values of CLint, in vivo predicted from in vitro studies using human liver microsomes and CYP3A4 and CYP3A5 recombinants were within 2.5 times of the observed value calculated from literature data. The average CLint value (sum of 4- and ,-hydroxylation) obtained using three human liver microsomal samples was 4-fold higher than that obtained using three small intestinal microsomal samples from the same donors, indicating the minor contribution of intestinal metabolism to alprazolam disposition. The area under the plasma concentration-time curve (AUC) of alprazolam is reported to increase following co-administration of ketoconazole and the magnitude of the increase predicted from the in vitroKi values and reported pharmacokinetic parameters of ketoconazole was 2.30,2.45, which is close to the value observed in vivo (3.19). A quantitative prediction of the AUC increase by cimetidine was also successful (1.73,1.79 vs 1.58,1.64), considering the active transport of cimetidine into the liver. In conclusion, we have succeeded in carrying out an in vitro/in vivo scaling of alprazolam metabolism using human liver microsomes and human CYP3A4 and CYP3A5 recombinants. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||