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HCT
Kinds of HCT Selected AbstractsAllogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre studyEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006Martin Bornhäuser Abstract:,Objective:,To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods:,We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total-body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results:,The incidence of grades II,IV and III,IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age ,40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion:,These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality. [source] Myeloablative hematopoietic stem cell transplantation for myelodysplastic syndrome in patients younger than 55 years: impact of comorbidity and disease burden on the long-term outcomeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010H. KANAMORI Summary We retrospectively investigated 31 myelodysplastic syndrome (MDS) patients receiving myeloablative hematopoietic stem cell transplantation (HCT) and focused on prognostic factors affecting the long-term outcome. Patients were classified according to the French-American-British classification and the HCT-comorbidity index was determined. Cytosine arabinoside or thiotepa combined with cyclophosphamide and total body irradiation was used as myeloablative conditioning in eight and 23 patients respectively. After a follow-up period of 0.8,14.2 years from transplantation (median: 6.4 years), 23 patients were alive in complete remission, and the 5-year overall survival (OS) and disease-free survival (DFS) rates were 79% and 72% respectively. The cumulative nonrelapse mortality (NRM) rate was 22% at 5 years. According to multivariate analysis, ,20% blasts in the bone marrow and an HCT-comorbidity score , 3 were significantly associated with poor OS and DFS. Patients with a high HCT-comorbidity score and male patients receiving transplantation from female donors were significantly more likely to have a higher NRM according to the univariate, but not the multivariate analysis. These data suggest that comorbidity and the tumor burden at the time of transplantation may be useful variables for predicting the outcome in MDS patients receiving myeloablative HCT. [source] Curcumin downregulates H19 gene transcription in tumor cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Renata Novak Kujund Abstract Curcumin (diferuloymethane), a natural compound used in traditional medicine, exerts an antiproliferative effect on various tumor cell lines by an incompletely understood mechanism. It has been shown that low doses of curcumin downregulate DNA topoisomerase II alpha (TOP2A) which is upregulated in many malignances. The activity of TOP2A is required for RNA polymerase II transcription on chromatin templates. Recently, it has been reported that CTCF, a multifunctional transcription factor, recruits the largest subunit of RNA polymerase II (LS Pol II) to its target sites genome-wide. This recruitment of LS Pol II is more pronounced in proliferating cells than in fully differentiated cells. As expression of imprinted genes is often altered in tumors, we investigated the potential effect of curcumin treatment on transcription of the imprinted H19 gene, located distally from the CTCF binding site, in human tumor cell lines HCT 116, SW 620, HeLa, Cal 27, Hep-2 and Detroit 562. Transcription of TOP2A and concomitantly H19 was supressed in all tumor cell lines tested. Monoallelic IGF2 expression was maintained in curcumin-treated cancer cells, indicating the involvement of mechanism/s other than disturbance of CTCF insulator function at the IGF2/H19 locus. Curcumin did not alter H19 gene transcription in primary cell cultures derived from normal human tissues. J. Cell. Biochem. 104: 1781,1792, 2008. © 2008 Wiley-Liss, Inc. [source] Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epitheliumJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Jeffrey W. Keller Activating mutations of the RAS family of small GTPases are among the most common genetic events in human tumorigenesis. Constitutive activation of the three canonical family members, KRAS, NRAS, and HRAS segregate strongly by tissue type. Of these, KRAS mutations predominate in human tumors, including those arising from the colon and lung. We sought to compare the oncogenic contributions of different RAS isoforms in a comparable genetic setting and to explore downstream molecular changes that may explain the apparent differential oncogenic effects of the various RAS family members. We utilized colorectal cancer cell lines characterized by oncogenic KRAS in parallel with isogenically derived lines in which the mutant allele has been disrupted. We additionally attempted to reconstitute the isogenic derivatives with oncogenic forms of other RAS family members and analyze them in parallel. Pairwise analysis of HCT 116 and DLD-1 cell lines as well as their isogenic derivatives reveals distinct K-RASG13D signatures despite the genetic similarities of these cell lines. In DLD-1, for example, oncogenic K-RAS enhances the motility of these cells by downregulation of Rap1 activity, yet is not associated with increased ERK1/2 phosphorylation. In HCT 116, however, ERK1/2 phosphorylation is elevated relative to the isogenic derivative, but Rap1 activity is unchanged. K-RAS is uniquely oncogenic in the colonic epithelium, though the molecular aspects of its oncogenic contribution are not necessarily conserved across cell lines. We therefore conclude that the oncogenic contribution of K-RAS is a function of its multifaceted functionality and is highly context-dependent. J. Cell. Physiol. 210: 740,749, 2007. © 2006 Wiley-Liss, Inc. [source] A reliable body condition scoring technique for estimating condition in African buffaloAFRICAN JOURNAL OF ECOLOGY, Issue 4 2009Vanessa O. Ezenwa Abstract Evaluating animal body condition is a necessary component of many ecological studies. Although many methods for assessing animal body condition have been developed, relatively few can be used for estimating condition on live animals. Noninvasive body condition scoring techniques have been developed for assessing condition in livestock and more recently such techniques have been applied to wild ungulates. In this study, we examined the reliability of a body condition scoring technique for assessing condition in African buffalo (Syncerus caffer caffer). We compared a body condition score (BCS) based on visual assessment and manual palpation of an animal's body to two standard metrics of condition widely used in mammals: kidney fat index (KFI) and haematocrit (HCT). Across all buffalo, BCS was significantly and positively correlated with both KFI and HCT. For HCT, this pattern was observed among adults, juveniles, males and females; and in the wet season but not in the dry season. For KFI, BCS was significantly and positively correlated with KFI among adults, juveniles and males, but not in females. Overall, our results suggest that the BCS technique can serve as a useful method for estimating body condition in buffalo. Résumé L'évaluation de la condition corporelle d'un animal est une composante nécessaire de nombreuses études écologiques. Bien que l'on ait mis au point de nombreuses méthodes pour réaliser cette évaluation, relativement peu peuvent servir à estimer la condition d'animaux vivants. Des techniques noninvasives ont été développées pour évaluer la condition physique chez le bétail et, plus récemment, de telles techniques ont aussi été appliquées aux animaux sauvages. Dans cette étude, nous avons examiné la fiabilité d'une technique d'évaluation de la condition physique conçue pour étudier celle du buffle africain (Syncerus caffer caffer). Nous avons comparé un indice de condition corporelle (Body condition score , BCS) basé sur une évaluation visuelle et la palpation manuelle du corps d'un animal à deux indicateurs standards de condition largement utilisés chez les mammifères: l'indice graisseux des reins (Kidney fat index , KFI) et l'hématocrite (HTC). Chez tous les buffles, le BCS était significativement et positivement lié avec le KFI et le HTC. Pour le HTC, ce schéma tenait pour les adultes et les juvéniles, mâles et femelles; et en saison des pluies mais pas en saison sèche. En ce qui concerne le KFI, le BCS lui était significativement et positivement lié chez les adultes, les juvéniles et les mâles, mais pas les femelles. En général, nos résultats suggèrent que la technique de BCS peut être une méthode utile pour évaluer la condition corporelle des buffles. [source] Metformin,pioglitazone and metformin,rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndromeJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2006G. Derosa MD PhD Summary Background and objective:, Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. Methods:, This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration ,6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA1c), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. Results and discussion:, No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA1c decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. Conclusion:, For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not. [source] Overeducation in the Labour MarketJOURNAL OF ECONOMIC SURVEYS, Issue 3 2006Séamus McGuinness Abstract., This paper presents a review of the literature on overeducation. The paper assesses the consistency of overeducation within the context of a number of theoretical frameworks including Human Capital Theory (HCT) and Assignment Theory. The analysis goes on to discuss the various measurement controversies associated with the study of overeducation in order to provide an assessment of the extent to which the impacts of the phenomenon represent an economic reality as opposed to a statistical artefact. After reviewing the literature, it is concluded that the impacts of overeducation are likely to be non-trivial and that the phenomenon may potentially be costly to individuals and firms, as well as the economy more generally. The existence of overeducation also raises some doubts with respect to the validity of some of the central assumptions and predictions of HCT that are unlikely to be fully explained by gaps in the standard wage equation framework. [source] Principles of Peripheral Blood Mononuclear Cell Apheresis in a Preclinical Canine Model of Hematopoietic Cell TransplantationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2008M. Lupu Background: Preclinical studies of peripheral blood mononuclear cell (PBMC) transplantation conducted in a well-established canine hematopoietic cell transplantation (HCT) model have been successfully translated to human patients over the past 5 decades. Objective: We retrospectively investigated the safety and feasibility of PBMC apheresis in the canine model of HCT by analyzing apheresis parameters, cell yields, and the impacts of donor-related and apheresis-related variables on collection yields and donor stability. Animals: One hundred and twenty dogs that underwent PBMC aphereses were evaluated. Methods: Aphereses were performed with a COBE Spectra blood separator and a central dual-lumen catheter, with or without recombinant canine granulocyte colony-stimulating factor (rcG-CSF) stem cell mobilization. Results: Aphereses from dogs not given rcG-CSF yielded an average volume of 280 ± 42 mL containing an average of 15,086 ± 9,834 leukocytes/mL. Aphereses from dogs given rcG-CSF yielded an average volume of 261 ± 55 mL containing an average of 39,711 ± 24,488 leukocytes/mL. Higher pre-apheresis white blood cell (WBC) counts correlated with higher apheresis WBC yields (R=0.50, P<.0001). The correlations of collection time, inlet volume, and collection flow rate on WBC yields were statistically significant but only weak to moderate in magnitude (R=0.34, P=.0001; R=0.38, P=.0006; R=0.26, P=.002, respectively) as were the correlations of collection time and inlet volume on collection volumes (R=0.30, P=.002; R=0.42, P<.0001, respectively). All dogs recovered promptly after PBMC aphereses and catheter removal, without complications. Conclusions and Clinical Importance: These data may be useful for translating PBMC apheresis technology to the field of veterinary oncology for the treatment of dogs with hematologic malignancies. [source] Structure elucidation of new oleanane-type glycosides from three species of AcanthophyllumMAGNETIC RESONANCE IN CHEMISTRY, Issue 5 2010Gaoussou Timité Abstract From the roots of three species of Acanthophyllum (Caryophyllaceae), two new gypsogenic acid glycosides, 1 and 2, were isolated, 1 from A. sordidum and A. lilacinum, 2 from A. elatius and A. lilacinum, together with three known saponins, glandulosides B and C, and SAPO50. The structures of 1 and 2 were established mainly by 2D NMR techniques as 23- O -,- D -galactopyranosylgypsogenic acid-28- O -,- D -glucopyranosyl-(1,3)-[,- D -glucopyranosyl-(1,6)]-,- D -galactopyranoside (1) and gypsogenic acid-28- O -,- D -glucopyranosyl-(1,3)-[,- D -glucopyranosyl-(1,6)]-,- D -galactopyranoside (2). The cytotoxicity of several of these saponins was evaluated against two human colon cancer cell lines (HT-29 and HCT 116). Copyright © 2010 John Wiley & Sons, Ltd. [source] The outcome of IgD myeloma after autologous hematopoietic stem cell transplantation is similar to other Ig subtypes,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Manish Sharma IgD myeloma is a rare subtype of myeloma that is associated with an aggressive course, resistance to chemotherapy, and a poor outcome. We identified 17 patients with IgD myeloma, who received a hematopoietic stem cell transplantation (HCT) at our institution between August 1988 and June 2008. Fifteen of these 17 patients underwent an autologous (auto) HCT. Complete responses (CRs) were seen in 6 of 15 (40%) patients; three converted from partial response to CR, two from minimal response to CR, and one from very good partial response to CR. The overall response rate after auto HCT was 86% (13 of 15). Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median PFS and OS were 18 and 45 months, respectively. These results were comparable with patients receiving autologous HCT for other Ig subtypes of myeloma. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Saiko Kurosawa Relapse/progression after allogeneic hematopoietic cell transplantation (allo-HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo-HCT. Among them, 93 (32%) showed relapse/progression. Cohort 1 was chosen to receive no interventions with curative intent (n = 25). Cohort 2 received reinduction chemotherapy and/or donor lymphocyte infusion (n = 48), and Cohort 3 underwent a second allo-HCT (n = 20). Sixty-three patients received reinduction chemotherapy, and 27 (43%) achieved subsequent complete remission (CR). The incidence of nonrelapse mortality (NRM) was similar among the three cohorts (4, 15, and 5%). The 1-year overall survival (OS) after relapse was significantly better in patients with a second HCT (58%) than in others (14%, Cohorts 1 and 2; P <.001). However, the 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after the second HCT. Multivariate analysis showed that reinduction chemotherapy, CR after intervention, second HCT, and longer time to post-transplant relapse were associated with improved survival. In conclusion, for patients with relapse after allo-HCT, successful reinduction chemotherapy and a second HCT may be effective for prolonging survival without excessive NRM. However, effective measures to prevent disease progression after a second HCT clearly need to be developed. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] First phase insulin release and glucose tolerance in children with Fanconi anemia after hematopoietic cell transplantationPEDIATRIC BLOOD & CANCER, Issue 2 2009Lynda E. Polgreen MD Abstract Background Fanconi anemia (FA) is an autosomal and X-linked recessive disease of chromosomal instability, which results in bone marrow failure. Children with FA have been shown to have an increased risk of diabetes mellitus (DM). Procedure A cross-sectional study of glucose and insulin metabolism was conducted in 17 children with FA who had undergone hematopoietic cell transplantation (HCT) at the University of Minnesota. First phase insulin release (FPIR) was determined by intravenous glucose tolerance test (IVGTT). Oral glucose tolerance test (OGTT), lipid panel, blood pressure, and medical history were reviewed for additional metabolic abnormalities. Results Seventeen FA participants, median age 11.3 (range 5.5,17.6) years, were evaluated. IVGTT identified three separate groups: low FPIR, normal FPIR, and high FPIR. Those with low FPIR were more likely to have low BMI, but had normal glucose levels. Those with high FPIR, had high BMI, elevated lipids, and body fat. One patient with normal FPIR had impaired glucose tolerance and another with normal FPIR had impaired fasting glucose. No participant was diagnosed with DM by fasting glucose, 2 hr glucose during OGTT, or hemoglobin A1C. Conclusions The majority of children with FA had normal glucose tolerance and normal beta-cell function after HCT. Two small subsets of patients had lower than expected and higher than expected FPIR. The clinical significance of these differences is not yet known given the normal glucose tolerance and fasting glucose levels in these two groups. Pediatr Blood Cancer 2009;53:191,196. © 2009 Wiley-Liss, Inc. [source] Pulmonary function in long-term survivors of pediatric hematopoietic cell transplantationPEDIATRIC BLOOD & CANCER, Issue 5 2006Paul A. Hoffmeister MPH Abstract Background The purpose of this study was to determine the prevalence of pulmonary dysfunction in pediatric hematopoietic cell transplant (HCT) survivors and to identify associated risk factors. Procedure In a cross-sectional study, patients surviving at least 5 years after pediatric HCT were requested to undergo pulmonary function testing (PFT). Risk factors for restrictive lung disease (RLD) and obstructive lung disease (OLD) were analyzed using multivariate analysis. Results Among 472 patients contacted, 260 (55%) participated and 215 were selected for analysis. These patients were transplanted at a median age of 8.3 (0.3,18.0) years; 175 for hematologic malignancies and 40 for non-malignant diseases. The preparative regimens for 133 patients included fractionated TBI (FTBI), 29 single-fraction TBI (SFTBI), and 53 non-TBI regimens. PFT was performed at a median of 10 (5.0,27.5) years after HCT. Forty percent of patients had either RLD or OLD (28% RLD, 9% OLD, 3% mixed RLD/OLD) and at least 15% had an isolated low-DLCO. Moderate-to-severe impairment was present in 45% of patients with RLD or OLD. In multivariate analysis, risk factors associated with RLD included transplant regimen, transplant diagnosis, scleroderma/contracture, and donor relation. Patients treated with SFTBI had the highest risk of RLD. Risk factors for OLD included chronic graft-versus-host disease, transplant regimen, and time after HCT. Patients surviving 20 or more years after HCT had the highest risk of OLD. Conclusions Fifty-five percent of long-term pediatric HCT survivors had pulmonary dysfunction. These findings stress the need for long-term follow-up to detect pulmonary dysfunction. Pediatr Blood Cancer 2006; 47:594,606. © 2005 Wiley-Liss, Inc. [source] BK virus nephropathy after allogeneic stem cell transplantation: A case report and literature review,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Lazaros J. Lekakis Polyomaviruses are increasingly recognized as important human pathogens. Among those, BK virus has been identified as the main cause of polyomavirus-associated nephropathy (PVAN), a major cause of renal allograft failure. PVAN has also been well described in the setting of non-renal solid organ transplantation. The reports of PVAN after hematopoietic stem cell transplantation (HCT) are surprisingly very few. Here, we describe a patient with treatment-related myelodysplastic syndrome who received an unrelated donor HCT after ablative conditioning and in vivo T cell depletion with alemtuzumab. He developed a biopsy-proven BK nephropathy, which contributed to his renal failure. Leflunomide as well as cidofovir were given at different times, both in combination with intravenous immunoglobulin. Both treatments were effective in reducing the BK viral load, the cystitis symptoms and both stabilized but did not really improved the renal function. The patient was still dialysis-dependent when he died from Pseudomonas sepsis 13 months after HCT. A critical review of the literature and the treatment modalities for post-HCT PVAN are provided. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] History of pediatric stem cell transplantationPEDIATRIC TRANSPLANTATION, Issue 2004Rainer Storb Abstract:, During the past 50 yr, intensive studies into the use of hematopoietic cell transplantation (HCT) for therapy of cancer and non-malignant hematologic diseases have changed this treatment modality from one that was thought to be plagued by insurmountable complications to one that is now standard therapy for some diseases. Continued research by transplant teams worldwide is likely to allow continued progress toward developing novel and improved treatment modalities and even wider application of the use of pluripotent hematopoietic stem cells in the treatment of human diseases. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioningAMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2008Tania N. Masmas Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5°C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were retransplanted. All but one engrafted successfully, but with decreased OS and PFS. Two patients received pentostatin infusion prior to donor lymphocyte infusions in unsuccessful attempts at reversing rejection. Storage temperature and donor chimerism had a significant effect on rejection. Following rejection, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection. Am. J. Hematol. 2008. © 2008 Wiley-Liss, Inc. [source] Effects of Nigella orientalis and N. segetalis fixed oils on blood biochemistry in ratsPHYTOTHERAPY RESEARCH, Issue 1 2006G. Kökdil Abstract Nigella orientalis and N. segetalis fixed oils were administered orally (1 mL/kg/day) to Wistar Kyoto rats for 4 weeks. The effects of the oils on biochemical parameters were compared with a control group that received distilled water under identical conditions. LDL-cholesterol level was decreased significantly in both oil groups while serum total cholesterol and VLDL-cholesterol were decreased significantly following administration of only N. orientalis fixed oil when compared with the control group. The HDL-cholesterol levels were increased significantly in both oil groups. N. orientalis fixed oil significantly reduced Aspartateaminotransferase (AST), Alkaline Phosphatase (ALP), bilirubin and urea levels in rats. There was an increase in the albumin, uric acid and mean corpuscular volume (MCV) concentrations, while the mean corpuscular hemoglobin concentration (MCHC) and RDW (red cell distribution width) levels decreased significantly. In N. segetalis fixed oil treated rats, the levels of ALP, Blood Urea Nitrogen (BUN), MCHC, RDW were decreased significantly, whereas a significant increase was found in albumin, fibrinogen, Hematocrit (HCT) and MCV levels. The effects of 4 weeks oral intake of N. orientalis and N. segetalis fixed oils on blood malondialdehyde (MDA) and total antioxidant status (TOS) were also investigated in rats. The study showed that the oils had no significant effect on MDA production. N. orientalis and N. segetalis fixed oils caused a significant increase in the total antioxidant status in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Positive reinforcement training affects hematologic and serum chemistry values in captive chimpanzees (Pan troglodytes)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 3 2006Susan P. Lambeth Abstract Positive reinforcement training (PRT) techniques have received considerable attention for their stress reduction potential in the behavioral management of captive nonhuman primates. However, few published empirical studies have provided physiological data to support this position. To address this issue, PRT techniques were used to train chimpanzees (Pan troglodytes) to voluntarily present a leg for an intramuscular (IM) injection of anesthetic. Hematology and serum chemistry profiles were collected from healthy chimpanzees (n=128) of both sexes and various ages during their routine annual physical examinations over a 7-year period. Specific variables potentially indicative of acute stress (i.e., total white blood cell (WBC) counts, absolute segmented neutrophils (SEG), glucose (GLU) levels, and hematocrit (HCT) levels) were analyzed to determine whether the method used to administer the anesthetic (voluntary present for injection vs. involuntary injection) affected the physiological parameters. Subjects that voluntarily presented for an anesthetic injection had significantly lower mean total WBC counts, SEG, and GLU levels than subjects that were involuntarily anesthetized by more traditional means. Within-subjects analyses revealed the same pattern of results. This is one of the first data sets to objectively demonstrate that PRT for voluntary presentation of IM injections of anesthetic can significantly affect some of the physiological measures correlated with stress responses to chemical restraint in captive chimpanzees. Am. J. Primatol. 68:245,256, 2006. © 2006 Wiley-Liss, Inc. [source] Chronic Kidney Disease Following Non-Myeloablative Hematopoietic Cell TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2006A. S. Weiss Chronic kidney disease (CKD) following myeloablative allogeneic hematopoietic cell transplantation (HCT) occurs in 20% of survivors at 1 year and is believed to be due to radiation nephritis. Non-myeloablative allogeneic HCT is a recent procedure that employs significantly lower doses of chemoradiotherapy, however, incidence and risk factors for CKD following non-myleoablative HCT have not been defined. We performed a retrospective cohort study of 122 patients from three institutions who were available for analysis at 6 months following non-myeloablative HCT. Patients received two Gy of radiation; 62% received fludarabine as preconditioning. CKD was defined as at least a 25% reduction in glomerular filtration rate (GFR) from baseline using the abbreviated modified diet in renal disease (MDRD) equation. Eighty-one of 122 patients (66%) showed evidence of CKD at follow-up. Multivariate analysis revealed that acute renal failure (ARF) during the first 100 days post-transplant was associated with development of CKD (Adjusted OR 32.8 with 95% CI 4.3,250) after controlling for other variables. Previous autologous HCT, long-term calcineurin inhibitor use and extensive chronic GVHD were independently associated with CKD. CKD following non-myeloablative HCT appears to be a distinct clinical entity and likely not related to radiation nephritis. Future research should focus on possible mechanisms for alleviating chronic injury and decreasing use of calcineurin inhibitors. [source] The effect of Eucommia ulmoides leaf supplementation on the growth performance, blood and meat quality parameters in growing and finishing pigsANIMAL SCIENCE JOURNAL, Issue 1 2009Sung Dae LEE ABSTRACT The aim of the present study was to investigate the effect of Eucommia ulmoides leaf (EUL) supplementation on the growth performance, blood and meat quality parameters in growing and finishing pigs. Ninety gilts (L × LW × D, 20 kg initialBW) were housed 10 per pen in a front-open building with three replicate pens per treatment. Experimental treatment was started from the beginning of the growing stage (20 ± 3 kg) by supplementing EUL at 0(C), 3(T1) and 5% (T2) to the growing and finishing diet. Pigs were slaughtered by electrical stunning at 105 ± 3 kg live weight. Average daily feed intake (ADFI, kg/day) decreased (P < 0.05) by addition of EUL in growth performance, average daily gain (ADG, kg/day) was lower (P < 0.05) in T1 and T2 than in C. In hematology, leukocytes (WBC, 103/mm3) decreased (P < 0.05) in T1 and T2 than in C. Erythrocytes (RBC, 106/mm3), hemoglobin (HGB, g/dL) and hematocrit (HCT, %) increased (P < 0.05) in T1 and T2 than in C. Platelet (PLT, 103/mm3) was lower (P < 0.05) in T2 than in C and T1. In biochemical composition of serum, total protein (g/dL), r-GTP (,/L), total cholesterol (mg/dL) and triglycerides (mg/dL) were lower (P < 0.05) in T1 and T2 than in C. On longissimus dorsi muscle, crude protein was higher (P < 0.05) in T1 than in C. Crude ash was higher (P < 0.05) in T1 and T2 than in C. Yellow to blue color scale (CIE b*) in meat color was higher (P < 0.05) in T2 than in C. CIE b* in back fat color was higher (P < 0.05) in T2 than in the other treatments. In sensory evaluation scores for fresh meat, the values of meat color, fat color, drip loss and marbling were not significantly affected by addition of EUL. In cooked meat, the values of chewiness and overall acceptability were higher (P < 0.05) in T1 and T2 than in C. The results indicate that the addition of EUL affected growth performance, blood parameters and meat quality parameters in growing and finishing pigs. [source] Perioperative Monitoring of Thromboelastograph on Hemostasis and Therapy for Cyanotic Infants Undergoing Complex Cardiac SurgeryARTIFICIAL ORGANS, Issue 11 2009Yongli Cui Abstract This study investigated features and treatments of perioperative coagulopathies in cyanotic infants with complex congenital heart disease (CCHD). Thirty-six infants with cyanotic CCHD were involved and divided into two groups: In group H (n = 20), hematocrit (HCT) > 54%, and in group L (n = 16), HCT < 54%. Blood was sampled at anesthesia induction (T1), rewarming to 36°C (T2), after heparin neutralization (T3), and 4 h after operation (T4). The hemostatic changes were evaluated by thromboelastograph (TEG). After surgery, group H was treated with fibrinogen-combined platelets (PLT), while group L was treated with PLT only. We observed the effect at T4. At T1, the hemostatic function in group H, deteriorating with the increase of HCT (P < 0.01), was obviously lower than that in group L (P < 0.01), but the PLT function was still complete. In group H, the hemostatic function at T2 decreased with a significant drop of PLT function (P < 0.01) and had little change of functional fibrinogen (Ffg) (P > 0.05). At T3, compared with T2, there were improvements in hemostatic function and Ffg (P < 0.01, respectively) without increase of PLT (P > 0.05) in group H. After therapy, PLT function in both groups restored to T1 level (P > 0.05); Ffg at T4 was significantly better than at T1 (P < 0.01) in group H, but Ffg at T4 with still normal function was lower than at T1 in group L (P < 0.01). Whole hemostatic function at T4 was back to normal and had no differences between two groups. So, we proposed that fibrinogen and PLT transfusion in combination should be better for infants with high HCT CCHD, but PLT alone might be enough for low HCT ones. [source] Surveys in Papua New Guinea to detect the presence of Trypanosoma evansi infectionAUSTRALIAN VETERINARY JOURNAL, Issue 12 2000SA REID Objective To confirm serological evidence that Trypano-soma evansi is present in Papua New Guinea. Design Three surveys were undertaken in PNG during 1997/1998. Animals were selected for sampling on the basis of convenience. Samples of blood were examined for the presence of T evansi b y the haematocrit centrifugation technique (HCT) and mouse inoculation test (MI). Sera were tested in the field using the card agglutination test for trypanosomiasis/T evansi(CATT). Bovine sera were tested at James Cook University using an antibody-detection ELISA (Ab-ELISA). Results from testing bovine sera with the Ab-ELISA and sera from wallabies with the CATT were analysed using FreeCalc to determine the probability that animals in these populations were infected with T evansi. Results A total of 545 serum samples were collected. during the three surveys of which 39 cattle, two pig and three agile wallaby samples were positive with the CATT. All bovine sera collected were negative when tested with an Ab-ELISA. T evansi was not isolated using the HCT or the MI from any of these animals. Conclusion Based on the Ab-ELISA results it was concluded that T evansi infection was not present in cattle in villages around Balimo at a minimum expected prevalence of 10% (P < 0.05) and, based on the CATT results, that infection was not present in wallabies on the Bula plain at a minimum expected prevalence of 10% (P < 0.1). These results indicate that it is unlikely that T evansi is endemic in PNG [source] High-Level Expression of Proteins in Mammalian Cells Using Transcription Regulatory Sequences from the Chinese Hamster EF-1, GeneBIOTECHNOLOGY PROGRESS, Issue 3 2004Jennifer Running Deer High-level expression of a recombinant protein in Chinese hamster ovary (CHO) cells typically requires the laborious and time-consuming procedure of stepwise gene amplification. We hypothesized that use of transcription control regions from a highly expressed gene in CHO cells to drive expression of a gene of interest might reduce the requirement for gene amplification. To this end, we cloned a 19 kb DNA fragment containing the Chinese hamster elongation factor-1, (EF-1,) gene, as well as 12 kb of 5, flanking sequence and 4 kb of 3, flanking sequence. Expression vectors containing 5, and 3, flanking sequences from the Chinese hamster EF-1, (CHEF1) gene were constructed and, after insertion of six different reporter genes, transfected into CHO cells. For comparison, CHO cells were also transfected with the same six reporter genes inserted into commercial vectors utilizing either the immediate early promoter from cytomegalovirus (CMV) or the human EF-1, promoter. The striking result from these studies was that average expression levels from pooled, stable transfectants of CHEF1 vectors were 6- to 35-fold higher than expression levels from commercial vectors that utilize the CMV or the human EF-1, promoters. We also used a CHEF1 vector to express a secreted and a membrane-bound protein in stably transfected non-CHO cell lines. CHEF1-driven expression of secreted alkaline phosphatase (SEAP) in three of four cell lines tested (HEK 293, K562, L1.2, and HCT 116) was 13- to 280-fold greater than that from a commercial vector employing the CMV promoter. After transfection of four different cell lines of hematopoietic origin (K562, L1.2, JY, and Jurkat), the CHEF1 vector was found to express the chemokine receptor CCR4 at >10-fold higher levels than that driven from a commercial vector utilizing the CMV promoter. Results from these experiments suggest that the CHEF1 vectors will be useful for high-level protein expression not only in CHO cells, but also in a variety of other mammalian cell lines. [source] Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant ResearchBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007Julie A. Panepinto Summary We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy. [source] Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005J. Zanis-Neto Summary Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft- versus -host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2,3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44,58) months and 16 (3,52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients. [source] Access to hematopoietic stem cell transplantationCANCER, Issue 14 2010Effect of race Abstract BACKGROUND: The purpose of the current study was to determine whether the use of hematopoietic stem cell transplantation (HCT) to treat leukemia, lymphoma, or multiple myeloma (MM) differs by race and sex. METHODS: The annual incidence of leukemia, lymphoma, and MM was estimated in the United States in people aged <70 years by race and sex using the Surveillance, Epidemiology, and End Results (SEER) cancer registry between 1997 and 2002 and US census reports for the year 2000. The annual incidence of autologous, human leukocyte antigen (HLA) identical sibling, and unrelated HCT performed in these groups was estimated using Center for International Blood and Marrow Transplant Research data from 1997 through 2002. Logistic regression analysis was used to calculate the age-adjusted odds ratio (OR) of receiving HCT for Caucasians versus African Americans and for men versus women. RESULTS: The likelihood of undergoing HCT was found to be higher for Caucasians than for African Americans (OR, 1.40; 95% confidence interval [95% CI], 1.34-1.46). This difference existed for each type of HCT: autologous (OR, 1.24; 95% CI, 1.19-1.30), HLA identical sibling (OR, 1.59; 95% CI, 1.46-1.74), and unrelated donor (OR, 2.02; 95% CI, 1.75-2.33). Overall, men were more likely than women to receive HCT (OR, 1.07; 95% CI, 1.05-1.1 [P < .0001]); however, this difference was found to be significant only for autologous HCT (OR, 1.10; 95% CI, 1.07-1.13 [P < .0001]). CONCLUSIONS: HCT is more frequently used to treat leukemia, lymphoma, and MM in Caucasians than in African American individuals. African Americans have lower rates of both autologous and allogeneic HCT, indicating that donor availability cannot fully explain the differences. Women are less likely than men to receive autologous HCT for reasons unexplained by age or disease status. Cancer 2010. © 2010 American Cancer Society. [source] Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantationCANCER, Issue 18 2009Stephanie Campbell BA Abstract BACKGROUND: Avascular necrosis (AVN) is a debilitating condition reported after chronic steroid use. The purpose of this study was to describe the magnitude of risk in individuals who survived ,1 years after hematopoietic cell transplantation (HCT), and to investigate the role of immunosuppressive agents such as prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and cyclosporine (CSA) in the development of AVN after HCT. METHODS: Using a retrospective study design, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. Cox proportional regression techniques were used to identify associated risk factors. RESULTS: The median age at HCT was 34 years (range, 7 months-69 years), and median length of follow-up for those surviving was 8.2 years. Seventy-five patients developed AVN of 160 joints. The cumulative incidence of AVN at 10 years was 2.9% after autologous HCT, 5.4% after allogeneic matched related donor HCT, and 15% after unrelated donor HCT (P < .001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (RR, 2.2); and exposure to CSA, FK506, prednisone, and MMF rendered patients at increased risk, especially in patients with a history of exposure to ,3 drugs (RR, 9.2; 95% CI, 2.42-35.24). CONCLUSIONS: Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition. Cancer 2009. © 2009 American Cancer Society. [source] Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactionsCANCER SCIENCE, Issue 8 2007Yoshiki Akatsuka Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versus-leukemia/lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed self-proteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT. (Cancer Sci 2007; 98: 1139,1146) [source] Two New Sesquiterpene Derivatives from the Tunisian Endemic Ferula tunetanaPom.CHEMISTRY & BIODIVERSITY, Issue 2 2010Aymen Jabrane Abstract A new sesquiterpene ester, tunetanin A (1), a new sesquiterpene coumarin, tunetacoumarin A (2), together with eight known compounds, i.e., coladin (3), coladonin (4), isosmarcandin (5), 13-hydroxyfeselol (6), umbelliprenin (7) propiophenone (8), , -sitosterol (9), and stigmasterol (10), were isolated from the roots of Ferula tunetana. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D- and 2D-NMR experiments and MS analysis, as well as by comparison with published data. The cytotoxicity of compounds 1,7 towards two human colon cancer cell lines, HT-29 and HCT 116, was evaluated. Compounds 3, 4, and 6 showed weak cytotoxic activities. [source] | |||||||||||||||||||||||||||||||||||||||||||