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51.
Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow 总被引:4,自引:8,他引:4
In the course of ontogeny, the homing site for the hematopoietic stem cells (HSC) moves with certain predictability from the yolk sac to the liver/spleen and then to the marrow. The pattern of this migration has thus far been established mostly on a morphologic basis. To delineate further the course of this migration and to gain insight into its possible mechanism, we used in utero transplantation of allogeneic or xenogeneic HSC in preimmune sheep fetuses. Sex chromosome, type of hemoglobin, and species-specific surface markers were used to follow the path of transplanted cells in the fetus. Before the development of the bone marrow, transplanted HSC (liver- or marrow-derived) homed exclusively to the liver/spleen. With the development of marrow, around day 60 of gestation (term, 145 days), homing occurred also in the nascent marrow and by day 80 transplanted cells homed exclusively to the marrow. This suggests that there may be a hierarchy in homing sites, with those of the marrow having higher affinity than those of liver/spleen. Interestingly, despite a change in homing that was followed by the expansion of the marrow compartment of HSC (ie, HSC proliferation), these cells did not participate actively in blood cell formation during most of the prenatal period. Liver remained the major hematopoietic organ throughout the gestation. It was only during the perinatal period that this organ assumed the function of hematopoiesis from the liver. This lack of expression of HSC in fetal marrow can possibly be attributable to the immaturity of marrow stroma required for differentiation and maturation of progenitors and the orderly egress of mature cells into the blood stream. The availability of this model allows us to begin studies in the molecular mechanism of stem cell homing in vivo during ontogeny. 相似文献
52.
Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen 总被引:1,自引:0,他引:1
We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML. 相似文献
53.
A new quantitative immunoperoxidase method is presented for determining absolute amounts of peroxidase and, consequently, surface antigen densities of individual cells in B lymphocytes from normal individuals, from subjects with CLL and prolymphocytic leukemia, and during ontogeny of B lympocytes in the mouse. The following results were observed: (1) The density of B antigenic sites were lower on CLL than on normal B lymphocytes. (2) The B antigens density of leukemic lymphocytes varied less from cell to cell, forming a homogeneous peak on histograms. (3) In a very rare case of CLL, the antigen density was measured at the time of initial diagnosis (22,500 sites or 647 U) and during the development of a blastic crisis (135,000 sites or 2576 U). The cell by cell distribution changed from a homogeneous peak with a low number of antigenic sites per cell to a heterogeneous peak with a high number of antigenic sites per cell. (4) In prolymphocytic leukemia, the density of B antigenic sites was greater than on normal B lymphocytes and much more heterogeneous than on CLL lymphocytes. (5) During ontogeny of B lymphocytes in the mouse, maturation is associated with the appearance of a population of cells of intermediate to high Smig density. The finding of a decrease in, and altered distribution of, surface markers in CLL is compared with these ontologic findings in the mouse, and the concept that a monoclonal B lymphocyte in CLL may be arrested at a particular stage in its differentiation is discussed. 相似文献
54.
Amalio Ruiz Salas José Peña Hernández Carmen Medina Palomo Alberto Barrera Cordero Fernando Cabrera Bueno José Manuel García Pinilla Ana Guijarro Luis Morcillo-Hidalgo Manuel Jiménez Navarro Juan José Gómez Doblas Eduardo de Teresa Javier Alzueta 《Revista espa?ola de cardiología》2018,71(12):1018-1026
Introduction and objectives
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC.Methods
This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing.Results
Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics.Conclusions
The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.Full English text available from:www.revespcardiol.org/en 相似文献55.
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59.
Andrew M. Zeiger Meghan E. McGarry Angel C. Y. Mak Vivian Medina Sandra Salazar Celeste Eng Amy K. Liu Sam S. Oh Thomas J. Nuckton Deepti Jain Thomas W. Blackwell Hyun Min Kang Goncalo Abecasis Leandra Cordero Oate Max A. Seibold Esteban G. Burchard Jose Rodriguez‐Santana 《Pediatric pulmonology》2020,55(2):533-540