210,149 research outputs found
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[Letter from Deborah Marrow to Phillip C. Diebel, September 7, 1999]
No full textA letter from Deborah Marrow to Phillip C. Diebel about informing Diebel that The Getty Grant Program has approved a one-to-one matching grant for the North Texas Institute for Educators on the Visual Arts
Clinical relevance of circulating tumour cells in the bone marrow of patients with SCCHN
No full textBackground: Clinical outcome of patients with head and neck squamous cell carcinoma (SCCHN) depends on several risk factors like the presence of locoregional lymph node or distant metastases, stage, localisation and histologic differentiation of the tumour. Circulating tumour cells in the bone marrow indicate a poor prognosis for patients with various kinds of malignoma. The present study examines the clinical relevance of occult tumour cells in patients suffering from SCCHN. Patients and Methods: Bone marrow aspirates of 176 patients suffering from SCCHN were obtained prior to surgery and stained for the presence of disseminated tumour cells. Antibodies for cytokeratin 19 were used for immunohistochemical detection with APAAP on cytospin slides. Within a clinical follow-up protocol over a period of 60 months, the prognostic relevance of several clinicopathological parameters and occult tumour cells was evaluated. Results: Single CK19-expressing tumour cells could be detected in the bone marrow of 30.7% of the patients. There is a significant correlation between occult tumour cells in the bone marrow and relapse. Uni- and multivariate analysis of all clinical data showed the metastases in the locoregional lymph system and detection of disseminated tumour cells in the bone marrow to be statistically highly significant for clinical prognosis. Conclusion: The detection of minimal residual disease underlines the understanding of SCCHN as a systemic disease. Further examination of such cells will lead to a better understanding of the tumour biology, as well as to improvement of diagnostic and therapeutic strategies
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Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease
No full textBackground— Cell therapy with bone marrow–derived stem/progenitor cells is a novel option for improving neovascularization and cardiac function in ischemic heart disease. Circulating endothelial progenitor cells in patients with coronary heart disease are impaired with respect to number and functional activity. However, whether this impairment also extends to bone marrow–derived mononuclear cells (BM-MNCs) in patients with chronic ischemic cardiomyopathy (ICMP) is unclea
Rescue of myeloid lineage-committed preprogenitor cells from cytomegalovirus-infected bone marrow stroma
No full textThe effect of murine cytomegalovirus on myelopoiesis was studied in long-term bone marrow culture to find an in vitro correlate for the lethal virus interference with bone marrow reconstitution (W. Mutter, M. J. Reddehase, F. W. Busch, H.-J. Bühring, and U. H. Koszinowski, J. Exp. Med. 167:1645-1658, 1988). The in vitro generation of granulocyte-monocyte progenitors (CFU-GM) discontinued after infection of the stromal cell layer, whereas the proliferation and differentiation of CFU-GM to granulocyte-monocyte colonies remained unaffected. A protocol was established to probe the functional integrity of earlier hematopoietic cells. Pre-CFU-GM (the progenitors of the CFU-GM) could be recovered from an infected bone marrow donor culture by transfer onto an inductive recipient stromal cell layer. Thus, at least in vitro, infection of bone marrow stroma appears to be the only cause of the defect in myelopoiesis
Bone marrow derived cells as endothelial precursors and the role of multi-potent progenitor cells in repairing ischaemic tissues.
No full textPhDIntroduction: Atherosclerosis and its complications are a major cause of death and
disability and it remains a major challenge to develop new therapies for patients with
irreversible end organ damage and ongoing ischaemia. The discovery of adult stem
and progenitor cells with the ability to regenerate adult tissues holds great promise.
Bone marrow is the source of both endothelial progenitor cells (EPCs) and multi-potent
adult progenitor cells (MAPCs). MAPCs are rare pluripotent bone marrow derived cells
with the theoretical potential to differentiate into tissues of all three germ cell layers,
including endothelium. These cells may have the potential to facilitate cardiac repair.
The aim of this thesis was to further characterise bone marrow derived endothelial
progenitor cells including multi potent adult progenitor cells and assess their angiogenic
potential and mechanisms of action in animal models of cardiovascular disease.
Findings: EPCs were isolated from humans and mice and their phenotype, markers
and function determined, including gene tracking experiments in mice utilising the
Cre/Lox system. It was not possible to isolate cells with the same phenotype as
MAPCs from rodent bone marrow. However, cells with pluri-potent properties, named
rat multi-potent progenitor cells (rMPCs), were isolated from rat bone marrow. These
cells had the ability to up regulate tissue specific antigens from all 3 germ cell lineages
and in addition secreted multiple cytokines related to angiogenesis and inflammation.
To investigate the in vivo properties of rMPCs a rat hind limb model of ischaemia was
established and syngeneic rMPCs were transplanted into the ischaemic hind limbs.
rMPCs engrafted selectively into the adventitia of arterioles of ischaemic muscles.
However, engrafted cells did not differentiate into an endothelial or smooth muscle
phenotype. Cytokine analysis of muscles 5 days after rMPC injection revealed raised
levels of cytokines, including chemokines MCP1 and SDR. Limb perfusion, measured
by microspheres, increased after rMPC injection. In addition a novel MRI based
assessment of ischaemic muscles revealed a significant normalisation of MRI signal
after rMPC transplantation. However, there was no improvement in limb function
assessed by treadmill running distance 4 weeks after cell injection. These findings
suggest that transplantation of rMPCs into ischaemic muscles may modulate local
inflammatory and angiogenic responses through paracrine mechanisms.
Conclusion: Despite the potential for stem and progenitor cells to be used for the
treatment of chronic cardiac ischaemia the biology of stem cells is still relatively poorly
understood, as is the mechanism of action of cells after transplantation. As set out in
the aims, the work in this thesis adds further to our understanding of both EPCs and
BM derived pluri-potent stem cells. In addition it provides insight into the hind limb
ischaemia model and the mechanism of action of cell therapy after transplantation into
ischaemic muscle
Transplant anxieties : discourses about bone marrow
No full textIncludes bibliographical references (leaves 89-94).This minor dissertation examines the various discourses in the Bone Marrow Transplant (BMT) network in South Africa. The organisations in the network which were observed using participant observation were the South African Bone Marrow Registry and the Sunflower Fund to complement this, the researcher interviewed staff members at these organisations as well as at a public hospital haematology unit in the Cape Town area that conducts BMT. Additionally patients, donors, and their family members were interviewed. Some media related to the BMT network was also analysed. Informed heavily by Troy Duster's work on genetic and social feedback loops, it was found that the discourses reflect a complex interweaving of biological materiality, ethnicity, culture, mortality, health resource rationing, South African nationhood, and the limits of bodily integrity. There is extensive discussion of how the BMT discourses demonstrate the necessity of engagement with several issues: the hybridity of expert and lay intercultural communication, health inequalities, human rights, and the prioritisation of first and third world medicine, the meanings of race, culture, ethnicity, and nationhood in a diverse South Africa, conceptions of donor shortage, and the imperative of saving lives through medical practise
Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite
Prospective isolation of human bone marrow stromal cell subsets: a comparative study between Stro-1-, CD146- and CD105-enriched populations
No full textStro-1 has proved an efficacious marker for enrichment of skeletal stem and progenitor cells although isolated populations remain heterogeneous, exhibiting variable colony-forming efficiency and osteogenic differentiation potential. The emerging findings that skeletal stem cells originate from adventitial reticular cells have brought two further markers to the fore including CD146 and CD105 (both primarily endothelial and perivascular). This study has compared CD146-, CD105- and Stro-1 (individual and in combination)-enriched human bone marrow stromal cell subsets and assessed whether these endothelial/perivascular markers offer further selection over conventional Stro-1. Fluorescent cell sorting quantification showed that CD146 and CD105 both targeted smaller (2.22% ± 0.59% and 6.94% ± 1.34%, respectively) and potentially different human bone marrow stromal cell fractions compared to Stro-1 (16.29% ± 0.78%). CD146+, but not CD105+, cells exhibited similar alkaline phosphatase-positive colony-forming efficiency in vitro and collagen/proteoglycan deposition in vivo to Stro-1+ cells. Molecular analysis of a number of select osteogenic and potential osteo-predictive genes including ALP, CADM1, CLEC3B, DCN, LOXL4, OPN, POSTN and SATB2 showed Stro-1+ and CD146+ populations possessed similar expression profiles. A discrete human bone marrow stromal cell fraction (2.04% ± 0.41%) exhibited positive immuno-labelling for both Stro-1 and CD146. The data presented here show that CD146+ populations are comparable but not superior to Stro-1+ populations. However, this study demonstrates the critical need for new candidate markers with which to isolate homogeneous skeletal stem cell populations or skeletal stem cell populations which exhibit homogeneous in vitro/in vivo characteristics, for implementation within tissue engineering and regenerative medicine strategies
Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues derived from different adult human CD34-negative progenitor cell clones
No full textAdult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates ( spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment. Copyright (C) 2005 S. Karger AG, Basel
High-dose melphalan with autologous hematopoietic stem cell transplantation for acute myeloid leukemia: results of a retrospective analysis of the Italian Pediatric Group for Bone Marrow Transplantation
No full textThis retrospective study from the Italian Association of Pediatric Hematology Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the results of consolidation with high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1). From October 1994 to July 1999, 20 patients (median age 9.9 years, range 0.11-16.2) were treated in six centers. Eighteen had de novo AML and two had secondary AML. According to BFM criteria, 10 were classified as standard- and 10 as high-risk patients, respectively. The median time from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months (range 0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging with either mafosfamide (three) or in vivo interleukin-2 (four) was performed in seven of 20 patients. Melphalan was administered at a dosage of 150-220 mg/m(2) (median 180). Median total number of nucleated cells infused was 2.5 x 10(8)/kg (range 1.1-8.9). The myeloablative regimen was well tolerated with no toxic death, veno-occlusive disease or life-threatening complications. All patients had hematopoietic recovery in a median time of 27 days for neutrophils and 44 days for platelets. Eight of 20 patients relapsed after a median time of 7.2 months from transplant (range 5.7-15.9). Six of them died (five of progression of disease and one of sepsis) while the remaining two patients are alive in CR2. The 3-year cumulative probability of survival and event-free-survival (EFS) is 62% and 56%, respectively. This study showed that in pediatric patients with AML consolidation of CR1 with high-dose melphalan allows survival and EFS to be obtained comparable to other auto-HSCT or chemotherapy published series with a potential sparing effect both on duration of treatment (with respect to chemotherapy) and on long-term side-effects (with respect to auto-HSCT with TBI or busulfan containing regimens). PMID:11509930[PubMed - indexed for MEDLINE] Free full tex
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