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A Keating

Publications and source records attributed to A Keating.

155 records · Page 9Linked to original sources
PubMed1984

Evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies of patients with clonal hematopoietic neoplasia.

The origin and nature of cells forming the in vitro microenvironment in long-term cultures of human marrow were studied in five patients with clonal myeloproliferative disorders who were heterozygous for glucose-6-phosphatase dehydrogenase (G6PD). The results showed that cells in the adherent stromal layer forming the in vitro microenvironment were derived from the same clonal progenitors involved by the neoplasm in the four patients whose diseases originated in multipotent stem cells. In contrast, stromal cells were derived from normal progenitors in a patient with acute non-lymphocytic leukemia whose clone showed differentiative expression confined to cells in the granulocytic lineage. Mixing experiments demonstrated that the G6PD type displayed by the adherent marrow stromal cells was not obscured by contaminating non-adherent hematopoietic cells or marrow fibroblasts. The data suggest the existence of a pluripotent cell in normal hematopoiesis that gives rise to hematopoietic cells and to their micro-environment.

Adult↗
PubMed1984

The generation of human long-term marrow cultures from marrow depleted of Ia (HLA-DR) positive cells.

Successful long-term cultures were generated from marrow buffy-coat cells incubated with either of two monoclonal anti-Ia antibodies, 7.2 and HBIOa, and complement. The mean CFU-GM toxicity for 7.2 and HBIOa was 81% and 94%, respectively, of the complement control. Cultures generated from marrows treated with 7.2 and complement produced between 30% and 163% of the CFU-GM (mean, 78.2 +/- 52.4%) and 33% of the BFU-E produced by the complement control cultures. Long-term cultures from marrows treated with the more cytotoxic HBIOa antibody yielded 261% of the CFU-GM present at culture initiation. Our data suggest that the progenitor cells necessary for generation of long-term cultures from human marrow are Ia-negative and may represent less mature stem cells than those measurable by semisolid colony assays. Furthermore, marrow treated with cytotoxic anti-Ia antibodies may be suitable for use in autologous transplantation.

Antibodies, Monoclonal↗
PubMed1983

Studies on the in vitro microenvironment in man.

In a preliminary manner, the data presented here characterize some features of MSC and their progenitors. The progenitors, at least in chronic myelogenous leukemia, are derived from the neoplastic pluripotent stem cell that also differentiates along lymphoid and myeloid pathways. In addition, we have demonstrated that the precursor for MSC is lacking both the Ia and CALLA determinants. Several antigenic and functional characteristics of the mature stromal cell population have also been identified. Stromal cells express CALLA, synthesize types I, III, and IV collagen, and may express factor VIII associated antigen. It is of interest that fibroblasts do not express factor VIII associated antigen, do not synthesize type IV collagen in measurable quantities, but do express CALLA [9]. Endothelial cells express factor VIII associated antigen, synthesize type IV collagen, but are not CALLA positive. Thus, MSC have some features in common with fibroblasts and others with endothelial cells. The unique characteristics of MSC are that they are transplantable and are derived from a common progenitor with other hematopoietic cells. These features clearly distinguish this cell population from fibroblasts, which are neither transplantable nor derived from the neoplastic clone in CML.

Anemia, Aplastic↗
PubMed1983

Cultured marrow stromal cells express common acute lymphoblastic leukaemia antigen (CALLA): implications for marrow transplantation.

This study demonstrates the presence of an antigenic determinant associated with the common acute lymphoblastic leukaemia antigen (CALLA), and presumably CALLA itself, on stromal cells in normal human long-term marrow cultures by using two monoclonal anti-CALLA antibodies, J-5 and 24.1. Treatment of cultured stromal cells with antibody and complement resulted in the loss of most flat angulated cells and many of the fat-containing cells. However, long-term cultures were generated with cytotoxic antibody-treated marrow buffy coat cells, and the stromal cells in these cultures were also CALLA-positive. We conclude that CALLA-bearing stromal cells arise from CALLA-negative progenitors. CALLA therefore could be either a differentiation antigen acquired on mature marrow stromal cells or may arise as a proliferation-dependent antigen. These studies suggest that the generation of long-term cultures from cytotoxic antibody-treated marrow may be an appropriate in vitro model for the functional assessment of such marrow prior to its use in autologous transplantation.

Antibodies, Monoclonal↗
PubMed1983

Long-term stable hematopoietic chimerism following marrow transplantation for acute lymphoblastic leukemia: a case report with in vitro marrow culture studies.

This article describes the course of a patient who received an allogeneic marrow graft from his HLA-identical sister for acute lymphoblastic leukemia in second remission. In the second month after grafting, marrow aspirates showed the presence of 7%-10% lymphoblasts. In addition, cytogenetic examination indicated the persistence of host cells. Thereafter, the patient had morphologically normal marrow examinations, with no evidence for recurrent leukemia. In addition, stable hematopoietic chimerism in both the lymphoid and myeloid cell lines has persisted for over 5 yr. Between 20% and 50% of phytohemagglutinin-stimulated peripheral blood mononuclear cells were host-derived on repeated studies. A marrow sample 4 yr after transplantation was established in long-term culture and produced 2% host granulocyte-macrophage colonies at its inception, but 24% host colonies by week 4. Despite this persistent chimerism, no in vitro or in vivo abnormalities of hematopoiesis have been detected.

Bone Marrow Transplantation↗
PubMed1982

Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man.

The method for long-term culture of marrow cells in vitro as described by Dexter has recently been successfully applied to human marrow and is dependent on the development of an adherent stromal cell layer consisting of cells described as "endothelial-like cells, fat cells, and macrophages". The present study was designed to determine the origin and composition of the stromal cells forming the in vitro 'microenvironment' and maintaining haematopoiesis in long-term cultures grown from marrows of 14 patients who received marrow transplants from HLA identical siblings of the opposite sex. The presence of a Y chromosome was used as a marker to establish the donor or recipient origin of the cells. We found that the stromal cells became progressively donor in origin with time after transplantation and some reacted with antibody directed against factor VIII-associated antigen. In addition, donor-derived in vitro stromal cells synthesized both interstitial and basal lamina collagen types, indicating that the in vitro microenvironment is transplantable and composed in part of endothelial-like cells.

Adipose Tissue↗
PubMed1981

Malakoplakia: evidence for an acquired disease secondary to immunosuppression.

A 44-year-old man was maintained on prednisone and azathioprine after renal transplantation. One and a half years after transplantation, he developed multiple perianal Escherichia coli abscesses. These became chronic and resisted antibiotic therapy. Histologically, the lesions were typical of malakoplakia. Peripheral blood neutrophils and monocytes had impaired killing of Staphylococcus aureus and E. coli in vitro. No abnormality of hexose monophosphate pathway activity, tetrazolium dye reduction, lysosomal degranulation, or cyclic nucleotides could be demonstrated in either neutrophils or monocytes. Cholinergic agonists in vitro and in vivo did not improve bacterial killing by these cells. The infection resolved rapidly and bacterial killing returned to normal when the dose of azathioprine was reduced. Our findings, when considered with previous reports, suggest that there are different causes of malakoplakia and malakoplakia may be more common than previously thought. The etiology of malakoplakia should be identified for each patient if appropriate treatment is to be given.

Adult↗
PubMedDate not supplied

Blood stem cell collection: factors influencing the recovery of granulocyte-macrophage colony forming cells.

We evaluated data from all blood cell (BC) collections performed in our institution between 1989 and 1995 to determine factors influencing the outcome of collection. One hundred and thirty-three collections were performed on 106 patients. Malignant diagnoses were: non-Hodgkins lymphoma (NHL) in 35%, multiple myeloma in 31%, breast cancer in 26%, and Hodgkin's disease in 8%. Collections were obtained routinely in myeloma and breast cancer and due to bone marrow involvement with malignancy or inaspirable bone marrow in lymphoma patients. Collections were obtained on a Cobe Spectra or Baxter-Fenwall CS3000+. Engraftment potential was determined by methylcellulose colony assay (CFU-GM), with a target of > 10 x 10(4) CFU-GM/kg. Apheresis nucleated cell count correlated significantly, albeit weakly (r = 0.26), with CFU-GM with a cell count of > 5 x 10(8)/kg resulting in an adequate number of CFU-GM in 78% of patients. In univariant analysis outcome of collection was significantly influenced by the patients age (p = 0.01), malignant diagnosis (p < 0.001), reason for collection (p = 0.002), and the mobilization regimen (p = 0.01). The nature of the apheresis device used did not influence outcome. Only malignant diagnosis was significant (p < 0.001) in multivariate analysis. We conclude that the outcome of BC is most strongly influenced by patient factors such as malignant diagnosis. These factors must be considered when comparing the outcome of different mobilization regimens and when planning collection strategies.

Adolescent↗
PubMedDate not supplied

Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay.

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.

Adolescent↗