Search PubMed⌕ Search

Biomedical subjects

L Kearney

Publications and source records attributed to L Kearney.

67 records · Page 4Linked to original sources
PubMed1991

DNA sequences of chromosome 21-specific YAC detect the t(8;21) breakpoint of acute myelogenous leukemia.

The t(8;21)(q22;q22) is a nonrandom translocation specifically marking blasts of acute myelogenous leukemia (AML) with undifferentiated phenotype. The breakpoint on chromosome 21 involved by this rearrangement has been precisely localized relative to cloned DNA markers by physical and genetic linkage analysis enabling the use of positional cloning for its isolation. Yeast artificial chromosome (YAC) clones for loci proximal (D21S65) and distal (ERG) to the (21q22) breakpoint have been developed and their chromosome 21 origin and location relative to the breakpoint has been established. By using in situ hybridization analysis, a 240 kb YAC clone for the D21S65 locus clearly identified both derivative chromosomes of the (8;21) translocation in metaphase spreads of leukemia blasts with the rearrangement. The characterization of the DNA sequences contained in this 240 kb YAC can reveal the functional consequences of their derangement in leukemia with abnormalities of the (21q22) region.

Base Sequence↗
PubMed1990

Enhancing the Viability of Lactobacillus plantarum Inoculum by Immobilizing the Cells in Calcium-Alginate Beads Incorporating Cryoprotectants.

Many literature reports have cited the importance of the rehydration conditions of lyophilized cultures in determining viability. The rate of rehydration and the volume of fluid used have been identified as two important factors. One possible means of controlling these is by immobilizing the cells before lyophilization within a gel matrix in which the subsequent rehydration rate and fluid volume would be controlled by the properties of the gel. In this study Lactobacillus plantarum was immobilized and lyophilized in Ca-alginate beads in which 1 M glycerol or 0.75 M adonitol with skim milk were incorporated as a cryoprotectant. The properties of these Ca-alginate beads were examined before and after lyophilization and rehydration. The beads incorporating glycerol were smaller and stronger than those with adonitol. After lyophilization, size decreased and strength increased but to a greater extent in the beads with glycerol, indicating that the microenvironment within the two bead types was probably different. The protective effect of the bead microenvironment on immobilized L. plantarum was also examined. Lyophilization and rehydration within the alginate beads with either polyol yielded higher survival rates than that attained with free cell cultures during rehydration in optimal or suboptimal conditions. During rehydration under suboptimal conditions, the immobilized cell survival was greatest when 0.75 M adonitol was the incorporated cryoprotectant.

Journal Article↗
PubMed1987

Establishment and characterization of three new malignant lymphoid cell lines.

We have established 3 new EBV-negative cell lines, designated Sc-1, Ri-1 and Ci-1, from patients with B-cell lymphoma/leukemia. We characterized them by cytogenetics and by study of surface membrane antigens with a panel of monoclonal antibodies (MAbs), surface and cytoplasmic immunoglobulin (Ig) expression and Ig heavy- and light-chain genes. All 3 lines had a 14q+ abnormality. Ri-1 also had translocations involving chromosomes 2, 8 and 18. Ci-1 also had abnormalities involving chromosomes 2, 8 and 22 and its karyotype was 46, XX, t(2;8), t(14;22). The t(2;8) had the same breakpoints as those reported in some cases of Burkitt's lymphoma. We also studied a classical Ph1-positive cell line previously established by Pegoraro et al. (1983) and designated BV173. The phenotypes of these 4 lines based on Ig expression and marker studies correlated well with their respective genotypes. Our results are in keeping with the notion that leukaemic cell populations are clonal expansions of cells "frozen" at a particular stage in their differentiation. Specifically, BV173 cells are at an early stage of B-cell differentiation, Ri-1 and Ci-1 cells are at intermediate stages and Sc-1 cells are at a relatively late stage in the B-cell lineage.

Adult↗
PubMed1987

Mechanisms of the development and resolution of paradoxical interventricular septal motion after uncomplicated cardiac surgery.

Of 16 patients with normal preoperative left ventricular (LV) function studied by simultaneous two-dimensional and M-mode echocardiography before and after uncomplicated cardiac surgery, M-mode interventricular septal motion remained normal in seven (group I) and was paradoxical in nine (group II) 7 to 13 days postoperatively, but was normal in all 12 patients (7 group II) studied 3 to 18 months later. An abnormal systolic increase in normalized septal curvature, the essential feature of truly paradoxical septal motion, was not observed in either group during any study period (mean = 0.92 +/- 0.08), nor were significant differences found in septal thickening, LV fractional shortening, or fractional area change. In contrast, systolic anterior motion of the LV center increased from -0.1 +/- 1.6 mm preoperatively to 4.8 +/- 2.5 mm postoperatively in group II (p less than 0.001), and the LV posterior wall motion:thickening ratio increased from 1.10 +/- 0.33 to 2.16 +/- 0.45 (p less than 0.01), but both parameters had returned to preoperative levels at the follow-up study. Both parameters remained stable in group I during all study periods. In addition, direct intraoperative M-mode recordings (n = 14) demonstrated normal septal motion in both groups before chest closure, but esophageal echocardiograms (n = 10) demonstrated exaggerated anterior systolic LV motion within 2 hours of surgery in those from group II. Thus, early after uncomplicated cardiac surgery, apparently paradoxical septal motion relative to a fixed reference point is an artifact due to exaggerated cardiac mobility that resolves with the progressive restraining effect of postoperative adhesions.

Adult↗
PubMed1986

Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL.

We carried out cytogenetic analysis in 23 patients with Ph-positive chronic granulocytic leukemia in blast crisis. In all cases the type of blast cell was characterized by cytochemistry, immunologic markers, and ultrastructural studies. Twelve cases were classified as myeloid transformation, six as lymphoid, two as mixed (lymphoid and myeloid), and two were unclassifiable. Duplication of Ph was the most frequent abnormality in the whole series. Trisomy 8, i(17q) and trisomy 19 were seen only in patients with myeloid blast crisis (53%, 30%, and 23%, respectively). Our findings suggest that the nature of additional chromosome abnormalities arising in blasts with features of myeloid differentiation are different from those in blasts showing lymphoid differentiation.

Adult↗
PubMed1985

Blast crisis of chronic granulocytic leukemia with mast cell and basophilic precursors.

The authors report a patient with Ph1-positive chronic granulocytic leukemia (CGL) who developed "blast crisis" after six years of chronic phase. The presence of mast cell precursors and basophil blasts was demonstrated by ultrastructural morphology and cytochemistry. Membrane phenotype studies with monoclonal antibodies helped in the further characterization of these cells. The possible implication of these findings in the origin of mast cells and the relationship of these cells with basophils are discussed.

Adult↗
PubMed1985

Osteolytic lesion as the presenting feature of chronic granulocytic leukaemia.

We describe a woman in whom the first manifestation of chronic granulocytic leukaemia (CGL) was an osteolytic lesion. Six months later the peripheral blood showed the picture of CGL in blast crisis. Chromosome studies confirmed the diagnosis and immunological and ultrastructural studies demonstrated the presence of two blast populations: basophil blasts and megakaryoblasts.

Aged↗
PubMed1984

Chemotherapy and autografting for chronic granulocytic leukaemia in transformation: probable prolongation of survival for some patients.

Between June 1977 and July 1983 51 patients with Ph1-positive chronic granulocytic leukaemia (CGL) in transformation were treated either by chemotherapy or by chemoradiotherapy followed by autografting with haemopoietic stem cells collected from their peripheral blood at the time of diagnosis. Forty-eight patients were restored to a second chronic phase. The median duration of survival after autografting was 26 weeks (range 2-152 weeks). Twenty-one patients with relatively long durations of second chronic phase were treated again by autografting as consolidation or when transformation recurred; this selected group of patients survived longer than the 30 patients treated by autografting only once (medians 52 v. 13 weeks respectively, P less than 0.01). There was no significant influence of the patients' age, splenectomy status, type of transformation, treatment pre-autograft or number of nucleated cells autografted on the duration of survival. Three patients treated in myeloid blastic transformation were restored to partially Ph1-negative haemopoiesis. We conclude that this approach to the management of CGL in transformation can offer benefit for a minority of patients and that further chemotherapy and autografting for patients still in second chronic phase may be valuable.

Adolescent↗
PubMed1983

Effects of human marrow stromal cells on proliferation by human granulocytic (GM-CFC), erythroid (BFU-E) and mixed (Mix-CFC) colony-forming cells.

We have investigated the effects of the major components of bone marrow stroma (fibroblasts, fat cells, macrophages and endothelial cells) on colony-forming haemopoietic precursor cells. Selective cultures of the different stromal cell types, grown to confluence, were used as underlayers for agar or methylcellulose cultures containing bone marrow cells. In different experiments, colony-stimulating factor (CSF) was added to stimulated granulocyte-macrophage colony-forming cells (GM-CFC), erythropoietin was used to induce erythroid burst (BFU-E) formation or erythropoietin and medium conditioned by leucocytes in the presence of phytohaemagglutinin (PHA-LCM) was added to induce the formation of colonies of mixed myeloid lineage (Mix-CFC). Fibroblasts grown from human marrow enhanced granulopoiesis when CSF was present in the cultures but suppressed the formation of BFU-E and mixed colonies. Treatment of the cultures with methylprednisolone induced the formation of fat cells in the fibroblast cultures and prevented both the fibroblast-mediated enhancement of granulopoiesis and the fibroblast-mediated suppression of erythropoiesis. Stromal macrophages reduced granulocyte colony formation but had little effect on the proliferation of BFU-E or mixed colony-forming cells. Endothelial cells stimulated granulopoiesis by releasing CSF into the culture supernatant; supernatant from endothelial cell cultures had no marked effects on either BFU-E or Mix-CFC. We conclude that different components of marrow stroma have contrasting effects on erythropoiesis and granulopoiesis; thus, marrow stroma may regulate the expression of stem cell differentiation in vivo.

Bone Marrow Cells↗
PubMed1982

HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells.

We studied the capacity of murine monoclonal antibodies with HLA-DR specificity to inhibit the proliferation in vitro of erythroid (BFU-E and CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in normal bone marrow and the blood of patients with chronic granulocytic leukaemia (CGL). Two IgG2 antibodies (CA 2.06 and L243) inhibited the proliferation of normal BFU-E and CFU-GM at relatively high dilution; a third antibody, DA2, had no effect on either progenitor cell. A complement-fixing monoclonal antibody with T-cell activity (OKT3) produced only minor reduction in progenitor cel proliferation. Further studies with L243 showed that BFU-E and CFU-GM from the blood of patients with CGL were inhibited to the same degree as normal marrow progenitor cells. The inhibition of progenitor cell proliferation by a given antibody was always complement dependent and was therefore presumed to be due to a direct cytotoxic effect. The inhibitory effect of monoclonal antibodies is a valuable approach to the characterization of antigenic determinants on myeloid progenitor cells and the differential cytotoxicity of selected monoclonal antibodies might be exploitable for therapy.

Animals↗
PubMedDate not supplied

Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres.

We report an innovative fluorescence in situ hybridization technique which exploits a unique resource of 41 telomere-specific probes and allows the simultaneous analysis of the subtelomeric region of every chromosome for deletion, triplication and balanced translocation events. This technique requires only a single microscope slide per patient and is expected to be a useful diagnostic tool with applications in the fields of idiopathic mental retardation, the detection of congenital abnormalities and in some forms of cancer. This will lead to more accurate genetic counselling of patients and their families and will provide the basis for future diagnostic, therapeutic and preventative measures.

Chromosome Aberrations↗