Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters










Publication year range
1.
Br J Haematol ; 105(4): 1081-3, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10554823

ABSTRACT

The transport of deferiprone (L1) in normal (N), sickle (S) and thalassaemic (T) red blood cells (RBC) was determined by incubation with 14C-L1 at 37 degrees C. Following incubation with 0.5 mM 14C-L1 for 4 h, the intracellular concentration of L1 in T RBC was 3 times higher than was found extracellularly. In contrast, no concentration gradient across N and S RBC membranes was detected. Efflux studies showed that T RBC released only 17 +/- 2% of 14C-L1 into the extracellular space. We hypothesize that L1 accumulation in T RBC results from their high content of chelatable iron and formation of large, hydrophilic L1-Fe(III) complexes trapped within the cytosol.


Subject(s)
Anemia, Sickle Cell/metabolism , Erythrocytes/metabolism , Iron Chelating Agents/pharmacokinetics , Pyridones/pharmacokinetics , Thalassemia/metabolism , Adult , Biological Transport , Deferiprone , Humans
2.
Br J Haematol ; 97(4): 844-7, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9217187

ABSTRACT

Chromosome 13q deletion is among the most common cytogenetic abnormalities in chronic lymphocytic leukaemia (CLL). We investigated the 13q14.3 deletion in 44 CLL patients by Southern blotting following purification of clonal B CLL cells to >90%. Two sets of probes were used to investigate the site of clonal deletion, the D13S25 and D13S319 markers (at 13q14.3) and probes for exons 11 and 26-27 of the BRCA2 gene (at 13q12). Homozygous and heterozygous deletion at the 13q14.3 region was found in five and 17 patients, respectively. Despite the recent report of the BRCA2 gene involvement in >80% of CLL patients, we failed to detect a single case of homozygous or heterozygous deletion involving the 13q12 region. Our data support previous findings that the 13q14.3, and not the 13q12 region, is the major site of candidate tumour suppressor gene(s) in CLL.


Subject(s)
Chromosomes, Human, Pair 13/genetics , Gene Deletion , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Neoplasm Proteins/genetics , Transcription Factors/genetics , BRCA2 Protein , Blotting, Southern , Heterozygote , Homozygote , Humans , Molecular Sequence Data
4.
Hum Immunol ; 50(2): 121-6, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8891735

ABSTRACT

The regulation of bcl-2 and fas (Apo-1/CD95) gene product expression plays a significant role in lymphocytes proliferation, survival, and apoptosis. Dexamethasone (Dex) and the immunosuppressive agent cyclosporin-A (CsA) inhibit primary activation of lymphocytes by distinct, though overlapping mechanisms that trigger undefined signals and can induce or prevent apoptosis in lymphoid cells in vitro. Here we demonstrate that Dex and CsA, at concentrations that markedly inhibit phytohemagglutinin (PHA)-induced proliferation of normal human peripheral blood lymphocytes, suppress the activation-dependent expression of interleukin 2 (IL-2) and the alpha-chain IL-2 receptor in a dose-dependent fashion without affecting the inducible accumulation and kinetics of either bcl-2 or fas mRNAs. Similar results were obtained when PHA-stimulated lymphocytes were cultured in the presence of the CsA analogue FK-506 or rapamycin. Moreover, the inducible maximal expression of either bcl-2 or fas protein levels on 48-h PHA-activated lymphocytes was not changed in the presence of either Dex or CsA. These findings show that the cell activation-induced biosynthesis of bcl-2 and fas proteins is not affected by immunosuppressive agents, suggesting that the expression of IL-2 and both bcl-2 and fas genes is regulated through independent mechanisms.


Subject(s)
Cyclosporine/pharmacology , Dexamethasone/pharmacology , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Lymphocyte Activation/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , fas Receptor/genetics , Cells, Cultured , Humans , Leukocytes, Mononuclear/metabolism , Phytohemagglutinins/pharmacology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/drug effects , fas Receptor/biosynthesis , fas Receptor/drug effects
5.
Leuk Res ; 20(9): 733-7, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8947582

ABSTRACT

Six patients with acute promyelocytic leukaemia (APL) and t(15;17) were investigated by cytogenetics and by reverse transcriptase polymerase chain reaction (RT-PCR) for the fusion transcript PML-RARA. The clone was detected in remission following all-trans retinoic acid and chemotherapy by cytogenetics and/or by RT-PCR up to 2 months from diagnosis. Thereafter the PML-RARA transcript was not seen in 20/21 first remission samples in five cases studied. Remission was maintained in two patients, one following bone marrow transplantation (BMT). Despite serial negative RT-PCR results, PML-RARA reemerged at or prior to relapse following BMT in the remaining three cases. Frequent molecular monitoring and caution in the interpretation of negative RT-PCR results are indicated in APL.


Subject(s)
Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 17 , Leukemia, Promyelocytic, Acute/genetics , Polymerase Chain Reaction , Translocation, Genetic , Adolescent , Adult , Female , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Male , Middle Aged , Recurrence , Remission Induction , Sensitivity and Specificity , Transcription, Genetic
6.
Br J Haematol ; 92(1): 104-15, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8562380

ABSTRACT

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of < 1 leukaemic in 10-100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 10(5)-10(6) normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B-cell lineage by using a combined PCR approach which estimates levels of disease between 1:10(3) and 1:10(5). The sequential use of allele-specific oligoprimer (ASO) independent tests (using framework 1. FR1 and 3, FR3 primers with a JH consensus primer, sensitivity up to 1:5 x 10(3)) and ASO-dependent PCR (sensitivity up to 1:10(5)) assays were applied to 64 bone marrow (BM) follow-up samples in a sequential array of tests. Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease > 1:5 x 10(3). Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO-dependent tests, as expected. However, the ASO-dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO-dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size < 15 bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO-dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease < 1:10(3).


Subject(s)
Burkitt Lymphoma/diagnosis , DNA Fingerprinting/methods , Immunoglobulin Heavy Chains/genetics , Neoplasm, Residual/drug therapy , Polymerase Chain Reaction/methods , Adolescent , Adult , Alleles , Antibodies, Neoplasm/genetics , Base Sequence , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Immunoglobulin Variable Region/genetics , Male , Molecular Sequence Data , Prospective Studies , Sensitivity and Specificity
7.
Arch Dis Child ; 70(1): 30-4, 1994 Jan.
Article in English | MEDLINE | ID: mdl-7509151

ABSTRACT

One hundred and twenty patients with homozygous beta thalassaemia were selected to determine the clinical effects of certain genetic factors which may modify disease severity. Genetic analysis defined specific beta thalassaemia mutations, the alpha thalassaemia genotype, and the presence of an XmnI restriction enzyme site, associated with increased fetal haemoglobin (HbF) production under certain conditions. Genotypic data with globin chain synthesis were related to the age when regular transfusions began and subsequent pubertal development. This study showed that the major determinants of disease severity in beta thalassaemia were the beta thalassaemia mutations, with co-inheritance of alpha thalassaemia trait and coinheritance of a high HbF determinant acting as ameliorating factors. The presence of an alpha thalassaemia deletion significantly reduced initial disease severity, although the effect on pubertal development was less clear. It is concluded that detailed genetic analysis should be performed in all newly diagnosed patients with thalassaemia. This, in conjunction with clinical assessment, will help to predict disease severity and prognosis.


Subject(s)
alpha-Thalassemia/genetics , beta-Thalassemia/genetics , gamma-Globulins/genetics , Adolescent , Adult , Blood Transfusion , Blotting, Southern , Deferoxamine/therapeutic use , Female , Fetal Hemoglobin/genetics , Gene Deletion , Genotype , Humans , Male , Mutation/genetics , Polymerase Chain Reaction , Prognosis , Puberty, Delayed/genetics , beta-Thalassemia/therapy
8.
Sarcoidosis ; 6(2): 87, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2602691
10.
Leuk Res ; 11(2): 155-61, 1987.
Article in English | MEDLINE | ID: mdl-3493393

ABSTRACT

A 17-year old caucasian male presented with B-cell acute leukemia which proved aggressive and refractory to treatment. Cytogenic investigation showed a single clone with a complex karyotype 49,XY,del(2)(p13),+4,del(4)(p11),-6,+i(6)(p),+7,+8, t(8;14), (q24;q32),del(17)(p11). This includes the Burkitt's translocation and a deletion at the site of the immunoglobulin kappa light chain gene. Clonal evolution included tetraploidy, duplication of the derived chromosomes and, terminally, trisomy 1q. Immunological investigation revealed a monoclonal population of B-cell blasts, expressing the kappa light chain, and with an extremely rare combination of SIg and TdT positivity. Immunoglobulin gene rearrangement confirmed monoclonalility. Tetraploidy of the clone and del(17)(p11) have been previously described only in a cell line or at end stage disease in B-ALL. It is suggested that the chromosomal abnormalities present at diagnosis were directly related to the refractory nature of this leukemia.


Subject(s)
B-Lymphocytes , Chromosome Aberrations/genetics , Leukemia/genetics , Acute Disease , Adolescent , Chromosome Banding , Chromosome Disorders , Humans , Karyotyping , Male
11.
Leuk Res ; 11(7): 649-54, 1987.
Article in English | MEDLINE | ID: mdl-3112472

ABSTRACT

Normal and malignant T cells as well as T-cell hybridomas have frequently been reported to produce factors which stimulate the growth of committed hemopoietic progenitors. One previous report described a lymphokine produced by a T-cell clone which inhibited hemopoietic progenitor cell proliferation. We now describe the simultaneous production of two activities by a Thy-ALL cell line (JM), a sub-line of Jurkat. Two sets of culture conditions were used: the Fauser & Messner and Iscove's assays. We have been able to separate both inhibitory and stimulatory factors for the growth of multipotent and committed bone marrow progenitors (CFU-GEMM, BFU-E, CFU-E and CFU-GM). The stimulatory factor has an apparent mol. wt of less than 30,000 and the inhibitor an apparent mol. wt of 65-80,000. The growth promoting activity for BFU-E and CFU-GEMM could replace that of phytohemagglutinin stimulated leucocyte conditioned medium (PHA-LCM). We do not know if the production of both activities is due to the malignant phenotype or if there is a normal counterpart to JM that could produce both inhibitory and stimulatory factors.


Subject(s)
Hematopoietic Stem Cells/drug effects , Leukemia, Lymphoid/pathology , Lymphokines/metabolism , T-Lymphocytes/metabolism , Antigens, Differentiation, T-Lymphocyte , Antigens, Neoplasm/analysis , Antigens, Surface/analysis , Bone Marrow/pathology , Cell Line , Colony-Forming Units Assay , Hematopoietic Stem Cells/pathology , Humans , Leukemia, Lymphoid/immunology , Phenotype , T-Lymphocytes/immunology , T-Lymphocytes/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...