摘要:

AUogeneic bone marrow transplantation (BMT) is considered to be the only curative therapy for chronic myelogenous leukemia (CML). The cytogenetic marker of CML, the Philadelphia (Ph) chromosome, or the molecular alterations caused by the BCR-ABL gene fusion can be used to monitor the success of treatment. A sensitive two-step reverse-transcription polymerase chain reaction (RT-PCR) was done to score BCR-ABL-mRNA-positive leukemic cells in frozen bone marrow samples of 15 CML patients retrospectively. These patients, 4 females, 11 males, had undergone BMT during the first chronic phase after a preparative regimen consisting of total body irradiation (TBI) and cyclophosphamide; median age at BMT was 38 years (range 20-49 years). At the time of this study, 8 patients were in cytogenetic and/or clincal remission. Seven patients relapsed after BMT; all presented with Ph-chromosome-positive metaphases and BCR-ABL-positive cells at the time of relapse. In only 1 patient in hematologic remission was no positive PCR analysis obtained in the two samples tested. However, 5 patients have remained or became Ph-chromosome and/or PCR-positive after BMT without clinical symptoms of disease. In samples from another patient, transient presence of leukemic cells was observed only early after BMT. Clinically, these patients were relapse free at days 3,055, 2,581, 2,252, 1,846, 1,839, 1,747, and 1,173 after BMT, respectively. Based on these data, the presence of single BCR-ABL-positive cells > 1 year after BMT has no prognostic significance.

ISSN:0001-5792    

DOI:10.1159/000204215

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes of 18 βs chromosomes from patients followed in three hospitals in Kuwait. Of the 30 chromosomes from 15 patients with Hb H disease, 26 (86.7%) carried the polyadenylation (poly A) signal mutation (AATAAA→AATAAG) in the α2-globin gene, 3 (10%) had the -α (3.7 kb) deletion, and 1 (3.3%) had the pentanucleotide deletion in the 5´ IVS-I splice junction (α-5ntα). As many as 12 different β-thal mutations were identified; 6 Mediterranean alleles [IVS-II-1 (G→A), IVS-I-6 (T→C), codon (CD) 39 (C→T), IVS-I-110 (G→A), CD 8 (-AA), and IVS-I-1 (G→A)] were present in 79 (64.2%) of the chromosomes tested. Four East Indian alleles [IVS-I-5 (G→C), IVS-I 3´ end -25 nt deletion, CDs 8/9 (+G), and 619-bp deletion] were found in 31 (25%), and the two Kurdish/Iranian alleles [CD 44 (-C) and CDs 36/37 (-T)] were found in 13 (10.6%) chromosomes. Fourteen βs chromosomes carried haplotype No. 31 (Saudi Arabia/ India); 3 had haplotype No. 19 (Benin), and 1 was a hybrid with haplotype No. 31-specific characteristics in the locus control region hypersensitive site-2 (LCR-HS-2), and haplotype No. 19-specific mutations in the 5´ flanking region of the Gγ-promoter. The patient homozygous for haplotype No. 19 was a Jordanian, while the others were Kuwaiti Arabs. The latter appear to be fairly homogeneous in terms of the prevalent α-thal determinants and βs-haplotypes, but there is considerable heterogeneity of their β-thal alleles. This has implications for genetic counseling an

ISSN:0001-5792    

DOI:10.1159/000204216

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We studied the toxic effects of azidothymidine (AZT) on the hemopoietic colony growth (CFU-E, BFU-E and CFU-GM) of bone marrow in a murine model of AIDS (MAIDS). A sparing effect by recombinant hemoglobin (r-Hb) on AZT suppression of MAIDS bone marrow was found when 10 μM of r-Hb was included in bone marrow cultures. The AZT toxicity dose response curve showed that at a concentration of 0.1 μM, AZT inhibited CFU-E by 66%, BFU-E by 55% and CFU-GM by 67%. The addition of r-Hb (10 μM) to AZT-treated cultures stimulated CFU-E, BFU-E and CFU-GM by 89, 125 and 160%, respectively, as compared with AZT-treated (control). The addition of r-Hb to non AZT-treated cultures showed further stimulation of CFU-E, BFU-E and CFU-GM to 100, 160 and 187% of the control, respectively. These results indicate that exogenous r-Hb reverses AZT-induced hemopoietic toxicity and may prove to be useful in ameliorating AZT toxicity in immunosuppressive diseas

ISSN:0001-5792    

DOI:10.1159/000204217

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Comparison is made between the reliability of two imaging methods (ultrasound and magnetic resonance imaging) to measure changes in the size of the liver in patients undergoing treatment for Gaucher disease. The reliability of either modality in estimating liver size is comparable, as is the reliability of demonstrating changes in the size of the liver with time. The precision of the two measurements is roughly the same.

ISSN:0001-5792    

DOI:10.1159/000204218

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The BCR-ABL fusion gene is directly involved in the pathogenesis of chronic myeloid leukemia (CML). Specific inhibition of the BCR-ABL gene expression with antisense oligodeoxynucleotides has been shown to have profound effects on cell growth in vitro. We examined antisense phosphodiester oligonucleotides (16-mers at a concentration of 60 μg/ml) spanning the two possible junction sites K28 (b3a2) and L6 (b2a2) in a clonogenic assay. Single colonies from 9 patients with CML and from patients with normal bone marrow were screened for BCR-ABL expression with a new ‘single-tube nested PCR’ method. There was a marked reduction in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colonies, however, was not reduced in the CML group. This indicates a nonspecific growth inhibition

ISSN:0001-5792    

DOI:10.1159/000204219

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To understand at what level hematopoiesis is impaired in AIDS patients, we quantitated bone marrow cells of the myeloid and lymphoid lineages in their different stages of differentiation. The bone marrow aspirates of 20 HIV-infected patients (18 with CDC IV) and 11 controls were analyzed by flow cytometry, using a panel of monoclonal antibodies. The mean percentages of CD34+ and CD 10+ hematopoietic precursor cells were not significantly altered in the HIV-infected patients. The values of these patients however scattered in a much wider range than in the control group, some patients showing extremely high values. Patients with high levels of CD34+ and CD 10+ precursor cells in the bone marrow had lower blood leukocyte counts and lower blood and bone marrow CD4 cell numbers than patients with a low percentage of CD 10+ and CD34+ cells (p < 0.01). The percentages of the CD34+ cell subsets studied (CD34+CD33+, CD34+CD14+, CD34+CD15+) were not altered. Bone marrow CD4+ lymphocytes, especially those of CD45RA- phenotype, were reduced, while the CD8+ cells (especially HLA-DR+/CD45RA+ cells) were increased. These results show that the hematologic disorders in AIDS are not simply caused by an altered number or composition of bone marrow precursor cells. We postulate that hematopoiesis is inhibited due to an imbalance in the bone marrow T lymphocyte populations.

ISSN:0001-5792    

DOI:10.1159/000204220

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Clinical, laboratory and molecular biological features are presented from a patient with Sézary syndrome associated with long-term phenytoin therapy

ISSN:0001-5792    

DOI:10.1159/000204221

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We describe two kindreds of Arab ancestry characterized by multiple cases of acute lymphoblastic leukemia. Consanguinity and intermarriages were prevalent in the two families. Age, mode of presentation, characteristics of the leukemic cells, response to treatment and prognosis were remarkably similar among the patients. A short review of the literature on familial leukemia is given.

ISSN:0001-5792    

DOI:10.1159/000204222

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000204223

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000204224

出版商:S. Karger AG    

年代:1994

数据来源: Karger