摘要:

AbstractThe Philadelphia chromosome (Ph) is found in both chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The Ph translocation, t(9;22)(q34;q11), can disrupt theBCRgene on chromosome 22 in one to two areas called the major (Mbcr1) and minor (mbcr1) breakpoint cluster regions. In CML the breakpoint has been mapped almost exclusively to Mbcr1, whereas in Ph positive ALL both Mbcr1 and the upstream mbcr1 breakpoints have been described. In this communication we describe an unusual patient with typical chronic phase Ph positive CML and evidence of the uncharacteristic mbcr1 breakpoint, predicting expression of the ALL‐type p190 fusion protein. Fluorescence in situ hybridization demonstratedBCRgene rearrangement, the reverse transcription polymerase chain reaction detected theBCR‐ABLfusion mRNA characteristic of the mbcr1 breakpoint, and failed to detectBCR‐ABLmRNA characteristic of the Mbcr1 breakpoint. Southern blot analysis revealed no rearrangement in Mbcr1, and direct sequencing of the PCR product confirmed it to be the ALL‐type mbcr1 fusion mRNA with the first exon of theBCRgene fused toABLexon a2. This case differs from the previously reported cases of “p190” CML in that the patient presented without abnormal hematopoietic features other than those found in typical CML and provides further evidence that the p190 mRNA is not sufficient to cause an acute rather than chronic leukemia. © 1996 Wil

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<129::AID-AJH1>3.0.CO;2-V

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractAbnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso‐occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow‐based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll‐Isopaque gradient, the less dense 10% (reticulocyte‐rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the “middle” cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37°C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4°C. On the other hand, incubation at 37°C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction. © 1996

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<135::AID-AJH2>3.0.CO;2-U

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractSeveral different deletions underlie the molecular basis of α‐thalassemia. The most common α‐thalassemia determinant in Spain is the rightward deletion (−α3.7). To our knowledge, however, no cases of α‐thalassemia due to nondeletional mutations have so far been described in this particular Mediterranean area. Here, we report the existence of nondeletional forms of α‐thalassemia in ten Spanish families. The α2‐globin gene was characterized in ten unrelated patients and their relatives only when the presence of deletional α‐thalassemia was ruled out. The α2‐globin gene analysis was performed using the polymerase chain reaction (PCR) followed by restriction enzyme analysis or by allele‐specific priming. This allowed the identification of a 5‐base pair (bp) deletion at the donor site of IVS I (αHphα) in 9 cases and the α2initiation codon mutation (αNcoα) in one case. Although these α2‐globin gene mutations are found in other Mediterranean areas, our results demonstrate their presence in the Spanish population and suggest that the αHphα/αα genotype is probably the most common nondeletional form of α‐th

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<144::AID-AJH3>3.0.CO;2-T

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractCompared with subjects with homozygous SS disease (Hb SS), persons with hemoglobin SC (Hb SC) are known to have a more gradual loss of splenic function, a lower incidence of bacterial infections, and fewer end‐organ failures. We studied hematological indices and lymphocyte subpopulations of 27 Hb SC subjects and compared them with 173 Hb SS patients and 131 black controls. Hb SC patients had higher hemoglobin levels than Hb SS subjects, lower total leukocyte, granulocyte, monocyte, and lymphocyte counts. Platelets decresed with age but not significantly, instead of incressing as among Hb SS patients. Mononuclerar cells were generally similar to controls with the exception of CD8+HLA‐DR+counts resembling Hb SS, Hematologic changes in Hb SC are limited to moderate granulocytosis in children and aduts, mild monocytosis in aduts, and increased activation of just one lymphocyte subset among those measu

ISSN:0361-8609    

DOI:10.1002/1096-8652(199607)52:3<150::AID-AJH2830520302>3.0.CO;2-6

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractBinding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a series of events like polymerization of actin and tubulin, orientation of cells, chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of microbicidal pathways which includes lysosomal degranulation and generation of reactive oxygen species. Earlier studies from our laboratory have shown that stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML PMNL in response to a synthetic chemotactic peptide formyl‐methionyl‐leucyl‐phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not known whether this lower response of CML PMNL to fMLP is a global phenomenon involving different chemoattractant receptors or is restricted to the fMLP pathway. We have evaluated chemoattractant induced degranulation process in normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B4(LTB4), and an analogue of fMLP viz formyl‐methionine‐1 aminocyclooctane 1 carboxylic acid‐phenylalanine‐O‐methionine (FACC8) using release of lysozyme as a parameter. We find that after stimulation with fMLP and FACC8, the mean percent release of lysozyme was significantly lower in CML PMNL as compared to that in normal cells (P<0.001). There was no significant difference between the two after stimulation with PAF and LTB4. The results indicate that the fMLP pathway is suppressed in CML granulocytes whereas PAF and LTB4pathways appear unaltered in these cells. We therefore also studied the kinetics of peptide‐receptor interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor. Our results show that the number of fMLP receptors/cell is significantly lower in CML PMNL (P<0.05) than in normal PMNL, while their affinity constants and dissociation constants were comparable. © 19

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<155::AID-AJH4>3.0.CO;2-S

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 ± 90 pg/ml) and TFPI (252 ± 125 ng/ml) levels were significantly increased in patients with DIC compared with non‐DIC patients. Plasma TF antigen level was significantly increased in pre‐DIC patients (285 ± 85 pg/ml), while the plasma TFPI level (152 ± 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre‐DIC patients (2.10 ± 0.90), and low in the DIC patients (1.40 ± 0.87) and healthy volunteers (0.84 ± 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 ± 133 ng/ml) was significantly higher than that in those with a poor outcome (187 ± 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC. © 1996

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<165::AID-AJH5>3.0.CO;2-R

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractA clonal‐specific polymerase chain reaction technique to detect T‐cell receptor delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non‐Hodgkin's lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease. A sensitive and specific technique to detect minimal residual disease for T‐cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V‐D‐J segment of T‐cell receptor delta (TCRδ) gene from malignant cell specimens of patients with leukemia and lymphoma of T‐cell lineage. The PCR product was sequenced and from the DNA sequences of the V‐D‐J region, a 3′ anti‐sense primer was designed and synthesized for clonal specific PCR (CS‐PCR). T‐cell receptor delta (TCR‐δ) gene rearrangement was studied in 40 cases of acute leukaemia and lymphoma of T‐cell lineage at diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18 T‐lymphoma and 22 T‐ALL, respectively. A one stage Polymerase Chain Reaction (PCR) technique was used to detect the rearrangement in Southern positive cases and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a sensitivity of 0.1%. Serial follow‐up marrow specimens were available from 4 T‐ALL patients following chemotherapy for monitoring of minimal residual disease. Their PCR products were DNA sequenced. A 3′ was designed for each case for a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was applied to detect minimal residual disease in serial follow‐up marrow samples. The first patient had persistent negative CS‐PCR results and enjoyed continuous remission for more than 3 years. The second patient with negative one stage PCR but positive CS‐PCR results had eventual relapse of leukaemia. The other two patients never achieved a morphological remission. These preliminary results appeared to support the usefulness of these PCR techniques in detecting minimal residual disease and predicting relapses for ALL. However, further clinical correlation in larger populations

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<171::AID-AJH6>3.0.CO;2-Q

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractInjection of bacterial endotoxin or granulocyte/macrophage colony‐stimulating factor (GM‐CSF) into exhypoxic polycythemic mice simultaneously with erythropoietin (EPO) suppressed erythroid cell formation, as monitored by59Fe incorporation into circulating red blood cells. This effect was dose‐dependent and time‐dependent. GM‐CSF did not inhibit erythroid cell formation directly, as the antibody to the GM‐CSF did not neutralize the effect of endotoxin, the inducer of GM‐CSF. The suppression of both agents could be partially corrected by prior injection of a monoclonal antibody to tumor necrosis factor α (anti‐TNFα). These results indicate that the suppression of EPO‐induced erythroid cell formation by endotoxin and GM‐CSF was due in part to the production of TNFα.

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<178::AID-AJH7>3.0.CO;2-Q

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractFour of 55 (7%) adult acute lymphocytic leukemia patients, age 27–58 years, who were treated with methotrexate, vincristine, L‐asparaginase, and dexamethasone (MOAD) developed avascular necrosis (AVN) of one or both femoral heads 16–39 months after beginning treatment. All patients were treated with total joint replacement without compromise of quality of life during more than 3–9 years of follow‐up, and they have remained in complete remission for a total of 6.5+ to 10.5+ years. A review of the literature revealed 11 previously reported cases of AVN of bone in patients with acute lymphocytic leukemia, 10 of whom received dexamethasone. The patients in the present report received a total dexamethasone dose equivalent to that of prednisone, 3.4–5.0 g/M2. Although AVN of bone has been reported in patients receiving chemotherapy without corticosteroids, corticosteroids appear to be the most common class of agents associated with its development, and dexamethasone treatment may be more likely to result in AVN of bone than other corticosteroids, for unknown reasons. © 1996 Wil

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<184::AID-AJH8>3.0.CO;2-P

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe asked the question, is the haplotype found with the sickle hemoglobin gene associated with different hematological characteristics in patients who were combined heterozygotes for sickle hemoglobin and hemoglobin C (Hb SC disease)? In 73 adults with Hb SC disease, a Benin haplotype chromosome was present in 56%, and Bantu (or Central African Republic; CAR), Senegal, and atypical haplotype chromosomes were found in 25%, 6%, and 12%, respectively. No significant differences were found in hematological characteristics or fetal hemoglobin levels of patients with Benin/C, CAR/C, Senegal/C, and atypical/C haplotypes. There were 71%C I, 18% C II, and 11% other βchaplotypes. Fetal hemoglobin levels are lower in Hb SC disease than in sickle‐cell anemia. Perhaps because haplotype has no discernible effect on fetal hemoglobin level in Hb SC disease, it does not modulate its hematological features. © 1996 Wiley‐Liss

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199607)52:3<189::AID-AJH9>3.0.CO;2-P

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY