摘要:

AbstractA human common acute lymphoblastic leukemia (ALL) cell line, REH, was treated in vitro with γ‐interferon (γ‐IFN) or 12‐O‐tetradecanoylphorbol 13‐acetate (TPA). Untreated (control) and treated cells were analyzed for changes in growth patterns, morphology, cytochemistry, surface phenotype, and terminal transferase (TdT) activity. TPA but not γ‐IFN induced further maturation of REH cells along the B‐cell lineage. There was a dramatic decrease in CALLA expression, loss of TdT activity, induction of Leu M5, and increase in Leu 14 expression. TPA also induced monocytoid morphological features on REH cells. Enzymatically, the induced cells strongly expressed acid phosphatase (tartrate sensitive), α‐naphthol acetate esterase (NAE), and periodic acid Schiff (PAS). We conclude that TPA induced monocytoid B‐lymphocyte features on REH cells within the B‐cell lineage, which should not be confused with monocytes/macrophage. The phenotype of cells in this stage is Leu 14 +, Leu M5 +, BL1 +, Leu 12 +, AcP +, PAS +, NAE +, CALLA

ISSN:0361-8609    

DOI:10.1002/ajh.2830330302

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non‐Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy‐ and/or light‐chain or the T‐cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy‐ and light‐chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, by NHL while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B‐cell lineage, while the immunogenotype demonstrated a T‐cell lineage. IGA also demonstrated a clonal population in 1 case of T‐chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of pa

ISSN:0361-8609    

DOI:10.1002/ajh.2830330303

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe report the development of a radiometric assay for platelet‐bound IgG that is both sensitive and quantitative. The assay utilized 96‐well millititer plates incorporating a 0.2 μm filter membrane in the bottom. A125l‐labeled monoclonal antihuman IgG, as a secondary antibody, detected the platelet‐bound human IgG. Since 5 ± 106platelets were used for each assay, tests for platelet‐bound IgG can be performed on persons with severe thrombocytopenia. For the detection of circulating antiplatelet alloantibodies, as little as 10 μl of platelet‐free plasma per assay is required.Antiplatelet IgG was quantitated by using anti‐PlA1antibody that was purified with affinity and elution and DEAE chromatography. This purified antiplatelet antibody was labeled with125l and was used to determine the binding ratio of secondary antibody to primary antibody. Under our standard conditions, this ratio was found to be stable at approximately 0.35 over the sensitivity range of the assay. The assay can detect approximately 200 molecules of human IgG per platelet (0.1 ng of secondary antibody bound per 5 ± 106platelets). It has a linear range from ) to 7,000 molecules per platelet.Quantitation of anti‐PlA1binding for platelets stored for up to 6 months under refrigeration showed no change in number of PlA1binding sites. Clinical studies showed that 18 of 19 ITP patients had an increased number of IgG molecules per platelet as did patients with malignancy and drug‐induced immune thrombocytopenia. Patients who had received multiple platelet transfusions had antiplatelet antibody in their plasma. Normal amounts of PAlgG were observed in platelets and plasma of patients with nonimmune thrombocytopenia. The advantages of this method are that it is: 1) a more precise quantitation of PAlgG via direct measurement of binding ratio with PlA1antibody; 2) performed with small amounts of platelets and plasma; 3) both sensitive and specific; and 4) reliably reproducible with both fresh

ISSN:0361-8609    

DOI:10.1002/ajh.2830330304

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe effect of azidothymidine (Zidovudine, AZT) on pyrimidine (thymidine, deoxyuridine, and thymidine triphosphate) incorporation into DNA in folate‐ and/or vitamin B12‐deficient and normal human bone marrow cells was studied to Investigate whether such vitamin deficiency affects susceptibility to AZT‐induced hematologic toxicity. Bone marrow cells from 12 patients were studied: 5 had folate and/or vitamin B12 deficiency; 7 controls included 5 with anemia related to chronic disease and 2 with iron deficiency.At 0.2 μM AZT (3 hr, 37°C), the approximate pharmacologic serum trough level, pyrimidine incorporation into DNA was suppressed by 12 to 19% in folate‐ and/or vitamin B12‐deficient cells and by 16 to 23% in normal cells. At 2.0 μM AZT (3 hr, 37°C), the approximate pharmacologic serum peak level, this was suppressed by 15 to 40% in folate‐ and/or vitamin B12‐deficient cells and by 32 to 47% in controls. Deoxyuridine incorporation into DNA was inhibited signlficantly greater than thymidine at 2.0 μM AZT (3 hr, 37°C) in both groups. Inhibition of deoxyuridine incorporation was not reversed with methyltetrahydrofolate or vitamin B12. There tended to be less striking suppression by AZT of deoxyuridine incorporation into DNA in bone marrow cells from vitamin B12‐deficient patients, which was made more striking by adding vitamin B12. This suggests that some of what passes for “AZT damage” to bone marrow cells may in fact be coincident deficiency of vitamin B12.AZT Inhibition of DNA synthesis in 3 hr bone marrow cultures is relatively consistent in a varlety of hematologic disorders. As approximately two‐thirds of AIDS patients appear to be in negative balance with respect to folate and/or vitamin B12, the fact that AZT‐induced inhibition of pyrimidine incorporation into DNA is occurring in cells which may be megaloblastic, i. e., In a state of Impaired DNA synthesis, suggests that these cells may be more susceptible to AZT toxicity. The data also support the notion that AZT inhibition results predominantly from termination of DNA chain elongation.Whether folate or vitamin B12 supplementation may partially overcome apparent “AZT inhibition” of DNA synthesis (hematologic toxicity) and whether the benefit of such therapy exceeds th

ISSN:0361-8609    

DOI:10.1002/ajh.2830330305

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

年代:1990

数据来源: WILEY

摘要:

AbstractIntravenous infusion of gammaglobulin (IVGG) has been shown to be effective in the maintenance treatment of children and adults with immune thrombocytopenic purpura (ITP). The objective of this treatment is not to increase the platelet count into the normal range but rather to keep the platelet count above a safe level, usually 20,000—30,000/μI. This use requires periodic infusion whenever the platelet count falls. The dose of gammaglobulin in previous studies was 1 gm/kg/Infusion in the majority of patients. This study compared doses of 0.5 and 1.0 gm/kg/Infusion by alternating the two doses in the maintenance treatment of 11 patients with ITP. There was no significant difference in the duration of response following single IVGG infusion between these two doses. This finding suggests that there is no advantage to the greater dose of IVGG and will substantially lower the cost of as well as facilitating IVGG maintenance treatment. It was not possible to determine whether a lower dose would impact adversely on the curative potential of IVGG. This effect of IVGG has never been proved and, if it exists, may be mediated by a different mechanism from the acute platelet respon

ISSN:0361-8609    

DOI:10.1002/ajh.2830330306

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

年代:1990

数据来源: WILEY

摘要:

AbstractIn an attempt to stimulate granulopoiesis, we administered recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) to 11 patients with lymphoprolif‐erative disorders. Ten patients had neutropenia, six of whom had severe neutropenia (5‐fold) increased as well. In contrast, no significant increases were seen in total lymphocytes or in different phenotypic subsets of lymphocytes during treatment. The overall proportion of myeloid and lymphoid elements in bone marrow remained stable. These results indicate that GM‐CSF is effective in stimulating myelopoiesis in neutropenic states associated with lymphopro‐liferative disorders. Further studies will be necessary to determine whether the correction of neutropenia ultimatel

ISSN:0361-8609    

DOI:10.1002/ajh.2830330307

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe have generated a murine hybridoma that secretes a monoclonal antibody (mAb) that is highly specific for hemoglobin C (HbC) [α2ß26(A3)Glu→Lys] and shows no cross reactivity with HbA2, HbF2, HbS, HbE, or Hb O‐Arab. Using this antibody, we developed a simple and rapid enzyme linked immunosorbent assay (ELISA) technique for the detection of HbC in both adult and cord blood. The assay can be carried out using either whole blood samples or hemolysates. With as little as 10 μl/well of whole blood or 5 μg Hb/well of hemolysates, and, with dilutions of the antibody up to 10−5we were able to detect HbC unequivocally in cord blood samples. The ELISA procedure could detect HbC in proportions as low as 0.01%. This simple diagnostic test represents a technological advance in Hb identification and can easily be used for mass screening (96 samples in less than 45 min) to detect HbC. Furthermore, this assay, when employed in conjunction with an mAb specific for β6GLU of HbA, allows the discrimination between HbC homozygotes, heterozygotes, a

ISSN:0361-8609    

DOI:10.1002/ajh.2830330308

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe efficacy of interferon alpha in treatment of hairy cell leukemia is well established. Our experience with low doses of 2′‐deoxycoformycin, a competitive inhibitor of adenosine deaminase, showed that it was also effective against hairy cell leukemia in 10 of 11 patients studied whose disease was resistant to interferon alpha. Ten patients entered complete remission after five to 12 doses of 2′‐deoxycoformycin (4 mg/m2every other week), and one patient did not respond. No relapses were observed after median followup of 18.5 months; unmaintained complete remissions lasted from more than 10 to more than 30 months. The study demonstrated that 2′‐deoxycoformycin induces a high rate of durable, unmaintained complete remissions in patients with hairy cell leukemia resistant to inter

ISSN:0361-8609    

DOI:10.1002/ajh.2830330309

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

年代:1990

数据来源: WILEY

摘要:

AbstractRearrangements affecting the long arm of chromosome 3 have been linked to abnormalities of platelet production and morphology in hematologic disorders. We present five patients with myelodysplastic syndromes or acute leukemia in whom inv(3)(q21q26) was seen. One of the patients showed an inversion of both homologs involving precisely the same breakpoints, suggesting apparent duplication of the abnormal chromosome 3 and loss of the normal homolog. To our knowledge this is the first report detailing such a condition.

ISSN:0361-8609    

DOI:10.1002/ajh.2830330310

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

年代:1990

数据来源: WILEY

摘要:

AbstractTo clarify the idea that an alteration of the transferrin receptor (TF‐R) gene, localized to 3q26, may be of pathogenetic significance in hematological disorders with 3q anomaly, we studied the TF‐R systems of erythroblasts from both functional and genetic aspects. The patient described here had refractory anemia with an excess of blasts (RAEB), with paracentric inversion, inv(3)(q21q26). The patient had the characteristic findings of mi‐ cromegakaryocytosis and thrombocytosis, with giant platelets. There was no functional abnormality of TF‐R as far as number of binding sites, affinity, molecular weight, or recycling kinetics were concerned. Furthermore, we could not recognize any rearrangement of the TF‐R gene with Southern blot analysis. These data suggest that TF‐R is not involved in the pathogenesis of leukemogenesis and thrombocytosis of

ISSN:0361-8609    

DOI:10.1002/ajh.2830330311

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

年代:1990

数据来源: WILEY