摘要:

AbstractThree family members from two successive generations had a bleeding tendency. Their template bleeding time was prolonged and platelet aggregation induced by ADP and adrenaline showed no second wave; collagen at low to moderate concentrations failed to aggregate and release ATP, whereas higher amounts aggregated and released. Aggregation and release due to thrombin, ristocetin, and synthetic epoxy derivatives (U 44069 and U 46619) were normal. Arachidonate (AA) was inactive, and was not converted either in thromboxane (TX) A2activity evaluated on the rabbit aorta strip, nor in TXB2evaluated by radioimmunoassay and by radiochromatography. The parallel impairment of TXB2and PGE2formation by the patient's platelets are compatible with a platelet cyclo‐oxygenase deficiency. This study suggests that transmission is autosomal dominant. and confirms that cyclo‐oxygenase is not needed for aggregation and ATP release by high amounts of colla

ISSN:0361-8609    

DOI:10.1002/ajh.2830140102

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

年代:1983

数据来源: WILEY

摘要:

AbstractHow the metabolic defect of pyruvate kinase deficiency (PK(–)) accelerates red blood cell (RBC) destruction is not established, but may be related to RBC membrane abnormalities associated with altered cellular metabolism. Furthermore, it has been shown that PK(–) reticulocytes are especially sensitive to metabolic depletion. Therefore, we compared the membranes of reticulocyte‐rich PK(–) RBC, both fresh and ATP depleted, with membranes of fresh and ATP depleted normal mature RBC and reticulocytes. There was no difference between the specific gravity (SG) of the membranes of normal mature RBC (SG 1.152 ± 0.004) and membranes of reticulocyte‐rich RBC from several anemias (SG 1.150 ± 0.002). However, membranes from fresh, reticulocyte‐rich PK(–) RBC were dense with SG of 1.165 ± 0.004 which correlated with a corresponding increase of protein to lipid phosphorus ratio of 66 ± 8 μg protein/μg lipid phosphorus (normal 52 ± 6 μg/μg). The membrane density of PK(–) RBC was further increased when the PK(–) RBC ATP was depleted by anaerobic incubation (SG 1.188 ± 0.004) or cyanide inhibition (SG 1.182 ± 0.001). When ATP was depleted in normal RBC and in non‐PK(–) reticulocytes, corresponding increases in membrane SG occurred. A distinctive 50,000 MW peptide is adsorbed from the cytoplasm to the membranes of reticulocytes (both normal and PK(–) when these cells were depleted of ATP. The increased membrane adsorption of cytoplasmic proteins by PK(–) RBC was not associated with increased RBC calcium uptake, sulfhydryl oxidation, or altered membrane protein phosphorylation. All the observed abnormalities of PK(–) RBC membranes could by reproduced by ATP depletion

ISSN:0361-8609    

DOI:10.1002/ajh.2830140103

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

年代:1983

数据来源: WILEY

摘要:

AbstractProstaglandin E inhibits granulocyte‐macrophage colony formation in vitro in man and mouse, suggesting that it plays a role in feedback regulation of granulocyte production in vivo. Therefore, we examined the role of PGE in normal canine hematopoiesis and its potential role in the pathogenesis of cyclic hematopoiesis in grey collie dogs. The prostaglandin synthesis in hibitors indomethacin and ibuprofen (10−5M) increased CFU‐C growth to 194 and 160% of control, respectively, while PGE2addition caused a dose‐dependent inhibition of bone marrow CFU‐C growth in both normal and grey collie dogs. These concentrations of indomethacin and ibuprofen decreased bone marrow cell elaboration of PGE measured by radioimmunoassay to less than 5% of control values. The levels of PGE in leukocyte conditioned medium prepared from grey collies correlated with the number of monocytes in the conditioning cell suspension (r=0.78, n=10, p<0.05) so that PGE production per monocyte was no different in normal and grey collie dogs. The effect of PGE2upon CFU‐C was to inhibit formation of macrophage, but not neutrophil colony subtypes. These findings make aberrant PGE‐mediated inhibition of precursor cells an unlikely mechanism to cause cyclic hematopoiesis, and show that PGE produced by monocytes acts as a feedback inhibitor for precursor cells destined to produce monocytes but not for those destined to for

ISSN:0361-8609    

DOI:10.1002/ajh.2830140104

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

年代:1983

数据来源: WILEY

摘要:

AbstractBoth cytogenetic abnormalities and in vitro growth patterns of leukemic cells have prognostic significance in acute nonlymphocytic leukemia (ANLL). The present study was undertaken to analyze the interrelationship between these two factors and response to therapy. Blast cells from 43 patients with de novo ANLL, four patients with secondary ANLL, and two patients with ANLL following a preleukemic phase were studied using both in vitro culture in methylcellulose and quinacrine chromosome banding techniques. In 19 patients with de novo ANLL, minimal growth in culture (≤ 5 colonies without prominence of small clusters) was noted (Pattern I). Blast cells from the remaining 24 patients formed numerous abnormal clusters and colonies in a continuum distribution (Pattern II). Sixty‐three percent of Pattern I patients had completely normal karyotypes (NN). Only 29% of Pattern II patients were NN. No Pattern I patient had only abnormal karyotypes (AA), while 25% of Pattern II patients were AA (p<0.05). All six patients with secondary leukemia or leukemia following a preleukemic phase demonstrated both Pattern II growth and cytogenetic abnormalities. Fifty‐six percent of Pattern I patients with de novo ANLL responded to chemotherapy, 35% of Pattern II patients responded, and 0% of patients with secondary or post‐preleukemic ANLL responded. The correlation between the presence of cytogenetic abnormalities in leukemic cells and a pattern of excessive, abnormal growth in vitro coupled with the trend toward poor prognosis in these patients suggests that cytogenetically abnormal cells may have a proliferative advantage both in vitro and

ISSN:0361-8609    

DOI:10.1002/ajh.2830140105

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

年代:1983

数据来源: WILEY

摘要:

AbstractFour patients with the leukemic phase of hairy cell leukemia were treated with leukapheresis. Two patients failed to respond, and the other two had only transient responses; hematologic improvement lasted one month in one case and four months in the second. The patient with a four‐month response underwent a second series of leukapheresis resulting in a response lasting at least 8 months. Two of the four patients subsequently had an adequate trial of prolonged chlorambucil therapy and continued to have a clinical response. We conclude that leukapheresis has little to offer to the majority of hairy cell patients for the long‐term management of post‐splenectomy patients who develop the leukemic phase. However, an occasional patient can have a transient, and even, rarely, a prolonged res

ISSN:0361-8609    

DOI:10.1002/ajh.2830140106

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

年代:1983

数据来源: WILEY

摘要:

AbstractWe have used an automated system to measure serial reticulocyte samples from phlebotomized rats and rats treated with the chemotherapeutic agent actinomycin‐D. In performing the automated samples, we utilized two different methods. The first method employed a fluorescent dye, acridine orange, which stains RNA in a manner similar to supravital stains presently used in performing reticulocyte counts. The second method is unique in that we utilized an immunofluorescent assay with antitransferrin recptor antibody which identifies the transferrin receptor found on the cell surface of reticulocytes but not on mature red cells. Both methods gave reproducible values in estimating the increase in reticulocytes seen after phlebotomy and the initial reticulocytopenia followed by recovery of the peripheral blood reticulocyte count seen after treatment with actinomycin‐D. Also, since the antitransferrin receptor antibody appears to recognize the more immature reticulocytes, both methods taken together may provide an estimate of the maturity of a population of reticulocy

ISSN:0361-8609    

DOI:10.1002/ajh.2830140107

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

年代:1983

数据来源: WILEY

摘要:

AbstractIsoelectric focusing in polyacrylamide gels has been widely used to separate fetal (HbF) and adult (HbA) hemoglobins, and the relative synthesis of HbA and HbF has been estimated by fluorography or autography of dried gels. In order to measure the absolute synthesis of hemoglobin, we developed a system that utilizes isoelectric focusing in agarose and quantitates the total radioactivity of separated hemoglobins. After isoelectric focusing, the protein bands are individually eluted from the agarose and the radioactivity measured by liquid scintillation counting. We used this technique to study the synthetic capabilities of erythroid precursors at sequential times in culture. As previously reported, the relative ratio of HbF decreased over time in culture. However, our results clearly revealed that the absolute synthesis of HbF did not decrease until there was a parallel decrease in hemoglobin A, and that changes in the relative ratio occur because of disproportionate increases in HbA. This methodology, allowing independent evaluation of the radioactivity in synthesized hemogrlobin, enabled us to gain new insight into the biosynthetic capabilities of erythroid precursors in clonal cell culture.

ISSN:0361-8609    

DOI:10.1002/ajh.2830140108

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

年代:1983

数据来源: WILEY

摘要:

AbstractTwo patients with thrombotic thrombocytopenia purpura (TTP) are described in whom vincristine administration appeared to play a role in successful outcomes. The first patient with chronic TTP responded partially to plasma exchange followed by plasma infusion and transiently to splenectomy, but developed a complete long lasting remission after a single injection of intravenous vincristine. The second patient developed a complete remission following vincristine administration and plasma exchange. Although vincristine's mechanism of action in TTP is obscure, we suggest that vincristine is effective in the treatment of this infrequent and often fatal disease.

ISSN:0361-8609    

DOI:10.1002/ajh.2830140109

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

年代:1983

数据来源: WILEY

摘要:

AbstractA case of paroxysmal nocturnal hemoglobinuria (PNH) which developed terminal transfer‐ase (TdT)‐positive leukemia 5 years after the diagnosis of PNH was studied. Most of the leu‐kemic cells were suggestively lymphoid by cytochemistry and electron microscopy, and TdT‐positive by immunofluorescence studies. The development of acute lymphoblastic leukemia during the course of PNH suggests that in PNH the clonal abnormality may involve lymphoid cells as well as myeloid cells, thus raising the possibility of the disease being a disorder of the pluripotential st

ISSN:0361-8609    

DOI:10.1002/ajh.2830140110

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

年代:1983

数据来源: WILEY

摘要:

AbstractA female infant presented at seven weeks of age with failure to thrive, progressively severe pancytopenia, hypogammaglobulinemia and, mucosal ulceration. Bone marrow morphology showed severed megaloblastic changes in the myeloid series with a shift to the left and an increased number of blasts with abnormal morphology. Erythroid precursors and megakaryocytes were markedly decreased. Cytogenetic studies showed marked aneuploidy and increased chromosomal breakage. Treatment with high doses of vitamin B12resulted in a dramatic clinical response with hematological values becoming normal. The patient's serum showed absence of transcobalamin II, and very little TC I and TC III binding. The patient's parents had only half the lower limits of normal transcobalamin II. QUSO G‐32 was used for separation of transcobalamins, and the results were confirmed by Sephacryl S‐300. This case illustrates the usefulness of QUSO in the rapid diagnosis of transcobalamin II deficie

ISSN:0361-8609    

DOI:10.1002/ajh.2830140111

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

年代:1983

数据来源: WILEY