摘要:

AbstractIn this study we have correlated the severity of the hematological features to the type of the β‐thalassemia mutation [codon 39 (C→T), IVS‐I nt 110 (G→A), IVS‐I nt 1 (G→A), IVS‐I nt 6 (T→C), IVS‐II nt 745 (C→G), −87 (C→G) and β6 (‐1bp)], in a group of β‐thalassemia heterozygotes of Italian descent in whom we excluded the presence of iron deficiency or deletion α‐thalassemia. The β‐thalassemia mutation was defined by dot blot analysis on amplified DNA with allelic specific oligonucleotide probes. We found that (a) heterozygotes for β+IVS‐I nt 6 and β+‐ 87 mutations produce larger and better hemoglobinized red blood cells, and )b) heterozygotes for β+IVS‐I nt 6 and β+IVS‐I nt 110 mutations have a less marked increase of Hb A2levels as compared to heterozygotes for the other mutations investigated. These findings indicate that milder β‐thalassemia mutations such as the β+IVS‐I nt 6 and β+‐ 87, express also in the heterozygous state a milder phenotype as compared to β°+‐thalassemia or severe β+thalassemia (β+IVS‐I, nt 110. The Hb A2levels, on the other hand, were not related to the severity of the mutation because of less marked increase was found in a mild (β+IVS‐I nt 6) as well in a severe (β+IVS‐I nt 110) mutation. From the practical point of view these findings shoul

ISSN:0361-8609    

DOI:10.1002/ajh.2830390102

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

年代:1992

数据来源: WILEY

摘要:

AbstractAnalysis of polymorphisms of the β‐globin gene cluster was performed on 12 families and on one unrelated individual of Sicilian origin who carried hemoglobin C (Hb C). Two different haplotypes were found in association with βcSicilian alleles, corresponding to haplotypes I and II previously described in American blacks. In our population, the more frequent one (haplotype I) was linked to the lack of a polymorphicHpal site 3′ to the β gene (13.0‐kb fragment), similarly to haplotype I in blacks, while the less frequent one was linked to a 7.0‐kbHpal fragment attributable to a site that had never been previously described in linkage with βcalleles. In Italy, these two haplotypes have been found in rare cases in association with βAalleles. These findings provide new insights into the origin of Hb C present in Sicily, suggesting that (1) the βcmutation detected in Sicily derived from African black chromosomes and does not represent a new mutation; and (2) Hb C may have originated either by multiple mutational events on separate chromosomes or by mutation in theHpal site 3′ to the β gene in a pre‐exis

ISSN:0361-8609    

DOI:10.1002/ajh.2830390103

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe mechanism underlying the impaired uptake of iron from transferrin by reticulocytes from the Belgrade laboratory rat was investigated using125I‐ and59Fe‐labeled transferrin isolated from homozygous Belgrade rats and from Wistar rats, nontransferrin‐bound Fe(II) in an isotonic sucrose solution, and reticulocytes from Belgrade and Wistar rats. The Belgrade rat transferrin had the same molecular weight and net charge as Wistar rat transferrin, donated iron equally well to both types of reticulocytes, and competed equally for transferrin binding sites on the cells. Hence, the defect in iron uptake by Belgrade rat reticulocytes could not be attributed to an abnormality of the transferrin molecule. The rate of uptake of Fe(II) from sucrose into the cytosolic and stromal fractions of Belgrade rat reticulocytes was only about 35% as great as that by Wistar rat reticulocytes. With both types of cells, the uptake process was saturable, suggesting the presence of a carriermediated process. It was therefore concluded that the defect in iron uptake by Belgrade rat erythroid cells is probably the consequence of a deficiency in a membrane carrier for

ISSN:0361-8609    

DOI:10.1002/ajh.2830390104

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

年代:1992

数据来源: WILEY

摘要:

AbstractLymphocytotoxicity test (LCT) and platelet suspension immunofluorescence test (PSIFT) were used together to screen platelet‐associated antibodies in patients who received long‐term platelet transfusion. Twenty‐four of 53 patients (45.3%) were immunized subsequently. Since the concordence of LCT and PSIFT was 100%, most of the platelet associated antibodies were of HLA specificity, and platelet specific antibody alone (in absence of HLA) was not detected. The identified antibodies were anti‐A2, A11, A24, B5, B46, B57, B60, and B62. The majority of them were against the high frequency HLA antigens in the Chinese population. The development of antibody could not be correlated with the number of platelet‐donors exposed, the time interval after the initiation of platelet transfusion, or the percentage of reactive lymphocytotoxic panels. HLA antibody was the major factor in causing platelet alloimmunization in the Chinese patients. However, some other unknown factors should be looked for. In addition, ABO incompatibility did not affect the posttransfusional increment while the platelet was compatible with LCT cros

ISSN:0361-8609    

DOI:10.1002/ajh.2830390105

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

年代:1992

数据来源: WILEY

摘要:

AbstractPlasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP.

ISSN:0361-8609    

DOI:10.1002/ajh.2830390106

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

年代:1992

数据来源: WILEY

摘要:

AbstractRecently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen‐induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2, in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2‐loaded platelets. In contrast, thrombin caused TXB2, formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The lgG from the ITP‐patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPla/lla and thrombospondin were normally present. These results indicate that impaired collagen‐induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet act

ISSN:0361-8609    

DOI:10.1002/ajh.2830390107

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

年代:1992

数据来源: WILEY

摘要:

AbstractIn this study, specific binding sites were examined for erythropoietin (EPO) on the mouse leukemic cell line, L8057. This cell line is megakaryoblastic in origin as evidenced by an enlargement of cell size, multinuclearity, intense activity of acetylcholinesterase, more expression of glycoprotein Ilb and IIIa antigen, and higher ploidy distribution after the treatment with 12‐o‐tetradecanoylphorbor‐13‐acetate (TPA). The original undifferentiated cells possessed a single class of low affinity binding sites for recombinant human (rh) EPO with a Kd of 3.5 nM. Following the treatment with TPA, high affinity binding sites (Kd; 440 pM) were expressed in addition to the low affinity sites. EPO stimulated the incorporation of3H‐leucine into TPA‐treated L8057 cells, and the maximal effect of EPO was observed at the same order as the Kd value of high affinity sites.The present data demonstrates that the expression of high affinity binding sites for EPO is associated with the differentiation of L8057 cells which have megakaryocytic characteristics. Furthermore, protein synthesis stimulated by EPO may be mediated through the high aff

ISSN:0361-8609    

DOI:10.1002/ajh.2830390108

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

年代:1992

数据来源: WILEY

摘要:

AbstractEthacrynic acid, a loop diuretic, has been shown to inhibit hemoglobin S polymerization. Until now, however, most studies were performed using purified solutions of hemoglobin S. The experiments reported here were designed to examine the effects of ethacrynic acid and its n‐butryic acid derivative on the rheological and physiological properties of intact red blood cells. Using net and unidirectional flux measurements, both agents were shown to cause ion and water loss from normal and sickle erythrocytes. Since cell shrinkage adversely influences red cell rheology, it is unlikely that this class of compounds, despite its ability to inhibit hemoglobin S polymerization, will prove useful in the treatment of sickle cell diseas

ISSN:0361-8609    

DOI:10.1002/ajh.2830390109

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

年代:1992

数据来源: WILEY

摘要:

AbstractLittle is known about the role of tumor infiltrating T lymphocytes (TIL‐T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved.In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B‐cell non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 ± 15.0% in B‐cell NHL, and 37.4 ± 18.6% in HD) than in reactive hyperplasia (54.7 ± 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment.A further heterogeneity in the relative proportion of naive and memory TIL‐T was also observed within lymphoma (range: 11 to 68% in B‐cell NHL, 5 to 69% in HD). In B‐cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P<.0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 ± 7.4%) than class 3 NHL, which are more aggressive (40.1 ± 16.1%). Among the monoclonal antibodies (mAb) defining the B‐cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (p = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL‐T, activated CD3 D

ISSN:0361-8609    

DOI:10.1002/ajh.2830390110

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

年代:1992

数据来源: WILEY

摘要:

AbstractTen previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara‐C), 10 mg/m2injected subcutaneously every 12 hours for 14‐28 days. Six patients achieved a complete remission (CR) for periods ranging for 6‐23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10‐24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low‐dose Ara‐C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug‐related deaths. These observations suggest that low‐dose Ara‐C is effective in treating elderly patients with hypocellul

ISSN:0361-8609    

DOI:10.1002/ajh.2830390111

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

年代:1992

数据来源: WILEY