摘要:

AbstractThe search for bone marrow clone neoplastic precursors in the peripheral blood of multiple myeloma (MM) patients has been the subject of a number of studies which, using different methodological approaches, have led to conflicting results. With the aim of contributing toward resolving this controversy, immunoglobulin (lg) gene rearrangement in the bone marrow mononuclear cells (BMMC) and B‐lymphocyte enriched peripheral cells (BePBC) of 11 appropriately selected advanced MM patients was studied by means of Southern blotting.Peripheral mononuclear cells (PBMC) and BePBC were studied immunophenotypically by evaluating the presence of cytoplasmic Ig positive cells (Cylg+) and CD19/PCA‐1 reactivity. A pattern of Ig gene rearrangement identical to that observed in the respective BMMC was found in only two patients who, moreover, had a significant number of Cylg+ cells. Ig gene rearrangement was not found in any of the remaining patients who showed no evidence of the presence of Cylg+ cells, although there were CD19/PCA‐1 positive cells. Consequently, the significance of the presence of malignant pre‐plasma cell peripheral B‐lymphocytes needs to be reconsidered and, in any case, these cells should be looked for in cell populations greatly enriched in B‐lymphocytes and, above all, completely lacking in plasma cells or

ISSN:0361-8609    

DOI:10.1002/ajh.2830370102

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

年代:1991

数据来源: WILEY

摘要:

AbstractA new β°‐ halassemia mutation, a frameshift mutation with an insertion of a single cytosine nucleotide in codon 27–28, is described. The propositus, who is compound heterozygous for this mutation and the IVSII‐654 C→T β°‐thalassemia mutation, has the phenotype of severe β‐t

ISSN:0361-8609    

DOI:10.1002/ajh.2830370103

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

年代:1991

数据来源: WILEY

摘要:

AbstractIncreased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti‐phospholipid antibodies, acquired deficiencies of natural anti‐thrombotic mechanisms (protein C, protein S, anti‐thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P<.01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl,P<.01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%,P<.01). Cross‐linked fibrin derivatives (D‐D dimers) were negative in all patients with SLE. Sixty‐eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti‐thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial

ISSN:0361-8609    

DOI:10.1002/ajh.2830370104

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

年代:1991

数据来源: WILEY

摘要:

AbstractVitronectin is one of the glycoproteins that mediate cell adhesion and spreading of a variety of cells through the RGD(S) sequence. Vitronectin is demonstrated to bind to glycoprotein IIb‐IIIa and play a role in platelet aggregation. Synthetic peptides containing the RGD(S) sequence can inhibit vitronectin binding to platelets, but the affinity of these peptides is less than 1/100th that of native vitronectin. The present study thus examined the ability of modified RGD(S)‐containing peptide to inhibit vitronectin binding to thrombin‐stimulated platelets. The cyclicization of GRGDSPA peptide was done by the linkage of NH2‐terminal glycin and the COOH‐terminal alanin. The circular dichroism spectrum of cyclic GRGDSPA peptide only showed negative minimum at approximately 220 nm, but those of other linear peptides such as GRGDSPA and GRGESPA had no effect. This result indicated that only the cyclic GRGDSPA peptide retained some conformational structure to restrict its flexibility. Inhibition experiments revealed that the affinities of the ligands for the receptor decreased in the order of vitronectin = fibronectin = fibrinogen = von Willebrand factor (vWF)>cyclic GRGDSPA peptide>GRGDSPA peptide. GRGESPA peptide had no effect. These results demonstrate that the conformational structure of the RGD(S) sequence plays the important role for the affinity of vitronectin binding to activated platelets and the increased affinity of the modified peptide is a prerequisite for the potential antithrom

ISSN:0361-8609    

DOI:10.1002/ajh.2830370105

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

年代:1991

数据来源: WILEY

摘要:

AbstractWaldenstrom's macroglobulinemia (WM) has been hypothesized to be a pleomorphic B‐cell malignancy with persistent maturation towards plasma cells in all lymphoid tissue. This proposal is based on detection of a heterogeneous density of monoclonal Ig on peripheral blood B‐cells in patients with WM. We now present data derived from 2‐ and 3‐color immunofluorescence and flow cytometric analysis that strongly supports this hypothesis. Abnormally high numbers of B lineage cells, defined by expression of CD19, CD20, and CD24, were found among peripheral blood mononuclear cells (PBMC). These B‐cells are monoclonal as defined by light chain expression and by the existence of rearranged Ig genes (Southern blot analysis), although they exhibit heterogeneity in the density of surface light chain. Unlike normal PBMC B‐cells, the monoclonal B‐cells bear CD5 and CD10 (CALLA), express adhesion and adhesion‐related molecules (CD11b, CD9), and appear to be actively differentiating during the course of the disease, based on the pattern of CD45 isoform expression. At any given point in time, the population of monoclonal B‐cells is heterogeneous in differentiation stage based on transitions in the expression of CD45 isoforms from expression of CD45RA, the high molecular mass isoforms of CD45, to the low molecular mass isoform CD45R0 which appears only on very late stage B‐cells and early plasma cells. For one patient, analysis of CD45 isoform expression over 2 years showed that the monoclonal B‐cell population as a whole progressed towards terminal differentiation as defined by loss of CD45RA and acquisition of CD45R0. This indicates a continuously differentiating lineage of an unusual B‐cell phenotype, and/or malignant transformation of a distinct l

ISSN:0361-8609    

DOI:10.1002/ajh.2830370106

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty‐five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 ± 5.4% to 28.1 ± 6.7% (P<0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 ± 1.8% to 25.2 ± 2.4% (P<0.01) within the first 2 weeks and up to 27.5 ± 3.7% (P<0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side e

ISSN:0361-8609    

DOI:10.1002/ajh.2830370107

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

年代:1991

数据来源: WILEY

摘要:

AbstractNeonatal RBC contain many more spontaneous endocytic vacuoles than do adult RBC. It is not known if this difference is a result of an increase in production of vacuoles in the neonatal RBC (as is the case in drug‐induced endocytosis), or is the result of a less effective neonatal macrophagic “pitting” process.Using an in vitro model of spontaneous endocytosis, we compared the rate and quantity of vacuoles and the shape of cord and adult RBC containing pits, visible by interference contrast microscopy (Nomarski method). The mechanism of the spontaneous endocytosis was explored using different inhibitors: sodium vanadate an inhibitor of ATPases, sodium fluoride which inhibits the generation of ATP and sodium cyanide a potent inhibitor of oxidative phosphorylation. We then compared spontaneous endocytosis with two other forms of RBC endocytosis: drug‐induced endocytosis and receptor‐mediated endocytosis.Spontaneous endocytosis is in fact increased in neonatal RBC initially but the increase in number of RBC containing pits after 144 hr of incubation is almost the same in adult RBC and neonatal RBC. Comparing spontaneous endocytosis with drug‐induced endocytosis, it appears that their mechanisms are different in that spontaneous endocytosis is not preceded by stomatocytic shape change and is not inhibited by sodium vanadate or sodium fluoride as is the case for drug‐induced endocytosis. Spontaneous endocytosis is different than transferrin receptor‐mediated endocytosis because it occurs in many RBC, not only in the motile R1 reticulocytes and is not inhibited by sodium cyanide as is receptor‐mediated endocytosis.Thus spontaneous endocytosis appears to be different than drug‐induced endocytosis and transferrin receptor‐mediated endocytosis. The increase in spontaneous endocytosis in cord RBC seen in vivo is probably a consequence of an immaturity of the neonatal macro

ISSN:0361-8609    

DOI:10.1002/ajh.2830370108

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe best‐documented mode of transmission of familial sideroblastic anemia is as an X‐linked trait. Mitochondrial mutation has also occasionally been noted in association with sideroblastic anemia, but it is likely to be present more often than has so far been described. It should especially be suspected in cases of inherited multisystem disease, where the pedigrees do not indicate a sex predominance among those affected, and where there is no evidence of transmission by the paternal line. Sporadic cases of sideroblastic anemia may represent mitochondrial mutations either at the germ cell or the somatic cell, and the most sensitive strategy of screening for both would be the study of mitochondrial DNA from circulating erythrocytes. It seems likely that such studies would extend the understanding of mitochondrial function and dise

ISSN:0361-8609    

DOI:10.1002/ajh.2830370109

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe report a case of refractory anemia with excess blasts (RAEB) developing in a 67‐year old man with a history of polycythemia vera; results of cytogenetic and immunophenotyping studies are described. In this report the clinical, cytogenetic and hematologic features of myelodysplasia complicating polycythemia vera are reviewed. Results of immunophenotyping and cytogenetic studies, and the preponderance of cases developing after myelosuppressive therapy suggest that in the majority of cases myelodysplasia is treatment‐rela

ISSN:0361-8609    

DOI:10.1002/ajh.2830370110

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe are describing a rare case of acquired factor VIIIC inhibitor in postpartum period who also had strongly positive antinuclear antibody. On immunosuppression with prednisolone and azathioprine, both antibodies disappeared after 4 months of therapy.

ISSN:0361-8609    

DOI:10.1002/ajh.2830370111

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

年代:1991

数据来源: WILEY