摘要:

AbstractCerebrospinal fluid beta‐2‐microglobulin (CSF‐β2m) was measured longitudinally in 48 patients affected by acute lymphoblastic leukemia (ALL). Thirteen developed a central nervous system (CNS) involvement during the course of the disease; although moderately higher mean CSF‐β2m levels were found in these subjects, no significant statistical differences were observed in comparison with patients without this complication and compared with the control group. No correlations were found between β2m and other biochemical parameters in CSF. Furthermore, CSF‐β2m levels appeared to be influenced by previous combined chemoradiotherapeutic treatment for CNS prophylaxis, presence of meningeal non‐neoplastic infiltrates, patients' ages, amount of CSF blasts, and their immunological phenotype. In particular, only clearly B‐committed leukemic cells, when tested, showed a strong surface expression of β2m, as demonstrated by immunocytochemical detection of this protein on cell membrane. However, in specific cases, CSF β2m measurement and CSF/serum β2m ratio were helpful in diagnosing and monitoring isolated CNS disease. Such findings suggest that CSF‐β2m assay may be a useful tool in the management of CNS involvement in the course of ALL in only selected patients, as several factors

ISSN:0361-8609    

DOI:10.1002/ajh.2830280402

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe ability of mature erythrocytes to spontaneously form intracellular vesicles has been implied from clinical studies but has not been examined experimentally. An in vitro model was developed to demonstrate whether mature erythrocytes are capable of spontaneously forming intracellular vesicles. Normal human erythrocytes were incubated in vitro at 37°C for 144 hr in a synthetic medium. During the course of these incubations, approximately 4% of erythrocytes developed intracellular vesicles which were quantitated by using interference contrast microscopy. Electron microscopic studies confirmed the intracellular nature of these vesicles. Incubation of erythrocytes in autologous plasma produced similar results. The rate of vesicle acqulsition in vivo was measured by quantitating erythrocyte vesicles immediately prior to and following splenectomy. The rates of vesicle acquisition in vivo and in vitro were comparable. This in vitro model confirms the ability of mature erythrocytes to spontaneously form intracellular vesicles and strongly supports the concept that this is a physiologic process

ISSN:0361-8609    

DOI:10.1002/ajh.2830280403

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

年代:1988

数据来源: WILEY

摘要:

AbstractTo elucidate the precise mechanisms of molecular and cellular regulation of hemopoiesis, it is necessary to develop a chemically defined culture assay for purified hemopoietic progenitors. To approach this long‐term goal, we attempted to develop a serum‐free culture system for enriched human progenitors that permits expression of all hemopoietic lineages and stages of development. Preliminary studies indicated that α‐medium was superior to iscove's modified Dulbecco's medium (IMDM) and that culture under low (5%) oxygen condition was better than an ambient level of oxygen. We developed an attenuated (modified quarter‐strength) α‐medium and compared the colony‐supporting ability of the three media by plating 1,000 bone marrow null cells per dish in the presence of a combination of recombinant human colony‐stimulating factors (CSFs). The numbers of colonies supported in α‐medium and attenuated α‐medium were approximately 70% of those in serum‐containing cultures. IMDM failed to support colony formation. While, in general, the colony sizes were smaller in the serum‐free cultures than in the serum‐containing cultures, a variety of types of single lineage and multilineage colonies were seen in serum‐free culture. A linear relationship between cell number and colony formation was seen in 100‐2,000 cells per dish. Serum‐free cultures of enriched human progenitors should be an important tool for analysis of t

ISSN:0361-8609    

DOI:10.1002/ajh.2830280404

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

年代:1988

数据来源: WILEY

摘要:

AbstractDuring their in vivo ageing, red blood cells (RBC) increase in density and become smaller. Age‐defined RBC subpopulations are usually collected by centrifugation. A fractionation according to RBC volume has been proposed as an improved alternative to such age separation. Because a few data reported in the literature indicate some discrepancies between the two methods, blood samples were separated either by centrifugation or by counterflow centrifugation, and some characteristics of the RBC thus fractionated were studied. The enzyme activities decrease either when the density rises or when the volume (MCV) decreases. However, the comparison of other RBC characteristics strongly suggests that these two procedures do not lead to the collection of the same RBC subpopulations: for instance, the hemoglobin content increases when the MCV rises, whereas it remains constant whatever the RBC density is. With radiolabelled cells, it is shown 1) that the most dense RBC are recovered in all the size‐separated RBC subpopulations, even though they tend to concentrate in the fractions with the largest MCV, and 2) that the smallest RBC are almost fairly distributed in all the RBC subpopulations, whatever their density, whereas the largest RBC are mainly, but not exclusively, present in the high‐density fractions. Thus, fractionation according to size does not match separation according to density. Taken together with results from in vivo experiments carried out in mice and with the fact that reticulocytes are present in all the size‐separated fractions, these data suggest that counterflow centrifugation may be a very questionable procedure to achieve a RBC fractionation according to age and therefore that RBC volume might not be a reliable criterion of

ISSN:0361-8609    

DOI:10.1002/ajh.2830280405

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

年代:1988

数据来源: WILEY

摘要:

AbstractTwenty‐two patients, splenectomized 1 to 26 years earlier for hematologic disorders, were studied to determine possible defects in immunologic function or complement levels. Quantitation of B cells and T‐cell subsets revealed slight decreases in the proportions of CD3 and CD4 cells but normal or increased absolute numbers of all cell populations. IgM synthesis in vitro by peripheral blood mononuclear cells was markedly diminished, but IgG synthesis was normal. Fractionation studies, in which various B‐cell‐ and T‐cell‐enriched populations from controls and patients were combined, demonstrated diminished B‐cell function in the patients. Sickle cell patients, who were functionally asplenic, showed similar deficits. Complement levels in splenectomized and sickle cell patients in both the classical and alternative pathways were generally normal. A modest decrease in component H in the alternative pathway in splenectomized and sickle cell patients probably was not clinically significant. In summary, splenectomized patients have a diminished capacity for IgM synthesis that can be attributed primarily to defective B‐cell function. This may be partially responsible for their increased susceptibility to infection by encapsu

ISSN:0361-8609    

DOI:10.1002/ajh.2830280406

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

年代:1988

数据来源: WILEY

摘要:

AbstractThirty‐eight patients with advanced Hodgkin disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) from 1970 to 1973 and followed prospectively. Long‐term results after a median follow‐up of 14 years are reported. Seventeen of the 28 complete responders (61%) survived more than 10 years from the initiation of chemotherapy. At the current time, 12 of the 28 patients (43%) are continuously disease‐free 12.8 to 15.3 years after completing induction chemotherapy. Two additional patients are alive in third and fifth remissions. All relapses occurred within 5.5 years of completing induction chemotherapy. Late complications included sterility, aseptic osteonecrosis, severe pulmonary fibrosis, and chronic uveitis. Four of the complete responders (14%) developed second neoplasms, including acute myelogenous leukemia, non‐Hodgkin lymphoma and small cell carcinoma of the lung. All second malignancies were fatal and developed 5‐13 years after initiation of induction chemotherapy. Our data confirm that cure is possible with alternative regimens to MOPP (nitrogen mustard, vincristine, procarbazine, and

ISSN:0361-8609    

DOI:10.1002/ajh.2830280407

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe successful demonstration and localisation of acetylcholinesterase (AChE), in cells by a cytochemical technique requires maximal expression of enzyme activity, minimal loss of AChE and precise, quantitative generation of reaction product at the actual site of the protein in vivo. These requirements are addressed in a standard technique that has been modified to avoid or optimise fixation and to exhibit enzyme activity under close‐to‐physiological conditions of osmolality, pH, and temperature. With these refinements and with the use of a variety of substrates and enzyme inhibitors of different specificities, true AChE was demonstrable on the membrane of erythrocytes and in the nucleus and cytoplasm of erythroblasts in bone marrow and of the constituent cells of erythroid clones in vitro. The activity in erythrocytes from umbilical cord blood was less than that in corresponding cells from the peripheral circulation of adults. AChE was observed also in human megakaryocytes and in leucocytes at all levels of differentiation, including the components of granulocyte‐macrophage clones. Pseudocholinesterase was detected likewise across the spectrum of erythroid (and leucocyte) ontogeny, suggesting that these enzymes may exercise an important function in hematopo

ISSN:0361-8609    

DOI:10.1002/ajh.2830280408

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

年代:1988

数据来源: WILEY

摘要:

AbstractAcetylcholinesterase (AChE) is an integral erythrocyte membrane protein. A role for the enzyme in the developing human erythron is being explored. Assays of AchE by the standard Ellman technique overestimate the amount of enzyme by failing to account for the contribution of hemoglobin to the optical density of the reaction mixture. Furthermore, reliance on substrate selection alone for specificity is unsatisfactory. Incorporation of inhibitors of “true” AchE and of pseudocholinestearase confer greater ability to distinguish one enzyme from the other. In our experience, the inhibitor constant (K1) for edrophonium, which is highly specific for AChE, is approximately 5 × 10−5M against adult human erythrocytes that contain significantly more total cholinesterase activity than do erythrocytes from umbilical cord blood. This consists of both “true” and “pseudo” enzyme, the former predominating and accounting for 0.75–1.65 (mean 1.02, median 0.87) femtomoles of substrate hydrolysed per min per cell in adult blood, with values of 0.15–1.04 (mean 0.71, median 0.73) obtained on cord blood. Moreover, the enzyme activity in neonatal erythrocytes has a rather different inhibitor profile from that of adult cells. AChE was also demonstrated in fresh (ALL) and cultured (K562 and HL60) human leukemic cells, as well as in primitive granulocyte‐macrophage and erythroid cells cloned from normal human bone marrow. In the erythroid colonies the enzyme activity was 0–3.76 (mean 1.20, median 0.76) femtomoles per min per cell, apparently the first successful measurement

ISSN:0361-8609    

DOI:10.1002/ajh.2830280409

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

年代:1988

数据来源: WILEY

摘要:

AbstractA myeloproliferative disorder having the phenotype of chronic myeloid leukemia (CML) with t(8;21) is reported. Neither t(9;22) nor a DNA rearrangement in thebcrregion was detected. The presence of t(8;21), in contrast with previous experience, does not appear to prevent full maturation of the granulocytic series.

ISSN:0361-8609    

DOI:10.1002/ajh.2830280410

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

年代:1988

数据来源: WILEY

摘要:

AbstractA 68‐year‐old male who suffered from thrombocytopenia and mild splenomegaly for 18 years was found to present agranular gray platelets on peripheral blood smear. Bone biopsy revealed a mild, diffuse, reticular fibrosis with no collagen, and electron microscopy of the platelets showed an absence of almost all the α‐granules. Platelet thrombospondin and fibronectin analysed by SDS‐polyacrylamide gel electrophoresis and Rocket immunoelectrophoresis were absent. Follow‐up of 4 years showed the same parameters with no evidence of active myeloproliferative or dysmyelopoietic disorders. Hemorrhagic diathesis was limited to ecchymoses and postprostatectomy bleeding, necessitating platelet transfusion. This led us to conclude that our patient probably had a constitutional primary α‐granule deficiency or gray platelet syndrome. This extremely rare defect has been described in less than 10 patients, all of them very young. Our observation shows that these patients may have a long, uneven

ISSN:0361-8609    

DOI:10.1002/ajh.2830280411

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

年代:1988

数据来源: WILEY