摘要:

AbstractIntracellular and extracellular superoxide (O2.−) generation by human monocytes and macrophages was quantitated by the nitroblue tetrazolium (NBT) reduction method. Human monocytes reduced 4.4 ± 0.9 nmoles/106cells/15 minutes with an increase to 12.4 ± 1.3 during phagocytosis of zymosan. Based on inhibition by superoxide dismutase, superoxide generation of these cells was 1.8 ± 0.3 nmoles in the resting state and 16.8 ± 2.8 nmoles with zymosan phagocytosis. Human macrophages obtained by thoracentesis had comparable levels of NBT reduction and O2.−generation. Monocytes from a patient with chronic granulomatous disease demonstrated no increment in O2.−production during phagocytosis. Thus, human monocytes and macrophages appear capable of generating substantial amounts of O2.−during phagocytosis which may play an important role in bactericidal and other cel

ISSN:0361-8609    

DOI:10.1002/ajh.2830040102

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

年代:1978

数据来源: WILEY

摘要:

AbstractDeformability of normal and sickle erythrocytes was measured by means of micropipette elastimetry with determination of intrinsic membrane rigidity (P) and total cell deformability (Pt). In the elastimetric technique employed, negative pressure at the pipette tip was generated and measured continuously. Membrane rigidity is defined as the negative pressure, in mm H2O, required to induce a hemispherical projection of the cell surface into the micropipette, and total cell deformability as the negative pressure required to aspirate the entire cell into the pipette lumen. Membrane rigidity for oxygenated sickle discocytes was not statistically different from that of control normal discocytes, but Pt measurements were significantly higher for sickle than normal discocytes. Irreversibly sickled cells (ISCs) had markedly increased membrane rigidity and whole cell deformability when compared to control normal cells. Mildly deformed ISCs and severely deformed ISCs at ambient pO2, both showed significantly higher mean membrane rigidity values than sickle discocytes and reversibly sickled cells. Sickle and normal discocytes both showed membrane elasticity with reversion to original cell shape following release of the cell from its aspirated position at the pipette tip. ISCs, however, exhibited elastic deformation of the membrane. These studies provide further evidence of progressive alteration of the sickle cell membrane induced by the sickling‐unsickling process, culminating in formation of the ISC, and suggest a role for the ISC membrane abnormality in the pathologic rheology of sickle cell diseas

ISSN:0361-8609    

DOI:10.1002/ajh.2830040103

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

年代:1978

数据来源: WILEY

摘要:

AbstractPlatelet aggregation was studied following intravenous injection of heparin to nine healthy adults. Heparin is known to produce an increase in the concentration of free fatty acids (FFA) within 10 minutes of intravenous injection. A significant correlation was found between the intensity of primary platelet aggregation and changes in plasma FFA levels. No correlation was found between plasma FFA levels and the intensity of secondary platelet aggregation.

ISSN:0361-8609    

DOI:10.1002/ajh.2830040104

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

年代:1978

数据来源: WILEY

摘要:

AbstractMurine marrow cells, when incubated in methylcellulose culture in the presence of erythropoietin and conditioned medium for two weeks, produced large macroscopic bursts containing normoblasts, macrophages, and often megakaryocytes. The clonal nature of these mixed colonies was supported by linearity studies and analyses of the percentages of constituent cells in different plating conditions. Time course observations and studies of the effects of L‐cell‐conditioned medium revealed that colony‐forming cells for the mixed colonies (CFU‐mix) are at earlier stages of hemopoietic development than burst‐forming units (BFU‐E). The mean of the modal sedimentation velocities of CFU‐mix was 3.4 mm/hr and was in close agreement with that reported for the spleen colony‐forming units. Almost none of the CFU‐mix was in a DNA synthetic phase as measured by short‐term exposure to tritiated thymidine. These results strongly indicate that CFU‐mix represent a population of pluripotent hemopoietic stem c

ISSN:0361-8609    

DOI:10.1002/ajh.2830040105

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

年代:1978

数据来源: WILEY

摘要:

AbstractA newly developed micromethod to evaluate the cytotoxic effects of drugs on rapidly growing lymphoid cell lines is described, which permits evaluation of more than one variable. This technique allows a checkerboard titration of two drugs to determine the optimum concentration of each needed for the augmentation of the other's cell‐killing activity. Such studies have shown that the minimum concentration of vincristine capable of killing a human lymphoid cell population is 5.6 ng/ml. The addition of prednisolone at a concentration of 460 ng/ml reduces the minimum lethal concentration of vincristine to 1.6 ng/ml. When prednisolone is added to vincristine at concentrations of 2.8 μ/ml (a level readily achieved in the serum in vivo) concentrations of vincristine as low as 200 pg/ml are clearly cytotoxic. Similar potentiation of cytotoxicity following the addition of prednisolone has been demonstrated for cytosine arabinoside, but not for daunorubicin and only slightly for methotrexate. The micromethod for the study of optimal doses to be used in drug combinations is simple and gives highly reproducible results. It should be of considerable utility to anyone interested in screening a wide variety of drug concentrations for augmentation or synergistic effec

ISSN:0361-8609    

DOI:10.1002/ajh.2830040106

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

年代:1978

数据来源: WILEY

摘要:

AbstractVinblastine has been an effective single agent for initial induction therapy of advanced Hodgkin disease. To investigate the efficacy of this drug in combination chemotherapy‐resistant Hodgkin disease, 29 patients with Stage III or Stage IV disease who had previously received MOPP (nitrogen mustard, vincristine, prednisone, procarbazine) or C‐MOPP (cyclophosphamide, vincristine, prednisone, procarbazine) for initial remission induction were treated with vinblastine at the time of relapse, either as the first single agent at relapse (n = 17) or following unsuccessful attempts at reinduction with combination chemotherapy (n = 9) or other single agents (n = 3). Eighteen patients (62%) achieved an objective regression of disease. Two patients (7%) had a complete remission of nine and ten months duration and 16 patients (55%) had a partial remission with a median duration of four months. A response to combination chemotherapy did not predict for a vinblastine response, nor did nodal versus visceral involvement at time of relapse or initial stage of Hodgkin disease. There were no significant differences in age, sex, vinblastine dose, or disease duration between those patients who responded to vinblastine and those who did not. Patients with nodular sclerosis histology responded better to subsequent vinblastine therapy. Hematologic toxicity was moderate with 17 patients developing leukopenia (<3,000 cells/mm3) and 12 patients developing thrombocytopenia (<100,000 cells/mm3). The overall response rate of vinblastine in combination chemotherapy‐resistant Hodgkin disease is comparable to vinblastine single‐agent therapy for initial induction and appears not to be cross‐resistant with combinations containing vi

ISSN:0361-8609    

DOI:10.1002/ajh.2830040107

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

年代:1978

数据来源: WILEY

摘要:

AbstractA search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECF was obtained by a combination of gel filtration and ion‐exchange column chromatography. The factor is a low‐molecular‐weight (<2,000) substance and is probably a peptide or peptide‐nucleotide complex. The biologic activity of the ECF was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemi

ISSN:0361-8609    

DOI:10.1002/ajh.2830040108

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

年代:1978

数据来源: WILEY

摘要:

AbstractAcute lymphoblastic leukemia was observed in a 22‐year‐old white female patient and was manifested by normal platelet counts, 50–60% hand mirror cells (HMC) in the bone marrow, and prolonged survival without treatment. The characteristic neoplastic cell had a nucleus within the “mirror” portion and a cytoplasmic uropod forming the “handle” portion. The presence of acid phosphatase and B‐glucuronidase activity suggested that the cell was a T cell lymphoblast. However, extensive immunologic surface marker studies indicated the cells were non‐T, non‐B. Terminal transferase activity further supported the lymphoid nature of the cell. The hand mirror cells were considered a real phenomenon since they were demonstrated on phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The cells did not grow in tissue culture and cytogenetics revealed a normal female karyotype. From the above observations, the HMC is a lymphoblast with morphological, cytochemical, and immunological features which may differentiate it from the usual cell in acute lymphoblastic leukemia. Therefore, cases involving increased numbers of hand mirror cells in the bone marrow and acute lymphoblastic leukemia require further investigation to elucidate the full importance of this cell. This study represents the first attempt to investigate

ISSN:0361-8609    

DOI:10.1002/ajh.2830040109

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

年代:1978

数据来源: WILEY

摘要:

AbstractThe clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakarocyte aplasia.

ISSN:0361-8609    

DOI:10.1002/ajh.2830040110

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

年代:1978

数据来源: WILEY

摘要:

AbstractThe predisposition of immunodeficient patients to the development of peripheral blood abnormalities is well documented. Less often recognized is the presence of immune defects in patients who initially present with “idiopathic” forms of thrombocytopenic purpura or autoimmune hemolytic anemia in the absence of symptomatology indicative of an immunodeficiency. In this report we describe two children, each of whom had intermittent and at times severe hemolysis and thrombocytopenia secondary to formation of autoantibodies. Although the initial clinical impression was the presence of an “idiopathic” form of platelet or red cell destructive phenomenon, subsequent observations demonstrated abnormalities of the immune system which affected both B and T lymphocytes. In one of the patients there was a marked deficiency of IgA with a moderate but progressive decrease in IgM and IgG. The other patient had a moderate decrease in IgA and a failure to sensitize to dinitrochlorobenzene. Both exhibited dysmorphic features, including small stature, abnormal dentition, hyperelasticity of the skin, and hyperextensibility of the joints. Neither had significant problems with bacterial, fungal, or viral infections. These observations highlight the importance of evaluating the immune system in children with “idiopathic” forms of hemolytic anemia or thrombocytopenia. Demonstration of these abnormalities can have important therapeutic implications and may also provide information regarding the etiology of the blood ab

ISSN:0361-8609    

DOI:10.1002/ajh.2830040111

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

年代:1978

数据来源: WILEY