bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cells suppress human erythroid stem cell proliferation in vitro
Authors: Mangan KF , Hartnett ME , Matis SA , Winkelstein A , Abo T 
Published: October 2019

Abstract
To determine the role of natural killer (NK) cells in the regulation of human erythropoiesis, we studied the effects of NK-enriched cell populations on the in vitro proliferation of erythroid stem cells at three different levels of maturation (day 14 blood BFU-E, day 5–6 marrow CFU-E, and day 10–12 marrow BFU-E). NK cells were enriched from blood by Percoll density gradient centrifugation and by fluorescence- activated cell sorting (FACS), using the human natural killer cell monoclonal antibody, HNK-1. The isolated enriched fractions were cocultured with autologous nonadherent marrow cells or blood null cells and erythropoietin in a methylcellulose erythroid culture system. Cells from low-density Percoll fractions (NK-enriched cells) were predominantly large granular lymphocytes with cytotoxic activity against K562 targets 6–10-fold greater than cells obtained from high- density Percoll fractions (NK-depleted cells). In coculture with marrow nonadherent cells (NA) at NK:NA ratios of 2:1, NK-enriched cells suppressed day 5–6 CFU-E to 62% (p less than 0.025) of controls, whereas NK-depleted cells slightly augmented CFU-E to 130% of controls (p greater than 0.05). In contrast, no suppression of day 10–12 marrow BFU-E was observed employing NK-enriched cells. The NK CFU-E suppressor effects were abolished by complement-mediated lysis of NK-enriched cells with the natural killer cell antibody, HNK-1. Highly purified HNK- 1+ cells separated by FACS suppressed marrow CFU-E to 34% (p less than 0.025) and marrow BFU-E to 41% (p less than 0.025) of controls. HNK- cells had no significant effect on either BFU-E or CFU-E growth. NK- enriched cells were poor stimulators of day 14 blood BFU-E in comparison to equal numbers of NK-depleted cells or T cells isolated by E-rosetting (p less than 0.01). Interferon boosting of NK-enriched cells abolished their suboptimal burst-promoting effects and augmented their CFU-E suppressor effects. These studies provide evidence for a potential regulatory role of NK cells in erythropoiesis. The NK suppressor effect is maximal at the level of the mature erythroid stem cell CFU-E. These findings may explain some hypoproliferative anemias that develop in certain NK cell-activated states.
Liver endothelium and not hepatocytes or Kupffer cells have transferrin receptors
Authors: Soda R , Tavassoli M 
Published: October 2019

Abstract
Using a visual probe, consisting of latex minibeads covalently linked to transferrin (TF), we found that, in rat liver cell suspensions, transferrin receptors were limited to endothelial cells. Neither hepatocytes nor Kupffer cells contained an appreciable number of TF receptors. Specificity of this reaction was demonstrated by preincubation with non-derivatized TF, which inhibited the binding. This was further confirmed by fractionation of liver cell suspensions on metrizamide gradients. The uptake of either the visual probe or 125I- labeled TF was again limited to the endothelium-rich fraction. Transferrin bound to endothelial membrane was internalized at 37 degrees C, but not at 4 degrees C, via a coated pit system. Again, hepatocytes and Kupffer cells did not internalize the probe. The findings suggest that iron may be first taken up by liver endothelium and then transmitted to parenchymal cells. These results emphasize the generally unappreciated role of endothelium in the transport across the tissue-blood barrier.
Studies on pure red cell aplasia. XI. Results of immunosuppressive treatment of 37 patients
Authors: Clark DA , Dessypris EN , Krantz SB 
Published: October 2019

Abstract
Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.
Leukemic cell differentiation in vivo and in vitro: arrest of proliferation parallels the differentiation induced by the antileukemic drug Harringtonine
Authors: Boyd AW , Sullivan JR 
Published: October 2019

Abstract
A variety of chemical agents have been shown to induce differentiation in in vitro cultured neoplastic cell lines. We noted that blast cells in the peripheral blood of acute nonlymphoid leukemia patients treated with the drug Harringtonine appeared to undergo morphological changes that suggested differentiation. In view of the relatively minimal myelotoxicity of Harringtonine, we hypothesized that harringtonine was acting by differentiation-induction, which concomitantly arrested cell division. We tested this hypothesis using two different experimental approaches. First, the promyelocytic leukemic cell line, HL-60, was cultured with Harringtonine and shown to differentiate into a cell, which, by functional cell surface marker and morphological criteria, closely resembled normal monocytes. Furthermore, these changes were accompanied, and indeed slightly preceded by, loss of proliferative capacity. Second, to prove that the leukemic blasts were the cells undergoing the changes observed in vivo, freshly isolated leukemia cell populations were cultured with Harringtonine, and morphological changes paralleling those seen in the patients were observed. Thus, the antileukemic effect of Harringtonine appeared to be due to diversion of the proliferating blast cells into a differentiation pathway, which, as in normal myeloid cells, resulted in the arrest of proliferation.
Pre-B cell leukemia responds poorly to treatment: a pediatric oncology group study
Authors: Crist W , Boyett J , Roper M , Pullen J , Metzgar R , van Eys J , Ragab A , Starling K , Vietti T , Cooper M 
Published: October 2019

Abstract
Seventy-eight of 362 children with acute lymphocytic leukemia (ALL) had leukemic cells similar in phenotype to normal pre-B cells. When the clinical and laboratory features of patients with pre-B and “null” cell phenotypes of ALL were compared, no significant differences were noted, except that the pre-B cell ALL phenotype had a higher percentage of black children. In contrast, patients with T cell ALL had a higher median age at diagnosis, frequent thymic involvement, and higher WBC counts. Patients with pre-B and “null” cell ALL were treated identically and patients with T cell ALL differently. Although no difference in remission induction rates was noted between patient groups with pre-B and “null” cell ALL, the remissions were of shorter duration for patients with pre-B cell ALL (p = 0.004). Similarly, overt leukemic involvement of both the central nervous system (CNS) and bone marrow was noted sooner in the patient group with pre-B cell ALL. Univariate and multivariate Cox life table regression analyses demonstrate the independent prognostic significance of the pre-B phenotype and illustrate that the prognostic influence of potential relapse risk factors, such as WBC, sex, and age, are specific for leukemia phenotype. These findings may have importance for the design and tailoring of therapy for children with acute leukemia.
Polymorphonuclear leukocyte elastase activity is increased by bacterial lipopolysaccharide: a response inhibited by glucocorticoids
Authors: Hart DH 
Published: October 2019

Abstract
Human neutrophil elastase is thought to play an important role in connective tissue destruction in diseases such as emphysema and arthritis. In this article, it is demonstrated that the elastase activity of mature human peripheral blood neutrophils can be rapidly increased in vitro by treatment of the cells with lipopolysaccharide from E. coli and that this increase is inhibited by corticosteroid pretreatment of the cells and by inhibitors of protein synthesis. Alterations in intracellular enzyme content of the mature polymorph in response to bacterial products or other stimuli may be important for amplification of the inflammatory response.
Platelet secretion defect in patients with the attention deficit disorder and easy bruising
Authors: Koike K , Rao AK , Holmsen H , Mueller PS 
Published: October 2019

Abstract
Platelet function was evaluated in 12 patients with the attention deficit disorder and lifelong history of easy bruising. Aggregation and 14C-serotonin secretion studies in platelet-rich plasma in response to adenosine diphosphate (ADP), epinephrine, and arachidonic acid did not reveal striking abnormalities. Secretion of adenosine triphosphate (ATP), ADP, beta-hexosaminidase, and beta-glucuronidase by gel-filtered platelets in response to the divalent cation ionophore A23187 and low concentrations of thrombin (less than or equal to 0.1 U/ml) was impaired in patients as compared to normals. The aggregation response to A23187 (4 microM) was absent in 8 of the 12 patients. The total stores of the secretable constituents, the retention of incorporated 14C-serotonin, and the arachidonate metabolism of the platelets were normal. Our findings suggest a new platelet disorder with impaired secretion mechanism, without storage pool deficiency or impaired arachidonate metabolism. The secretion defect in platelets represents a tissue disorder in a functional psychiatric disease. We refocus attention on the role of platelets as a model for neurons in functional disorders, with emphasis on secretion mechanisms rather than amine uptake, storage, and metabolism.
Development of factor VIII:C antibodies in dogs with hemophilia A (factor VIII:C deficiency)
Authors: Giles AR , Tinlin S , Hoogendoorn H , Greenwood P , Greenwood R 
Published: October 2019

Abstract
Classic hemophilia A (factor VIII:C deficiency) was diagnosed in a miniature Schnauzer dog and a breeding program established. Inbreeding and crossbreeding produced 16 hemophilic animals. All were initially treated with canine cryoprecipitate, as required, for sporadic hemorrhagic events. Five animals developed potent antibodies to canine factor VIII:C. All were the offspring of obligate carriers, resulting from the mating of a hemophilic purebred miniature Schnauzer male to a normal female Brittany spaniel. The mean age at first treatment and factor VIII exposure at the time of inhibitor development was 10.3 wk and 286.3 U, respectively. The remaining hemophilic animals have not developed antibodies, despite receiving a mean factor VIII dosage of 1.5 X 10(3) U. This group includes animals derived from a mating between the same purebred miniature Schnauzer hemophilic male and a purebred miniature Schnauzer carrier female. In each case, the antibodies recognize both canine and human but not porcine VIII:C. They are non-precipitating IgG immunoglobulins. Following inhibitor development, infusion of canine cryoprecipitate was hemostatically ineffective and factor VIII:C recovery at 30 min was negligible. Infusion of a concentrate of porcine factor VIII resulted in a correction of the hemostatic defect and optimal factor VIII:C recovery. All animals receiving porcine factor VIII:C subsequently developed antibodies to this protein. The chance occurrence of this complication should facilitate further studies directed at elucidating the pathogenesis and management of hemophilia complicated by the development of antibodies to factor VIII:C.
Beta-2-microglobulin in myeloma: optimal use for staging, prognosis, and treatment--a prospective study of 160 patients
Authors: Bataille R , Grenier J , Sany J 
Published: October 2019

Abstract
Previous reports have shown that serum beta-2-microglobulin (S beta2M) is a reliable marker of presenting tumor mass, response to chemotherapy, and prognosis of patients with multiple myeloma (MM). In order to more thoroughly evaluate the optimal use of S beta2M in plasma cell dyscrasias (PCD), S beta2M levels were serially measured in 160 patients with MM, in comparison with 37 normal controls (NC) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS). In MGUS, S beta2M did not differ significantly from that of NC, but was significantly lower than that of MM (p less than 0.001), including low cell mass MM (p less than 0.02). In MM, S beta 2M was highly correlated with the total body burden of myeloma cells as derived from the staging of Durie and Salmon, both at diagnosis and in remission (residual tumor mass) (p less than 0.001). During the plateau phase, S beta 2M remained very stable and was always within the normal range for patients with greater than or equal to 75% tumor regression. The most striking finding was that S beta 2M gave an extremely reliable fit for survival prediction at (1) diagnosis, (2) remission, and (3) early relapse, with higher S beta 2M levels in each instance being in favor of poorer prognosis. We conclude that S beta 2M is an extremely useful marker in initial stratification and follow-up of patients with MM.
Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean
Authors: Miedema F , Terpstra FG , Smit JW , Daenen S , Gerrits W , Hegde U , Matutes E , Catovsky D , Greaves MF , Melief CJ 
Published: October 2019

Abstract
The neoplastic T cells from five patients with adult T cell lymphoma/leukemia (ATLL), born in the Caribbean, were studied with respect to immunoregulatory activity on pokeweed mitogen (PWM) driven immunoglobulin (Ig) synthesis as well as surface-marker phenotypes with monoclonal antibodies. The neoplastic T cells in all patients had an OKT1+4+8–11+M1-I1–3A1- phenotype, but differed in the reactivity with OKT3. None of the patients' cells exerted helper activity on PWM- induced Ig synthesis. The neoplastic cells of three patients had suppressor activity on PWM-induced Ig synthesis. All patients were positive for human T cell leukemia/lymphoma virus (HTLV) or had antibodies against HTLV antigens. It has previously been shown that the neoplastic cells in Japanese ATLL patients and in patients from the Caribbean are indistinguishable by morphology and marker phenotype. We now show them to be also similar with respect to their functional properties.
Fibrinogen proteolysis and platelet alpha-granule release in preeclampsia/eclampsia
Authors: Borok Z , Weitz J , Owen J , Auerbach M , Nossel HL 
Published: October 2019

Abstract
Serial measurements of the plasma concentration of fibrinopeptide A, thrombin-increasable fibrinopeptide B (reflecting B beta 1–42), desarginyl fibrinopeptide B, beta thromboglobulin, and platelet factor 4 were made before, during, and after delivery in patients with preeclampsia/eclampsia. The data were correlated with routine coagulation studies, hematologic and renal status, as well as with the clinical manifestations. In 11 patients with mild preeclampsia, there were small increases in the fibrinopeptides at the time of delivery, but no other hematologic changes. In 5 patients with severe preeclampsia/eclampsia, there were marked increases in plasma levels of fibrinopeptides and platelet alpha granule proteins, which correlated in time with the clinical manifestations. When the changes in these patients were compared with those occurring in patients undergoing intraamniotic hypertonic saline infusion, it was noted that: (1) patients with severe preeclampsia/eclampsia usually presented when plasmin action on fibrinogen exceeded that of thrombin; (2) in patients with preeclampsia/eclampsia the increase in fibrinopeptides lasted from 3 to 7 days, rather than for several hours as occurred after the infusion of hypertonic saline, indicating a more persistent stimulus to intravascular coagulation in preeclampsia/eclampsia; (3) severe thrombocytopenia and increased platelet protein levels were seen in these patients and were disproportionate to the degree of increase in the fibrinopeptide A level, suggesting that a mechanism other than thrombin must have contributed to the platelet changes; and (4) in two patients with severe preeclampsia/eclampsia, high desarginyl fibrinopeptide B levels preceded renal insufficiency, possibly reflecting fibrin II formation in renal vessels.
Antigenic analysis of hematopoiesis: II. Expression of human neutrophil antigens on normal and leukemic marrow cells
Authors: Strauss LC , Skubitz KM , August JT , Civin CI 
Published: October 2019

Abstract
The binding of five antineutrophil monoclonal antibodies AHN-1, -2, -3, -7, and -8, to normal and leukemic bone marrow cells was studied. AHN-7 bound to many granulocytic precursors, particularly myelocytes, and both lymphoid and blast cells in normal marrow, and to most but not all granulocyte-macrophage progenitors (CFC-GM). AHN-8 bound only to late (band and segmented) neutrophilic cells and not to CFC-GM. AHN-1, -2, - 3 bound to morphologically identifiable neutrophil precursors, but not to (day-14) CFC-GM. Approximately half of nonlymphoid leukemia specimens were positive with AHN-1 or AHN-7; by contrast, lymphoid leukemia specimens were rarely positive. AHN-8 was rarely found on leukemic cells. These antineutrophil antibodies appear to detect distinct granulopoietic subsets and may be useful in the analysis of hematologic differentiation and in the subclassification of leukemias.
The effect of splenectomy on platelet formation and megakaryocyte DNA content in rats
Authors: Tanum G , Sonstevold A , Jakobsen E 
Published: October 2019

Abstract
The DNA content of rat bone marrow megakaryocytes (MK) was studied by Feulgen photometry following splenectomy and sham operation, respectively. The DNA measurements were preceded by acetylcholinesterase staining for identification of the 2N-8N MK. The number of 2N-8N MK decreased to minimum values, while the number of 16N- 64N MK increased to maximum values about 4 days following both splenectomy and sham operation. However, the changes were somewhat more pronounced following splenectomy than sham operation. The total MK number did not change significantly. Platelet production, measured by 35S incorporation into platelets, increased during the first 2 days and remained high for 6–7 days, increasing the platelet counts. All values were about normal 30 days after surgery, except for a minor thrombocytosis following splenectomy. The early, highly significant thrombocytosis, following both splenectomy and general surgery, is caused by increased production of platelets due to the surgical trauma. This is caused by a direct action on bone marrow MK by transforming 2N- 8N MK into higher ploidy classes. Lack of splenic platelet pooling may influence the grade and duration of the early thrombocytosis after splenectomy. The late, long-lasting, minor thrombocytosis, which occurs after splenectomy but not after sham operation, can be explained by the removal of the splenic platelet pool.
alpha-Actinin and vinculin in normal and thrombasthenic platelets
Authors: Langer BG , Gonnella PA , Nachmias VT 
Published: October 2019

Abstract
Recently, the contractile protein alpha-actinin was identified in normal human platelets by its antigenic cross-reaction with a monospecific antibody to purified muscle alpha-actinin. In this study, we extend that preliminary identification of platelet alpha-actinin. Amino acid analysis, one-dimensional peptide maps, and silver stain analysis on polyacrylamide gels demonstrate that human platelet alpha- actinin shows a greater degree of similarity to smooth muscle alpha- actinin than to striated muscle alpha-actinin. There is no evidence to suggest that alpha-actinin is a glycoprotein. In addition, we find that thrombasthenic platelets, which are deficient in glycoproteins IIb and IIIa (GPIIb and GPIIIa) contain normal amounts of alpha-actinin, confirming the recent finding that alpha-actinin and GPIIIa are different proteins in human platelets. We demonstrate that both normal and thrombasthenic platelets also contain vinculin, a 130,000-dalton polypeptide found in many cell types at sites of end-on attachment of microfilaments to the plasma membrane. Thus, the thrombasthenic defect in GPIIb and GPIIIa does not diminish the content of either alpha- actinin or vinculin.
Burkitt's lymphoma in AIDS: cytogenetic study
Authors: Whang-Peng J , Lee EC , Sieverts H , Magrath IT 
Published: October 2019

Abstract
Cytogenetic studies were done in two cases of Burkitt's lymphoma in homosexual individuals with possible acquired immune deficiency syndrome (AIDS). The chromosomal abnormalities found are consistent with those previously described in the nonendemic form of Burkitt's lymphoma, with one of the two patients having the variant translocation, t(8;22). The production of the kappa light chain immunoglobulin by the tumor cells from the patient having t(8;22) and the occurrence of the different sites of translocation of the duplication of 1 q in the second patient are unusual findings. Whether there is an increase in the incidence of the variant translocation t(8;22) is yet to be determined.
L-asparaginase: acute effects on protein synthesis in rabbits with normal and increased fibrinogen production
Authors: Alving BM , Barr CF , Tang DB 
Published: October 2019

Abstract
The acute effects of a single intravenous dose of L-asparaginase on protein synthesis were studied in normal rabbits and in animals that had received turpentine to stimulate fibrinogen production. Male New Zealand rabbits received L-asparaginase (500 U/kg) 16 hr before the injection of the radiolabeled amino acid [75Se]selenomethionine (75SeM). Incorporation of 75SeM into fibrinogen and serum proteins in the L-asparaginase-treated rabbits was the same as for saline-treated controls, with fibrinogen representing approximately 5% of the labeled plasma proteins. In turpentine-treated rabbits, the maximal incorporation of 75SeM into serum proteins remained unchanged, whereas 75SeM-fibrinogen increased sixfold and accounted for 25% of the labeled proteins. Animals that received L-asparaginase at the same time as turpentine or 14 hr later showed significant decreases in synthesis of both serum proteins and fibrinogen. 75SeM-fibrinogen that was purified from L-asparaginase-treated rabbits underwent normal catabolism when injected into normal recipient rabbits. These data indicate that L- asparaginase can acutely cause partial inhibition of both serum protein and fibrinogen synthesis when administered to rabbits shortly before or during a period of increased fibrinogen production. Fibrinogen that is synthesized in the presence of L-asparaginase does not have an abnormal rate of catabolism.