bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor
Authors: Ingraham LM , Coates TD , Allen JM , Higgins CP , Baehner RL , Boxer LA 
Published: October 2019

Abstract
The phospholipid mediator of anaphylaxis, platelet-activating factor (PAF) is chemotactic for polymorphonuclear leukocytes (PMN). We have examined this agent's effects on several other PMN functions. Human PMN were prepared from heparinized venous blood by Ficoll gradient. Metabolic burst was examined by measurement of O2 use and O2.- production in the presence or absence of PAF (10(-6)--10(-9) M). Unless cells were treated with cytochalasin-B (5 micrograms/ml), no significant respiratory burst was demonstrated. However, pretreatment with PAF (10(-7) M) enhanced approximately threefold the O2 utilization found when cells were subsequently stimulated with 10(-7) M FMLP. PAF also stimulated arachidonic acid metabolism in 14C-arachidonic acid- labeled PMN. Thin-layer chromatography analysis of chloroform-methanol extracts showed substances that comigrated with authentic 5- hydroxyeicosatetraenoic acid had a marked increase in radioactivity following PAF stimulation at 10(-7) M. PAF failed to stimulate release of granule enzymes, B-glucuronidase, lysozyme, or myeloperoxidase unless cytochalasin-B were added. PAF from 10(-6) M to 10(-10) M affected PMN surface responses. PMN labeled with the fluorescent dye, chlorotetracycline, showed decreased fluorescence upon addition of PAF, suggesting translocation of membrane-bound cations. Further, the rate of migration of PMN in an electric field was decreased following PAF exposure, a change consistent with reduced cell surface charge. PMN self-aggregation and adherence to endothelial cells were both influenced by PAF (10(-6) M--10(-9) M). Aggregation was markedly stimulated by the compound, and the percent PMN adhering to endothelial cell monolayers increased almost twofold in the presence of 10(-8) M PAF. Thus, PAF promotes a variety of PMN responses: enhances respiratory burst, stimulates arachidonic acid turnover, alters cell membrane cation content and surface charge, and promotes PMN self- aggregation as well as adherence to endothelial cells.
Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor
Authors: Udupa KB , Lipschitz DA 
Published: October 2019

Abstract
The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.
Genetic aspects of susceptibility to multiple myeloma
Authors: Ludwig H , Mayr W 
Published: October 2019

Abstract
An up-dated survey of the information pertaining to the role of genetic factors in susceptibility to multiple myeloma is attempted. Our own results include the HLA-A, B, and C types in 68 patients, the G1m and Km allotypes in 86 patients, and the frequencies of ABO blood groups in 126 patients with multiple myeloma. The allotype G1m(x) was significantly (p less than 0.05) more frequent in the patient group. Since the results in the literature on a possible HLA association have been inconsistent, all relevant available data were combined for an assessment of 379 patients versus 5041 controls. In this comparatively large patient group, the previously reported increase of HLA-4c (HLA-B5 + B18 + Bw35) complex could be confirmed and identified as a weak (RR = 1.7) but significant (p less than 0.05) association of susceptibility to multiple myeloma with HLA-B5. Evaluation of G1m allotypes in the combined sample of 258 patients and 4550 controls and Km in 179 and 2457, respectively yielded no significant differences.
Factor VIII/von Willebrand factor protein: sensitivity of periodic acid Schiff stain to carbohydrate deficiency
Authors: Gralnick HR , Jackson GM , Williams SB , Cregger MC 
Published: October 2019

Abstract
We have investigated the periodic acid Schiff (PAS) Coomassie staining ratio of the human factor VIII/von Willebrand factor (fVIII/vWf) protein. The PAS-Coomassie staining ratio is consistent over 8 days. The PAS-Coomassie ratio of fVIII/vWf protein purified from different starting materials does not appear to be significantly different. The PAS stain can detect as little as 300 ng of carbohydrate in the fVIII/vWf protein. Desialation did not affect the PAS-Coomassie ratio, while removal of penultimate galactose resulted in a marked reduction in the PAS-Coomassie ratio. This reduction was further accentuated with the removal of N-acetylglucosamine. The smaller multimers of the fVIII/vWf protein have a reduced sialic acid and PAS-Coomassie staining ratio. This difference does not appear to be related to the sialic acid deficiency but may be related to the distribution or organization of the carbohydrate moieties on the smaller fVIII/vWf multimers.
The Effect of Intravenous Histamine Administration on the Level of the White Blood Count in the Peripheral Blood
Authors: BIERMAN HOWARD R. , KELLY KEITH H. , PETRAKIS NICHOLAS L. , CORDES FAUNO , FOSTER MARILEE , LOSE ELIZABETH A. 
Published: October 2019

Abstract
1. By simultaneously sampling venous and arterial blood by cardiac catheterization or vessel cannulation, the number of leukocytes entering and leaving the lungs was observed in 12 patients on 14 occasions.
2. The intravenous administration of histamine phosphate in doses of 0.1 to 0.3 mg. (as base) over 10 to 60 seconds, was accompanied by a prompt decrease in leukocyte number in the arterial blood 20 to 60 seconds before the venous white cell count fell. This was interpreted as demonstrating that the leukocytes were removed from tine peripheral blood in the pulmonary circulation. The granulocytic series appeared to be more involved in the leukopenia, although a similar but less apparent change was noted in the agranulocytes.
3. The leukopenia persisted for 40 to 180 seconds following which the arterial leukocyte count exceeded that in the venous blood indicating a return of leukocytes from the lungs into the peripheral circulation.
4. The intravenous administration of histamine also resulted in an immediate decrease in clotting time as determined both by glass and siliconed tube technics.
5. The intravenous injection of histamine affords a relatively simple technic to study one type of leukocyte removal mechanism present in the pulmonary circulation.
The quantitation of platelet-associated IgG on cohorts of platelets separated from healthy individuals by buoyant density centrifugation
Authors: Kelton JG , Denomme G 
Published: October 2019

Abstract
Evidence suggests that as platelets age in the circulation they become progressively smaller and less dense through the loss of protein. The smallest, least dense platelets have a significantly shortened survival, but the mechanism of clearance of these platelets is not known. To evaluate whether the binding of IgG could play a role in the clearance of senescent platelets, we measured platelet size, total protein, and platelet-associated IgG on subpopulations of platelets isolated from 6 healthy individuals using a discontinuous iso-osmotic arabinogalactan (stractan) gradient. There was a close correlation between density, size, and total protein content (r greater than 0.9) for all platelet fractions. There was also a relationship between the amount of platelet-associated IgG (PAIgG), total protein, and platelet size (r greater than 0.9) for the first 3 progressively less dense platelet factions. However, the fourth platelet fraction containing the smallest, least dense, and on current evidence, oldest platelets had very elevated amounts of IgG. This amount was approximately 10 times higher than the mean platelet IgG for the same individual and was similar to the amount of PAIgG found on platelets from patients with immune thrombocytopenia. A progressive increase in the ratio of PAIgG measured after platelet solubilization to PAIgG measured on intact platelets was also noted for the first three populations, indirectly suggesting that platelets clear IgG from their surface during aging. Increased binding of IgG to senescent platelets may mediate their destruction.
A monoclonal immunoblastic sarcoma in donor cells bearing Epstein-Barr virus genomes following allogeneic marrow grafting for acute lymphoblastic leukemia
Authors: Schubach WH , Hackman R , Neiman PE , Miller G , Thomas ED 
Published: October 2019

Abstract
A patient undergoing marrow grafting for acute lymphoblastic leukemia from his partially HLA-mismatched sister displayed a widely disseminated immunoblastic sarcoma at autopsy. The tumor was monoclonal by immunoglobulin light-chain staining. Blot hybridization analysis, using a cloned highly polymorphic locus in human DNA as a probe, showed the tumor to be of donor-cell origin. Cytogenetic analysis also demonstrated donor-cell origin. Blot hybridization analysis demonstrated Epstein-Barr virus (EBV) genomes in the tumor. By contrast, reexamination of material from a previously reported case of a donor-type relapse showed no evidence of EBV DNA. In neither case was there evidence of cytomegalovirus DNA. This study documents the association of EBV with a malignant, monoclonal B-cell lymphoma arising in a marrow graft recipient. We conclude that DNA restriction fragment length polymorphisms can be used to prove the origin (donor or host) of neoplastic relapse following allogeneic marrow grafting. Further, cell types different from those of the original leukemia may be involved.
The demarcation membrane system of the megakaryocyte: a misnomer?
Authors: Radley JM , Haller CJ 
Published: October 2019

Abstract
The concept that the demarcation membrane system delineates platelets within the cytoplasm of megakaryocytes has been examined. In short-term culture of mouse bone marrow, mature megakaryocytes extended long, attenuated processes that were found by electron microscopy to have a limited amount of invaginated membrane. When such megakaryocytes were exposed to microtubule depolymerizing agents, the attenuated processes retracted, became thicker, and an extensive demarcation membrane reappeared. It is suggested from the results that the demarcation membrane system functions to provide a membrane reserve that undergoes evagination during the formation of attenuated processes and thereby envelops putative platelets, rather than to demarcate platelets in the maturing megakaryocyte. The term “invaginated membrane system” is considered more appropriate than “demarcation membrane system.”
Subcellular localization of H2O2 production in human neutrophils stimulated with particles and an effect of cytochalasin-B on the cells
Authors: Ohno Y , Hirai K , Kanoh T , Uchino H , Ogawa K 
Published: October 2019

Abstract
The ultrastructural localization of H2O2 production in suspended polymorphonuclear leukocytes (PMN) stimulated with particles was studied using CeCl3 technique. PMN stimulated with opsonized zymosan or polystylene latex with or without IgG were incubated in 0.1 M Tris- maleate buffer with 1 mM CeCl3 and 10 mM aminotriazole. Cells were then fixed and embedded in a resin for electron microscopy. The reaction product of cerium perhydroxide was observed on the phagosomal membranes and on the areas of the plasma membrane engulfing the particles. Catalase or ferricytochrome-c decreased the deposits. p-Benzoquinone (O2- scavenger) inhibited the formation of the deposits, but KCN or NaN3 enhanced it. Pretreatment with p-diazobenzenesulfonic acid inhibited the reaction. In some PMN pretreated with cytochalasin-B, cellular aggregation was observed. The H2O2 production in these cells were observed on the membrane adherent to the particles and on the contact surface of the membrane of adjoining PMN. The plasma membrane was damaged and the electron-dense product was diffused into the cytoplasm. These results clearly show that H2O2 production is initiated at the area of the plasma membrane adherent to the particles and that H2O2 is released before the completion of phagocytosis.
A shortened variant of red cell membrane protein 4.1
Authors: Alloisio N , Dorleac E , Delaunay J , Girot R , Galand C , Boivin P 
Published: October 2019

Abstract
In a healthy 32-yr-old woman with normal red cell morphology, a shortened variant of cytoskeletal membrane protein 4.1 is described at the heterozygous state. One haploid set of protein 4.1 migrates below protein 4.2 and displays a reduction in mass of approximately 8500 with regard to the normal haploid set. The shortening corresponds to a deletion of about 75 amino acids and concerns both subcomponents a and b of protein 4.1. It seems to involve some phosphorylation site(s). It was transmitted to the proposita's son (who inherited elliptocytosis with band 4.1 deficiency from his father). To our knowledge, the present abnormality is the first unequivocal variant of erythrocyte membrane protein 4.1 recognized up to now.
Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations
Authors: Krigel R , Liebes LF , Pelle E , Silber R 
Published: October 2019

Abstract
Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholesterol content, cholesterol/phospholipid ratio, and the lymphocyte subpopulations. This article confirms previous reports on the efficacy of chlorambucil in this setting and describes some morphological, and biochemical concomitant events.
Radioimmunoassay of factor V in human plasma and platelets
Authors: Tracy PB , Eide LL , Bowie EJ , Mann KG 
Published: October 2019

Abstract
Homogeneous, single-chain human factor V was used to develop a double antibody competition radioimmunoassay to measure factor V concentrations in plasma and platelets. Standard curves were constructed that allow for the detection of as little as 20 ng factor V/ml of plasma. Normal factor V concentrations range from 4 to 14 micrograms/ml of plasma with an average value of 7.0 +/- 2.0 micrograms/ml (n = 64). No correlation was observed between antigen levels and age or sex. The radioimmunoassay data are consistent with factor V clotting assays, providing freshly drawn plasma is used in the bioassay. Radioimmunoassay of washed platelets indicate that 0.63–1.93 microgram of factor V is present per 2.5 X 10(8) platelets (4612–14128 molecules of the factor V platelet). When normalized to individual hematocrits and platelet count, the data indicated that platelets contribute approximately 18%-25% of the factor V found in whole blood. In addition, two individuals with functionally deficient factor V were examined and found to be deficient in both antigen and activity.
A new case of phosphoglycerate kinase deficiency: PGK Creteil associated with rhabdomyolysis and lacking hemolytic anemia
Authors: Rosa R , George C , Fardeau M , Calvin MC , Rapin M , Rosa J 
Published: October 2019

Abstract
A new case of phosphoglycerate kinase (PGK) deficiency is described. The propositus displayed episodes of rhabdomyolysis crises and acute renal failure but did not exhibit any sign of hemolysis. A severe deficiency in phosphoglycerate kinase was revealed in muscle and was also found in erythrocytes, white cells and platelets. A partial defect in the same enzyme was present in the mother's and the two daughters' erythrocytes, indicating a X-linked recessive genetic transmission of the enzyme defect. In the propositus, erythrocyte ATP concentration was normal, although 2,3-diphosphoglycerate and triose phosphate levels were moderately increased. Lactate production from glucose, in vitro, was close to normal in intact red cells. The partial PGK was characterized by an increased Km for ADP and more especially for ATP, reduced thermostability, and diminished electrophoretic mobility. Lack of this enzyme, which is a key step in the glycolytic process (generation of one molecule of ATP), is thought to be responsible for rhabdomyolysis, a fact that has not been reported previously.
Increased calcium permeability of cold-stored erythrocytes
Authors: Wiley JS , McCulloch KE , Bowden DS 
Published: October 2019

Abstract
The calcium, sodium, and magnesium permeability of erythrocytes from blood stored at 4 degrees C in various anticoagulant media has been studied and compared to that of fresh erythrocytes. Passive influx of CA2+ was measured at 37 degrees C in cells pretreated to abolish Ca2+ pumping and was up to fivefold greater for cold-stored erythrocytes than for fresh cells. The Ca2+ leakiness developed gradually after day 2 and reached a maximum by day 7 of cold storage in ACD, CPD, CPD- adenine, or heparin anticoagulants. The total calcium content of cold- stored erythrocytes in ACD was not significantly different from that of fresh erythrocytes. However, when cold-stored erythrocytes were reincubated at 37 degrees C in media containing 1.5 mM ionized calcium and substrates to regenerate ATP, a net gain of Ca2+ occurred that was greater for stored than for fresh erythrocytes. Cold storage of blood for up to 6 wk in any anticoagulant did not alter either sodium or magnesium permeability. Red cell ATP was also measured and fell steadily during cold storage in ACD or CPD, but more increase in Ca2+ permeability preceded any significant change in red cell ATP, it is likely that a selective calcium leak develops independently of the fall in ATP concentration that occurs on cold storage.
Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations
Authors: Lichtman MA , Rowe JM 
Published: October 2019

Abstract
The abnormal multimeric composition of plasma von Willebrand factor in type IIB von Willebrand's disease is transiently corrected after infusion of 1-deamino-[8-D-arginine]-vasopressin. However, the larger multimers released into the circulation disappear more rapidly in these patients than in type I von Willebrand's disease or normals. We demonstrate that the larger multimers of normal von Willebrand factor transfused into a type IIB patient are cleared from the circulation more slowly than multimers of similar size endogenously released from tissue stores. The rate of disappearance of large von Willebrand factor multimers after infusion of cryoprecipitate is similar in IIB, IIA, and severe homozygous-like von Willebrand's disease. Platelets from the IIB patient exhibited normal ristocetin-induced binding of normal von Willebrand factor. However, like normal platelets, they bound IIB von Willebrand factor at lower ristocetin concentrations than required for normal von Willebrand factor. These findings provide evidence that absence of the larger multimers from IIB plasma is related to a molecular abnormality of von Willebrand factor rather than to enhanced affinity of abnormal tissue or cellular binding sites, as is the case in the recently described “pseudo” von Willebrand's disease and “platelet-type” von Willebrand's disease.
Diagnosis and management of disseminated intravascular coagulation: the role of heparin therapy
Authors: Feinstein DI 
Published: October 2019

Abstract
Disseminated intravascular coagulation (DIC) is caused by a variety of underlying disorders, and criteria for diagnosis are not well defined. However, the most helpful are a low platelet count, positive plasma protamine test, and fibrinogen and fibrin degradation product levels viewed in the context of the patient's underlying disease. The cornerstone of therapy is prompt treatment of the underlying disease and elimination of the trigger mechanism. Additional treatment must be individualized, and generalizations are difficult to make. However, if the patient has low hemostatic factors and is actively bleeding or requires an invasive procedure, then replacement with the appropriate hemostatic factors should be tried. Heparin is indicated in patients with purpura fulminans and venous thromboembolism, but there is little evidence that heparin reverses organ dysfunction associated with DIC. In addition, heparin is also probably indicated in patients with retained dead fetus and hypofibrinogenemia prior to induction of labor, excessive bleeding associated with a giant hemangioma, and neoplastic disease, particularly promyelocytic leukemia. Although the use of heparin in acute forms of DIC remains controversial, the majority of studies suggest that it is not helpful. The role of antithrombin III (AT-III) concentrates is unknown, but they theoretically may be helpful when DIC is associated with very low AT-III levels, as is seen in liver disease.
Suppression of lymphocyte responses by monocytes with untreated and treated multiple myeloma
Authors: Twomey JJ , Laughter AH , Rice L , Ford RJ 
Published: October 2019

Abstract
Studies were performed on 15 untreated and 14 treated patients with multiple myeloma. The monocyte content was normal in blood but elevated in mononuclear leukocytes (MNL) from treated but not untreated patients (p less than 0.001). This correlated with the severity of lymphopenia in blood (p less than 0.01). Three patterns of immunoglobulin(Ig) synthesis emerged. (1) Most untreated patients showed normal polyclonal responses to pokeweek mitogen. (2) Of 12 treated patients, the 8 whose MNL included greater than 30% monocytes had subnormal Ig responses to pokeweek mitogen. Ig synthesis increased when adherent cells that suppressed Ig synthesis were depleted. Suppression in vitro bore no relationship to polyclonal immunoglobulin levels in serum. (3) Three patients had early blood invasion by plasmacytoid cells. Their MNL spontaneously released large amounts of the Ig class of their serum gammopathies. Proliferative responses to phytohemagglutinin by MNL from all patients were reduced, in part due to monocytoid cell suppression and in part to intrinsic T-cell hyporesponsiveness. B- and T-cell responses in vitro are sometimes suppressed with myeloma. This is related to elevated monocyte percentages in MNL preparations. This excess of monocytes is a function of lymphopenia secondary to therapy, rather than the primary malignant process itself. No evidence was found that suppression by monocytes is qualitatively altered by myeloma or its treatment.