bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitation of protein 3 content of circulating erythrocytes at the single-cell level
Authors: Jennings LK , Brown LK , Dockter ME 
Published: October 2019

Abstract
The density and size of human erythrocytes has been roughly correlated with cell age, with the denser and smaller cells being older. Observations of this type have led to a hypothesis that the membranes of circulating erythrocytes are dynamic with respect to composition and that material is lost from the membrane during cell maturation and circulation. In this study, flow cytofluorimetry was used to investigate the distribution of the human erythrocyte anion transport protein (protein 3) in heterogeneous samples of circulating red cells. We verified that protein 3 can be specifically and quantitatively labeled in intact human erythrocytes with eosin-5-maleimide, a luminescent probe. Individual cells were accordingly analyzed for size by forward light scattering and for protein 3 content by quantitation of eosin fluorescence. Initial results indicated that the smallest erythrocytes had a protein 3 content equal to that of the largest circulating erythrocytes. This result was independently verified by light scatter-activated cell sorting; direct measurement of cell diameters by microscopy verified that the cell sizes of erythrocytes showing the 10% greatest and 10% smallest light-scattering signal were indeed distinct. Independent analysis of the size-sorted erythrocytes for protein 3 content was accomplished by gel electrophoresis of stroma from 150,000 large and small erythrocytes. Quantitative scanning densitometry of silver-stained gels of prepared stroma showed that protein 3 content of each set of fractionated cells was equal and did not vary as a function of cell size. Taken in combination with the reported correlation between increasing red blood cell age and decreasing cell size, these results indicate that any loss of membranous material during the cell aging process is not random.
Enhanced plasminogen-activator production by leukocytes in the human and murine Chediak-Higashi syndrome
Authors: de Saint Basile G , Fischer A , Dautzenberg MD , Durandy A , Le Deist F , Angles- Cano E , Griscelli C 
Published: October 2019

Abstract
We have studied the coagulation status of eight patients with the Chediak-Higashi syndrome (CHS), both in the chronic and the accelerated phase of the disease. It has been shown that during the accelerated phase there are coagulation abnormalities. These abnormalities include a peripheral thrombocytopenia, minor alterations of liver clotting factors, and mainly a profound hypofibrinogenemia and hypoplasminogenemia, which cause life-threatening bleedings. These disorders are of complex origin, but a fibrinolytic process, possibly primary, appears to play a significant role, since the present evidence for intravascular coagulation is not definitive. The accelerated phase of the CHS is characterized by a visceral infiltration by macrophages and lymphocytes. Therefore, we have investigated the possible role of the macrophages in the fibrinolytic process. We have found an excessive plasminogen activator (PA) production by CHS mononuclear cells in the accelerated phase and to a lesser extent in the chronic phase, except in one patient in whom no anomaly was found. Single-cell studies revealed an increased number of PA-producing cells among the monocyte- macrophage lineage rather than a higher level of production per cell. Polymorphonuclear cells (PMN) from patients with CHS were also shown to contain more PA. Slight but significant abnormalities in PA production were observed in obligatory heterozygotes (five out of nine), indicating the inherited nature of the excessive PA production. Finally, an enhanced PA production was similarly demonstrated using beige mice macrophages. The exacerbated production of PA by macrophages in the accelerated phase of the CHS can account to some extent for the coagulation abnormalities that have been observed.
Zinc-induced platelet aggregation is mediated by the fibrinogen receptor and is not accompanied by release or by thromboxane synthesis
Authors: Heyns A du P , Eldor A , Yarom R , Marx G 
Published: October 2019

Abstract
We demonstrate that zinc (0.1 to 0.3 mmol/L) induces aggregation of washed platelet suspensions. Higher concentrations (1 to 3 mmol/L) of zinc were needed to aggregate platelets in platelet-rich plasma obtained from blood anticoagulated with low-molecular-weight heparin, probably due to the binding of zinc to the plasma proteins. Zinc- induced aggregation of normal washed platelets required added fibrinogen and no aggregation occurred with thrombasthenic platelets or with normal platelets pretreated with a monoclonal antibody (10E5) that blocks the platelet fibrinogen receptor. These data indicate that the platelet membrane fibrinogen receptor-glycoproteins IIb and IIIa mediate the effect of zinc. Zinc-induced aggregation was blocked by the agent TMB-8, which interferes with the internal calcium flux, and by prostacyclin, which elevates platelet cyclic adenosine monophosphate levels. Zinc-induced aggregation was not accompanied by thromboxane synthesis or by the secretion of dense-body serotonin and was not affected by preexposure of platelets to acetylsalicylic acid. Experiments with creatine phosphate/creatine phosphokinase showed that the zinc effect on platelets was independent of extracellular adenosine diphosphate (ADP). Zinc had an additive effect when platelet aggregation was stimulated with subthreshhold concentrations of collagen or ADP. Together with the known effects of nutritional zinc on in vivo bleeding, on platelet aggregation, and on lipid metabolism, the results suggest that zinc may have an important bearing on normal hemostasis, thrombosis, and atherosclerosis.
Late expression of M and N antigens on glycophorin A during erythroid differentiation
Authors: Ekblom M , Gahmberg CG , Andersson LC 
Published: October 2019

Abstract
The M/N blood groups are carried by the major human red cell sialoglycoprotein, glycophorin A. O-glyosidic carbohydrate is needed for the activity, but the M/N specificity is due to amino acid replacements in the NH2-terminal portion of the molecule. We have used monoclonal antibodies specific for M and N blood groups to study their expression during normal erythropoiesis. Here we report that the M/N blood group activities are very weakly or not at all expressed before the polychromatic normoblast stage. Using polyclonal anti-glycophorin A antiserum, it was shown that glycophorin A molecules are already abundantly present on the earliest morphologically recognizable erythroid precursor, the proerythroblast. These findings can be explained by our previous observation that the O-glycosylation of glycophorin A gradually increases during erythroid maturation.
Distinctive lymphocyte subpopulation abnormalities in patients with congenital coagulation disorders who exhibit lymph node enlargement
Authors: Prince HE , Kreiss JK , Kasper CK , Kleinman S , Saunders AM , Waldbeser L , Mandigo G , Kaplan HS 
Published: October 2019

Abstract
The majority of patients with congenital clotting disorders who use clotting factor concentrate exhibit lymphocyte subpopulation abnormalities. A subset of these patients develop lymph node enlargement (LNE), part of the spectrum of clinical disease associated with the acquired immune deficiency syndrome (AIDS). It is therefore important to determine if these patients with LNE exhibit specific immune alterations suggestive of early infection with the AIDS agent. We used one- and two-color immunofluorescence to distinguish the lymphocyte subpopulation alterations associated with concentrate use from those associated with LNE. Patients who use concentrate had elevated levels of Leu-2+ (T suppressor phenotype) cells and Leu-7+ (phenotype of some natural killer) cells. These increased levels were largely caused by a dramatic (2.6-fold) increase in the number of lymphocytes co-expressing Leu-2 and Leu-7 (2+7+). A dose-response effect between amount of concentrate infused during the preceding year and level of 2+7+ cells was observed. Concentrate recipients, as a group, also showed increased levels of T cells expressing Dr antigen (T+Dr+ phenotype, characteristic of activated or immature T cells) and cells expressing the T10 antigen (phenotype of some null cells and activated/immature T cells). Patients with LNE showed a further increase in T10+ cells as well as a distinctive decrease in Leu-3+ (T helper phenotype) lymphocytes. All LNE patients exhibited either low Leu-3+ levels, high T10+ levels, or both. Thus, concentrate use was associated with increased levels of Leu-2+ (particularly 2+7+) cells and T+Dr+ cells, whereas LNE was associated with decreased levels of Leu-3+ cells and high levels of T10+ cells.
Biochemical and functional consequences of dissociation of the platelet membrane glycoprotein IIb-IIIa complex
Authors: Shattil SJ , Brass LF , Bennett JS , Pandhi P 
Published: October 2019

Abstract
The platelet membrane glycoproteins, IIb and IIIa, form a Ca2+- dependent heterodimer complex that functions as the fibrinogen receptor in activated platelets to mediate platelet aggregation. Little is known about factors that affect the IIb-IIIa complex within the platelet membrane. It has been observed that platelets incubated with ethylene glycol tetra-acetic acid (EGTA) at 37 degrees C are unable to aggregate or to bind monoclonal antibodies specific for the IIb-IIIa complex. To determine whether this is due to a dissociation of IIb from IIIa, we developed a method for quantitating the complex on nondenaturing, polyacrylamide gradient gels. Platelets were surface-labeled with 125I and then solubilized and electrophoresed in 0.2% Triton and 10 mmol/L CHAPS. Under these conditions and in the presence of 1 mmol/L Ca2+, glycoproteins IIb and IIIa migrated on the gels as a discrete band at Rf = 0.33. Protein that was eluted from this band bound to an immunoaffinity column specific for the IIb-IIIa complex. In contrast, when the IIb-IIIa complex was solubilized and then dissociated with EGTA, the discrete band at Rf = 0.33 was no longer present, and IIb and IIIa were now found in a broad band at Rf = 0.45 to 0.50. To study IIb and IIIa within the surface membrane, the 125I-labeled platelets were first incubated with 0.5 mmol/L EGTA (1 nmol/L free Ca2+) at 22 degrees C and then solubilized in the absence of EGTA. The IIb and IIIa from these platelets migrated at Rf = 0.33, indicating the presence of the intact IIb-IIIa complex. In contrast, when the platelets were incubated at 37 degrees C for one hour with the EGTA, the discrete band at Rf = 0.33 representing the IIb-IIIa complex gradually disappeared. This phenomenon could not be reversed by adding Ca2+ back to the platelets before solubilization and electrophoresis. This loss of the IIb-IIIa complex from intact platelets was accompanied by (a) a progressive and irreversible decrease in adenosine diphosphate (ADP)-induced platelet aggregation and (b) decreased binding of a complex-dependent monoclonal antibody to the platelets. These studies demonstrate that when platelets are exposed to low Ca2+ at 37 degrees C, the IIb-IIIa heterodimer complexes in their surface membranes are irreversibly disrupted. Because intact IIb-IIIa complexes are required for platelet aggregation, the loss of these complexes may account for the failure of these platelets to aggregate in response to ADP.
Granulated T cell lymphocytosis with neutropenia: malignant or benign chronic lymphoproliferative disorder?
Authors: McKenna RW , Arthur DC , Gajl-Peczalska KJ , Flynn P , Brunning RD 
Published: October 2019

Abstract
The clinical, morphological, immunologic, and cytogenetic features of seven cases of chronic granulated T cell lymphocytosis with neutropenia were studied. The disorder was characterized by moderate blood and bone marrow lymphocytosis, neutropenia, polyclonal hypergammaglobulinemia, splenomegaly, absence of lymphadenopathy, and a chronic, relatively stable clinical course. The proliferative lymphocytes manifested a cytotoxic/suppressor T lymphocyte phenotype. In two of four cases studied, blood lymphocytes showed clonal chromosome abnormalities. One patient treated with pulse steroid therapy had reversal of lymphocytosis and severe neutropenia with subsequent resolution of an intractable infection. The lymphocytosis and neutropenia recurred when steroids were withdrawn. Six of the seven patients were living three months to 17 years from diagnosis; one died at 4.3 years of an unrelated cause. Five of the patients, including the two with lymphocyte chromosome abnormalities, had persistent lymphocytosis and neutropenia from three months to 13 years from diagnosis. In two patients, the disease appears to have undergone spontaneous regression. No differences in clinical presentation or the morphological or immunologic characteristics of the proliferative lymphocytes were apparent between those patients with lymphocyte chromosome abnormalities and persistent disease and those who had a spontaneous regression. The finding of clonal chromosome abnormalities in the blood lymphocytes of two of the patients in this study suggests a neoplastic origin for chronic granulated T cell lymphocytosis with neutropenia. However, apparent spontaneous regression in two patients, one after 11 years, lends support to a chronic reactive or immunoregulatory disorder as the etiology. It is probable that cases of granulated T cell lymphocytosis with neutropenia, although morphologically and immunologically similar, are biologically heterogeneous.
Favism: disordered erythrocyte calcium homeostasis
Authors: De Flora A , Benatti U , Guida L , Forteleoni G , Meloni T 
Published: October 2019

Abstract
The biochemical events that take place during acute hemolysis of G6PD- deficient subjects in favism are far from being elucidated. Evidence is here reported for a constantly and heavily disordered calcium homeostasis in the erythrocytes from seven favic patients. The abnormality, ie, a significantly impaired calcium ATPase activity and a parallel marked increase of intracellular calcium levels, was characteristic of the acute hemolytic crisis although unrelated to the attendant reticulocytosis. Concomitantly, a remarkable decrease of intracellular potassium was also observed. The mean +/- SD Ca2+-ATPase activity in the favic patients was 20.8 +/- 7.8 mumol Pi/g Hb/h compared with 37.2 +/- 8.5 in the matched controls represented by 12 healthy G6PD-deficient subjects (P less than .001). The mean +/- SD intraerythrocytic calcium content was 288 +/- 158 mumol/L of erythrocytes in the favic patients as compared with 22.0 +/- 8.2 in the G6PD-deficient controls (P less than .001). The intraerythrocytic potassium content was 76.6 +/- 19.3 mmol/L of erythrocytes in the favic patients and 106.6 +/- 8.2 in the G6PD-deficient controls (P less than .001). In vitro incubation of normal and G6PD-deficient erythrocytes with divicine, a pyrimidine aglycone present in fava beans and strongly implicated in the pathogenesis of favism, reproduces most of these events, including drop of calcium ATPase, increased intracellular calcium, and leakage of erythrocyte potassium.
Differential interleukin-1 elaboration by density-defined human monocyte subpopulations
Authors: Elias JA , Chien P , Gustilo KM , Schreiber AD 
Published: October 2019

Abstract
Interleukin-1 (IL-1) is an important immunoregulatory peptide produced by monocytes and macrophages. Because mononuclear phagocytes are morphologically and functionally heterogeneous, we examined whether they differ in their ability to elaborate IL-1. We used discontinuous Percoll gradients to obtain five density-defined human blood monocyte subpopulations. Unfractionated monocytes and their subsets were compared for their ability to stimulate thymocyte proliferation. Supernatants obtained from the denser monocytes consistently contained more IL-1 activity than did supernatants from the less dense cells. This difference in IL-1 activity was the result of differences in IL-1 elaboration, not the selective production of an inhibitor of IL-1- induced thymocyte proliferation. These data demonstrate that density- defined human monocyte subpopulations differ in their capacity to elaborate IL-1.
Anti-My-28, an antigranulocyte mouse monoclonal antibody, binds to a sugar sequence in lacto-N-neotetraose
Authors: Spitalnik SL , Schwartz JF , Magnani JL , Roberts DD , Spitalnik PF , Civin CI , Ginsburg V 
Published: October 2019

Abstract
Anti-My-28 is an IgM kappa monoclonal antibody produced by a hybridoma prepared from spleen cells of a mouse immunized with normal human granulocytes. By immunofluorescence it binds to human granulocytes but not to monocytes and lymphocytes. However, after treating cells with neuraminidase, the antibody also binds to lymphocytes and monocytes and to many leukemic cell lines and patient leukemic blast cells. Anti-My- 28 binds to several neutral glycolipids and desialylated gangliosides of leukocytes and erythrocytes as detected by radioimmunoassay and immunostaining of thin-layer chromatograms. It recognizes a sugar sequence in lacto-N-neotetraose, Gal beta 1–4GlcNAc beta 1–3Gal beta 1–4Glc. This tetrasaccharide occurs in the glycolipids paragloboside and sialosylparagloboside, and its distal trisaccharide sequence is found in higher glycolipids and in glycoproteins.
Minactivin expression in human monocyte and macrophage populations
Authors: Stephens RW , Golder JP , Fayle DR , Hume DA , Hapel AJ , Allan W , Fordham CJ , Doe WF 
Published: October 2019

Abstract
Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or “tissue”-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.
Impaired responsiveness to B cell growth factor in a patient with common variable hypogammaglobulinemia
Authors: Perri RT , Weisdorf DJ 
Published: October 2019

Abstract
Common variable hypogammaglobulinemia (CVH) is a clinical syndrome that includes a diverse group of patients with heterogeneous defects resulting in impaired B cell proliferation and terminal differentiation into mature plasma cells capable of normal immunoglobulin synthesis and secretion. In this study, we report our identification of a previously undescribed intrinsic B cell defect in a patient with CVH. This patient's B cells showed a marked impairment in hemolytic plaque- forming cell (HePFC) formation compared with control B cells (15 v 80 HePFCs per culture, respectively). In addition, this patient's B cells displayed decreased B cell colony formation compared with control B cells (5 +/- 2 v 93 +/- 8, respectively). When examined for their responsiveness to phytohemagglutinin-T cell conditioned media (PHA- TCM), the patient's B cells displayed impaired B cell proliferation compared with control B cells (stimulation index [SI] 1.3 +/- 0.20 v 26 +/- 1.4 with 20% control PHA-TCM [vol/vol]). Impaired proliferation by the patient's B cells persisted with increasing concentrations of B cell growth factor (BCGF). Additionally, PHA-TCM prepared from the patient's T cells when compared with control PHA-TCM consistently showed less support for control B cell proliferation (SI 1.27 +/- 0.21 v 26 +/- 1.4, respectively). In coculture studies of B cell proliferation and immunoglobulin synthesis, patient's T cells showed no evidence of an enhanced suppressive effect or decreased helper effect. This patient's immune defects involve, first, an intrinsic B cell defect characterized by an impaired responsiveness to BCGF's proliferation signal and, second, impaired production of BCGF by the patient's T cells.
Diagnostic and prognostic significance of Sezary cells in peripheral blood smears from patients with cutaneous T cell lymphoma
Authors: Vonderheid EC , Sobel EL , Nowell PC , Finan JB , Helfrich MK , Whipple DS 
Published: October 2019

Abstract
Blood smears stained with Wright-Giemsa were obtained from 124 patients with pathologically confirmed cutaneous T cell lymphoma (CTCL), 70 patients with various other cutaneous disorders, and ten healthy adult volunteers. These were examined in a blinded fashion for atypical lymphocytes with cerebriform nuclei (CLs), which were characterized further according to cell diameter. CLs, comprising up to 15% of lymphocytes in smears, were observed in 20% of the patients with benign dermatitis. CLs, comprising up to 89% of lymphocytes in smears, were found in 22%, 30%, 50%, and 96% of patients with patch, plaque, tumor, and erythrodermic CTCL, respectively. Large-diameter CLs (15 to 20 micron) were observed only in smears from patients with CTCL. Total CL counts above 15 per 100 lymphocytes and/or the presence of large CLs occurred in 33 of 49 (67%) patients with erythrodermic disease and in only two patients with other skin manifestations. Blood smears obtained at the time of cytogenetic studies indicated that a total CL count above 15% was the smear criterion that correlated best with the demonstration of a chromosomally abnormal malignant clone in the blood. The presence of large CLs per se, although also predictive of a malignant clone, was less useful. Multivariate survival analysis showed that the duration of disease before the blood smear and the proportion of large CLs within the total CL population were the covariates that correlated most significantly with survival. We speculate that the reduced survival of patients with increased proportions of large CLs in smears reflects the presence of polyploid malignant lymphocytes in the blood.
A study of liver biopsies and liver disease among hemophiliacs
Authors: Aledort LM , Levine PH , Hilgartner M , Blatt P , Spero JA , Goldberg JD , Bianchi L , Desmet V , Scheuer P , Popper H 
Published: October 2019

Abstract
Hepatic histologic materials (biopsy or autopsy) and associated clinical data from 155 hemophiliacs were collected by an ad hoc hemophilia study group and analyzed retrospectively in an effort to determine the spectrum of liver disease in this population and to examine the relationship between the severity of liver disease and treatment history. Clinical information on the frequency of complications from 126 biopsies in 115 hemophilic patients provided a unique opportunity to assess the safety of liver biopsy in such patients. The incidence of cirrhosis (15%) and chronic active hepatitis (7%) was lower than previously reported. The frequency of severe liver disease (chronic active hepatitis or cirrhosis) in patients receiving large pooled concentrates was no greater than in patients treated principally with cryoprecipitate or plasma. The risks of liver biopsy in this setting are relatively high: clinically significant hemorrhage followed 12.5% of the procedures.