bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts
Authors: Martin PJ , Hansen JA , Buckner CD , Sanders JE , Deeg HJ , Stewart P , Appelbaum FR , Clift R , Fefer A , Witherspoon RP 
Published: October 2019

Abstract
We report results of a pilot study designed to evaluate the effects of in vitro depletion of T lymphocytes from donor marrow in patients receiving HLA-identical marrow grafts for treatment of hematologic malignancies. Twenty patients aged 31 to 50 years were prepared for transplantation with cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0 or 15.75 Gy). All received cyclosporine after grafting. The donor marrows were treated with a mixture of eight murine monoclonal antibodies and rabbit serum complement in a manner that achieved a 2- to 3-log depletion of T cells in most patients. Initial engraftment occurred promptly in 19 of the patients, and only three had clinically significant acute graft-versus-host disease. Depletion of donor T cells, however, was associated with an increased incidence of graft failure, which occurred as late as 244 days after transplantation. Graft failure was transient in one patient but apparently was irreversible in seven others. Three of the seven patients had cytogenetic but not morphological evidence of leukemic relapse at the time of graft failure. All seven patients with irreversible graft failure have died, six after receiving second bone marrow transplants. Seven of the eight cases of graft failure occurred among the 11 patients prepared for transplantation with 12.0 Gy of total-body irradiation, and only one occurred among the nine patients with advanced malignancies who received 15.75 Gy of total-body irradiation. This association with irradiation dose suggests that host factors were partly responsible for the graft failures. Because graft failure seldom occurs in irradiated recipients of unmodified HLA- identical allogeneic marrow transplants, it appears that T cells in the donor marrow may serve a beneficial function in helping to maintain sustained engraftment possibly by eliminating host cells that can cause graft failure. Optimal application of in vitro manipulation of donor marrow as a method for preventing graft-versus-host disease will require more effective immunosuppression of the recipient in order to assure sustained engraftment and function of donor stem cells.
Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies
Authors: Cramer EM , Meyer D , le Menn R , Breton-Gorius J 
Published: October 2019

Abstract
Immunogold staining was used to study the ultrastructural distribution of von Willebrand factor (vWF) in unstimulated platelets. vWF was detected in the alpha-granules with a specific eccentric distribution pattern opposite the nucleoids. Similar findings were obtained with a polyclonal antibody or a pool of monoclonal antibodies to human vWF. This labeling coincided with the presence of tubular structures located at the periphery of the alpha-granules. These structures were better visualized on platelets treated for standard electron microscopy: they formed a group of one to four tubules ranging from 200 A to 250 A in diameter. They closely resembled the internal tubular structures found in Weibel-Palade bodies, which are the storage organelles of vWF in endothelial cells.
Glycoprotein IIb-IIIa complex and Ca2+ influx into stimulated platelets
Authors: Powling MJ , Hardisty RM 
Published: October 2019

Abstract
Changes in intracellular Ca2+ concentrations [( Ca2+]i) in platelets stimulated with aggregating agents were measured with the fluorescent indicator dye quin 2. Ca2+ influx, but not intracellular mobilization, in response to adenosine diphosphate (ADP), platelet aggregating factor (PAF-acether), and sodium arachidonate was significantly inhibited by monoclonal antibodies against the glycoprotein (GP) IIb-IIIa complex; inhibition of thrombin-stimulated influx was inhibited to a lesser extent and reached statistical significance only at thrombin concentrations of 0.1 U/mL and below. Anti-GP Ib and HLA-ABC monoclonal antibodies had no effect on Ca2+ influx in response to any agonist. Thrombasthenic platelets gave normal [Ca2+]i responses to ADP and thrombin, which were not inhibited by an anti-GP IIb-IIIa antibody. It is suggested that Ca2+ influx in response to weak agonists occurs predominantly via a channel closely adjacent to the GP IIb-IIIa complex, but that higher concentrations of thrombin and A23187 also stimulate influx via another pathway.Changes in intracellular Ca2+ concentrations [( Ca2+]i) in platelets stimulated with aggregating agents were measured with the fluorescent indicator dye quin 2. Ca2+ influx, but not intracellular mobilization, in response to adenosine diphosphate (ADP), platelet aggregating factor (PAF-acether), and sodium arachidonate was significantly inhibited by monoclonal antibodies against the glycoprotein (GP) IIb-IIIa complex; inhibition of thrombin-stimulated influx was inhibited to a lesser extent and reached statistical significance only at thrombin concentrations of 0.1 U/mL and below. Anti-GP Ib and HLA-ABC monoclonal antibodies had no effect on Ca2+ influx in response to any agonist. Thrombasthenic platelets gave normal [Ca2+]i responses to ADP and thrombin, which were not inhibited by an anti-GP IIb-IIIa antibody. It is suggested that Ca2+ influx in response to weak agonists occurs predominantly via a channel closely adjacent to the GP IIb-IIIa complex, but that higher concentrations of thrombin and A23187 also stimulate influx via another pathway.
Diadenosine 5',5'''-p1,p4-tetraphosphate deficiency in blood platelets of the Chediak-Higashi syndrome
Authors: Kim BK , Chao FC , Leavitt R , Fauci AS , Meyers KM , Zamecnik PC 
Published: October 2019

Abstract
Diadenosine tetraphosphate (AP4A) is an unusual nucleotide found in a variety of cells, including platelets. It has been suggested that platelet AP4A is stored in the dense granules and is metabolically inactive. We have studied the AP4A content of blood platelets in two patients and three cattle with Chediak-Higashi syndrome (CHS), a hereditary platelet defect with dense granule deficiency. Acid-soluble extractions of whole blood and platelets were neutralized. The adenosine triphosphate (ATP) level was measured by luminescence technique. To measure the AP4A content, the neutralized extract was treated with phosphomonoesterase for removal of ATP. The AP4A content was then measured by coupling the phosphodiesterase and luciferase reaction. The AP4A content was 0.43 nmol/mg protein for normal human platelets and 0.004 nmol/mg protein for CHS platelets. The ATP/AP4A ratio was 67 for normal and 3,023 for CHS platelets. The whole blood AP4A was reduced by 89% in CHS patients who had only a slight decrease in ATP level (26% reduction). Similarly, bovine platelets with CHS showed a marked decrease of AP4A content and a moderate reduction of the ATP level. The platelet ATP/AP4A ratio was 351 and 3,133 for normal and CHS cattle, respectively. Results demonstrate a marked reduction of AP4A in CHS platelets and suggest that AP4A may be a useful marker for the measurement of dense granule content in platelets.
Natural antibodies in sera from Japanese individuals infected with HTLV- I do not recognize HTLV-III
Authors: Hattori T , Robert-Guroff M , Chosa T , Matsuoka M , Yamaguchi K , Ishii T , Gallo RC , Takatsuki K 
Published: October 2019

Abstract
Seventy-one sera from Japanese individuals infected with human T cell leukemia virus type I (HTLV-I) were examined for the presence of antibodies to HTLV-III by an enzyme-linked immunosorbent assay (ELISA) and by a strip radioimmunoassay based on the Western blot technique. The sera were from 23 healthy carriers and from 48 patients, including 18 with smoldering adult T cell leukemia (ATL), 13 with chronic ATL, and 17 with acute ATL. All people tested lived in the southwestern part of Japan, a known endemic area for HTLV-I infection. Antibodies against HTLV-I were detected in all sera both by indirect immunofluorescent methods and strip radioimmunoassay using cell lysates. Six sera were reactive in the ELISA assay for HTLV-III. But these sera did not react specifically to HTLV-III-related proteins (p15, p24, gp41) when analyzed by strip radioimmunoassay. Our data suggest that coincidental infection of HTLV-I and HTLV-III is quite rare in Japan.
Application of molecular genetics to prenatal diagnosis and carrier detection in the hemophilias: some limitations
Authors: Graham JB , Green PP , McGraw RA , Davis LM 
Published: October 2019

Abstract
Prenatal diagnosis and carrier detection in the hemophilias have received much attention in recent years. The error rate in prenatal diagnosis by fetoscopy is less than 1%; fetoscopy is not possible, however, until the second trimester of pregnancy. Carrier detection based on bioassays of plasma has an irreducible error rate (approximately 5%?), because of the “lyonization” phenomenon in heterozygous women, and the final results are always probabilistic. New DNA methods promise to alleviate these difficulties. Prenatal diagnosis can be accomplished in the first trimester. “Lyonization” is bypassed in carrier detection, and the results may sometimes be essentially nonprobabilistic. But the DNA methods have certain limitations of their own which are not widely appreciated. Aside from cost and the necessity to adopt a new technology, there are inherent genetic problems: mothers must be heterozygous for both a disease gene and a marker gene, final results are probabilistic if the marker gene lies outside the disease gene, and multiple marker genes are often in linkage disequilibrium. We have concluded that a clinical unit planning to use the DNA methods must also maintain the conventional methods at a high level of performance.
Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure
Authors: Tollefsen DM , Pestka CA 
Published: October 2019

Abstract
Heparin cofactor II (HCII) is a glycoprotein in human plasma which inactivates thrombin rapidly in the presence of heparin or dermatan sulfate. We have developed a functional assay for HCII in which inhibition of thrombin by plasma is determined in the presence of dermatan sulfate. The assay is specific for HCII by the following criteria: (a) under the conditions of the assay, 125I-thrombin forms complexes in plasma which comigrate with the thrombin-HCII complex during sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS- PAGE); (b) activity detected by the assay is decreased in plasma absorbed with monospecific antibodies against HCII; and (c) purified antithrombin III (ATIII) is unreactive in the assay system. Addition of Polybrene to the assay permits determination of HCII activity in samples containing less than or equal to 12 U/mL of heparin. The range of HCII concentrations in normal individuals is 1.2 +/- 0.4 mumol/L (mean +/- 2 SD, n = 34). HCII activity was determined in 54 consecutive patients undergoing evaluation for the possibility of disseminated intravascular coagulation (DIC). Ten of the 11 patients with documented DIC had decreased HCII activity as compared with only 7 of the 43 patients without DIC (chi 2 = 19.3, P less than .0001). The concentrations of HCII and ATIII varied in parallel in most of the patients tested. A significant correlation between decreased HCII activity and decreased serum albumin concentration was also observed in these patients and in eight additional patients with hepatic failure in the absence of DIC. We conclude that HCII activity is decreased in many patients with DIC and hepatic failure.
Serum lactic dehydrogenase level has prognostic value in childhood acute lymphoblastic leukemia
Authors: Pui CH , Dodge RK , Dahl GV , Rivera G , Look AT , Kalwinsky D , Bowman WP , Ochs J , Abromowitch M , Mirro J 
Published: October 2019

Abstract
Serum lactic dehydrogenase (LDH) levels were measured at diagnosis in 293 children with “standard-risk” acute lymphoblastic leukemia (ALL) to determine the prognostic value of this biologic feature. Standard risk assignment was based on an initial leukocyte count of less than 100 X 10(9)/L, the absence of a mediastinal mass, the absence of meningeal involvement, and the presence of lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. Serum LDH levels ranged from 97 to 6,595 U/L, with a mean of 547 U/L. Higher LDH levels were associated with higher leukocyte counts, lower blast cell DNA indices, lower platelet counts, a larger spleen size, and nonwhite race. LDH levels were not related to the percentage of marrow S-phase cells, liver size, French-American-British (FAB) classification, hemoglobin levels, age, sex, or the presence of the common ALL antigen on marrow blasts. Patients with the highest LDH levels (greater than 1,000 U/L) were most likely to fail treatment, whereas those with the lowest levels (less than 300 U/L) had the lowest risk of failure (P less than .0001). The prognostic significance of serum LDH level was retained in a subset of patients that included only those with leukocyte counts less than 25 X 10(9)/L (P = .0018). When 11 presenting characteristics were subjected to multivariate analysis, serum LDH level was found to have independent prognostic strength, contributing clinically important information to that gained from leukocyte count. Early measurement of serum LDH could be useful in identifying a group of standard-risk ALL patients with a high relapse hazard.
Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro
Authors: Wilson BS , Platt JL , Kay NE 
Published: October 2019

Abstract
Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H- thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response.
Stimulation of bone marrow-derived and peritoneal macrophages by a T lymphocyte-derived hemopoietic growth factor, persisting cell- stimulating factor
Authors: Crapper RM , Vairo G , Hamilton JA , Clark-Lewis I , Schrader JW 
Published: October 2019

Abstract
Several lines of evidence indicated that P cell-stimulating factor (PSF), a T lymphocyte-derived lymphokine known to stimulate the growth of hemopoietic stem and progenitor cells, also acted on macrophages. PSF was absorbed from medium that had been mixed for two hours at 0 degrees C with either resident or thioglycollate-elicited peritoneal cells, suggesting the presence of receptors for PSF on cells in the population. The addition of pure PSF to populations highly enriched in either resident or elicited adherent peritoneal macrophages resulted in stimulation of macrophages with morphological changes, including increases in size, spreading, vacuolation, and the number of cytoplasmic processes, together with stimulation of proliferation and the phagocytosis of opsonized yeast. PSF also stimulated the incorporation of [3H]thymidine by bone marrow-derived adherent macrophages. Addition of pure PSF to cultures that contained only a single macrophage resulted in enhanced survival and proliferation of these isolated cells, demonstrating that the effect of PSF on macrophages was direct. These results indicate that PSF can stimulate well-differentiated functional macrophages and raise the possibility that the effects of PSF on macrophages may play a regulatory role in immune responses.
Altered glycosaminoglycan production by HL-60 cells treated with 4- methylumbelliferyl-beta-D-xyloside
Authors: Luikart SD , Sackrison JL , Thomas CV 
Published: October 2019

Abstract
Glycosaminoglycans, mainly chondroitin 4-sulfate, are located in the primary granules of human myeloid cells. These polyanionic carbohydrates are believed to play an important role in leukocyte maturation and function. To study the effect of altered chondroitin sulfate metabolism on human promyelocytic leukemia cells, we have treated HL-60 cells with 4-methylumbelliferyl-beta-D-xyloside. beta-D- Xylosides initiate the synthesis of free chondroitin sulfate chains. Cytochemical studies of treated cells demonstrated a marked increase in cytoplasmic granules stained with cationic dyes. This was confirmed by radiolabeled precursor incorporation studies that demonstrated a 344% increase in 35S-sulfate uptake into glycosaminoglycans associated with the cells and a 39% increase in incorporation into glycosaminoglycans released into the media. Chromatographic analyses of these glycosaminoglycans from treated cells demonstrated that the newly formed chondroitin sulfate chains were not attached to protein core and were of shorter length, but of greater charge density than chondroitin sulfate produced by control cells. Thus, beta-D-xyloside appears to alter the protein linkage, chain length, and sulfation of chondroitin sulfate produced by HL-60 cells, and these changes are morphologically evident. These biochemically altered cells may provide important information concerning the role of these macromolecules in myeloid development.
Transferrin saturation, plasma iron turnover, and transferrin uptake in normal humans
Authors: Cazzola M , Huebers HA , Sayers MH , MacPhail AP , Eng M , Finch CA 
Published: October 2019

Abstract
The relationship between plasma iron, transferrin saturation, and plasma iron turnover was studied in 53 normal subjects whose transferrin saturation varied between 17% and 57%, in 25 normal subjects whose transferrin saturation was increased by iron infusion to between 67% and 100%, and in five subjects with early untreated idiopathic hemochromatosis whose transferrin saturation was continually elevated to between 61% and 86%. The plasma iron turnover of all of these subjects ranged from 0.45 to 1.22 mg/dL whole blood/d. The mean values for the above-mentioned three groups were 0.71 +/- 0.17, 1.01 +/- 0.11, and 1.01 +/- 0.13 mg/dL whole blood/d, respectively. Most of this variation, estimated at 72% by regression analysis, was due to a direct relationship between transferrin saturation and plasma iron turnover. This effect was attributed to a competitive advantage of diferric over monoferric transferrin in delivering iron to tissues. This was confirmed by the demonstration of a more rapid clearance of diferric as compared to monoferric transferrin in an additional group of eight normal subjects. Calculations were made of the amount of transferrin reacting with membrane receptors per unit time. Allowance was made for the noncellular (extravascular) exchange and for the 4.2:1 preference of diferric over monoferric transferrin demonstrated in vitro. The amount of iron-bearing transferrin leaving the plasma to bind to tissue receptors for 53 subjects with a transferrin saturation between 17% and 57% was 71 +/- 13; for 25 subjects with a saturation from 67% to 100%, 72 +/- 12; and for five subjects with early idiopathic hemochromatosis, 82 +/- 11 mumol/L whole blood/d. There were no significant differences among these groups. These studies indicate that while the number of iron atoms delivered to the tissues increases with increasing plasma iron and transferrin saturation, the number of iron-bearing transferrin molecules that leave the plasma per unit time to bind to tissue receptors is relatively constant and within the limits studied, independent of transferrin saturation.
Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin
Authors: Zeitlin HC , Sheppard K , Baum JD , Bolton FG , Hall CA 
Published: October 2019

Abstract
A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.
The immunohistology of follicle lysis in lymph node biopsies from homosexual men
Authors: Wood GS , Garcia CF , Dorfman RF , Warnke RA 
Published: October 2019

Abstract
Follicle lysis is a characteristic alteration of B cell follicles described recently in lymph node biopsies from homosexual men. It consists of disruption of germinal centers by aggregates of small mature lymphocytes variably associated with erythrocyte extravasation. We studied the immunohistology of follicle lysis identified in lymph node biopsies from 11 homosexual men. The results indicate that follicle lysis has two principal immunohistologic features: (1) intrafollicular aggregates of small lymphocytes predominantly of polytypic mantle B cell phenotype (T015+/Leu-8+/mu+/delta+/k+ or lambda+), and (2) disruption of the normal, unified follicular meshwork of R4/23+ dendritic reticulum cells by these B cell aggregates. These structural alterations may affect the functional integrity of the germinal center as it pertains to the abnormal B cell effector function and the increased prevalence of B cell lymphoma recently documented in the acquired immunodeficiency syndrome and related disorders. Because dendritic reticulum cells weakly express the Leu-3 (T4) antigen, which is known to be an essential component of the receptor for human T- lymphotropic virus type III/lymphadenopathy-associated virus (HTLV- III/LAV) retrovirus infection, it is possible that retroviral infection of dendritic reticulum cells may play a role in the pathogenesis of follicle lysis.
Quantitation of adenosine-5'-triphosphate used for phosphoinositide metabolism in human erythrocytes
Authors: Dale GL 
Published: October 2019

Abstract
The human erythrocyte actively phosphorylates and dephosphorylates phosphatidylinositol present in the membrane in an apparent “futile cycle.” Recent reports have proposed that this phosphorylation/dephosphorylation cycle is a significant consumer of adenosine-5′-triphosphate (ATP) in the erythrocyte. This study details two independent techniques for quantitating the ATP consumed by this phosphoinositide futile cycle. With the first technique a quasi-steady- state labeling of erythrocyte ATP with 32P-phosphate was obtained, and the rate of synthesis of 32P-phosphoinositides was then monitored. The second technique used a novel labeling strategy that allowed only ATP to be labeled with 32P; the transfer of 32P from ATP to phosphoinositides was then an independent measure of the ATP consumed for phosphoinositide synthesis. These two techniques documented that 0.5% to 1.0% of net ATP produced by the erythrocyte is used for phosphoinositide synthesis.