bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Dependent Enhancements by Interferon-γ on Functional Responses of Neutrophils From Chronic Granulomatous Disease Patients
Authors: Åhlin Anders , Elinder Göran , Palmblad Jan 
Published: October 2019

AbstractInterferon-γ (IFN-γ) is recommended as prophylaxis against infections in patients with chronic granulomatous disease (CGD). However, since the optimal dose, the dosing interval, and the mechanisms of action are not well-defined, we studied the effects on CGD neutrophil (PMN) functions ex vivo of interferon-γ (IFN-γ). Evaluations were made on oxidative capacity, measured by superoxide anion production and chemiluminescence after stimulation with f-met-leu-phe (f-MLP) or phorbol-myristate-acetate, the killing of Aspergillus fumigatus hyphae (assessed as conversion of the tetrazolium salt MTT to formazan), and on the expression of FcγRI receptor (CD64). After randomization, 9 CGD patients (4 with gp91phox, 3 with p47phox, 1 with p67phox deficiency and 1 with unspecified CGD) were given IFN-γ, either 50 or 100 μg/m2 subcutaneously on 2 consecutive days after double blinded randomization. Furthermore, one female hyperlyonized X-linked carrier with a CGD phenotype was also studied separately after IFN-γ treatment. Evaluations were made the day before and on days 1, 3, 8, and 18 after IFN-γ administration. The killing of A fumigatus hyphae, being close to zero before IFN-γ, was enhanced on day 3, being 36% higher than pretreatment values in the high-dose CGD group and 17% in the low-dose group. The expression of FcγRI on PMN increased 3.7-fold in the high-dose and 2.3-fold in the low-dose CGD group, being maximal on day 1. Oxidative functions were raised in only selected patients represented by different subtypes of CGD. The hyperlyonized carrier of X-linked CGD responded to IFN-γ with more enhanced oxidative responses and Aspergillus killing of her PMNs than the other patients. This study suggests that a higher dose of IFN-γ than currently recommended confers transient enhancements of certain PMN functions in CGD patients.
The Antineoplastic Agent Bryostatin-1 Induces Proinflammatory Cytokine Production in Human Monocytes: Synergy With Interleukin-2 and Modulation of Interleukin-2Rγ Chain Expression
Authors: Bosco Maria Carla , Rottschafer Sandra , Taylor Lynn S. , Ortaldo John R. , Longo Dan L. , Espinoza-Delgado Igor 
Published: October 2019

AbstractThe antineoplastic agent bryostatin-1 (bryo-1) possesses powerful immunomodulatory properties and can function as a biological response modifier in vivo. However, there is currently little information regarding the effects of bryo-1 on cells of the monocytic lineage. In this study, we demonstrate that bryo-1 can potently induce the production of proinflammatory cytokines from human peripheral blood monocytes. Stimulation of monocytes with subnanomolar concentrations of bryo-1 significantly upregulated the constitutive levels of interleukin-8 (IL-8) mRNA and induced the expression of IL-1β, tumor necrosis factor-α (TNF-α), and IL-6 mRNA in a time and dose-dependent manner. Accordingly, secretion of all four proinflammatory cytokines was induced after monocyte exposure to bryo-1. Furthermore, we showed that bryo-1 selectively synergized with IL-2 in triggering monocyte activation, and this effect seemed to be dependent, at least in part, on the ability of bryo-1 to upregulate IL-2Rγ chain expression. Finally, we demonstrated that the responses of monocytes to bryo-1 could be blocked by the protein kinase C (PKC) inhibitors staurosporine and UCN-01, indicating a role for PKC in monocyte activation by bryo-1. These results show for the first time that bryo-1 is a powerful activator of human monocytes and suggest that stimulation of monokine secretion by bryo-1 may represent at least one of the mechanisms responsible for the in vivo antitumor activity of this drug.
Detection and Isolation of Gene-Corrected Cells in Gaucher Disease Via a Fluorescence-Activated Cell Sorter Assay for Lysosomal Glucocerebrosidase Activity
Authors: Lorincz Matthew , Herzenberg Leonard A. , Diwu Zhenjun , Barranger John A. , Kerr William G. 
Published: October 2019

AbstractGaucher disease type 1 results from the accumulation of glucocerebroside in macrophages of the reticuloendothelial system, as a consequence of a deficiency in glucocerebrosidase (GC) activity. Recent improvements in the methodologies for introducing foreign genes into bone marrow stem cells have prompted several groups to test the efficacy of gene transfer therapy as a curative treatment for Gaucher disease. Limitations of this approach include the potential for insufficient engraftment of gene-corrected cells and incomplete transduction of hematopoietic stem cells using retroviral gene transfer. Overcoming these obstacles may be critical in the case of treatment for Gaucher disease type 1, because GC transduced cells have not been shown to have a growth advantage over noncorrected cells. Here, we describe the development and application of a novel, fluorescence-activated cell sorter based assay that directly quantitates GC activity at the single cell level. In a test of this application, fibroblasts from a Gaucher patient were transduced, and high expressing cells sorted based on GC activity. Reanalysis of cultured sorted fibroblasts reveals that these cells maintain high levels of enzymatic activity, compared with the heterogeneous population from which they were sorted. The assay is sufficiently sensitive to distinguish GC activity found in Gaucher patient monocytes from that in normal controls. Furthermore, preliminary results indicate that increased GC activity can be detected in transduced, CD34+ enriched peripheral blood mononuclear cells isolated from a Gaucher patient. This method should be a useful addition to current gene therapy protocols as a means to quantitatively assess gene correction of relevant cell populations and potentially purify transduced cells for transplantation.
Phylogenetic Footprinting of Hypersensitive Site 3 of the β-Globin Locus Control Region
Authors: Shelton David A. , Stegman Lauren , Hardison Ross , Miller Webb , Bock Jeffery H. , Slightom Jerry L. , Goodman Morris , Gumucio Deborah L. 
Published: October 2019

AbstractHypersensitive site 3 (HS3) of the β-like globin locus control region has been implicated as an important regulator of the β-like globin genes, but the trans factors that bind HS3 have only been partially characterized. Using a five-species alignment (human, galago, rabbit, goat, and mouse) that represents 370 million years of evolution, we have identified 24 phylogenetic footprints in the HS3 core and surrounding regions. Probes corresponding to the human sequence at each footprint have been used in binding studies to identify the nuclear factors that bind within and near these conserved sequence elements. Among the high-affinity interactions observed were several binding sites for proteins with repressor activity, including YY1, CCAAT displacement protein, and G1/G2 complexes (uncharacterized putative repressors) and several binding sites for the stage selector protein. To complement this analysis, orthologous galago sequences were also used to derive probes and the pattern of proteins binding to human and galago probes was compared. Binding interactions differing between these two species could be responsible for the different expression patterns shown by the two γ genes (galago γ is embryonic; human γ is fetal). Alternatively, binding interactions that are conserved in the two species may be important in the regulation of common expression patterns (eg, repression of γ in adult life).
A Patient With Paroxysmal Nocturnal Hemoglobinuria Bearing Four Independent PIG-A Mutant Clones
Authors: Nishimura Jun-ichi , Inoue Norimitsu , Wada Hiroshi , Ueda Etsuko , Pramoonjago Patcharin , Hirota Toshiyuki , Machii Takashi , Kageyama Takashi , Kanamaru Akihisa , Takeda Junji , Kinoshita Taroh , Kitani Teruo 
Published: October 2019

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is characterized by clonal blood cells that are deficient in the surface expression of glycosylphosphatidylinositol-anchored proteins due to somatic mutation in the X-linked gene PIG-A. In some patients, more than one abnormal clone may be present. Analysis of bulk DNA/RNA from granulocytes has been useful in identifying the predominant PIG-A mutation in each patient. However, it is often not useful in determining the presence of minor clones. Many patients have cells with partial deficiency. Here, we analyzed the PIG-A gene in two B-cell lines bearing complete or partial deficiencies, cells of hematopoietic progenitor colonies and peripheral blood granulocytes from the same patient. We found that two B-cell lines had different mutations, the granulocytes contained at least two mutants, and the hematopoietic progenitors contained four mutants. Three of the four were shared by B cells and/or granulocytes whereas the other one was found only in the hematopoietic progenitors. The partial deficiency was caused by a point mutation near an alternative splice site within exon 2 that resulted in partial decreases of activity and quantity of the full-length transcript. These results further show the oligoclonal nature of PNH and differences in extent of expansion among mutant clones.
The Role of B7 Costimulation by Murine Acute Myeloid Leukemia in the Generation and Function of a CD8+ T-Cell Line With Potent In Vivo Graft-Versus-Leukemia Properties
Authors: Boyer Michael W. , Vallera Daniel A. , Taylor Patricia A. , Gray Gary S. , Katsanis Emmanuel , Gorden Keith , Orchard Paul J. , Blazar Bruce R. 
Published: October 2019

AbstractRelapse is more frequent after autologous than allogeneic bone marrow transplantation (BMT), due in part to lack of T-lymphocyte mediated allogeneic graft-versus-leukemia (GVL) effects. Infusions of leukemia-reactive T cells to patients after autologous BMT may be a means for providing a GVL effect. Costimulation of T cells by binding of the CD28 receptor on T cells with B7-counter receptors on antigen presenting cells amplifies antigen-specific T-cell responses. To enhance generation of leukemia reactive cytotoxic T lymphocytes (CTL), the murine B7-1– and B7-2–costimulatory molecule cDNAs were introduced into the MHC class I+, class II−, murine meyloid leukemia cell line C1498. B7-1 expression greatly enhanced the ability of the leukemia cells to generate and expand leukemia reactive CTL in vitro. A highly cytolytic and C1498 specific CD8+ CTL line was generated by B7-1 costimulation. This CTL line proliferated autonomously and produced interleukin-2 when provided B7-1 or B7-2 costimulation by C1498 leukemia cells. To test the in vivo antileukemia properties of this CTL line, irradiated syngeneic BMT recipients were given graded doses of leukemia cells on day 0, followed by CTL infusions beginning on day 1 post-BMT. Recipients of 107 CTL had a 3 log reduction in leukemia burden such that 100% of mice were protected from a supralethal leukemic cell dose. Sustained immune responses were detectable up to 3 months postinfusion of the CTL line. B7-1 or B7-2 costimulation in vivo did not augment antileukemia effects of infused CTL post BMT. These results suggest that B7 costimulation of leukemia reactive CTL may be important for their ex vivo generation and expansion for use in human adoptive immunotherapy of leukemia.
New Observations on Sickle Cells
Authors: BESSIS M. , BRICKA M. , BRETON-GORIUS J. , TABUIS J. 
Published: October 2019

Abstract
Observations made on sickle cells with phase contrast and with the electron microscope lead to the following conclusions.
1. When the red cell sickles, its oscillatory movements cease.
2. Spherical red cells give rise to a special form of sickle cell.
3. Myelin forms, whether attached to the cell or free, become rigid when the tension of oxygen is reduced.
4. The electron microscope, combined with the technic of moulage, shows that the sickle cell contains striated rod-like structures, which give a characteristic appearance to the surface of the sickle cell.
5. Agglutination by appropriate antisera does not occur to any extent in sickled cells, because these rigid structures do not form myelin forms. This is additional evidence of the importance of the formation of viscous surface layers already described as part of the mechanism of agglutination.
The Simultaneous Occurrence of Benign Thymoma and Refractory Anemia
Authors: ROSS JOSEPH F. , FINCH STUART C. , STREET RUSSELL B. , STRIEDER JOHN W. 
Published: October 2019

Abstract
1. The simultaneous occurrence of a benign thymoma and a severe anemia which failed to respond to therapy with recognized hematopoietic agents has been observed in two adult female patients.
2. Reports of seven other patients with a similar association of thymoma and refractory anemia have been found and the, salient features of these cases are summarized.
3. Possible explanations of the simultaneous occurrence of these two unusual conditions are discussed.
4. It is suggested that the thymus gland or tumors of the thymus may be etiologically responsible for certain cases of refractory anemia.
Chronic Acquired Hemolytic Anemia Associated with Hemoglobinuria and Raynaud's Phenomena
Authors: BONNIN J. A. 
Published: October 2019

Abstract
The clinical history and serological findings in a patient suffering from chronic hemolytic anemia with Raynaud's phenomena and hemoglobinuria are briefly reported. The patient's serum contained a cold antibody in very high concentration, which was active up to a temperature of at least 33.5 C. Its activity in vitro differed from that of the sera of previously reported cases in that the hemolysis of normal red cells was diminished rather than increased by lowering the pH. It is thought probable that the patient's frequent attacks of hemoglobinuria may be correlated with the ease with which hemolysis took place in vitro at the physiological pH.
Studies on Abnormal Hemoglobins
Authors: SINGER KARL , KRAUS ALFRED P. , SINGER LILY , RUBINSTEIN HERBERT M. , GOLDBERG SEYMOUR R. 
Published: October 2019

Abstract
1. A Negro family is described in which several individuals exhibit either the manifestations of thalassemia, or of the uncomplicated hemoglobin C trait; in two members the combined occurrence of these two anomalies is demonstrable. This combination is designated as hemoglobin C—thalassemia disease.
2. Hemoglobin C—thalassemia disease manifests itself in these two patients as a microcytic erythrocytosis. The red cells reveal a low MCV and low MCH, but a normal MCHC. About 45 per cent of the erythrocytes appear as target cells in the film. The amount of hemoglobin C in the hemolysates was about 75 per cent, the remainder being composed of A hemoglobin, and in one instance also of a small quantity of F hemoglobin. This is analogous to the results of the hemoglobin analyses in sickle cell—thalassemia disease, where 60 to 80 per cent of the pathologic hemoglobin S are found, though these individuals are heterozygous for both the pathologic hemoglobin and the thalassemia genes. The hypothesis is advanced that the thalassemia gene modifies (enhances) the expressivity of the gene for the pathologic pigment.
3. In genetic studies of families with thalassemia, hemoglobin analyses represent a necessary requirement. It is now established that thalassemia, as well as disorders associated with hemoglobin C, reveals a tendency to leptocytosis and thus may show erythrocytes with increased osmotic resistance.
4. The segregation of the thalassemia gene and of the genes for pathologic hemoglobins take place independently of each other. These genes are not allelomorphs.
Incorporation of Radioactive L-Cystine by Normal and Leukemic Leukocytes in Vivo
Authors: WEISBERGER AUSTIN S. , LEVINE BENNETT 
Published: October 2019

Abstract
Methods for studying the in vivo incorporation of radioactive amino acids by leukocytes are described. The incorporation of S35 L-cystine into normal and leukemic leukocytes was studied and compared with the utilization of S35 L-methionine, S35 sodium sulfate, and C14 sodium formate.
Radioactive L-cystine is rapidly absorbed and rapidly incorporated into the proteins of leukocytes. There are distinctive differences in rates and levels of utilization of S35 L-cystine by normal leukocytes and by leukocytes of acute and chronic leukemia.
The leukocytes of acute leukemia and of chronic myeloid leukemia have a greater avidity for L-cystine than normal leukocytes. This rapid utilization of an amino acid by immature leukocytes is not limited to L-cystine and is probably a manifestations of the rapid metabolic turnover characteristic of immature cells in general. However, in view of the observations on the specificity of L-cysteine and related compounds in modifying the leukotoxic effects of nitrogen mustard, the avidity of immature leukocytes for L-cystine may have greater significance than the utilization of other metabolites.
The data indicate that the life span of normal leukocytes is approximately 13 days. The life span of leukocytes in chronic myeloid leukemia is slightly less than that of normal leukocytes whereas the life span of acute leukemic leukocytes is much shorter than that of normal leukocytes. The life span of lymphocytes in chronic lymphatic leukemia appears to be much longer than that of normal leukocytes. Although L-cystine and L-methionine are readily utilized its acute leukemia, there is marked impairment in the utilization of sodium sulfate in vivo. By comparison, normal leukocytes readily utilize sodium sulfate in vivo. This discrepancy may be due to the rapid turnover of sulfur in acute leukemia or to an intrinsic metabolic defect of acute leukemic leukocytes.
Observations on the New Rh Agglutinin Anti-f
Authors: JONES ALAN RICHARDSON , STEINBERG ARTHUR G. , ALLEN FRED H. , DIAMOND LOUIS K. , KRIETE BERTRAND 
Published: October 2019

Abstract
1. An example of the new anti-Rh serum, anti-f, is described.
2. It is shown that anti-c and anti-e sera may contain anti-f.
3. The significance of the antigen f is discussed in terms of its genetics and practical importance.
Iron Metabolism in Steatorrhea
Authors: BADENOCH J. , CALLENDER SHEILA T. 
Published: October 2019

Abstract
The absorption and utilization of radioactive iron has been studied in sixteen patients with steatorrhea and a control group of twelve patients with hypochromic anemia without steatorrhea and three subjects without anemia.
The patients with idiopathic steatorrhea showed a poor absorption of the test dose given by mouth. This is in keeping with their poor clinical response to oral treatment with iron.
There is some evidence to suggest that poor absorption in such patients may not be the sole factor involved in the development of the anemia.
Observations on the Thrombocytopenia Due to Hypersensitivity to Quinidine
Authors: BARKHAM PERCY , TOCANTINS LEANDRO M. 
Published: October 2019

Abstract
Studies are reported on a patient who developed thrombocytopenic purpura following quinidine therapy. Quinidine caused lysis of the patient’s platelets in vitro within 40 minutes and complete inhibition of clot retraction. Platelet lysis preceded platelet agglutination. Increasing the concentration of the sodium citrate used as anticoagulant inhibited the in vitro action of the quinidine. No thrombocytolytic effect of the patient’s serum with quinidine could be shown when tested against normal blood.
A test dose of quinidine administered orally after the patient had recovered from the thrombocytopenia produced a profound decrease in the number of platelets within 90 minutes, associated with a prolongation of the bleeding time and disappearance of clot retraction.
The in vitro hypersensitivity to quinidine persisted for at least four weeks after recovery from the purpura; after six weeks it could no longer be demonstrated.
Proaccelerin Deficiency Following Irradiation with Therapeutic Doses of Radiophosphorus
Authors: VETTER HERBERT , VINAZZER HELMUT 
Published: October 2019

Abstract
In six out of seven polycythemic patients treated with radiophosphorus a significant decrease of the proaccelerin content of the plasma was observed.
This diminution began to become detectable by means of semiquantitative estimations on the second day after the radioactive isotope was given and lasted for three to sixteen days.
The degree of the deficiency seemed to depend on the amount of radiophosphorus administered, only the highest dose having been capable of impairing the coagulation severely.
Immunopancytopenia Associated with Incomplete Cold Hemagglutinins in a Case of Primary Atypical Pneumonia
Authors: MOESCHLIN S. , SIEGENTHALER W. , GASSER C. , HÄSSIG A. 
Published: October 2019

Abstract
In a case of primary atypical pneumonia (blood grounp O), incomplete antibodies of the cold agglutinin type with a very wide thermal spectrum (35 to 37 C.) led to a severe immunopancytopenia in the form of severe hemolytic anemia, agranulocytosis, and thrombocytopenia.
It is obvious that hemolysis was not induced by cold agglutinins which were active 1:1024 at 4 C. and only 1:32 at 22 C. The indirect cold antibodies which were probably responsible for the hemolysis which occurred were thermolabile (1:16 at 22 C., 1:8 at 37 C.) and could be demonstrated only in the antiglobulin plasma test. During the acute phase, too, a hemolysin of the Dacie type active for normal erythrocytes, but even more active for trypsinized cells, at 37 C. and at a pH of 6.8 and 7.6 could be demonstrated. The severe hemolysis could be stopped by ACTH treatment but the titer of the complete and incomplete cold antibodies showed no distinct change and the direct and indirect Coombs test remained positive for a long time. However, there was a distinct diminution of the thermal amplitude of the incomplete antibodies.
A severe agranulocytosis (140 granulocytes) developed which could be improved each time by cortisone. However, permanent improvement resulted only after the disappearance of the incomplete antibodies one year later.
A leukopenic factor could be demonstrated by transfusion of 300 cc. blood to a recipient of the same blood group producing a pronounced fall in the granulocytes of from 4200 to 910. Control transfusions from a normal inidividual to the same recipient showed no change and the same is true for the transfusion experiment performed one year later from the now cured patient to the same recipient. Leukocyte agglutination tests were negative, but it is presumed that agglutinins of the incomplete type may have been present. Opsonins could not be demonstrated. The thrombocytopenia never descended below 50,000.
The bone marrow showed a distinct shift to the left, i.e. a predominance of unripe forms. On the basis of our previous experimental work (amidopyrine agranulocytosis) it is believed that the changes in the marrow are brought about by a depletion and exhaustion of the bone marrow due to the enormously increased peripheral destruction of the granulocytes by agglutination rather than to an actual inhibition of the marrow.
The relation of this immunoleukopenia in our previous findings to the occurrence of leukocyte agglutination in agranulocytosis of allergic origin is discussed. Agranulocytosis and leukopenia may be produced on an immunologic basis in many other cases and thus some form of agranulocytosis may be related to the mechanism of erythrocyte destruction in acquired hemolytic anemia and to the agglutination of thrombocytes ins essential thrombocytopenia on an immunologic basis.