bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating inhibitors of blood coagulation associated with procainamide‐induced lupus erythematosus
Authors: Davis Stephen , Furie Barbara C. , Griffin John H. , Furie Bruce 
Published: February 2007

AbstractWe studied a patient being treated with procainamide in whom we observed a high antinuclear antibody titer and prolonged activated partial thromboplastin (PTT), prothrombin (PT), and Stypven times (ST). Serum antibody concentrations against single‐stranded DNA were elevated while those against native DNA were not elevated, suggesting the procainamide‐induced lupus syndrome. Dilution of the patient's plasma with normal plasma failed to correct the PTT and PT, indicating the presence of an inhibitor(s) to blood coagulation. The anticoagulant activity was associated with the IgG fraction of the patient's serum. Addition of purified or partially purified human factors IX, X, VIII, VII, XIa, prekallikrein, high molecular weight kininogen, or phospholipids to the patient's plasma failed to correct the PTT, PT, or ST; however, purified human factor XII and prothrombin corrected the PTT and ST, respectively. These results indicate that production of antibodies directed against antigenic determinants on coagulation proteins can be a manifestation of procainamide‐induced lupus erythematosus.
The “Hageman” connection: Interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation
Authors: Murano Genesio 
Published: February 2007

AbstractThe activation pathways for the generation of enzymes involved in blood clotting, clot lysis, complement activation, and kinin generation are briefly reviewed. The interrelationship of the four systems is illustrated by the multiple functions of four key enzymes: Factor XIIa, kallikrein, plasmin, and C1 esterase. The pivotal role of Factor XIIa in establishing this connection is elucidated.
Is the trimodality of Hb leslie (α2β2131Gln → 0) in heterozygotes the result of a variable number of active α‐chain genes? Evidence for posttranslational control of hemoglobin synthesis
Authors: Felice A. , Abraham E. C. , Miller A. , Stallings M. , Huisman T. H. J. 
Published: February 2007

AbstractWhether the trimodality in the relative concentration of the hemoglobin variant Hb Leslie in heterozygotes (Huisman, Hemoglobin 1: 349–382, 1977) is due to a polymorphism of the α‐chain structural genes was investigated by conventional incubation of reticulocytes with 14C‐leucine. In addition, an aliquot from each of the incubations was incubated under the same conditions but without isotope. Three Hb Leslie heterozygotes with presumably four, three (heterozygous α‐thalassemia‐2), and two (homozygous α‐thalassemia‐2) active α‐chain genes and with 33%, 22%, and 11% Hb Leslie respectively, and one patient with the Hb Leslie β0‐thalassemia condition with more than 85% Hb Leslie were studied. The data indicate that βLeslie chains have a lower affinity for α chains than βA chains. A concomitant α‐chain deficiency results in a reduced incorporation of βLeslie chains into the tetrameric Hb Leslie molecules, while the quantity of Hb Leslie produced correlates with the degree of α‐chain deficiency. Excess of βLeslie chains is preferentially degraded.
Hodgkin disease and red cell aplasia
Authors: Morgan Elaine , Pang Kin Man , Goldwasser E. 
Published: February 2007

AbstractA teenage boy with mixed‐cellularity Hodgkin disease presented with severe anemia secondary to pure red cell aplasia of marrow without evidence of lymphomatous infiltration or hemolysis. In vitro studies of the patient's serum demonstrated an inhibitor of erythropoietin activity which appeared to be an IgG but which did not directly bind erythropoietin. The patient's anemia resolved and the inhibitor disappeared following chemotherapy for Hodgkin disease. Presumably, the inhibitor was directed at a very early stage of red blood cell production. This phenomenon may be related to other autoimmune manifestations occasionally seen in patients with lymphomas. The case is presented to bring attention to the unusual occurrence of red cell aplasia in Hodgkin disease. Several hypotheses concerning significance and etiology of the anemia are detailed.
Four new electrophoretically slow‐moving glucose 6‐phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: Gd(‐) Kurume, Gd(‐) Fukushima, Gd(‐) Yamaguchi and Gd(‐) Wakayama
Authors: Miwa Shiro , Fujii Hisaichi , Nakatsuji Tadako , Ishida Yoji , Oda Etsuko , Sasai Shizuyo , Hiraoka Kozo , Kaneto Akira , Motokawa Masakazu , Ariga Yukio , Fukuchi Soitsu , Kashii Hiroomi , Kodama Teisuke 
Published: February 2007

AbstractFour new glucose 6‐phosphate dehydrogenase (G6PD) variants which had electrophoretically slow‐moving characteristics associated with congenital nonspherocytic hemolytic anemia were discovered in Japan. Gd(‐) Kurume was found in a 17‐year‐old male whose red cells contained only 0.8% of normal enzyme activity. Gd(‐) Kurume had a normal Km G6P, normal Km NADP, low Ki NADPH, normal utilization of 2‐deoxy‐G6P and deamino‐NADP, very low heat stability and a biphasic pH curve. The hemolytic anemia was mild. Gd(‐) Fukushima was characterized from a 33‐year‐old male and had 2.8% of normal enzyme activity, normal Km G6P, normal Km NADP, low Ki NADPH, normal utilization of 2‐dcoxy‐G6P, low utilization of deamino‐NADP, low heat stability and a normal pH curve. The hemolytic anemia was mild. Gd(‐) Yamaguchi was characterized from an 8‐year‐old boy and had 3.5% of normal enzyme.
Effects of triiodothyronine on the anemia of chronic renal failure
Authors: Ferrer José , García Rafael , Rubio Lírimo , Rodríguez‐Itube Bernardo , Diez‐Ewald María 
Published: February 2007

AbstractThe present study was done in order to determine whether treatment with triodothyronine (T3) would improve the anemia of chronic renal insufficiency.Four patients with stable renal failure and anemia were treated with 75 μg/day of T3 for a period of four weeks. The patients were not in chronic dialysis, had normochromic normocytic anemia and hypocellular bone marrow, and showed no evidence of external blood loss during the study. They had received no iron, folic acid, or androgenic steroids for at lcast six months prior to the study.The administered dose of T3 was adequate to depress the serum levels of thyroid‐stimulating hormone (TSH); however, there was no detectable improvement in the levels of hemoglobin, hematocrit, bone marrow cellularity, serum and erythrocyte folate dcterminations, serum iron (Fc), 59Fe halflife, plasma iron turnover rate, percentage Fe incorporated into red blood cells, or in the ratio of surface radioactive counting over bone marrow/liver and spleen.It is concluded that the experimental observations concerning direct bone marrow stimulation by T3 in anephric rats are probably not clinically applicable for the treatment of the anemia associated with uremia.
Decreased ribosomal RNA content and in vitro RNA synthesis in purified bone marrow erythroblasts of patients with idiopathic ineffective erythropoiesis and diguglielmo disease
Authors: Lourenço GraçA , Embury Stephen , Schrier Stanley L , Kedes Laurence H. 
Published: February 2007

AbstractRibsomal RNA content and in vitro3H‐uridine and3H‐thymidine incorporation were examined in purified marrow erythroblasts of patients with idiopathic ineffective eryth‐ ropoiesis (HE) and DiGuglielmo disease (DD) and compared with cells from normal marrows. Whereas H‐thymidine incorporation rates were normal in all patients,3H‐uridine incorporation was 42%‐75% of normal in cells from patients examined. Ribosomal RNA content was measured by spectrophotometric scanning of RNA electrophoresed on polyacrylamide gels and corrections made for contamination of the erythroblast preparations with ribosome bearing reticulocytes. In cells from every patient examined RNA content was decreased to 60‐76% of normal. Uridine incorporation and rRNA content of patients with β thalassemia minor and megaloblastic anemia were normal, suggesting that the defects observed in HE and DD were not due to ineffective erythropoiesis per se.Since erythroblast ribosomes may be rate limiting in protein synthesis, we postulate that even a minor decrease in ribosome content might engender the ubiquitous abnormalities reported in erythroid cells in both HE and DD.
Activity of the Epipodophyllotoxin VP‐16 in the Treatment of Combination Chemotherapy‐Resistant Non‐Hodgkin Lymphoma
Authors: Bender Richard A. , Anderson Tom , Fisher Richard I. , Young Robert C. 
Published: February 2007

AbstractTwenty patients with several histologic subtypes of non‐Hodgkin lymphoma who had become resistant to combination chemotherapy were treated with a five‐day course of the epipodophyllotoxin VP‐16. Of 19 evaluable patients, 8 (42%) responded to treatment with 1 complete response and 7 partial responses. The median duration of response was 5.5 months. Seven of the responders had a diffuse lymphoma and 1 had a nodular lymphoma. Of the responders who had diffuse histiocytic lymphoma (DHL), diffuse mixed lymphoma (DML), and diffuse undifferentiated lymphoma (DUL)–the more aggressive histologies in the Rappaport classification–6 of 13 (46%) evaluable patients responded to therapy. Responses were seen in node‐dominant, skin‐dominant, and marrow‐dominant disease. Toxicity was mainly hematopoietic, 53% of patients experiencing leukopenia (<2, 000 cells per cu mm) and 68% of patients experiencing thrombocytopenia (<100, 000 platelets per cu mm). There were two deaths attributable to profound leukopenia with sepsis. The activity of VP‐16 in patients who have previously been extensively treated with multiple drugs including vincristine supports its activity in the lymphomas and suggests its lack of cross‐resistance with vincristine. The inclusion of VP‐16 in primary treatment protocols in the diffuse lymphomas should be considered.
Inhibition of adriamycin‐induced human platelet lipid peroxidation by vitamin E
Authors: Stuart Marie J. , Dealarcon Pedro A. , Barvinchak Mary K. 
Published: February 2007

AbstractAdriamycin® is an important cancer chemotherapeutic agent whose clinical use is compromised by potentially lethal cardiotoxicity. In the mouse, cardiotoxicity is related to the peroxidation of cardiac lipids. Both phenomena, however, can be reduced by pretreatment of the animal with vitamin E. Using the platelet as our model we have demonstrated that Adriamycin induces lipid peroxidation of human platelets in a dose‐dependent manner. Platelet malonyldialdehyde (MDA) production was used as an indicator of lipid peroxidation. Adriamycin at 5, 10, 50, and 100 μg/ml produced 1.40 ± 0.2 (1 SD), 2.23 ± 0.41, 4.23 ± 0.4, and 6.13 ± 0.43 nmoies MDA per 109 platelets, respectively. Vitamin E both in vitro and in vivo inhibited this lipid peroxidation. In vitro, vitamin E at concentrations of 0.01, 0.05, and 0.1 mg/ml inhibited platelet MDA formation by 14 ± 2, 29 ± 5, and 38 ± 6%, respectively. In six controls who ingested 1,600 units vitamin E daily for two weeks, platelet MDA formation induced by N‐ethyl maleimide, thrombin, and Adriamycin was decreased by 11‐20%. In similar studies, the ingestion of 10 grains acelyl salicylic acid (ASA) also inhibited platelet lipid peroxidation induced by these same agents. ASA and vitamin E were not additive in their inhibition of MDA formation induced by N‐ethyl maleimide or thrombin. They were additive, however, in their inhibition of Adriamycin‐induced lipid peroxidation, which suggests that the effect of vitamin E on Adriamycin‐induced platelet lipid peroxidation is not due to inhibition of platelet cyclooxygenase. In the light of these observations on the inhibitory effect of vitamin E on lipid peroxidation in human platelets, further studies appear warranted on the clinical effects of E in inhibiting cardiac lipid peroxidation and concomitant cardiotoxicity in humans on Adriamycin therapy.
Potentiation of vincristine cytotoxicity by hormones: Corticosteroids, androgens, estrogens and progestins
Authors: Rosner Fred , Hirshaut Yashar , Grünwald Hans W. , Deutsch Stanley 
Published: February 2007

AbstractUsing an in vitro system to evaluate the simultaneous use of two drugs, we previously have confirmed the synergism of vincristine and prednisolone cytotoxicity against lymphoid cells. Experiments were now carried out to determine whether other steroid hormones can be substituted for prednisolone. Partial or complete potentiation of vincristine cytotoxicity comparable to that achieved by the addition of prednisolone was observed when the latter drug was replaced by a variety of mineralocorticoids (aldosterone, desoxycorticosterone and fludrocortisone), glucocorticoids (hydrocortisone, dexamethasone), androgens (testosterone, methyltestosterone, androsterone, dehydroepiandrosterone, etiocholanolone), estrogens (estrone, 17‐βestradiol) and progestins (progesterone, pregnanediol). No potentiation of cytotoxicity was observed when nonsteroidal hormones (thyroxin, ACTH) were added to vincristine. It is concluded that a wide variety of compounds with the basic perhydrocyclopentano‐phenanthrene nucleus of the steroid molecule are capable of enhancing the cytotoxicity achieved with vincristine.
Recent developments in understanding the pathogenesis of aplastic anemia
Authors: Fitchen John H. , Cline Martin J. 
Published: February 2007

AbstractBone marrow failure in aplastic anemia (AA) could result from abnormalities of hematopoietic stem cells, abnormal control of hematopoiesis, or abnormalities of the hematopoietic environment. Bone marrow transplantation, in vitro marrow culture techniques, and studies in animal models of marrow failure have provided insights on the possible pathogenetic mechanisms underlying AA. Studies in man and in murine models suggest that most often AA results from injuries to hematopoietic stem cells. Despite the intriguing report of abnormal regulatory cells in congenitally anemic mice, instances of marrow failure due to defective humoral or cellular control of hematopoiesis have not been identified in man. In vitro studies employing allogeneic marrow targets have suggested that immune suppression of hematopoiesis may occasionally mediate AA in man. Marrow failure due to abnormalities of the hematopoietic microenvironment has been suggested by experience with bone marrow transplantation, but no direct study of this possibility has been reported. Based on available evidence, it seems likely that AA will prove to be many diseases that share common clinical and morphologic features.
Sickle cell anemia as a syndrome: A review of diagnostic features
Authors: Huisman Titus H. J. 
Published: February 2007

AbstractSickle cell (SS) disease is a complex of various genetic conditions. In some, homozygosity for the βS gene may be present alone or in combination with the heterozygous or homozygous α‐thalassemia‐2 condition. Such combinations might ameliorate the clinical and hematological condition of the patient. The same may be true for the high levels of Hb F and F‐cells observed in many Hb S homozygotes. However, the chemical heterogeneity of Hb F appears not to be related to the clinical status of the Hb S homozygote. Combinations of a Hb S heterozygosity with a heterozygosity for a Hb D‐type of variant, for either one of two types of β‐thalassemia, two types of δβ‐thalassemia, and five types of HPFH are discussed, and data are compared with those obtained for Hb S homozygotes. The use of advanced laboratory procedures and family studies is often necessary for an accurate diagnosis.
Effects of thrombopoietin and erythropoietin on platelet production in rebound‐thrombocytotic and normal mice
Authors: McDonald T. P. , Clift Rose 
Published: February 2007

AbstractThe effects of thrombopoietin‐rich (TSF‐rich) kidney cell culture medium and partially purified preparations of human urinary and step I sheep plasma erythropoietin (Ep) on platelet production in mice were determined. After TSF and Ep preparations had been injected into mice in rebound thrombocytosis and into normal mice, the rate of incorporation of Na2 35SO4 into platelets was measured as an index of platelet production. TSF injections caused significant increases in platelet production of all the mice; however, greater effects were observed in rebound‐thrombocytotic mice than in normal mice. In rebound‐thrombocytotic mice, low dosages of Ep (0.25–1.0 units per mouse) significantly depressed percentage 35S incorporation into platelets. The same low dosage of Ep did not alter platelet production rates in normal mice, but large doses (2.5–5.0 units per mouse) stimulated 35S incorporation into platelets. Thus, these results show that Ep caused different responses in rebound‐thrombocytotic and normal mice. Endotoxin, injected in dosages previously shown to be present in Ep, gave responses similar to that of the low dosages of Ep, ie, depressed thrombocytopoiesis in rebound‐thrombocytotic mice but had no effect in normal mice. When two foreign proteins were injected in doses similar to the previously tested Ep protein content, platelet production was not stimulated. We conclude, therefore, that the thrombocytopoietic effects of Ep cannot be due to contamination with known humoral factors or foreign proteins.
Inhibition by antimicrotubular agents of the procoagulant activity generated by the blood monocytes: A biochemical and morphological study
Authors: de Prost Dominique , Cramer Elisabeth , Hakim Jacques 
Published: February 2007

AbstractDuring in vitro incubation, human blood leukocytes triggered by various stimuli, generate and release procoagulant activity (PCA), which was identified as tissue factor‐like activity. The cell responsible for this production is the monocyte. Monocytes, when incubated in aseptic conditions generate and release PCA in the incubation medium, after a lag period of 1–2 hours. Most of the activity (95%) remains cell bound while only 5% are released. In order to ascertain whether microtubules (MT) act as an intermediate in the generation and/or the release of PCA, monocytes were incubated with antimicrotubular agents ie, colchicine or vinblastine. Both drugs inhibited PCA generation and release.Colchicine added after two hours of incubation was inhibitor after a lag period of one hour as expected by its delayed effectiveness on MT. The inhibition was more effective on the generation than on the release of PCA. Ultrastructural studies showed that both drugs significantly (P < 0.01) disrupted microtubules while no modifications of the protein synthetizing apparatus or the lysosomes were observed. No accumulating material was seen inside the cells.These results suggest that colchicine or vinblastine act by their disrupting activity on MT, as inhibitors of PCA Generation by the monocytes. The decrease in PCA‐release would thus be secondary to a deficient generation of the activity. The absence of morphological modifications of the protein synthetizing apparatus suggest that antimicrotubular agents inhibit PCA synthesis by monocytes through the formation or transmission of the stimuli and not directly on the synthetizing sites.
Quantitative evaluation of antibody‐dependent lymphocyte‐mediated lysis of human red cells
Authors: Kurlander Roger J. , Rosse Wendell F. , Ferreira Euripides 
Published: February 2007

AbstractThe ability of lymphocytes to lyse human red cells coated with anti‐D antibody was assessed by measuring 51Cr release from labeled red cells incubated with peripheral blood leukocyte suspensions from 12 normal donors. Mixed mononuclear cell suspensions (containing monocytes and lymphocytes) from all donors produced lysis of sensitized red cells. Treatment with carbonyl iron reduced monocyte concentration to less than 1.2% in all donors, as measured by morphologic criteria, esterase staining and ingestion of latex particles. Lysis of red cells following monocyte depletion was markedly reduced in 8 of the 12 donors. Despite depletion of monocytes, unchanged or increased lysis was noticed with the leukocytes of the remaining 4 donors. This lysis was due to lymphocytes, not to residual monocytes. If target red cells were treated with papain or trypsin prior to sensitization, marked lysis occurred with lymphocytes of all donors, including those which did not lyse unmodified red cells. Direct cytolysis of sensitized red cells during contact with small lymphocytes was recorded using microcinematography, which confirmed the role of lymphocytes in mediating lysis.Lymphocyte‐mediated lysis of red cells increased with mounting levels of antibody sensitization regardless of prior treatment with papain. Papain increased antibody coating per red cell, yet lysis per molecule of antibody bound was also increased. Lysis was inhibited by IgG1 and IgG3 in the fluid phase but not by IgG2 or IgG4. At an equivalent level of antibody sensitization lysis was augmented by concurrent coating of the red cells with C3b, C3d and/or C4b, though these components could not produce lysis in the absence of antibody coating.
Three new variants of glucose‐6‐phosphate dehydrogenase associated with chronic nonspherocytic hemolytic anemia: G‐6‐PD Lincoln Park, G‐6‐PD arlington heights, and G‐6‐PD West Town
Authors: Honig George R. , Habacon Evelina , Vida Loyda N. , Matsumoto Florinda , Beutler Ernest 
Published: February 2007

AbstractGlucose 6‐phosphate dehydrogenase (G‐6‐PD) deficiency was identified in three children who were evaluated because of chronic nonspherocytic hemolytic anemia. One child is of German extraction, another Puerto Rican, and the third Mexican. In each of the patients the hemolytic process was well compensated, but each had one or more episodes of anemia following exposure to an oxidant drug or with infections. The electrophoretic, functional, and kinetic properties of the mutant enzymes, derived both from the patients' erythrocytes and from cultured fibroblasts, allowed each to be distinguished from G‐6‐PD variants previously described.
Intensive leukapheresis in the management of cytopenias in patients with chronic lymphocytic leukaemia (CLL) and lymphocytic lymphoma
Authors: Cooper I. A. , Ding J. C. , Adams P. B. , Quinn M. A. , Brettell M. 
Published: February 2007

AbstractThe role of leukapheresis was explored in the management of anaemia and thrombocytopenia complicating the accumulation of lymphoid cells in patients with chronic lymphocytic leukaemia and lymphoma. The aim of this study was to determine the efficiency of this procedure in correcting these complicating features and to assess the length of response and the clinical well being of the patients. Twenty such patients with either chronic lymphocytic leukaemia or lymphocytic lymphoma were studied using a Continuous Flow Cell Separator (Aminco Celltrifuge). All had persistent significant anaemia and/or thrombocytopenia prior to the institution of leukapheresis. The procedure was carried out on alternate days until significant reduction in total circulating lymphoid cells had been achieved, an average of 2.9 × 1011 cells being removed on each occasion. Thirteen of the twenty patients showed a significant elevation of both haemoglobin and platelet levels concomitant with the reduction in lymphoid cells. A reduction in organomegaly was also observed. These patients were classified as “responders,” but the other patients failed to show correction of the haematologic parameters. This procedure permitted a number of responder patients to receive more specific treatment but in some it obviated the necessity for any further management for up to 12 months.Surface marker studies were also carried out on the lymphocytes of these patients. The patients who showed the best response to leukapheresis had cells characteristic of those seen in chronic lymphocytic leukaemia. The reduction of cells (82%) was greater in those who responded to this treatment than in the non‐responder group (72%). The procedure was well tolerated by all patients and overall provided a long‐term control of disease which outweighed the initial cost incurred.