bluuebunny/crossref_metadata_2025 huggingface dataset:
Uptake of transferrin‐bound and nontransferrin‐bound iron by reticulocytes from the belgrade laboratory rat: Comparison with wistar rat transferrin and reticulocytes
Authors: Farcich Elizabeth A. , Morgan Evan H.
Published: February 2007

The mechanism underlying the impaired uptake of iron from transferrin by reticulocytes from the Belgrade laboratory rat was investigated using 125I‐ and 59Fe‐labeled transferrin isolated from homozygous Belgrade rats and from Wistar rats, nontransferrin‐bound Fe(II) in an isotonic sucrose solution, and reticulocytes from Belgrade and Wistar rats. The Belgrade rat transferrin had the same molecular weight and net charge as Wistar rat transferrin, donated iron equally well to both types of reticulocytes, and competed equally for transferrin binding sites on the cells. Hence, the defect in iron uptake by Belgrade rat reticulocytes could not be attributed to an abnormality of the transferrin molecule. The rate of uptake of Fe(II) from sucrose into the cytosolic and stromal fractions of Belgrade rat reticulocytes was only about 35% as great as that by Wistar rat reticulocytes. With both types of cells, the uptake process was saturable, suggesting the presence of a carriermediated process. It was therefore concluded that the defect in iron uptake by Belgrade rat erythroid cells is probably the consequence of a deficiency in a membrane carrier for iron.
Physiologic and rheologic effects of the antisickling agent ethacrynic acid and its N‐butylated derivative on normal and sickle erythrocytes
Authors: Orringer Eugene P. , Blythe David S. , Whitney James A. , Brockenbrough Scott , Abraham Donald J.
Published: February 2007

Ethacrynic acid, a loop diuretic, has been shown to inhibit hemoglobin S polymerization. Until now, however, most studies were performed using purified solutions of hemoglobin S. The experiments reported here were designed to examine the effects of ethacrynic acid and its n‐butryic acid derivative on the rheological and physiological properties of intact red blood cells. Using net and unidirectional flux measurements, both agents were shown to cause ion and water loss from normal and sickle erythrocytes. Since cell shrinkage adversely influences red cell rheology, it is unlikely that this class of compounds, despite its ability to inhibit hemoglobin S polymerization, will prove useful in the treatment of sickle cell disease.
Increased expression of natural‐killer‐associated and activation antigens in multiple myeloma
Authors: Gonźlez M. , San Miguel J. F. , Gascon A. , Moro M‐J. , Hernandez J. M. , Ortega F. , Jimenez R. , Guerras L. , Romero M. , Casanova F. , Sanz M. A. , Portero J. A. , Orfao A.
Published: February 2007

The expression of both natural‐killer (NK)‐associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.
A female hemophilia a combined with hereditary coagulation factor XII deficiency: A case report
Authors: Matsushita Tadashi , Takamatsu Junki , Kagami Kazuo , Takahashi Isao , Sugiura Isamu , Hamaguchi Motohiro , Kamiya Tadashi , Saito Hidehiko
Published: February 2007

A 2‐year‐old Japanese girl with easy bruising and arthropathy was demonstrated to have severe hemophilia A (Factor VIII activity: <0.01 U/ml). She had normal 46XX karyotype. Her brother also had hemophilia A, and her mother and grandmother seem to be hemophiliac carriers. Additionally, activated partial thromboplastin time (APTT) of the patient was disproportionately prolonged and there were reduced levels of coagulation factor XII in the patients and members of the maternal trait which are compatible with heterozygous factor XII deficiency. Her father had both normal factor VIII and factor XII levels. Southern blotting analysis of genomic DNA from the propositus and family members with factor VIII and factor XII DNA probes revealed no gross alterations. This patient represents a female hemophilia A combined with heterozygous factor XII deficiency. Nonrandom inactivation of a normal X‐chromosome (extreme lyonization) may be the basis for the expression of hemophilia A in this female patient.
Studies on the in vitro and in vivo expression of a dysfunctional α‐ globin gene
Authors: Safaya Surinder , Trauber David R. , Rieder Ronald F.
Published: February 2007

In a black family with members having α‐thalassemia and hemoglobin H (HbH) disease, a deletion of an AG dinucleotide at the 3′ end of exon 1 near the junction with intron 1 was shown previously to produce a dysfunctional α‐thalassemia gene with a reading frame‐shift and a nonsense codon (Safaya S, Rieder RF: J Biol Chem 263:4328‐4332, 1988). We have found that the same mutation is responsible for α‐thalassemia and HbH disease in a second unrelated black family (Bellevue R, Dosik H, Rieder RF: Br J Haematol 41:193‐202, 1979). Despite the loss of two nucleotides from the consensus sequence at the 5′ splice donor site of intron 1, studies employing an in vitro plasmid‐based expression system indicated that the mutant α‐globin mRNA was spliced normally and expressed in amounts equal to normal α‐globin mRNA in COS‐7 cells. The correct processing of the mRNA in these studies is probably due to the presence of a tandem repeat of the affected AG dinucleotide. However, in reticulocytes from subjects bearing the mutant gene, we were unable to detect any of the abnormal mRNA. These findings suggest that there is accelerated post‐transcriptional loss of mRNA bearing a premature terminator codon.
A radioimmune microfilter plate assay for the detection of anti‐granulocyte antibodies
Authors: Braman Ann Marie , Schwartz Kenneth A.
Published: February 2007

A radioimmune assay (RIA) for IgG anti‐granulocyte antibodies (AGA) was developed which utilized 96 well microfilter plates, required less than 50 μI plasma, and yielded reproducible autologous determinations on patients with absolute granulocyte counts as low as 300 cells/μI. Granulocytes were isolated by a single density ficoll‐hypaque gradient procedure with red blood cell (RBC) removal by lysis and washing. Anti‐granulocyte IgG coating the cells was detected by the addition of 125I labeled anti‐human IgG. Six patients with autoimmune granulocytopenia and three multiply transfused patients with febrile transfusion reactions believed to be secondary to allogeneic granulocyte antibodies had increased granulocyte IgG. Plasma containing anti‐a and/or anti‐B titers greater than or equal to 512 gave positive results when tested against ABO incompatible granulocytes. This technique was capable of detecting antibodies which were reactive in granulocyte agglutination and immunofluorescence tests as demonstrated with known anti‐NA‐1, anti‐NB‐1, and anti‐Mart sera. Comparison with granulocyte agglutination test (GAT) using clinical criteria for immune granulocytopenia demonstrated concordance with 19 negative samples and 8 positive samples, 1 false negative and 3 false positives were observed using the agglutination method. The multimeric and monomeric IgG fractions of G200 purified Cohn Fraction II were nonreactive by both RIA and GAT methods. However, granulocyte activation by phorbol myristate acetate (PMA) produced false positives in 5 out of 5 cases by GAT but 0 out of 4 by RIA. This RIA assay is not effected by nonimmune granulocyte activation and is more reproducible when compared to existing techniques.
Hypercalcemia in idiopathic myelofibrosis: Modulation of calcium and collagen homeostasis by 1,25‐dihydroxyvitamin D3
Authors: Voss A. , Schmidt K. , Hasselbalch H. , Junker P.
Published: February 2007

A case of idiopathic myelofibrosis (IMF) presenting with hypercalcemia and hypercalcitriolemia is reported. It is proposed that ectopic production of the active vitamin D metabolite related to ongoing clonal expansion in the bone marrow accounts for the hypercalcemic state. Consistently low levels of circulating type I procollagen propeptide (PICP) and lack of progression of the bone marrow fibrosis during almost 6 months of follow‐up point to an in vivo inhibition of type I collagen synthesis by 1,25‐dihydroxyvitamin D3.
Four‐agent induction/consolidation therapy for childhood acute lymphoblastic leukemia: An Indian experience
Authors: Advani S. H. , Lyer R. S. , Pai S. K. , Gopal R. , Saikia T. K. , Nair C. N. , Kurkure P. A. , Nadkarni K. S. , Pai V. R.
Published: February 2007

During 1984‐1986, a total of 128 children with acute lymphoblastic leukemia (ALL) were treated with an induction‐consolidation regimen consisting of doxorubicin, vincristine, cytosine‐arabinoside, and prednisolone. One hundred two (80%) patients belonged to high‐risk group. The complete remission rate for all the patients was 91%. The event‐free survival at 5 years was 32.0% ± 23%. On multivariate analysis the event‐free survival and disease‐free survival was not altered by age, sex, WBC count, platelet count, LDH level, and surface phenotype.

Infection due to prolonged marrow aplasia was a common complication, leading to mortality of 8 patients during induction and 33 patients during first remission. The relapse rate has been 36% (42 patients). The predominance of high‐risk ALL in the Indian population underscores the need for intensive therapy. Improved supportive care during induction and remission seems essential to decrease therapy‐related mortality, leading to improved survival.
Binding and suppressive activity of human recombinant ferritins on erythroid cells
Authors: Fargion Silvia , Cappellini Maria Domenica , Fracanzani Anna Ludovica , de Feo Tullia Maria , Levi Sonia , Arosio Paolo , Fiorelli Gemino
Published: February 2007

We studied the relation between ferritin cellular binding and suppressive activity of recombinant H‐ and L‐ferritin on human erythroid cells at different proliferation/differentiation phases. L‐ferritin failed to show any suppressive activity or detectable binding to erythroblasts at any stage of maturation. In contrast, H‐ferritin demonstrated binding to erythroblasts derived from peripheral BFU‐E cells which increased steadily between 7‐14 days of culture up to 15,000 molecules per cell. Reticulocytes and erythrocytes failed to bind either L‐ or H‐ferritin. H‐ferritin suppressed BFU‐E colony formation and reduced K562 cell proliferation at nanomolar concentrations. This suggests that the expression of H‐ferritin binding sites is modulated by cellular proliferation and differentiation, that cells expressing H‐ferritin binding sites are sensitive to ferritin suppressive activity and that a causal relation exists between ferritin cellular binding and suppressive activity.
Platelet regulatory prostanoids and platelet release products in sickle cell disease
Authors: Longenecker Gesina L. , Beyers Barbara J. , Mankad Vipul N.
Published: February 2007

Changes in platelet function have been observed for sickle cell disease (SCO). Levels of the arachidonic acid metabolites, thromboxane A2 (released by stimulated platelets) and prostacyclin (released from vascular endothelium), which stimulate and inhibit platelets, respectively, have been implicated in overall regulation of platelet function. Circulating basal levels of thromboxane and prostacyclin were determined in 1) a group of SCO volunteers (n = 21; at half‐yearly steady state intervals and also at 24 hr, 72 hr, and 7 days after start of pain crisis) and 2) an age‐, sex‐, and race‐matched control group (n = 18; single determinations). Circulating levels of β‐thromboglobulin (β‐TG), as well as throm‐bin (clotting)‐stimutated platelet release of thromboxane, were also determined. Statistically significant decreases were found for prostacyclin, basal thromboxane, and thrombin‐induced (maximal) thromboxane (alone or per platelet), for steady state SCD vs. normal controls. In addition, significant increases in maximal thromboxane were identified in crises (24, 72 hr) compared with steady state. Crisis β‐TG (24 hr) was significantly elevated compared with controls or steady state SCD. The ratio of basal thromboxane to prostacyclin was increased in crisis, but not significantly. Crisis frequency may correlate in part with changes in platelet function: steady state maximal thromboxane and released thromboxane per platelet were significantly lower in SCD volunteers who had crises during the study vs. those who did not (equivalent study time). The data support altered platelet function in SCD, possibly refractoriness (desensitization), manifest as decreased thromboxane release, to thrombin and/or other stimuli: alternate explanations are discussed. © 1992 Wiley‐Liss, Inc.
Concurrent protein C deficiency and lupus anticoagulants
Authors: Harrison Robert L. , Alperin Jack B.
Published: February 2007

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin‐induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin‐induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient. © 1992 Wiley‐Liss, Inc.
Abnormalities in immune regulation precede the development of multiple myeloma
Authors: Paglieroni Teresa , Caggiano Vincent , Mackenzie Malcolm
Published: February 2007

Immunosuppression of immunoglobulin synthesis seen in patients with multiple myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year longitudinal study of an IgA‐deficient blood donor who developed multiple myeloma, the presence of immunosuppressive CD5 positive B cells and T cells preceded the diagnosis of overt multiple myeloma and the appearance of immunosuppressive monocytes. These data argue that certain immune defects may be involved in the development of myeloma and are not simply a consequence of overt malignancy. © 1992 Wiley‐Liss, Inc.
Muir‐Torre syndrome in patients with hematologic malignancies
Authors: Cohen Philip R.
Published: February 2007

The Muir‐Torre syndrome (MTS) is defined as the concurrent or sequential discovery of at least one sebaceous gland tumor and a minimum of one internal malignancy. A man with Hodgkin's lymphoma who subsequently developed an ocular sebaceous carcinoma in situ is described and the world literature of patients with the MTS and hematologic malignancies is reviewed. © 1992 Wiley‐Liss, Inc.
Splenic sequestration associated with sickle cell trait and hereditary spherocytosis
Authors: Yang Yih‐Ming , Donnell Cynthia , Wilborn Walter , Goodman Steven R. , Files Bea , Moore R. Blaine , Mohandas Narla , Mankad Vipul N.
Published: February 2007

Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11‐year span, while the other had two episodes of this complication during a 4‐year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life‐threatening complication should be considered in this condition. © 1992 Wiley‐Liss, Inc.
A study of lymphoma of large granular lymphocytes with modern modalities: Report of two cases and review of the literature
Authors: Sun Tsieh , Schulman Philip , Kolitz Jonathan , Susin Myron , Brody Judith , Koduru Prasad , Muuse William , Hombal Shiril , Teichberg Saul , Broome John
Published: February 2007

Two cases of lymphoma of large granular lymphocytes are reported. The first case expressed natural killer (NK) cell, some T‐cell (CD 2, CD 5, CD 8), and HLA‐DR antigens, but was negative for other T‐cell (CD 3, CD 4, CD 7), T‐cell receptor (TCR), B‐cell, and myeloid antigens. Germline configuration was demonstrated for TCR, and immunoglobulin heavy and light chain genes. The second case expressed NK cell, some T‐cell (CD 3, CD 7, CD 8), and TCR antigens, but was negative for other T‐cell (CD 4, CD 5), B‐cell, myeloid, and HLA‐DR antigens. Rearrangement of TCR α and β chains were detected. Thus, the findings of case 1 were consistent with true NK cell lineage and case 2 with NK‐like T‐cell lineage. Our report underscores the heterogeneity of this newly recognized lymphoma, which nevertheless carries a consistently poor prognosis and is probably more prevalent in the Asian population. This study also provides information concerning immunopheno‐types of cellular infiltrates in internal organs and cytogenetic abnormalities in this lymphoma; neither has been reported frequently in the literature. The importance of detecting cytoplasmic granules in tissue imprints or electron micrographs for differentiating other T‐cell lymphomas is emphasized, and the classification of large granular lymphoproliferative disorders is discussed. © 1992 Wiley‐Liss, Inc.
Acquired von willebrand disease: Correction of hemostatic defect by high‐dose intravenous immunoglobulins
Authors: Delmer A. , Horellou M. H. , Bréchot J. M. , Prudent J. , Potevin F. , Lecrubier C. , Girard‐Longhini C. , Samama M. , Zittoun R.
Published: February 2007

High‐dose intravenous immunoglobulins (ivIG) were used in a 57‐year‐old patient with acquired von Willebrand disease in order to correct a hemostatic defect before pneumonectomy for lung carcinoma. IvIG induced a rapid and complete correction of factor VIII (F VIII) and von Willebrand factor (vWF) and allowed surgery without additional factor coverage. F VIII and vWF returned to baseline values within 10 days after ivIG. © 1992 Wiley‐Liss, Inc.
Genetic epidemiology of β‐thalassemia in sicily: Do sequences 5′ to the Gγ gene and 5′ to the β gene interact to enhance HbF expression in β‐thalassemia?
Authors: Ragusa Angela , Lombardo Mario , Beldjord Cherif , Ruberto Concetta , Lombardo Turi , Elion Jacques , Nagel Ronald L. , Krishnamoorthy Rajagopal
Published: February 2007

The present epidemiological study of the molecular characteristics of β‐thalassemia in Sicily was prompted by the disparate phenotypic expression (in clinical status and absolute HbF level) observed in two β‐thalassemic homozygotes who were also homozygous for the β‐like globin gene cluster haplotype III. We suspected that polymorphisms within haplotype III could be the cause for the discrepancy. Based on the association of particular conformations of the (AT)xTy motif (‐540 5′ to the β gene) with milder forms of thalassemia and sickle cell anemia, 38 homozygous β‐thalassemia patients were studied to define their haplotypes, the −158 site 5′ to the Gγ gene (linked to haplotype III) and the structure of the (AT)xTy motif. We found that the patient who was phenotypically mild and homozygous for β‐thalassemia, haplotype III, and the −158 C→T mutation was homozygous for the rare (AT)9T5 motif. In contrast, the patient homozygous for β‐thalassemia, haplotype III, and the —158 mutation, but exhibiting a severe clinical course, was homozygous for the (AT)7T7 configuration. Others have suggested that (AT)9T5 is a negative regulatory protein binding sequence, and it is a silent carrier state for β‐thalassemia. The usual configuration (AT)7T7, has considerably less affinity for regulatory protein binding, and it is the most common configuration in Sicilian β‐thalassemics (67 of the 78 chromosomes studied). Within the 38 patients studied, seven were informative because they had various combinations of the (AT)9T5 and (AT)7T7 motif, and the −158 C→T mutation. The results in these patients suggest that only the co‐presence of the (AT)9T5 configuration and a C→T change at −158.5′ to the Gγ gene is associated with high HbF expression and a mild clinical phenotype. We postulate that these two regions of the β‐like globin gene cluster interact, when endowed with the proper sequences, to enhance the expression of HbF secondary to anemia. © 1992 Wiley‐Liss, Inc.
Coagulation factor IX: Successful surgical experience with a purified factor IX concentrate
Authors: Goldsmith Jonathan C. , Kasper Carol K. , Blatt Philip M. , Gomperts Edward D. , Kessler Craig M. , Thompson Arthur R. , Herring Steve W. , Novak Patricia L.
Published: February 2007

The use of plasma‐derived coagulation factor concentrates has been marked by the transmission of viral agents. Infusions of factor IX complex concentrates have been additionally complicated by inappropriate thrombosis. Use of these concentrates in the neonate, in those with liver disease, and in surgical patients results in increased risk for this complication. Twenty patients have been infused with a purified coagulation factor IX concentrate for fall‐off and recovery studies. A two‐compartment model indicated an initial phase half‐life of 4.06 ± 2.86 hr and a β phase half‐life of 20.0 ± 3.8 hr following the administration of AlphaNine®, Coagulation Factor IX (Human). In vivo recovery was 62.7% ± 13.8%, with an average factor IX coagulant level of 73% ± 16% at 15 min after the infusion of a mean dose of 45 U/kg. Thirteen previously transfused patients with hemophilia B underwent major orthopedic or general or dental surgery using this purified factor IX. Operative outcomes were excellent in all patients. No excessive bleeding was noted. There was no laboratory or clinical evidence for a disseminated intravascular coagulopathy. The excellent surgical outcomes observed in this multitransfused group with biochemical evidence for active liver disease demonstrates the utility and safety of a purified coagulation factor IX concentrate. © 1992 Wiley‐Liss, Inc.
Effect of interleukin‐1, tumor necrosis factor‐α, and interferon‐α on the blast cells of acute myeloblastic leukemia
Authors: Carter Anna , Silvian‐Draxler Iiana , Tatarsky Iiana
Published: February 2007

In this study, we further established the role of interleukin‐1α (IL‐1α), interleukin‐1β, tumor necrosis factor‐α (TNF‐α), and interferon‐α (IFN‐α) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3H‐thymidine (3H‐TdR) in the absence of exogenous growth factors. The spontaneous DNA synthesis could be abrogated with monospecific antibodies directed toward IL‐1α, IL‐1β, or TNF‐α, as well as with antigranulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Human recombinant GM‐CSF reversed the inhibitory action of each of these antibodies and reinduced DNA synthesis in AML cells. Thus, in these cases, constitutively produced IL‐1 or TNF‐α had stimulated the synthesis of GM‐CSF, which resulted in GM‐CSF‐dependent proliferation of AML blasts. Exogenous IL‐1 up‐regulated the endogenous production of GM‐CSF, suggesting a positive regulation of autocrine growth factor production. We also present evidence that TNF‐α may exert both stimulative as well as inhibitory effects on DNA synthesis in AML cells. The enhancing effect of TNF‐α was mediated through the induction of GM‐CSF production, as stimulation of DNA synthesis in AML blasts could be abrogated with anti‐GM‐CSF antibody. A concentration‐dependent inhibitory effect of TNF‐α on 3H‐TdR incorporation into AML blasts was observed only when these cells were grown in the absence of GM‐CSF. Finally, we show that human recombinant IFN‐α is a potent inhibitor of AML cell proliferation in vitro. © 1992 Wiley‐Liss, Inc.
Regulation of transferrin receptors by iron in human erythroblasts
Authors: Abe Yasunobu , Muta Koichiro , Nishimura Junji , Nawata Hajime
Published: February 2007

We investigated the regulatory mechanism of human erythroblast transferrin receptors (Tf.R) under conditions of iron deprivation and iron loading. Treatment of erythroblasts with an iron chelator, desferrioxamine, induced an increase in surface Tf.R number associated with an elevation of biosynthetic rate and the mRNA level of Tf.R. Reduced cellular iron pool increased the Tf.R number by altering the level of mRNA, as in nonhemoglobinproducing cells. Although treatment of erythroblasts with hemin induced a decrease in the biosynthetic rate and in the level of mRNA, the number of surface Tf.R did not decrease. This phenomenon may explain the fact that a high level of serum iron has no influence on the surface Tf.R number in vivo, as we reported previously. We suggest the existence of a regulatory mechanism specific for hemoglobin‐producing cells that keeps surface Tf.R expression constant despite iron loading. © 1992 Wiley‐Liss, Inc.
Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia
Authors: Berney S. I. , Ridler C. D. , Stephens A. D. , Thomas A. E. , Kovacs I. B.
Published: February 2007

A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso‐occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA. © 1992 Wiley‐Liss, Inc.
Interleukin‐5 in eosinophilic gastroenteritis
Authors: Takahashi Takayuki , Nakamura Kishiko , Nishikawa Satoru , Tsuyuoka Reiko , Suzuki Akira , Murakami Masao , Amenomori Masahiro , Okuno Yoshiaki , Imura Hiroo
Published: February 2007

During a 4‐year period a 28‐year‐old female had 4 episodes of eosinophilia of over 10,000/μ1; these episodes were associated with nausea, vomiting, diarrhea, and abdominal pain. On one occasion, she had ascites and pleural effusion which contained numerous mature eosinophils. On each occasion, these attacks disappeared within several weeks without any specific treatment. A diagnosis of eosinophilic gastroenteritis was made. A plasma sample obtained during the eosinophilia generated in vitro eosinophilic colonies when added to granulocyte/macrophage‐progenitor (CFU‐GM) cultures without exogeneous growth factors. Colony formation was inhibited by anti‐interleukin‐5 (IL‐5) antibody but not by antibodies toward IL‐3, granulocyte colony‐stimulating factor (G‐CSF) or GM‐CSF. A high plasma interleukin‐5 (IL‐5) level was noted when measured by enzyme‐linked immunosorbent assay, while IL‐3, G‐CSF, and GM‐CSF were undetectable. During remission the plasma gave negative results both for colony formation and IL‐5 level. These results indicate that the eosinophilia of this disease is mediated by IL‐5. © 1992 Wiley‐Liss, Inc.
Spanish Rhnull family caused by a silent Rh gene: Hematological, serological, and biochemical studies
Authors: Pérez‐Pérez Carmen , Taliano Victor , Mouro Isabelle , Huet Martine , Salat‐Marti Antonio , Martinez Antonio , Rouger Philippe , Cartron Jean‐Pierre
Published: February 2007

Another example of rare red cells that failed to react with all anti‐Rh and anti‐LW antibodies was discovered in a Spanish woman suffering from a severe hemolytic anemia typical of the Rhnull syndrome. Family study and Rh blood typings demonstrated clearly that the proposita was homozygous for a silent Rh gene complex (Rhnull of the amorph type) that she inherited from her parents who are first cousins. Western blot analysis carried out with glycosylation‐independent antibodies directed against the Rh polypeptide and the LW glycoprotein, respectively, confirmed that these protein components were absent from the red cells of the proposita. In addition, the patient was typed U‐positive, again in agreement with the presence on her red cells of 45–75 kDa glycoproteins detected with the murine monoclonal antibody 2D10. © 1992 Wiley‐Liss, Inc.
Myelodysplastic syndromes and malignant solid tumors: Analysis of 21 cases
Authors: Sans‐Sabrafen Jordi , Buxó‐Costa Josep , Woessner Soledad , Florensa Lourdes , Besses Carles , Malats NÚRia , Porta Miquel
Published: February 2007

We studied the association between myelodysplastic syndromes (MDS) and malignancies in a cohort of 155 patients with MDS, 21 of whom presented malignant solid tumors. Myelodysplasia was present after the diagnosis of cancer in eight patients (interval between the diagnosis of both conditions 18 months, median survival 49.5 months), simultaneously with diagnosis in 11 (median survival 8 months), and before malignancy in two patients (interval between the diagnosis of both conditions 47 and 7 months). One patient was given chemotherapy for lung cancer, and three patients received radiotherapy for adenocarcinoma of the kidney and cancer of the prostate. At the time of diagnosis of MDS, nine patients already presented metastatic spread. Fourteen patients died, ten as a result of tumor‐related complications and four because of transformation to acute nonlymphocytic leukemia. The analysis of the incidence of malignancy in patients with MDS was statistically significant for males, and the relative risk was significant in both sexes. The results of this study show that MDS patients present a higher incidence of malignant tumors than the general population, that MDS may be of real paraneoplastic significance, and that the occurrence of MDS in cancer patients may be considered to be related to the malignancy rather than an independent phenomenon. © 1992 Wiley‐Liss, Inc.
Circulating thrombomodulin as a novel endothelial cell marker: Comparison of its behavior with von willebrand factor and tissue‐type plasminogen activator
Authors: Takahashi Hoyu , Ito Seiki , Hanano Masaharu , Wada Ken , Niwano Hiroe , Seki Yoshinobu , Shibata Akira
Published: February 2007

Circulating thrombomodulin is a novel endothelial cell marker, which may reflect the endothelial injury. Plasma levels of thrombomodulin were quantitated by an enzymelinked immunosorbent assay (ELISA) in patients with hematological malignancies, liver disease, diabetes mellitus, collagen disease, thrombotic disease, and disseminated intravascular coagulation (DIC), and the thrombomodulin values were compared with those of von Willebrand factor antigen (vWf:Ag) and tissue‐type plasminogen activator (t‐PA) which are released from stimulated or damaged endothelial cells. The mean plasma concentrations of thrombomodulin in these disease states were elevated as compared with healthy subjects. A relatively high mean thrombomodulin level was observed in DIC, liver disease, and collagen disease. Abnormally high thrombomodulin values (> normal mean value + 3 SD) were found in 32.3% of patients with hematological malignancies, 57.7% of patients with liver disease, 39.3% of patients with diabetes mellitus, 30.0% of patients with collagen disease, 23.1% of patients with thrombotic disease, and 69.0% of patients with DIC. Plasma concentrations of both vWf:Ag and t‐PA were also elevated in these patients. On the whole, the plasma thrombomodulin concentration was positively correlated with vWf:Ag (r = 0.441, P < 0.001) and t‐PA (r = 0.398, P < 0.001). These findings indicate that the elevation of plasma thrombomodulin is frequently seen in a variety of diseases and circulating thrombomodulin is possibly useful for evaluating the endothelial damage in selected disease states. © 1992 Wiley‐Liss, Inc.
Human interleukin‐9 supports formation of a subpopulation of erythroid bursts that are responsive to interleukin‐3
Authors: Sonoda Yoshiaki , Maekawa Taira , Kuzuyama Yuko , Abe Tatsuo , Clark Steven C.
Published: February 2007

We have investigated the biological activities of recombinant human interleukin‐9 (IL‐9) on enriched hematopoietic progenitors, alone or in combination with other cytokines, including Epo, G‐CSF, IL‐3, and GM‐CSF, under serum‐containing and serum‐free cultures. IL‐9 alone did not support colony formation. However, IL‐9 plus Epo induced erythroid burst (BFU‐E) formation derived from peripheral blood (PB) progenitors. Delayed addition experiments demonstrated that a part of bone marrow (BM) derived BFU‐E, which seems to be immature, only responded to IL‐9 and formed erythroid bursts. The burst‐promoting activity (BPA) of IL‐9 was confirmed using neutralizing aIL‐3, aGM‐CSF, and aIL‐9 antisera and serum‐free culture. IL‐9 supported a part of BFU‐E population that respond to IL‐3, which was almost identical to the number of BFU‐E supported by GM‐CSF. IL‐9 had no additive effect on erythroid and mixed colony formation supported by IL‐3. In contrast, IL‐9 showed an additive effect on erythroid burst formation supported by GM‐CSF in serum‐free culture. These data suggest that IL‐9 and GM‐CSF act on distinct IL‐3‐responsive BFU‐E population. In addition, delayed addition experiment clearly demonstrated that IL‐9 supports survival and the early stage of proliferation of BFU‐E. These results led us to propose that IL‐9 possibly acts as a BPA and selectively supports a subpopulation of early class of BFU‐E that respond to IL‐3. © 1992 Wiley‐Liss, Inc.
Black β‐thalassemia homozygotes with specific sequence variations in the 5′ hypersensitive site‐2 of the locus control region have high levels of fetal hemoglobin
Authors: Beris Ph. , Kitundu M. N. , Baysal E. , Öner C. , Lanclos K. D. , Dimovski A. J. , Kutlar F. , Huisman T. H. J.
Published: February 2007

We have sequenced the 5′ hypersensitive‐2 (5′HS‐2) site of the locus control region (LCR) and the promoters of the two γ‐globin genes located on chromosome 11 of a black patient with mild β‐thalassemia (β‐thal) major due to a homozygosity for the C → T mutation at position – 88 of the β promoter and with a high Hb F level. Sequence variations in the 5′HS‐2 were the same as observed for the βs chromosome with haplotype number 3, while most of the Gγ promoter and the Aγ promoter had sequences similar to that of the βs chromosome with haplotype number 19. This atypical haplotype (number 19A) is apparently associated with an increased γ chain production which is particularly evident during periods of severe hematopoietic stress. Additional studies on relatives of the proband and on 10 unrelated black β‐thal homozygotes with either the C → T mutation at – 88 or the A → G mutation at –29, confirm the possible importance of the sequence differences in the 5′HS‐2, and also suggest that at least two additional factors, namely a C → T mutation at position –158 of the Gγ promoter and a relative deficiency in α chain synthesis play a (perhaps less important) role in the increased Hb F synthesis in these patients. © 1992 Wiley‐Liss, Inc.
Sequential maturation stages of monoclonal B lineage cells from blood, spleen, lymph node, and bone marrow from a terminal myeloma patient
Authors: Jensen Gitte S. , Mant Michael J. , Pilarski Linda M.
Published: February 2007

In order to fully understand the complexity of the monoclonal B lineage cells in multiple myeloma, it is necessary to evaluate the extent to which these cells are resident in solid lymphoid tissues and the phenotypic differences and similarities as compared to the circulating or bone marrow derived B lineage cells. Peripheral blood mononuclear cells from a patient with multiple myeloma were obtained 8 and 3 days prior to death, and mononuclear cells from lymph nodes, spleen, and bone marrow were obtained at autopsy. Rapid changes in the stage of differentiation of blood late‐stage B lineage cells towards mature end‐stage plasma cells were observed during the last week prior to death. Lymphoid cells within the blood comprised very few T cells, sub‐normal numbers of monocytes, and 80% of B lineage cells which were at a late stage of differentiation. Shortly before death, plasma cells were found in the peripheral blood, indicating progression to plasma cell leukemia. At autopsy, the monoclonal B lineage cells in lymph node, spleen, and bone marrow represented different stages of terminal B cell differentiation. In each tissue, the B lineage cells were at an earlier differentiation stage, as defined phenotypically, than the circulating B lineage cells found in blood 3 days prior to death. Analysis of B cell markers and CD45 was used to define the differentiation stage of the relevant B cell populations, revealing a series of differentiation stages. The least mature B lineage cells (CD45hi) were found in lymph node. However, the CD45 isoform expressed was CD45R0, unlike most normal lymph node B cells. More differentiated B lineage cells (CD45mod) were found in the bone marrow, and three sequential stages of pre‐plasma cells were found in the spleen (CD45bright, CD45moderate and CD45low‐neg), all of which were CD45R0+. The B cells in normal spleen and bone marrow are CD45RA. The presence of monoclonal B lineage cells in spleen was confirmed by Southern blotting. The B lineage cells from peripheral blood 3 days prior to death were approaching an end‐stage plasma cell stage (CD45low/). On B lineage cells from the various myeloma tissues, a concomitant loss of CD11b and increasing density of CD29 were observed as a function of progression to terminally differentiated stages. © 1992 Wiley‐Liss, Inc.
Leukemic manifestation in a case of alpha‐chain disease with multiple polypoid intestinal lymphocytic lymphoma
Authors: Chang Chao‐Sung , Lin Sheng‐Fung , Chen Tyen‐Po , Liu Hong‐Wen , Liu Ta‐Chi , Li Chin‐Yang , Chao Mei‐Chyn , Wu Pei‐Lin
Published: February 2007

We describe a female aborigine from Taiwan with alpha‐chain disease associated with multiple polypoid intestinal lymphocytic lymphoma and leukemic manifestation. Initially, the patient experienced intermittent diarrhea, abdominal pain, and leukemic manifestation. No evidence of bone marrow involvement was found. Alpha‐chain protein was demonstrated in the serum. Gastroendoscopy and a series of radiographs of the small intestine revealed multiple polypoid tumors involving the entire length of the small intestine. Duodenal biopsy showed diffuse lymphocytic lymphoma. Immunohistochemical staining of tumor samples revealed features typical of alpha‐chain disease. Cytogenetic analysis showed the same abnormal karyotypes of neoplastic clones in intestinal tumor cells and in circulating leukemic cells. The data suggest that alpha‐chain disease can present initially with intestinal multiple polypoid lymphocytic lymphoma and leukemic manifestation without evidence of bone marrow involvement. The data also support the homing theory of lymphomas from mucosa‐associated lymphoid tissue. © 1992 Wiley‐Liss, Inc.
Autoimmune neutropenia following peripheral blood stem cell transplantation
Authors: Klumpp Thomas R. , Herman Jay H. , Macdonald John S. , Schnell Maryann K. , Mullaney Mark , Mangan Kenneth F.
Published: February 2007

The differential diagnosis of unexpected neutropenia following bone marrow transplantation includes several potentially life‐threatening complications including graft rejection, overwhelming infection, relapse of the underlying neoplasm, and intrinsic graft failure. However, a number of recent reports document that the differential diagnosis also includes autoimmune neutropenia, which, although potentially life‐threatening, often responds well to corticosteroids or splenectomy. Autoimmune neutropenia has been reported following both autologous and allogeneic bone marrow transplantation. Herein we report a 31‐year‐old woman who developed a rapidly falling neutrophil count 11 days following peripheral blood stem cell transplantation for non‐Hodgkin's lymphoma. A laboratory evaluation supported a diagnosis of autoimmune neutropenia, and the neutropenia resolved following treatment with steroids and granulocyte‐colony stimulating factor. © 1992 Wiley‐Liss, Inc.
Treatment with gallium nitrate: Evidence for interference with iron metabolism in vivo
Authors: Seligman Paul A. , Moran Patrick L. , Schleicher Rhoda B. , David Crawford E.
Published: February 2007

Gallium, when bound to transferrin, has been previously shown to cause tumor cell cytotoxicity by preventing cellular uptake of transferrin bound iron in vitro. Patients treated with constant infusion gallium nitrate for carcinoma show a rise in serum iron within 6 hr of the start of treatment. Serum iron returns to baseline by 24 hr post‐infusion. Atomic analysis of iron and gallium content of Sephadex G‐150 fractions of treatment sera indicate that about an equamolar amount of gallium and iron are associated with transferrin. These gallium and iron concentrations result in inhibition of transferrin mediated iron uptake in vitro, and in vivo allow for >90% saturation of transferrin with metal. All seven patients who completed two courses of gallium therapy exhibited hypochromic microcytic anemia (mean fall in hemoglobin 3.5 grams %). Evidence for red cell iron depletion was confirmed by an increase (mean 3.3‐fold) in zinc protoporphyrin levels. Since transferrin receptor increases on gallium treated iron requiring cells in vitro, we assessed cell surface transferrin receptor on peripheral blood lymphocytes by measuring fluorescent transferrin receptor antibody binding. A population of highly transferrin receptor positive cells peaks at 48 hr into the infusion. DNA analysis as well as double staining indicate the majority of transferrin receptor positive cells are unstimulated B lymphocytes. These studies provide the first documentation that constant infusion gallium treatment results in significant interference with iron metabolism and evidence for tissue iron depletion in vivo. These changes may correlate with therapeutic effects of gallium such as tumor response. © 1992 Wiley‐Liss, Inc.
Is persistent polyclonal b lymphocytosis caused by epstein‐barr virus? A study with polymerase chain reaction and in situ hybridization
Authors: Chow Kuan‐Chih , Witzig Thomas E. , Li Chin‐Yang , Nacilla Johnny Q.
Published: February 2007

Previous reports of patients with persistent polyclonal B lymphocytosis have found associations with female sex, cigarette smoking, HLA‐DR7 phenotype, and moderate elevation of peripheral blood polyclonal B lymphocytes. The presence of binucleated cells and atypical lymphocytes in the peripheral blood of these patients was highly suggestive of a viral infection, such as with the Epstein‐Barr virus. We report a 47‐year‐old asymptomatic woman who was incidentally found to have persistent polyclonal B lymphocytosis and serum IgG against virus capsid antigen (VCA) and Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA) of EBV. The presence of EBV was investigated in the peripheral blood lymphocytes from this patient by in situ hybridization and polymerase chain reaction methods. EBV DNA was demonstrated in the lympohcyte fraction by polymerase chain reaction, and it was further located in lymphoid cells by in situ hybridization. These results indicate that persistent polyclonal B lymphocytosis is strongly associated with EBV. © 1992 Wiley‐Liss, Inc.
Angiodysplasia and von willebrand's disease type IIB treated with estrogen/progesterone therapy
Authors: Chey William D. , Hasler William L. , Bockenstedt Paula L.
Published: February 2007

The association between angiodysplasia and von Willebrand's disease was first reported in 1967. The cases reported to date have involved patients with type I and IIA von Willebrand's disease. We report a patient with type IIB von Willebrand's disease who suffered gastrointestinal bleeding attributable to gastric angiodysplasia. The patient underwent endoscopic electrocautery acutely and has been treated long‐term with estrogen/progesterone therapy. She has suffered no recurrent gastrointestinal bleeding at over 11 months of follow‐up. We suggest hormonal therapy as an alternative to repeated blood product transfusion or extensive surgical resection in patients with von Willebrand's disease and gastrointestinal bleeding from angiodysplasia. © 1992 Wiley‐Liss, Inc.
Evidence that NADPH‐dependent methemoglobin reductase and administered riboflavin protect tissues from oxidative injury
Authors: Hultquist Donald E. , Xu Feng , Quandt Kim S. , Shlafer Marshal , Mack Christopher P. , Till Gerd O. , Seekamp Andreas , Betz A. Lorris , Ennis Steven R.
Published: February 2007

NADPH‐dependent methemoglobin reductase, first detected in erythrocytes sixty years ago, has subsequently been purified and characterized as a methylene blue reductase and a flavin reductase. The reductase plays no role in methemoglobin reduction under normal conditions, but its activity serves as the basis for the treatment of methemoglobinemia with methylene blue or flavin. On‐going studies demonstrate that this cytosolic protein is also present in liver and that its primary structure distinguishes it from other known proteins. The bovine erythrocyte reductase tightly binds hemes, porphyrins, and fatty acids with resulting loss of activity. Pyrroloquinoline quinone serves as a high‐affinity substrate of the reductase, suggesting that this naturally‐occurring compound may be a physiological substrate. The ability of the reductase to catalyze the intracellular reduction of administered riboflavin to dihydroriboflavin suggested that this system might be exploited to protect tissues from oxidative damage. This hypothesis was supported by our finding that dihydroriboflavin reacts rapidly with Fe(IV)O and Fe(V)O oxidation states of hemeproteins, states that have been implicated in tissue damage associated with ischemia and reperfusion. Preliminary studies demonstrate that, as predicted, administration of low concentrations of riboflavin protects isolated rabbit heart from reoxygenation injury, rat lung from injury resulting from systemic activation of complement, and rat brain from damage caused by four hours of ischemia. Data from these animal studies suggest that flavin therapy holds promise in protecting tissue from the oxidative injuries of myocardial infarction, acute lung injury, stroke, and a number of other clinical conditions. © 1993 Wiley‐Liss, Inc.