bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of β2‐glycoprotein i (apolipoprotein h)‐independent anticardiolipin antibody in human immunodeficiency virus‐1‐positive and‐negative hemophiliacs
Authors: Matsuda Juzo , Saitoh Noriko , Tsukamoto Miyo , Gohchi Kengo , Asami Katsuhisa , Hashimoto Masakatsu
Published: February 2007

The authors studied whether or not anticardiolipin antibody (aCL), which is frequently detected in hemophiliacs with human immunodeficiency virus‐1 (HIV‐1) infection, is dependent on β2‐glycoprotein I (GPI), a cofactor of cardiolipin (CL). GPI‐independent aCL was positive in 27 of 36 hemophiliacs with HIV‐1 antibody (75%) and in 23 of 29 patients without HIV‐1 antibody (79%). However, only six HIV‐1‐positive and four HIV‐1‐negative patients were positive for GPI‐dependent aCL. Thus the aCL in these hemophiliacs was GPI independent and therefore different from the aCL found in autoimmune diseases, such as systemic lupus erythematosus.
Comparison of the behavior of normal factor IX and the factor IX BM variant hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources
Authors: Lefkowitz Jerry B. , Monroe Dougald M. , Kasper Carol K. , Roberts Harold R.
Published: February 2007

A subset of hemophilia B patients have a prolonged bovine‐brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor × present in the sample. The prothrombin time changed as much as 20 seconds when the factor × concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor × concentrations are known.
Four years' experience with the treatment of all‐trans retinoic acid in acute promyelocytic leukemia
Authors: Wu Xingzhong , Wang Xuewen , Qien Xiaoping , Liu Hainin , Ying Jianshang , Yang Zhicheng , Yao Haiqien
Published: February 2007

A retrospective analysis was done on 43 patients with acute promyelocytic leukemia (APL) at our hospital from June 1987 to August 1992. All‐trans retinoic acid was used to induce these patients to differentiation. In the early period of induction there were risks of severe hemorrhage, which was the main cause of early death. Treatments combined with platelets and heparin or aminomethylbenzoic (PAMBA) were given to patients with abnormal coagulation. As a result only 4 out of 43 patients died of intracranial bleeding at 4–12 days when their white blood cell (WBC) counts peaked. The combination of retinoic acid (RA) and HA chemotherapy could reduce hyperleukocytosis during the RA induction course. None of 7 patients died at early stage with this treatment combination. Our studies showed that it could predict the onset of remission at early stage through observations on the successive changes of karyotypes and morphology of the bone marrow and peripheral blood cells. Our studies also showed that the growth of CFU‐F could be inhibited by RA. We think that it may play a role in the RA‐induced differentiation. In 4 years of follow‐up the overall leukemia‐free survival (LFS) was 80% with a relapse rate of 45%. Thirty‐five patients out of 43 cases were still alive in remission, and one was alive in relapse. All 11 out of 43 patients relapsed within 3 years, but the relapses occurred later, after 3 years duration of remission (P < .01). Retinoic acid failed to induce 5 patients who relapsed with the continuation treatment of RA and chemotherapy alternatively. In order to overcome the resistance to RA, the continuation treatment of simple chemotherapy had been administered following CR. Two cases achieved remission in this way. The difference of resistant events to RA reached significance between these 2 groups of different continuation treatment.
In vivo antimalarial action of a lipophilic iron (III) chelator: Suppression of plasmodium vinckei infection by reversed siderophore
Authors: Lytton Simon D. , Loyevsky Mark , Mester Brenda , Libman Jacqueline , Landau Irene , Shanzer Abraham , Cabantchik Z. Ioav
Published: February 2007

We assessed in vivo antimalarial action of a lipophilic iron (III) chelator belonging to a new synthetic family of biomimetic siderophores previously termed reversed siderophores (RSFs). The family member, RSF ileum2, was chosen for its high membrane permeability and fast irreversible inhibition of human malaria parasite growth in vitro. [Shanzer A, et al., Proc Natl Acad Sci USA 88:6585, 1991 and Lytton SD, et al., Blood 81:214, 1993]. The lipophilic drug was administered to Swiss mice by subcutaneous route in fractionated coconut oil at a dosage of 0.37 g/kg every 8 hr with no adverse reactions observed. After 3–4 injections demonstrable suppression of Plasmodium vinckei petteri infection was observed and an additional 3–4 injections resulted in 2–3‐fold lower parasitemia with prolonged survival time over sham‐injected control mice.
Dipyridamole enhancement of drug sensitivity in acute lymphoblastic leukemia cells
Authors: Sotomatsu Manabu , Yugami Shin‐Ichirou , Shitara Toshiji , Kuroume Takayoshi
Published: February 2007

The effect of dipyridamole (DPM) on cell sensitivity to anticancer drugs was examined in acute lymphoblastic leukemia (ALL) cell lines. We established two ALL cell lines (KMO‐90 and KMO‐R) from bone marrow samples of a 12‐year‐old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed that KMO‐R was about twofold more resistant to doxorubicin (DOX), mitxantrone (MIT), vincristine (VCR), and etoposide (VP‐16) than was KMO‐90. Considering that both KMO‐90 and KMO‐R were established from a patient with ALL at the time of presentation and relapse, respectively, these two cell lines might be novel and useful models for research into the acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO‐90 was about 6% at 1 μg/ml, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP‐16 at this concentration. Cytotoxicity of DPM in KMO‐R was less than 5% at 1,5, and 10 μgg/ml. In KMO‐R, DPM enhanced cell sensitivity to these four drugs in a dose‐dependent manner. The plasma concentrations achieved by oral administration of DPM is about 1 μg/ml. At clinically achievable concentrations, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP‐16 in both KMO‐90 and KMO‐R, thus showing DPM to be a useful agent for potentiating anticancer chemotherapy of hematopoietic malignancy.
Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative disorders
Authors: Batata Ai , Shen Bo
Published: February 2007

Cell suspensions from the peripheral blood of B‐chronic lymphoid leukemias (B‐CLL, n = 274) and reactive lymphocytosis (RLC, n = 132) and from solid tissue samples of B‐non‐Hodgkin's lymphoma (B‐NHL, n = 466) and reactive lymphadenopathy (RLA, n = 324) were analyzed to evaluate the diagnostic value of clonality of L‐ and H‐ chains in B‐CLL and B‐NHL. Cutoff levels for monoclonal L‐chain (mono‐L) and monoclonal H‐chain (mono‐H) were defined. In B‐CLL, the association patterns of L‐ and H‐ chains were as follows: mono‐L/mono‐H, 245 cases (89.42%); mono‐L/polyclonal H chain (poly‐H), 4 (1.46%); polyclonal L chain (poly‐L)/mono‐H, 2 (0.73%); poly‐L/poly‐H, 2 (0.73%); undetected (und) ‐L/mono‐H, 6 (2.19%); and und‐L/und‐H, 15 (5.47%). In B‐NHL, the association patterns were mono‐L/mono‐H, 433 cases (92.92%); mono‐L/poly‐H, 4 (0.86%); poly‐L/ mono‐H, 8 (1.72%); poly‐L/poly‐H, 2 (0.43%); und‐L/mono‐H, 4 (0.86%); and und‐Lund‐H, 15 (3.22%). Monoclonality of H chains are complementary to L‐chain restriction, especially in the cases with poly‐L or und‐L, and should be considered as a positive criterion in determining surface immunoglobulin (Slg) clonality. Monoclonality of Slg assessed by both L and H chains is both sensitive and specific for the diagnosis of B‐CLL and B‐NHL, and their differentiation from RLC and RLA, since none of the cases of RLC and RLA showed monoclonal Slg.
Prevalence of pyruvate kinase deficiency among the chinese: Determination by the quantitative assay
Authors: Feng Chi‐Shun , Tsang Sophia S. , Mak Ying‐Tat
Published: February 2007

The prevalence of pyruvate kinase (PK) deficiency among the Chinese population has not been established. Fung et al. (Arch Dis Child 44:373–376, 1969) and Wu et al. (Am J Hematol 20:139–144, 1985) indicate 3.4% and 2.1% PK deficiency prevalence rates, respectively, the higher figure based on Beutler's screening test [3] without confirmatory testing. Neither figure is consistent with the occurrence of hemolytic anemia from this cause in the experiences of hematologists in Hong Kong. Using the standard quantitative assay, we measured PK activity in blood samples from 1,100 local Chinese people. The assay was automated on a centrifugal analyzer, and the results were expressed in IU per gram of hemoglobin (IU/g Hb). Blood samples from 497 healthy male adults were measured, and PK activity was found to have a range of 15.2 ± 5.2 (mean ± 2 SD). A total of 100 cord blood samples were also measured, and the reference interval for this subgroup was 17.7 ± 4.8. Additionally, samples from 503 anaemic patients were measured, and all were found to have values above the lower limit of the reference interval. The prevalence of PK deficiency among the Hong Kong Chinese population determined by this study was < 0.1%.
Variation in DNA content of immature normal bone marrow cells
Authors: Widell S. , Auer G. , Hast R. , Reizenstein P.
Published: February 2007

A variability in DNA content detected was found with image cytometry, in immature bone marrow cells from 13 healthy donors (median age 31 yr). The mean coefficient of variation (C.V.) of the DNA content was found to be significantly (P = 0.0002) higher in immature blasts and promyelocytes than in mature granulocytes, lymphocytes, and monocytes. The finding was not due to high DNA contents secondary to DNA‐synthesis in immature cells, since the percentage of such cells with a reduced DNA content was also significantly (P = 0.0424‐0.0002) increased. The error of the method expressed as the variance of multiple measurements has been found to be 0.0002‐0.0004. A staining error has been found for some hydrolysis times, but not for times between 60 and 120 minutes. A measuring error was found for an average of 1.38 to 3.38% of the cells.
DDAVP in acquired hemophilia a: Case report and review of the literature
Authors: Mudad Raja , Kane William H.
Published: February 2007

One patient with an acquired factor VIII inhibitor is reported in which an acute lower intestinal hemorrhage was successfully managed using Desmopressin (DDAVP). The patient initially had a factor VIII level of 10% with a inhibitor titer of 1.9 Bethesda units. Following administration of DDAVP the factor VIII level rose to 86% and there was a decrease in the number and volume of bloody stools. The inhibitor disappeared following treatment with corticosteroids, however the patient ultimately expired due to complications of ischemic colitis. This case and 21 previously reported cases of acquired hemophilia treated with DDAVP are reviewed. The data support a role for DDAVP in the treatment of non life threatening hemorrhage in patients with acquired hemophilia and low titer factor VIII inhibitors (<5 Bethesda units or factor VIII≧5%).
Observation of serum estradiol testosterone and immune function in aplastic anemia
Authors: Cao Qingxue , Liu Jianbin
Published: February 2007

Letters and correspondence submitted for possible publication must be identified as such. Text length must not exceed 500 words and five bibliographic references. A single concise figure or table may be included if it is essential to support the communication. Letters not typed double‐spaced will not be considered for publication. Letters not meeting these specifications will not be returned to authors. Letters to the Editor are utilized to communicate a single novel observation or finding. Correspondence is to be used to supplement or constructively comment on the contents of a publication in the journal and cannot exceed the restrictions for Letters to the Editor. The Editor reserves the right to shorten text, delete objectional comments and make other changes to comply with the style of the journal. Permission for publication must be appended as a postscript. Submissions must be sent to Marcel E. Conrad, M.D., Associate Editor, American Journal of Hematology, USA Cancer Center, Mobile, Alabama 36688 to permit rapid consideration for publication.
Consequences of chronic hepatitis C: A review article for the hematologist
Authors: Aledort Louis M.
Published: February 2007

The hepatitis C virus (HCV) has been cloned, and assays capable of detecting antibody to HCV recombinant proteins (anti‐HCV) have been developed. Concurrent with the cloning and development of the anti‐HCV screening tests, trials with interferon alfa‐2b have documented biochemical and histologic improvement in the indices of hepatitis C and non‐A, non‐B (NANB) in patients who were chronically infected. Subsequently, the anti‐HCV assays and interferon alfa‐2b have become clinically available. These new detection and treatment modalities can now be used in the management of hemophilics and other chronically transfused patients who bear great risk for blood‐borne infections and manifest signs of chronic hepatitis. © 1993 Wiley‐Liss, Inc.
Hemolytic uremic syndrome developing during remission of acute myelomonocytic leukemia
Authors: Okumura Hirokazu , Nakamura Shinobu , Ohtake Shigeki , Yoshida Takashi , Kobayashi Kazumi , Okabe Yohko , Matano Sadaya , Kyohda Katsunori , Matsuda Tamotsu
Published: February 2007

A 47‐year‐old woman was diagnosed with acute myelomonocytic leukemia (AMMoL) and was treated with combination chemotherapy. After one cycle of remission induction therapy, she entered into complete remission and then received three cycles of consolidation therapy. A month after the last consolidation therapy, she was diagnosed with having the complication of chemotherapy‐related HUS (C‐HUS). The C‐HUS improved after initiation of plasma exchange and antiplatelet therapy. In the present case, it seems that the antileukemic agents might play an important role in the development of C‐HUS. © 1993 Wiley‐Liss, Inc.
Dapsone for autoimmune thrombocytopenic purpura
Authors: Godeau Bertrand , Oksenhendler Eric , Bierling Philippe
Published: February 2007

Twenty‐one human immunodeficiency virus (HIV)‐free and six HIV‐infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 × 109/L, range 3–49; after 109 × 109/L, range 69–241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP. © 1993 Wiley‐Liss, Inc.
Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia
Authors: Wada Hideo , Mori Yoshitaka , Kaneko Toshihiro , Wakita Yoshihiro , Nakase Tutomu , Minamikawa Kouzou , Ohiwa Michiaki , Tamaki Shigehisa , Tanigawa Motoaki , Kageyama Sinichi , Deguchi Katsumi , Nakano Takeshi , Shirakawa Shigeru , Suzuki Koji
Published: February 2007

Hypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue‐type plasminogen activator, plasminogen activator inhibitor‐l (PAl‐l), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin‐antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAl‐I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI‐I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non‐IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis. © 1993 Wiley‐Liss, Inc.
Combined hereditary factor XI (plasma thromboplastin antecedent) deficiency, von Willebrand's disease, and xeroderma pigmentosum in a Japanese family
Authors: Sano Masayuki , Saito Hidehiko , Shimamoto Yoshinori , Sugiura Isamu , Ohtsubo Haruhiko , Kohda Hiromu , Yamaguchi Masaya
Published: February 2007

We report a 28‐year‐old‐Japanese male who had a skin tumor derived from variant type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag) were remarkably decreased (<0.01 U/ml, <0.02 U/ml, respectively). Factor VIII (FVIII) clotting activity, von Wiliebrand factor antigen (vWf :Ag), and ristocetin cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin‐induced platelet agglutination (RIPA) revealed hyper‐aggregation compared with a normal control. Multimeric composition of vWf in plasma showed a reduction in high molecular weight forms. The family study revealed two other subjects with ho‐mozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous FXI deficiency. The relationship between FXI deficiency and vWd is discussed and previously reported cases are reviewed. © 1993 Wiley‐Liss, Inc.
Inversion of chromosome 16 and eosinophilia in refractory anemia with ring sideroblasts: Report of a case
Authors: Inaba Tohru , Shimazaki Chihiro , Inaba Eiko , Hirata Toshiyuki , Ashihara Eishi , Ohkawa Katsunori , Oku Naritoshi , Goto Hideo , Murakami Satoshi , Fujita Naohisa , Misawa Shinichi , Nakagawa Masao
Published: February 2007

A 72‐year‐old male who was admitted to our hospital with severe anemia was diagnosed as refractory anemia with ring sideroblasts (RARS), according to the French‐American‐British (FAB) classification of myelodysplastic syndromes (MDS). The patient showed persistent eosinophilia with no definite signs of either allergy or a parasitic infection. Chromosomal analysis of bone marrow cells revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia (AML) in the FAB classification.

This patient didn't exhibit leukemic transformation during his 20‐month clinical course, nor was any found at autopsy. Therefore, this is the first case of RARS to speculate that the chromosomal characteristic inv(16)(p13q22) might be specific for eosinophilia rather than AML. © 1993 Wiley‐Liss, Inc.
Characterization of nondeletion α‐thalassemia mutations in the Greek population
Authors: Traeger‐Synodinos Joanne , Kanavakis Emmanuel , Tzetis Maria , Kattamis Antonios , Kattamis Christos
Published: February 2007

α‐Thalassemia is usually due to deletions within the α‐globin gene cluster, leading to loss of function of one (‐α) or both [‐(α) or –] α‐globin genes. Nondeletion mutations (denoted ααT or αTα) are less frequent and in Greece are not well defined. We report the analysis of 16 nondeletion α‐thalassemia chromosomes using a polymerase chain reaction method to amplify specifically the α2‐globin gene, which was subsequently screened using ASO hybridization or restriction enzyme analysis for four mutations already characterized in other Mediterranean and Middle Eastern populations. Of the 16 nondeletion chromosomes, nine had the polyadenylation signal mutation (αPolyAα), two the IVSI 5′ pentanucleotide deletion (αHphα), two the Hb Icaria mutation (αicα), and one the initiation codon mutation (αNcoα). In two, the defects are still undefined. These findings show that nondeletion α‐thalassemia in Greece is heterogeneous and that the most frequent mutation (accounting for >50%) is the polyadenylation signal mutation, which to date was most commonly found in the Saudi Arabian population. © 1993 Wiley‐Liss, Inc.
Graft versus host anti‐Rho(D) following minor Rh‐incompatible orthotopic liver transplantation
Authors: Lee Jong‐Hoon , Mintz Paul D.
Published: February 2007

Hemolysis caused by ABO antibodies after ABO‐compatible, nonidentical solid organ transplantation has been previously reported. The passenger B lymphocytes within the donor organ presumably generate an acute, primarily red cell‐directed graft vs. host (GVH) response. Graft survival may also be compromised. GVH Rh antibodies have also been described, primarily in renal transplants. Only three cases, two only in abstract form, have been reported thus far describing GVH Rh antibodies in liver transplant patients, to which we add a fourth. A 62‐year‐old blood group A Rho(D)‐positive woman with cirrhosis underwent orthotopic liver transplantation from a group A Rho(D)‐negative, previously Rho(D)‐sensitized donor and subsequently developed acute, self‐limited hemolysis requiring four units of packed red cells. Anti‐Rho(D) was identified in both serum and red cell eluate. An antibody detection test, identification, and assessment of the antibody reactivity score from the pretransplant donor specimen may identify patients at risk for hemolysis due to GVH Rh antibodies. © 1993 Wiley‐Liss, Inc.
Human parvovirus B19 infection in bone marrow transplantation patients
Authors: Azzi A. , Fanci R. , Ciappi S. , Zakrzewska K. , Bosi A.
Published: February 2007

We report the results of a survey of parvovirus B19 infection carried out with the aim to evaluate the frequency and the role of this infection in bone marrow transplant (BMT) recipients, as it is known that B19 virus can persist in clinical circumstances of immunodeficiency. Fifty‐one patients subjected to BMT in the Bone Marrow Transplantation Center of Florence were enrolled in this study. Immunological and virological indications of B19 infection were tested weekly during the stay in hospital. A high rate of seroconversion or B19 antibody rise was observed, but, in absence of B19 IgM or B19 DNA presence, this result seems to be attributable to a passive immunization, rather than to a recent viral infection. In these 51 patients, as well as in 59 others not included in this study, clinical manifestations imputable to B19 infection have never been observed. It is possible that the isolation measures and the intravenous immunoglobulins (IVIG) administration may contribute in preventing B19 infection in the BMT recipients at least until the hospital discharge. © 1993 Wiley‐Liss, Inc.
Hypofibrinolysis in patients with hypercoagulability: The roles of urokinase and of plasminogen activator inhibitor
Authors: Lau Herbert K. F. , Teitel Jerome M. , Cheung To , Kung Sam K. P. , Garvey M. Bernadette
Published: February 2007

The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI‐1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI‐1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI‐1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI‐1 activity but also by reduced total uPA concentration. © 1993 Wiley‐Liss, Inc.
Hemolytic anemia associated with lead poisoning from shotgun pellets and the response to succimer treatment
Authors: Aly Mahmoud H. , Kim Hugh C. , Renner Stephen W. , Boyarsky Andrew , Kosmin Martin , Paglia Donald E.
Published: February 2007

Symptomatic lead poisoning with severe hemolytic anemia was observed in a patient with retained shot gun pellets. Surgical resection of the retained pellets and the use of a newer chelating agent, Succimer (2,3‐dimercaptosuccinic acid) successfully lowered blood lead level. Hemolytic anemia was associated with deficient erythrocyte pyrimidine 5′‐nucleotidase, and lowering of the lead level corrected the deficiency, suggesting that the enzyme deficiency is responsible for the hemolysis associated with lead poisoning. This case illustrates that retained lead pellets from shotgun wounds can cause severe lead poisoning. © 1993 Wiley‐Liss, Inc.
Polymorphic pattern of the (AT)x(T)y motif at −530 5′ to the β‐globin gene in over 40 patients homozygous for various β‐thalassemia mutations
Authors: Dimovski A. J. , Adekile A. D. , Divoky V. , Baysal E. , Huisman T. H. J.
Published: February 2007

Nucieotlde sequence analysis of the 5′ β‐globin gene flanking region has been carried out for numerous homozygous β‐thalassemla patients with difterent mutations and of various ethnic backgrounds. Four different rearrangements were found associated with numerous β‐thalassemia mutations. The (AT)x(T)y repeat motif at ‐530 showed polymorphic patterns among these patients as follows: All ten IVS‐II‐1 (G→A) chromosomes and the two with the ‐87 (C→G) mutation are associated with the (AT)9(T)5 rearrangement, while the 30 IVS‐I‐6 (T→C), the 16 codon 39 (C→T), the slx codon 8 (‐AA) chromosomes, and 12 chromosomes with different promoter mutations had the (AT)7(T)7 motif. Six chromosomes with the promoter mutation at position − 29 (A→ G) had the (AT)6(T)6 motif, while an (AT)5(T)4 motif appears characteristic for two IVS‐I‐5 (G→A and G→T). No direct association between any of the (AT)x(T)y arrangements and an increased γ gene expression [gγ and fetal hemoglobin (Hb F)] levels could be demonstrated, suggesting that variations In the (AT)x(T)y motif are common polymorphisms. © 1994 Wiley‐Liss, Inc.
Cytokine profile during high‐dose rhG‐CSF therapy in severe congenital neutropenia
Authors: Shitara Toshiji , Yugami Shin‐Ichiroh , Ijima Hiroko , Sotomatu Manabu , Kuroume Takayoshi
Published: February 2007

The effect of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) on cytokine profile was evaluated in a case of severe congenital neutropenia. The plasma levels of cytokines were measured before and during rhG‐CSF therapy. These included G‐CSF, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin‐1α, in‐terleukin‐1 β, interleukin‐2 (IL‐2), interleukin‐3 (IL‐3), interleukin‐4, interleukin‐6 (IL‐6), and tumor necrosis factor‐α. Soluble Interleukin‐2 receptor (sIL‐2R) was measured serially during rhG‐CSF therapy. Lymphocyte subpopulations Including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were also measured, rhG‐CSF was administered once daily as a 30‐min infusion. The patient was treated with Increasing dose levels of 100,200,400, 800, and 1,600 μg/m2/day. The level of endogenous G‐CSF was elevated to 334 pg/ml before treatment and GM‐CSF, IL‐2, IL‐3, and IL‐6 were slightly elevated. Clinically, he showed a moderate response to a high dose of rhG‐CSF (1,600 μg/m2/day). Plasma levels of G‐CSF markedly Increased during therapy but plasma levels of other cytokines did not show significant changes during therapy and iymphocyte subpopulations did not significantly change. A drastic Increase in siL‐2R expression was observed after rhG‐CSF infusion and an Increase in siL‐2R expression occurred even before a major increase in granulocyte counts. These results showed that a high dose rhG‐CSF therapy may influence the cytokine network as judged by the increased slL‐2R expression. © 1994 Wiley‐Liss, Inc.
Autoimmune‐thrombocytopenia and sle in a patient with 5q‐anomaly and deletion of the c‐fms oncogene
Authors: Jaeger Ulrich , Panzer Simon , Bartram Claus , Haas Oskar , Volc‐Platzer Beatrix , Graninger Wolfgang , Geissler Klaus , Radaszkiewicz Thaddaeusz , Lechner Klaus
Published: February 2007

Autoimmune‐thrombocytopenia was the striking feature in a patient with typical clinical symptoms of systemic lupus erythematosus (SLE), complement C4 deficiency, and positive lupus serology. However, myelodysplasia was found in the bone marrow and chromosome analysis revealed a deletion of the long arm of chromosome 5 (5q‐ anomaly), which was confirmed by a hemitygosity for the c‐fms oncogene (CSF‐1‐receptor) on Southern blot. Autoimmune phenomena reported In conjunction with myelodysplastic syndromes (MDS), e.g., an elevation of antinuclear antibodies, are usually regarded as nonspecific. This case report suggests that SLE can occur in patients with MDS and that a concomitant autoimmune‐thrombocytopenia may mask the typical signs of the 5q‐ syndrome. © 1994 Wiley‐Liss, Inc.
Laboratory monitoring of warfarin therapy in Utah
Authors: Garr Susan B. , Rodgers George M.
Published: February 2007

Accurate laboratory monitoring of oral anticoagulation has been emphasized as an important factor in providing safe and effective therapy for patients with thromboembolism. However, recent reports indicate that coagulation laboratories may not be providing optimal clinical information to clinicians who treat these patients. We surveyed all hospltal coagulation laboratories in Utah to determine their format for reporting prothrombin time results in patients receiving oral anticoagulants. We found that less than 50% of laboratories used the reliable reporting format, i.e., the interational Normalized Ratio (INR), and that many of the laboratories using the INR format may be reporting incorrect values. Our survey also found a significant lack of interest by physicians in requesting that their laboratories adopt reliable reporting methods. These results indicate a substantial lack of understanding by laboratories and clinicians of the importance of using reliable methods to monitor oral anticoagulation. Significant educational efforts will be required to correct this problem. © 1994 Wiley‐Liss, Inc.
Transgenic mouse model of pharmacologic induction of fetal hemoglobin: Studies using a new ribonucleotide reductase inhibitor, didox
Authors: Pace B. S. , Elford H. L. , Stamatoyannopoulos G.
Published: February 2007

Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing γ globin induction in response to a new rlbonucleotide reductase inhibitor, Didox. A transgenic mouse line carrying the human Aγ gene linked to a locus control region cassette was used. Treatment of transgenic mice with Didox resulted in induction of γ gene expression as documented by an Increase in F reticulocytes and F cells and an elevation of γ/γ + β biosynthetic ratio. Similarly, administration of Didox to a baboon in the nonanemic and chronically anemic state resulted In induction of γ gene expression as shown by increases in F reticuiocytes, F cells, and Hb F. These results suggest that the μLR‐Aγ transgenic mice can be used to screen new pharmacologic compounds for γ globin inducibillty. © 1994 Wiley‐Liss, Inc.
CD21 antigen in T‐lineage neoplastic lymphoid cells: Characteristic expression at thymic stage
Authors: Tatsumi Eiji , Yoneda Noriko , Kawano Seiji , Yamaguchi Nobuo
Published: February 2007

The expression of CD21 antigen, a receptor for the C3d fragment of complement and Epstein‐Barr vlrus (EBV), was Investigated in a total of 85 cases of neoplastic lymphoid cells Including 39 cases of T‐lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL), although CD21 antigen is usually regarded as a pan‐B antigen. The CD21 antigen was expressed by one of the eight cases of neoplastic lymphoid cells expressing the CD7 antigen as a sole pan‐T antigen, by three of the 20 cases of pro‐ or early thymic stage (CD7+ CD5+ CD2‐, CD7+ CD5‐ CD2+, or CD7+ CD5+ CD2+), and ten of 11 cases of thymic stage (CD3r CD4+ CD8+), but not by one case of late thymic stage (CD3 ± CD4+ CD8‐) T‐ALULBL cells. The CD21 antigen was not expressed by any of the 11 cases of adult T‐cell leukemia (ATL) or two cases of chronic T‐lineage leukemia. At most 4% of the normal thymocytes obtained from seven infants or children expressed the CD21 antlgen. While only a very limited population of normal thymocytes expresses CD21 antigen, T‐ALL/LBL cells at the thymic stage characteristically express CD21 antigen in contrast to pro‐ or early thymic ALL/LBL or peripheral‐stage neoplastic T cells. The estimation of the expression of CD21 antigen is useful for delineating stages of differentiation in T‐ALL/LBL. Furthermore, these observation are notable, considering the possibiilty that the reported EBV‐carrying T‐cell lymphomas result from the penetration of EBV into EBV‐negative neoplastic T cells. © 1994 Wiley‐Liss, Inc.
Expression, of the thrombospondin receptor (CD36) on the cell surface in megakaryoblastic and promegakaryocytic leukemias: Increment of the receptor by megakaryocyte differentiation in vitro
Authors: Imamura Nobutaka , Ota Hiromi , Abe Kazuhiro , Kuramoto Atsushi
Published: February 2007

In this report we describe four cases of acute megakaryocytic leukemia demonstrated by the presence of megakaryocyteplatelet‐related cell‐surface antigens. These were detected utilizing flow cytometry and monoclonal antibodies in addition to both platelet peroxidase activity, which was shown by ultrastractural cytochemistry, and emergence of differentiation antigens, while culturing these leukemic cells. The blasts of one patient possessed both platelet Gplb and Gpllb/llla cell‐surface antigens detected by AN51(CD42b), J15, P2, and HPL2(CD41), respectively, whereas the remaining three patients almost completely lacked Gplb cell‐surface antigen. Hence the former were diagnosed as immature(pro)megakaryocytic leukemia and the latter as acute megakaryoblastic leukemia from the viewpoint of immunophenotypic analysis. While we cultured these leukemic cells in conditioned medlum prepared from phytohemagglutinin‐stimulated leukocytes and interleukin 3, expression of CD36(OKM5) antigen (thrombospondin receptor) increased gradually according to the differentiation and maturation of these cells. Finally, all leukemic cells differentiated to mature megakaryocytes. The function of CD36 on these cells remains to be elucidated. © 1994 Wiley‐Liss, Inc.
Reversible encephalopathy after cryopreserved peripheral blood stem cell infusion
Authors: Dhodapkar Madhav , Goldberg Stuart L. , Tefferi Ayalew , Gertz Morse A.
Published: February 2007

We report two patients who experienced severe reversible encephalopathy following infusion of peripheral blood stem cells cryopreserved in 10% dimethylsulfoxide (DMSO). In one patient, reduction of DMSO level with plasmapheresis resulted in marked improvement in encephalopathy. Infusion of large volumes of cryopreserved stem cells may result in a signiflcant toxlc reaction. Plasmapheresis may be a treatment option for patients with significant toxicity related to DMSO. © 1994 Wiley‐Liss, Inc.
Detection of PML‐retinoic acid receptor‐α fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17)
Authors: Ikeda Kazuma , Sasaki Kazunori , Tasaka Taizo , Nagai Masami , Kawanishi Koichi , Takahara Jiro , Irino Shozo
Published: February 2007

Chromosome translocation t(15;17), the breakpoints of which are in the PML gene on chromosome 15 and retinoic acid receptor‐α (RARα) gene on chromosome 17, is specifically found in acute promyelocytlc leukemia (APL). Clinically typical APL without t(15;17) and with the PML‐RARα fusion transcripts or rearrangements in PML and/or RARα gene has been reported, suggesting submicroscopic changes at the molecular level without apparent t(15;17) or observation of normal metaphases. Trisomy 8 is common in APL as a secondary chromosomal abnormality in addition to t(15;17), as well as in acute myelogenous leukemia in general, but it is rare as a sole chromosomal anomaly in APL. PML‐RARα fusion transcript was detected in an APL case with trisomy 8 but without t(15;17), indicating that the leukemic cells lacked t(15;17) and still expressed the PML‐RARα fusion transcripts. This indicates that the same submicroscopic molecular changes as in APL with t(15;17) do occur in APL without t(15;17) and supports the use of molecular analysis for PML‐RARα fusion in APL. © 1994 Wiley‐Liss, Inc.
Malignant histiocytosis associated with autoimmune thrombocytopenia
Authors: Ohno Tatsuharu , Sugiyama Tateo , Furukawa Hiroo , Ishibashi Takafumi , Okuma Minoru
Published: February 2007

We describe a patient with malignant histlocytosis whose serum contained an autoantlbody against platelet protein. The patient was admitted because of nasal bleeding and high‐grade fever. The clinical course was fulminantly progressive and terminated with cerebral hemorrhage. Bone marrow aspirate showed the proliferation of large atypical cells, some of which exhibited phagocytic activity. At postmortem examination, there was diffuse infiltration of these atypical cells In the liver, spleen, kidney, and bone marrow. Morphological, cytochemlcal, immunohistochemlcal, and genotypic characteristics suggested that the proliferating cells were derived from the monocyte‐rnacrophage system. Western blot analysis revealed the presence of autoantibody against an ∼88 kd molecule of platelet proteins. Although the relationship of cause and effect remains to be clarified, this autoantibody appeared to have stimulated thrombophagocytosls of the neoplastic cells. © 1994 Wiley‐Liss, Inc.
Mild β+(−87)‐thalassemia CACCC box mutation is associated with elevated fetal hemoglobin expression in cis
Authors: Gilman John G. , Manca Laura , Frogheri Laura , Pistidda Paola , Guiso Luciana , Longinotti Maurizio , Masala Bruno
Published: February 2007

The β°‐thalassemia codon 39 nonsense mutation predominant in Sardinia is severe, and homozygotes are transfusion dependent. Two‐thirds of β° 39 alleles are linked to AγT (haplotype II). Onefourth are linked to AγI (haplotypes I and IX), as is the mild β+‐thalassemia −87 C→G mutation (haplotype VIII). β+/β°‐Thalassemla VIII/II compound heterozygotes have Significantly higher AγI:AγT (23:7) than β°‐thalassemia I/II (24:20) or IX/II (16:17) cases. This suggests that the β+ −87 mutation is associated with elevated γ expression in cis, which may contribute to the lack of transfusion‐dependence in β+/β° Cases. © 1994 Wiley‐Liss, Inc.
Alpha thalassemia and stroke risk in sickle cell anemia
Authors: Adams Robert J. , Kutlar Abdullah , McKie Virgil , Carl Elizabeth , Nichols Fenwick T. , Liu Jin Cal , McKie Kathleen , Clary Anthony
Published: February 2007

In an effort to identify possible risk factors for stroke in Sickle Cell Anemia (Hb SS), we analyzed the distribution of alpha‐globin gene deletions in a group of Hb SS patients with and without stroke. The group with stroke consisted of 44 patients, (27 male, 17 female) with a mean of 7.5 years at time of stroke. The control group (non‐stroke) had 256 Hb SS patients (126 male, 130 female) with a mean age of 7.7 years. There were 9 patients with heterozygous α‐thalassemia in the stroke group (20.5%). In the control group, there were 93 patients with heterozygous α‐thalassemia and 5 with homozygous α‐thalassemia. The incidence of α‐thalassemia in Hb SS patients without stroke (38%) was comparable to that reported for the African‐American population in general. The incidence in the stroke population (20.5%) was significantly lower (P = 0.02) These results indicate that α‐thalassemia is associated with a lower risk of stroke in Hb SS. This observation should be confirmed in studies involving larger numbers of patients. Possible protective effects of α‐thaiassemia are unknown but may be related to decreased hemolysis and more favorable rheologlc properties of red blood cells. © 1994 Wiley‐Liss, Inc.
Serum transferrin receptor in hereditary hemochromatosis and African siderosis
Authors: Baynes Roy D. , Cook James D. , Bothwell Thomas H. , Friedman Brian M. , Meyer Theo E.
Published: February 2007

The present investigation evaluated the serum transferrin receptor concentration in subjects with nontransfusional iron overload who were identified in two separate studies on the basis of a serum ferritin level above 400 μg/L. Subjects with preciinical hereditary hemochromatosis were evaluated in the first study and those with the African form of iron overload in the second. in the first study, hereditary hemochromatosis was identified in 14 white men on the basis of a persistent elevation in transferrin saturation above 55%. The serum receptor concentration was elevated above the upper cut‐off of 8.5 mg/L in two of the subjects, but the mean receptor of 6.1 ± 1.4 mg/L (mean ± 2 SE) did not differ significantly from the normal mean for this assay of 5.6 ± 0.3 mg/L. In the same study, 60 control subjects with secondary iron overload were identified on the basis of a serum ferritin persistently above 400 μg/L, with a normal serum C‐reactive protein concentration but with a transferrin saturation <55%. Three of these subjects had an elevated serum receptor concentration but the mean value of 5.5 ± 0.4 mg/L did not differ from normals nor from subjects with hemochromatosis. In the second study, 49 black Africans with iron overload were divided into those with or without an elevated transferrin saturation. The mean serum receptor concentration of 5.0 ± 0.8 mg/L and 4.5 ± 0.4 mg/L, respectively, did not differ statistically. It was concluded that there is no evidence of generalized dysreguiation of the transferrin receptor in hemochromatosis or African siderosis. © 1994 Wiley‐Liss, Inc.
Thrombotic microangiopathy and retroviral infections: A 13‐year experience
Authors: Ucar Antonio , Fernandez Hugo F. , Byrnes John J. , Lian Eric C‐Y , Harrington William J.
Published: February 2007

Eleven of fifty serum samples collected from patients with a diagnosis of thrombotic microangiopathy (TMA), from 1979 to 1991, tested positive for antlretroviral antibodies. Seven had human immunodeficiency virus (HIV) infection, and four had human iymphotrophic virus, type I (HTLV‐I) infection. All patients were treated with plasma exchange and for infusion, but only two of the HIV‐infected patlents obtained a complete response (CR) and one of them died after a few months. Combined results from the ilterature indicate that most patients with HIV infection survive less than one year from the initial diagnosis of TMA. In the setting of HIV infection, TMA Is a treatable condition, but survivai for most patients is less than 12 months. Three of the four HTLV‐I infected patients with TMA had a CR. These observations strongly suggest that both HIV and HTLV‐I infections are associated with TMA, but rigorous epidemiologic studies will be needed to determine the relative risk for each. Retrovirai Infections should be considered In patients with TMA, especially If the patient has associated risk factors and demographic characteristics. © 1994 Wiley‐Liss, Inc.
Studies on the platelet surface‐associated von Willebrand factor
Authors: Martin S. Eric , Johnson Margaret M. , Abel Robert F.
Published: February 2007

The contribution of platelets to the prevention and control of bleeding depends not only on the plasma and vessel wall yon Willebrand (vW) factor, but also on the vW factor originating from platelets. Although platelet vW factor is mainly stored in the α‐granules, small amounts of vW factor have been detected on the platelet surface under conditions without direct stimulation. This communication focuses on the small amount of vW factor associated with the surface of platelets.

EDTA‐washed platelets in a calcium‐free medium containing prostaglandin E1 (PGE1) were exposed to anti‐vW factor F(ab')2 fragments. The platelet‐associated anti‐vW factor antibodies were separated from the free fragments by gel chromatography. Normal platelets were compared to platelets from patients with Bernard Soulier syndrome, Glanzmann's thrombasthenia, and Hermansky‐Pudlak syndrome. These experiments showed that, in the absence of extracellular calcium, vW factor can be detected on the surface of washed platelets independent of glycoproteins lb and llb‐llla, and despite markedly reduced intracellular calcium content. This particular platelet surface expression of vW factor is probably the result of disturbing the platelet during the in vitro manipulation.

von Willebrand factor is an extremely important element in the multiple molecular interactions required to stop and anchor the platelet in areas of high flow rates. Mechanical perturbation of platelets leading to surface expression of the vW factor helps increase its availability for such critical interactions. © 1994 Wiley‐Liss, Inc.
Perioperative administration of a single dose of conjugated oestrogen to uraemic patients is ineffective in improving haemostasis
Authors: Jacobs Peter , Jacobson Jack , Kahn Delawir
Published: February 2007

The excessive bleeding that occurs in uraemic patients undergoing surgery is reported to be reversed by at least one schedule of prior oestrogen administration. To assess this possibility a single intravenous injection of 25 mg of the conjugated hormone was given to ten uraemic patients undergoing regular haemodialysis and randomly compared to eight matched patients who received only the diluent. Two hours later there was no reduction in bleeding time, improvement in platelet aggregation, nor an increase in plasma levels of factor VIII (VIII:C), von Willebrand factor (VWF:Ag), or the factor VIII‐related ristocetin cofactor state. Furthermore, there was no reduction in intraoperative blood loss, being a median of 558 ± 154 (range 225‐1, 260) mL in the test group and 412 ± 55 (range 270‐555) mL in the control and additional median postoperative portovac drainage was 123 ± 27 (range 0‐170) mL and 153 ± 41 (range 45‐240) mL, respectively. These findings differ from the shortening in bleeding time achieved by others with repeated administration of the same agent, and emphasize the importance of dose and duration of oestrogen therapy when used for this indication. © 1994 Wiley‐Liss, Inc.