bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple and rapid enzyme‐linked immunosorbent assay for the detection of hemoglobin C[α2β26(A3)Glu → Lys] in cord blood using a monoclonal antibody
Authors: Shyamala M. , Kiefer Charles R. , Moscoso Hugo , Garver Fred A.
Published: February 2007

We have generated a murine hybridoma that secretes a monoclonal antibody (mAb) that is highly specific for hemoglobin C (HbC) [α2ß26(A3)Glu→Lys] and shows no cross reactivity with HbA2, HbF2, HbS, HbE, or Hb O‐Arab. Using this antibody, we developed a simple and rapid enzyme linked immunosorbent assay (ELISA) technique for the detection of HbC in both adult and cord blood. The assay can be carried out using either whole blood samples or hemolysates. With as little as 10 μl/well of whole blood or 5 μg Hb/well of hemolysates, and, with dilutions of the antibody up to 10−5 we were able to detect HbC unequivocally in cord blood samples. The ELISA procedure could detect HbC in proportions as low as 0.01%. This simple diagnostic test represents a technological advance in Hb identification and can easily be used for mass screening (96 samples in less than 45 min) to detect HbC. Furthermore, this assay, when employed in conjunction with an mAb specific for β6GLU of HbA, allows the discrimination between HbC homozygotes, heterozygotes, and normals.
Apparent duplication of inv(3)(q21q26) in one of five cases with inv (3) in myelodysplastic syndromes and acute leukemia
Authors: Walter Thomas A. , Morgan Rodman , Ondreyco Sharon , Sandberg Avery A.
Published: February 2007

Rearrangements affecting the long arm of chromosome 3 have been linked to abnormalities of platelet production and morphology in hematologic disorders. We present five patients with myelodysplastic syndromes or acute leukemia in whom inv(3)(q21q26) was seen. One of the patients showed an inversion of both homologs involving precisely the same breakpoints, suggesting apparent duplication of the abnormal chromosome 3 and loss of the normal homolog. To our knowledge this is the first report detailing such a condition.
Enhanced botrocetin‐induced type iib von willebrand factor binding to platelet glycoprotein ib initiates hyperagglutination of normal platelets
Authors: Nishio K. , Fujimura Y. , Niinomi K. , Takahashi Y. , Yoshioka A. , Fukui H. , Usami Y. , Titani K. , Ruggeri Z. M. , Zimmerman T. S.
Published: February 2007

Botrocetin, a protein isolated from the venom of the snake Bothrops jararaca, induces platelet aggregation/agglutination by von Willebrand factor (vWF) binding to the membrane glycoprotein (GP) Ib, an action resembling that of ristocetin. However, some differences in the interaction between vWF and platelet GPIb induced by these two substances have been reported.

We have recently shown that the GPIb binding domain on the vWF molecule, in both instances, resides in the tryptic 52/48 kDa fragment extending from amino acid residue 449 to 728 of the constituent subunit. In the present report, we demonstrate that botrocetin does not induce agglutination of formalin‐fixed platelets from a patient with Bernard‐Soulier syndrome congenitally lacking GPIb and GPIX as well as GPV, a finding similar to that shown with ristocetin. A monoclonal antibody against GPIb (AP‐1) inhibits either ristocetin‐ or botrocetin‐dependent vWF binding to formalin‐fixed platelets from normal individuals. Therefore, botrocetin‐induced vWF binding to formalin‐fixed platelets may reflect the interaction between vWF and platelet GPIb. To strengthen this concept, we have now found that heightened botrocetin‐induced type IIB vWF binding to platelet GPIb causes hyperagglutination of normal platelets.
Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets
Authors: Antonucci Richard , Walker Richard , Herion John , Orringer Eugene
Published: February 2007

The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium‐containing buffer as when incubated in plasma. SS RBC suspended in autologous platelet‐rich plasma adhered to a greater extent than when suspended in autologous platelet poor plasma. Prostacyclin, thromboxane B2, and an inhibitor of collagen‐ and epinephrine‐induced platelet aggregation (B13.177) did not affect SS RBC adherence to endothelium. Aspirin in concentration of 5 μg/ml slightly decreased SS RBC adherence to endothelium in the presence of platelats may play a significant role in the increased adhesiveness of SS RBC to endothelium. To the extent that increasede SS RBC adhesiveness contributes to the genesis of painful crises and to the extent platelets augment this adhesiveness, agents affecting platelet function may prove useful in preventing painful crises.
Cyclosporin for treatment of life‐threatening alloimmunization
Authors: Tilly Hervé , Azagury Michael , Bastit Dominique , Lallemand Anne , Piguet Hubert
Published: February 2007

We describe a 16‐year‐old girl with aplastic anemia who, 1 year after initial diagnosis, developed a refractory state to platelet transfusions due to alloimmunication and resulting in severe bleeding. Treatment with cyclosporin, initially prescribed as treatment of the bone marrow failure, resulted in prompt decrease in lymphocytotoxic antibodies, which paralleled a marked improvement in platelet recovery. To our knowledge, such a dramatic effect of cyclosporin on alloimmunization has not been previously reported and merits further attention.
Anti‐leukemic potential of methyl‐cobalamin inactivation by nitrous oxide
Authors: Abels J. , Kroes A. C. M. , Ermens A. A. M. , Van Kapel J. , Schoester M. , Spijkers L. J. M. , Lindemans J.
Published: February 2007

Myelo‐cytotoxicity of extended nitrous oxide (N2O) inhalation was described almost forty years ago and then incidentally applied already with temporary success for suppressing leukemia. In 1948 the accompanying megaloblastic maturation arrest was explained by inactivation of the methylcobalamin coenzyme and subsequent folate deficiency. We studied the anti‐leukemic effect of N2O on a transplantable acute leukemia in B(rown) N(orway) rats. Progression of this B,N,M(yelocytic)L(eukemia) was measured as spleen and liver weights, and leukemic blood cell counts. The deoxyuridine (dU)‐suppression test provided in vitro indication of the functional folate activity of leukemic cells. Breathing of N2O‐oxygen considerably reduced but did not eradicate, BNML‐proliferation. Addition of anti‐metabolites, interfering with some enzyme in the folate metabolism beyond the methylcobalamin co‐enzyme dependent methionine synthase step, acted at least synergistically. The anti‐leukemic effect of cycloleucine, which reduces S‐adenosyl‐methionine synthesis by inactivation of methionine adenosyltransferase, was moderate but became much stronger with N2O inhalation. Methotrexate, a potent anti‐leukemic agent by inhibiting tetrahydrofolate (THF) generation through inactivation of di‐HF reductase, became highly anti‐BNML, even in low dosage when combined with or preceded by N2O. 5‐Fluorouracil, which inhibits methylene‐THF dependent thymidilate synthase, itself was surprisingly anti‐BNML, but also became much more potent with previous or concomittant N2O exposure. Preliminary dU‐suppression test results with human acute leukemia cells, exposed to N2O and/or folate antagonists in vitro, correlated well with the in vivo BNML‐experiments. Combining the anticobalamin activity of N2O with an anti‐folate therefore seems to be a promising chemotherapeutic approach.
Familial adult T‐cell leukemia/lymphoma
Authors: Ratner Lee , Heyden Nancy Vander , Paine Elizabeth , Frei‐Lahr Debra , Brown Randy , Petruska Paul , Reddy Satyanarayan , Lairmore Michael D.
Published: February 2007

Clinical and laboratory data are described for two siblings who both developed adult T‐cell leukemia/lymphoma resulting from infection by human T lymphotropic virus type I (HTLV‐I). These findings suggest that genetic factors or virus‐specific factors may determine which HTLV‐I‐infected individuals will develop leukemia.
Infant leukemia: An analysis of nine chinese patients
Authors: Chuu Wen‐Min , Tien Huei‐Fang , Lin Dong‐Tsamn , Lin Kai‐Hsin , Su Ih‐Jen , Chen Bow‐Wen , Lin Kuo‐Sin , Liang Der‐Cherng
Published: February 2007

A study was made of the cellular and molecular characteristics of nine Chinese infants, consecutively presenting with acute leukemia. Five cases were acute lymphoblastic leukemia (ALL); four were acute nonlymphoblastic leukemia (ANLL). Hyperleukocytosis, hepatosplenomegaly, and poor response to conventional therapy were common features, and CNS involvement was detected at diagnosis in three cases. The blast cells from all five cases with ALL expressed early B‐cell markers, i.e., HLA‐DR+, CD19 +, but CD10‐. Terminal deoxynucleotidyl transferase (TdT) was present in blasts from four of the five cases and periodic acid‐Schiff staining in blasts from two patients only. The leukemic cells of one patient also showed positive nonspecific esterase activity and expressed myeloid‐associated antigens CD33 (My9), CD11 (OkM1), and CD14 (My4 and Mo2). Molecular analysis of leukemic cell DNA from this and two other patients showed rearrangement of the immunoglobulin (Ig) heavy‐chain genes, but without any evidence of kappa light‐chain gene rearrangement. T‐cell receptor (TCR) genes remained in the germline configuration in these cases. Cytogenetic analysis showed translocation t(4;11) (q21;q23) in all four cases studied. In the group of ANLL, three cases belonged to the M4 and one to the M2 subtype. Chromosomal abnormality involving 11q23 was also detected in two patients: t(11;17)(q23;q11) and del(11)(q14q23) in each case respectively. Neither lg nor TCR gene rearrangement was present in blast cells from patients with ANLL. The data indicate that chromosomal rearrangement of band 11q23 was quite common in Chinese infants with either form of leukemia, a finding that may have pathogenetic implications.
Iron overload in chinese patients with hemoglobin H disease
Authors: Hsu Hui‐Chi , Lin Chung‐King , Tsay Shyh‐Haw , Tse Elizabeth , Ho Chao‐Hung , Chow Mo‐Ping , Yung Chien‐Hui , Peng Hong‐Wen
Published: February 2007

We examined the iron status of 23 adult patients with hemoglobin H (Hb H) disease. None of them had received multiple blood transfusions or prolonged iron therapy. Studies included serum iron and ferritin concentrations, transferrin saturation, a desferrioxamine test, computed tomography (CT) scan of the liver, and liver biopsy. Iron overload was found in 17 patients (73.9%), especially in males and in patients with splenomegaly (92.9% and 100%, respectively). Four patients with excessive alcohol consumption had clinical manifestations of severe iron overload. Idiopathic hemochromatosis associated HLA antigens, i.e., HLA‐A3, ‐B7, or ‐B14, were not found in any of the 15 patients tested. These findings indicate that iron overload is common in adult patients with Hb H disease; such patients should abstain from alcohol and be considered for treatment with an iron chelating agent before irreversible organ damage occurs.
Recent progress in the molecular genetic analysis of erythroenzymopathy
Authors: Fujii Hisaichi , Miwa Shiro
Published: February 2007

During the relatively recent period in which normal genes for most red cell enzymes have been isolated, the techniques of molecular biology have been applied to the studies of erythroenzymopathy. Single nucleotide substitutions have been identified in aldolase, triosephosphate isomerase, glucose 6‐phosphate dehydrogenase, and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. Up to now, all of the enzyme‐deficient variants which have been investigated have been caused by point mutations. An exception is a hemolytic anemia secondary to increased adenosine deaminase (ADA) activity. Red cell ADA activity increases on the order of a hundred‐fold in affected individuals. The basic abnormality appears to result from overproduction of structurally normal enzyme due to abnormal transcriptional or translational efficiency.
Role of heme metabolism in AZT‐induced bone marrow toxicity
Authors: Lutton J. D. , Mathew A. , Levere R. D. , Abraham N. G.
Published: February 2007

We studied the effects of azidothymidine (AZT) on rat bone marrow heme metabolism and colony growth as determined by assays of granulocyte‐macrophage (CFU‐GM), erythroid (CFU‐E), burst‐forming erythroid (BFU‐E), and α‐aminolevulinic acid synthase (ALAS), the first enzyme in the heme pathway. In all cases, AZT (1–0.01 μM) was found to be toxic to bone marrow colony growth. When AZT was included in colony assays, 1 μM resulted in 98–100% inhibition, whereas lower concentrations (0.01 μM) inhibited growth by 58–76%. In addition, cultures from AZT‐treated animals had a marked reduction in colony growth as compared with sham controls. In most cases, hemin (10−5 M) was found to overcome some of the colony inhibitory effects of AZT. Analysis of heme metabolism indicated that ALAS activity was reduced by 71% in bone marrow cells from treated animals. ALAS activity for control was 204 ± 33 pM ALA formed/4 ± 106 cells/hr, whereas ALAS activity from AZT‐treated animals was only 60 ± 3 pM ALA formed/4 ± 106 cells/hr. It is considered that AZT toxicity may be due in part to a depression in the pool of available heme, which is required for adequate hematopoiesis.
Rapid improvement of thrombotic thrombocytopenic purpura with vincristine and plasmapheresis
Authors: Welborn Jeanna L. , Emrick Pam , Acevedo Maxine
Published: February 2007

Many patients with thrombotic thrombocytopenic purpura (TTP) fail to respond to daily plasmapheresis and the results of alternative treatments have been inconsistent. Vincristine was given weekly with continued plasmapheresis to eight patients who were refractory to plasmapheresis, antiplatelet agents, and/or corticosteroids. A rapid response to the vincristine occurred in all eight patients in 5 days with a marked rise in the platelet count and resolution of symptoms. The results in these patients suggest that early initiation of vincristine therapy in conjunction with plasmapheresis is useful in TTP.
Discordance between phenotype and function of japanese adult T cell leukemia cells
Authors: Imamura Nobutaka , Mtasiwa Deodatus M. , Ota Hiromi , Kuramoto Atsushi
Published: February 2007

Phenotypes of cells from 12 patients with ATL were analysed by means of a fluorescence‐activated cell sorter by utilizing a panel of monoclonal antibodies. A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD2, CD3, CD4, CD5, Ti (WT31), CD25, CD38, CD45, and CD29, but did not express the antigens against CD1, CD13, CD14, CD33, CD36, CD10, CD19, CD20, CD21, CD24, CD41, CD42, CD45RA, CD56, and CD57. The expression of antigen for TQ‐1 or Leu8 was variable. Surface immunoglobulins were not detected. Phenotypes of cultured cells established by utilizing recombinant interleukin II were similar to those of the uncultured peripheral blood lymphoid cells except for the lack of expression of CD8. By means of two‐color fluorescence, the ATL cells possessing CD4 in peripheral blood and culture coexpressed CD29, but did not express CD45RA. The suppression of PWM‐induced B‐cell immunoglobulin synthesis by normal T and B cells was found in five cases in the presence of ATL cells. The ATL cells demonstrated helper T‐cell phenotypes (CD4+, CD29+) with suppressor function, paradoxically.

We conclude that the phenotype of the ATL cells was CD4+, CD29+, and CD45RA− but that the function of these cells was of suppressor T‐cells. Our results inevitably suggest the possible existence of suppressor T‐cells with CD4+, CD29+ phenotype in persons without evidence of any underlying hematologic disorder.
Th polyagglutination with fatal outcome in a patient with massive intravascular hemolysis and perforated tumor of colon
Authors: Levene N. A. , Sigler E. , Berrebi A. , Merhav H. , Levene C. , Gekker K.
Published: February 2007

Polyagglutination is a rare disorder which has been associated with intravascular hemolysis (Levene et al.: Transfus Med Rev 2:176–185, 1988). In this condition cryptantigens exposed on the red blood cell membrane agglutinate with compatible sera and with lectins. A 76 year‐old man with an acute abdomen due to a perforated tumor of the colon and severe fatal intravascular hemolysis is described. Th polyagglutination of the red blood cells was found.
Identification of p70 and p80 Associations With Class II MHC Molecules and Ii
Authors: Sorli Christopher H. , Reisert Patricia S. , Humphreys Robert E. , Welch William J.
Published: February 2007

Two proteins, p70 and p80, were found in chemically crosslinked complexes with class II MHC molecules and Ii after 3–12 hr labelings with [35S]methionine. Two‐dimensional, nonreduced/reduced SDS gel electrophoresis of immunoprecipitated complexes revealed 1) endogenous disulfide linkages between Ii‐Ii and Ii‐p70 and 2) chemically crosslinked, nearest neighbors of α‐β, α‐Ii, Ii‐p70, and α‐p80. Although such nearest neighbors within multimeric complexes were identified as dimers in nonreduced/reduced 2D gels, stoichiometries could not be determined in the high molecular weight complex(es), which included α, β, Ii, p70, and p80, and were not separated in the first dimension. p80 was not the chondroitin‐sulfate form of Ii (Ii‐CS) because it was not electrophoretically heterogeneous and was not sensitive to chondroitinase ABC. p70 was not hsp72/74 detected with C92 or N27 mAbs, and p80 was not BiP detected with its respective mAb. While only these two proteins associated prominently with class II MHC antigens and Ii late after synthesis, their functions are unknown.
Leukocyte depletion filters: A comparison of efficiency
Authors: Bodensteiner David C.
Published: February 2007

Four commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R‐500A® and the PALL RC50® were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100® which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The Imugard IG‐500® had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50® to 92.2% for the Sepacell R‐500A®.
Major prognostic factors of Japanese patients with lymphoma‐type adult T‐cell leukemia
Authors: Shimamoto Yoshinori , Suga Kenji , Nishimura Junji , Nawata Hajime , Yamaguchi Masaya
Published: February 2007

Fifty‐three Japanese patients with the lymphoma‐type adult T‐cell leukemia (ATL) were analyzed to study the prognostic value of various clinical findings recorded at the time of diagnosis. All patients were positive for human T‐cell leukemia virus type I (HTLV‐I) antibody and demonstrated monoclonal integration of HTLV‐I proviral DNA in their malignant cells. The important individual variables detected in a previous univariate analysis were placed in a multiple regression model to identify the major prognostic factors for survival. This analysis showed that serum lactate dehydrogenase (LDH), calcium, and total protein levels had a strong predictive relationship with the length of survival (in descending order of importance). Among the 53 patients, 46 were dead at the time of analysis. The cause of death in relation to the duration of survival is also reviewed in this article.
Acute myelomonocytic leukemia: An immunoelectron microscopic study
Authors: Saito Nagahito
Published: February 2007

Acute myelomonocytic leukemia (M4; French‐American‐British classification) is light microscopically defined as the leukemia constituting leukemic cells in both granulocytic and monocytic lineages. Therefore, the characteristics of M4 have not been fully elucidated. The author previously indicated that normal neutrophilic granulocytes could be ultrastructurally differentiated from normal monocytes by the double staining of lactoferrin and lysozyme. In this investigation, the ultrastructural localization of both proteins was observed in order to make the outline of M4 clear. The leukemic cells in acute myeloid leukemia (M2) were also examined in comparison with those in M4. The leukemic cells in M4 showed the double stainability of lactoferrin and lysozyme, and the positive reactions were localized in the cytoplasmic matrix and in the granules. The staining pattern was similar to that in M2. The coexistance of lactoferrin and lysozyme in the leukemic cells in M4, which has ultrastructurally the monocytic characteristics, implied that the leukemic cells also possess the characteristics of the cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells signifies the diversely abnormal maturations in vivo of the monocytes/granulocytes precursor cell and that M4 consists of not two kinds of distinguishable cells of granulocytic and monocytic lineages but various consecutive cells based on a malignant transformation of the precursor cell.
Developmental and inducible patterns of human θ1‐globin gene expression in embryonic/fetal and adult erythroid cells
Authors: Mamalaki Avgi , Anagnou Nicholas P. , Moschonas Nicholas K.
Published: February 2007

Human theta (θ1)‐globin gene represents a member of the α‐like globin gene family residing on chromosome 16. θ1‐Specific transcripts have been detected so far only in erythroid tissues and in erythroleukemia K562 cells. To investigate systematically its inducible expression and developmental specificity, we analyzed at the RNA level five additional human erythroleukemia cell lines with diverse developmental globin programs, two somatic cell hybrids between K562 and mouse erythroleukemia (MEL) cells, a human fetal liver x MEL somatic cell hybrid, and reticulocytes and bone marrow cells from normal adults. θ1‐Globin gene was expressed in all cell types. Inducible expression (two‐to sixfold) was documented both in HEL and K562 erythroleukemia cells after 5‐azacytidine treatment. Like K562 cells, HEL cells also displayed hemin‐inducible θ1‐globin gene expression. Following transfer of human chromosome 16 from embryonic/fetal K562 to the adult MEL cells, θ1‐globin gene remained active but lost its potential for inducibility, suggesting probably a trans regulation mechanism. Higher levels of θ1 mRNA were found in fetal liver cells compared with trace amounts in reticulocytes and normal adult bone marrow cells. These data clearly show that in contrast to the embryonic and adult patterns of expression of ζ and α‐globin genes, respectively, θ1‐globin gene displays a different profile, being active predominantly during the early stages of ontogeny, switching to lower levels of expression in adulthood.
Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: A case report
Authors: Bastion Yves , Coiffier Bertrand , Felman Pascale , Assouline David , Tigaud Jean‐Dominique , Espinouse Daniel , Bryon Paul‐André
Published: February 2007

A case of extramedullary hematopoiesis (EMH) with a massive mediastinal mass in a 72‐year‐old woman with hereditary spherocytosis is reported. Several cases of EMH have been described in nonsplenectomized adults with hereditary spherocytosis, and it is thought to be a consequence of long‐term stimulation of erythropoiesis. The exact mechanism remains controversial. EMH should be considered in the differential diagnosis of an asymptomatic paravertebral mass.
Extranodal T‐cell lymphoma mimicking malignant histiocytosis
Authors: Sun Tsieh , Brody Judith , Susin Myron , Boss Eleonore , Moskowitz Lisa , Lichtman Stuart
Published: February 2007

We report a case of extranodal T‐cell lymphoma with fever, hepatosplenomegaly, pancytopenia, and diffuse sinusoidal infiltration of the spleen, liver, and bone marrow by the tumor cells, mimicking malignant histiocytosis. This is the second case of T‐γ (T‐cell suppressor) lymphoma resembling the case reported by Kadin et al. [N Engl J Med 304:648, 1981]. The lack of lymph node involvement in this case supports the theory that this type of lymphoma arises in the spleen. This paper draws attention to the extranodal T‐cell lymphoma groups that mimic malignant histiocytosis and to the need of immunophenotyping for a correct diagnosis. The causes for the absence of T‐cell receptor gene rearrangement in T‐cell tumors are discussed.
Evaluation of an automated bleeding time device in the newborn
Authors: Andrew Maureen , Paes Bosco , Bowker Jan , Vegh Patsy
Published: February 2007

Sick infants frequently develop impaired hemostasis as a secondary event. Abnormal platelet‐vessel wall interaction contributes to the hemorrhagic side effects. Currently, the bleeding time is the best measure of in vivo platelet participation in small vessel hemostasis. Bleeding times in the newborn have been previously determined with an automated device designed for the adult or with nonautomated devices. The automated bleeding time device for the adult is not suitable for the infant (length 5 mm, depth 1 mm). We evaluated the performance of an automated bleeding time device designed specifically for the newborn making a cut 2.5 mm in length and 0.5 mm in depth. The results with the automated device showed a strong correlation with the modified template bleeding time device previously used for the newborn. The normal range was shorter and the sensitivity to abnormal vessel wall interaction was greater with the automated device. As well, the ease of determining the bleeding time with the automated device was considerably improved over the template device.
Induction of alkaline phosphatase activity in chronic myeloid leukemia cells: In vitro studies and speculative hypotheses
Authors: De Renzo A. , Micera V. , Vaglio S. , Luciano L. , Selleri C. , Rotoli B.
Published: February 2007

Three patients with Ph chromosome + chronic myeloid leukemia (CML) in chronic phase suffered from intercurrent pleuritis of undefined origin. At that time, leucocyte alkaline phosphatase activity (LAPA) score was low for circulating neutrophils, but high for those from pleural effusion. LAP negative circulating CML granulocytes were incubated with the pleural liquid: after 40–70 hr, almost all were intensely LAP positive. This finding suggests that the low LAPA score in resting CML neutrophils is attributable to the absence of appropriate stimuli rather than to an incapacity to synthesize the enzyme.
A fatal case of low titer anti‐PR cold agglutinin disease
Authors: Rousey Steven R. , Smith Roy E.
Published: February 2007

Cold agglutinin disease typically produces a low‐grade hemolytic anemia. We describe herein the unusual occurrence of an anti‐PR cold agglutinin with high thermal amplitude which caused significant and ultimately fatal hemolytic anemia at very low titers.
Circulating hyaluronan in the myelofibrosis/osteomyelosclerosis syndrome and other myeloproliferative disorders
Authors: Hasselbalch H. , Junker P. , Lisse I. , Lindqvist U. , Engstr Laurent A. Öm
Published: February 2007

The serum concentration of hyaluronan (HYA) was determined in 59 patients with various myeloproliferative disorders, including 33 patients with idiopathic myelofibrosis. In 18 patients the serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised serum HYA levels were seen in patients with active disease compared with age‐matched healthy subjects, whereas no significant difference in serum HYA was seen between patients with stable disease and age‐matched controls. Serum HYA concentrations correlated significantly with the leukocyte count (rho = 0.38; P < 0.02) and with the serum concentration of PIIINP (rho = 0.50; P < 0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations decreased in concert with declining leukocyte counts. These findings suggest that clonal expansion is accompanied by a bone marrow stromal reaction similar to the repair processes following injury to soft connective tissues. The relatively modest changes in serum HYA with frequent overlaps between patient categories and healthy subjects imply that the clinical utility of single determinations of serum HYA in the present disease groups is restrained. On the other hand, sequential measurements of HYA may provide a reflection of the myeloproliferative process in individual patients.
Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients
Authors: Kawano Yoshifumi , Takaue Yoichi , Minakuchi Jun , Abe Takanori , Matsunaga Keiko , Hirao Atsushi , Watanabe Tsutomu , Hirose Masao , Ninomiya Tsuneo , Kawashima Shuh , Kuroda Yasuhiro
Published: February 2007

The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P < 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units × 3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU‐E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.
Superwarfarin ingestion and detection
Authors: Routh Charles R. , Triplett Douglas A. , Murphy Michael J. , Felice Larry J. , Sadowski James A. , Bovill E. G. Ted
Published: February 2007

Because of the emergence of warfarin resistance, new potent long‐acting anticoagulants are now readily available in several over‐the‐counter rodenticide products. The availability of these “superwarfarin” compounds has led to accidental and purposeful human ingestions, one of which has resulted in a death. We summarize the prior case reports and report a second death. In addition, we report the availability of an assay to detect the presence of brodifacoum (a superwarfarin compound) in human plasma and tissues.
Acquired selective factor X deficiency in acute nonlymphocytic leukemia
Authors: Caimi M. T. , Redaelli R. , Cattarieo D. , Nosari A. M. , Baudo F. , De Cataldo F.
Published: February 2007

A case of acute nonlymphocytic leukemia (ANLL) and selective acquired FX deficiency at presentation is reported. The deficiency was not corrected by the infusion of fresh frozen plasma, but the patient's plasma had no neutralizing activity in vitro. The cause of the deficiency is unknown.
Hiv‐associated Hodgkin disease: A clinical study of 18 cases and review of the literature
Authors: Gold Jay E. , Altarac David , Ree H. J. , Khan Amjad , Sordillo Peter P. , Zalusky Ralph
Published: February 2007

Intermediate‐ and high‐grade B‐cell non‐Hodgkin lymphoma (NHL) occurring in a human immunodeficiency virus (HIV)‐infected patient is considered diagnostic of the acquired immunodeficiency syndrome (AIDS). Other neoplasms (both hematopoietic and nonhematopoietic) have also been reported in patients with HIV infection, although none except Kaposi sarcoma carries the same diagnosis of AIDS as B‐cell NHL in an HIV‐infected host. There have been previous reports in the literature of Hodgkin disease (HD) in HIV‐infected patients. We describe our clinical and pathological experience with HD from 1984–1989, in 18 patients with documented HIV infection and also review the literature on HD in HIV‐infected patients. Almost all patients described herein presented with advanced disease and mixed cellularity histology and did very poorly despite some good initial responses to therapy. By statistical analysis, we found that the patients with HIV‐associated HD had a strong tendency to be outside the age range seen in non‐HIV‐associated HD (P <0.005). We also discuss the possible relationship between HIV and HD and consider whether HIV‐associated HD, like B‐cell NHL, is a manifestation of AIDS.
Relationship between CD45 antigen expression and putative stages of differentiation in B‐cell malignancies
Authors: Caldwell Charles W. , Patterson William P.
Published: February 2007

The cell‐surface antigen CD45 is a complex family of high‐molecular‐weight glycoproteins expressed on all lymphohematopoietic cells, but not in the same molecular isoform. This antigen complex is known to exhibit protein tyrosine phosphatase (PTPase) activity and appears to have a role in regulation of cell differentiation. In that CD45 expression parallels stages of differentiation in normal bone marrow B cells, it was of interest to evaluate this process in malignant B cells. Monoclonal antibodies (MoAbs) were used to investigate the quantitative expression of CD45 and CD45RA on the B cells of lymphoid leukemias. Employing standardized flow cytometric methods, it was found that the fluorescence intensity (FI) of immunostained malignant B cells, as a reflection of the antigen content, demonstrated correlations with the putative stage of cell differentiation for malignancies at the earlier stages, but at the later stages, a progressive loss of CD45 was observed. Since this antigen family has been found to display PTPase activity, further investigation of CD45 alterations in malignancies may provide insight into potential regulatory disturbances.
Sickle cell anemia with few painful crises is characterized by decreased red cell deformability and increased number of dense cells
Authors: Ballas Samir K.
Published: February 2007

The frequency and severity of the painful sickle cell crisis vary greatly among affected patients. Aside from a high level of Hb F(>20%) there is no established parameter which may modulate the clinical severity of the disease. In this paper we describe two groups of adult patients with homozygous SS and present their characteristics. The division into these two groups was on the basis of relatively low RBC deformability (≤37% of control) and high RBC deformability (>65% of control) in the steady state. None of the patients had α‐gene deletion and all had Hb F level <6.0%. Each patient was followed for a minimum of 3 years. The number of dense cells was quantitated by centrifugation on discontinuous Stractan gradient. RBC deformability index in isotonic medium (DI 290) was determined by ektacytometry and expressed as % of control. The patients with low RBC deformability had significantly less painful crises and more leg ulcers than those patients with high RBC deformability. The average number of dense cells was 22.2% and 9.8% of total circulating cells in the first and second group respectively. Moreover, the group with high red cell deformability had 33% mortality during the study period whereas no deaths occurred in the group with low RBC deformability.

The data indicate that there is a subset of patients with SS who have relatively few painful crises despite low Hb F level. We wish to designate these by the acronym MIDDD syndrome: Mild disease as far as painful crises are concerned, Increased number of Dense cells, and Decreased red cell Deformability. In addition these patients have high incidence of leg ulcers, have low incidence of urinary tract infection, and less mortality. Cellular factors seem to contribute to the incidence of painful crises.
Blood zinc protoporphyrin is elevated only in sickle cell patients with low fetal hemoglobin
Authors: Hirsch Rhoda Elison , Pulakhandam Usha Rao , Billett Henny H. , Nagel Ronald L.
Published: February 2007

Increased levels of various porphyrin species have been reported in sickle cell anemia (SS) patients in the absence of lead poisoning and iron deficiency anemia, but conflicting data remain. Suspecting that SS patients may be heterogenous for this abnormality, we have studied zinc protoporphyrin (ZPP) and protoporphyrin IX (PPIX) blood levels and find abnormally elevated levels of ZPP in those with low peripheral fetal hemoglobin (%HbF) levels. Two groups exist: one with <9% HbF and elevated ZPP, and one with ≥9% HbF and normal ZPP levels (P < 8.1 × 10−4). There is a strong negative correlation of ZPP levels with %Hb F (r = –0.83, P < 8.0 × 10−5), and a moderate one with total hemoglobin levels (r = –0.55, P < 0.05). These results suggest that ZPP may indeed contribute to the pathophysiology of the disease and/or serve as a marker of the severity of the disease.
Prompt engraftment using autologous peripheral blood stem cells for double autologous bone marrow rescue
Authors: Hillyer Christopher D. , Comenzo Raymond L. , Miller Kenneth B. , Schenkein David P. , Tiegerman Karen O. , Fogaren Terry A. , Wazer David E. , Parker Leroy , Abrams Ross A. , Desforges Jane F. , Rudders Richard A. , Berkman Eugene M.
Published: February 2007

A patient with Hodgkin's Disease, stage IIIA, was treated for recurrent disease with autologous peripheral blood stem cells after ablative chemotherapy. Bone marrow rescue occurred promptly and his disease was significantly reduced. Ablative chemotherapy was administered again and a second bone marrow rescue with peripheral blood stem cells was successful. Sequential peripheral blood stem cell bone marrow rescue, following high dose chemotherapy, may provide an alternative approach in selected patients.
Helper‐suppressor T‐cell leukemia: Unusual phenotype controlled with low‐dose deoxycoformycin
Authors: Adler Mark J. , Hershberg Robert , Yu Alice
Published: February 2007

Presented is an unusual case of chronic T‐cell leukemia. Immunophenotypic profile revealed the leukemia cells to express T4 and T8 surface markers simultaneously. The patient was treated with low‐dose deoxycoformycin and control of symptoms and lymphocyte levels shown to correlate with ADA and dATP/ATP levels.
GM‐CSF‐mediated impairment of liver to synthesize albumin, cholinesterase, and cholesterol
Authors: Takahashi Masuhiro , Nikkuni Kohji , Moriyama Yoshiaki , Shibata Akira
Published: February 2007

Serum albumin, cholinesterase, and cholesterol were measured in ten patients with aplastic anemia and eight with myelodysplastic syndrome who received the administration of recombinant human GM‐CSF. Serum albumin, cholinesterase, and cholesterol were significantly lowered by the administration of GM‐CSF and recovered after the cessation of GM‐CSF. These data suggest that GM‐CSF impairs the biosynthesis of liver cells and that cholesterol‐lowering activity of GM‐CSF, which is previously reported, is due to the impairment of liver biosynthesis by GM‐CSF.
Platelet satellitosis to polymorphonuclears: Cytochemical, immunological, and ultrastructural characterization of eight cases
Authors: Bizzaro Nicola
Published: February 2007

Satellitosis of platelets to polymorphonuclears was observed in eight patients. This phenomenon occurred only in blood anticoagulated by EDTA at room temperature. In vivo and in vitro platelet and neutrophil function were normal. Electron microscopy studies showed normal structures in both cells but demonstrated platelet phagocytosis by neutrophils. In all cases we were able to transfer the platelet satellitosis factor by mixing platelet plasma (or serum) with whole blood from ABO compatible healthy controls; conversely, when the same plasma (or serum) was pre‐incubated with anti‐IgG serum, satellitosis to normal blood was not observed. While this finding suggests that a plasmatic protein with the properties of an IgG immunoglobulin was probably responsible for the phenomenon, we were unable to correlate it with the clinical condition of the patient, functional abnormalities of the blood components, or drugs.
Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L‐tryptophan use
Authors: Jaffe Jeffrry P. , Gertner Elie , Miller Wesley
Published: February 2007

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML) [1]. CML with eosinophilic differentiation (eosinophilic leukemia) is well described [2], and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis [3]. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L‐tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.
Treatment with granulocyte‐macrophage colony stimulating factor and the adult respiratory distress syndrome
Authors: Verhoef Gregor , Boogaerts Marc
Published: February 2007

We report a case of a patient who developed a fatal adult respiratory distress syndrome (ARDS) during treatment with rh granulocyte‐macrophage colony stimulating factor (rhGM‐CSF) (250 mcg/m2/day s.c.) and low‐dose cytosine‐arabinoside (Ara‐C) (20 mg/m2/day s.c.). Several mechanisms which might explain the lung tissue damage in this patient were explored. GM‐CSF increased the expression of the glycoproteins CD11B and CD18 on the surface of his neutrophils, which may have increased the adhesiveness of neutrophils to the pulmonary endothelium. In addition, GM‐CSF primed the neutrophils of the patient to an enhanced release of superoxide anions. Both findings may at least partially explain why GM‐CSF exerted a deleterious action on the pulmonary endothelial integrity in this patient. Other factors, such as increased platelet‐activating factor production by the neutrophils or tumor necrosis factor‐mediated mechanisms, may also have played a role. ARDS as a complication of low‐dose Ara‐C seems less plausible.
Acute lymphoblastic leukemia with azurophilic granules that contain ultrastructural myeloperoxidase activity
Authors: Tauchi Tetsuzo , Ohyashiki Kazuma , Ohyashiki Junko H. , Saito Midori , Nakazawa Shinpei , Enomoto Yasuhiro , Hosoda Yasuhiro , Toyama Keisuke
Published: February 2007

We present a case of acute lymphoblastic leukemia (ALL) in which the leukemic cells had cytoplasmic azurophilic granules. Surface marker studies revealed that the leukemic cells expressed CD10 (CALLA), CD19, CD20, and HLA‐DR antigens. Cytochemical studies by light microscopy revealed that the blasts were negative for myeloperoxidase, PAS staining, and double esterase staining, supporting the diagnosis of ALL. However, an ultrastructural study demonstrated that some of the cytoplasmic granules were myeloperoxidase (MPO) positive. Our findings suggested that leukemic transformation in this case may have taken place at a stage ontogenetically close to the pluripotent stem cell. Furthermore, the present case indicates the existence of a new form of ALL is characterized by MPO‐positive granules detectable by ultracytochemistry and lymphoid‐associated surface markers.
Transitions in CD45 isoform expression indicate continuous differentiation of a monoclonal CD5+ CD11b+ B lineage in Waldenstrom's macroglobulinemia
Authors: Jensen Gitte S. , Andrews E. Joy , Mant Michael J. , Vergidis Rucy , Ledbetter Jeffrey A. , Pilarski Linda M.
Published: February 2007

Waldenstrom's macroglobulinemia (WM) has been hypothesized to be a pleomorphic B‐cell malignancy with persistent maturation towards plasma cells in all lymphoid tissue. This proposal is based on detection of a heterogeneous density of monoclonal Ig on peripheral blood B‐cells in patients with WM. We now present data derived from 2‐ and 3‐color immunofluorescence and flow cytometric analysis that strongly supports this hypothesis. Abnormally high numbers of B lineage cells, defined by expression of CD19, CD20, and CD24, were found among peripheral blood mononuclear cells (PBMC). These B‐cells are monoclonal as defined by light chain expression and by the existence of rearranged Ig genes (Southern blot analysis), although they exhibit heterogeneity in the density of surface light chain. Unlike normal PBMC B‐cells, the monoclonal B‐cells bear CD5 and CD10 (CALLA), express adhesion and adhesion‐related molecules (CD11b, CD9), and appear to be actively differentiating during the course of the disease, based on the pattern of CD45 isoform expression. At any given point in time, the population of monoclonal B‐cells is heterogeneous in differentiation stage based on transitions in the expression of CD45 isoforms from expression of CD45RA, the high molecular mass isoforms of CD45, to the low molecular mass isoform CD45R0 which appears only on very late stage B‐cells and early plasma cells. For one patient, analysis of CD45 isoform expression over 2 years showed that the monoclonal B‐cell population as a whole progressed towards terminal differentiation as defined by loss of CD45RA and acquisition of CD45R0. This indicates a continuously differentiating lineage of an unusual B‐cell phenotype, and/or malignant transformation of a distinct lineage of B‐cells in WM.
Concise review: Genetic bases for sideroblastic anemia
Authors: Nusbaum Neil J.
Published: February 2007

The best‐documented mode of transmission of familial sideroblastic anemia is as an X‐linked trait. Mitochondrial mutation has also occasionally been noted in association with sideroblastic anemia, but it is likely to be present more often than has so far been described. It should especially be suspected in cases of inherited multisystem disease, where the pedigrees do not indicate a sex predominance among those affected, and where there is no evidence of transmission by the paternal line. Sporadic cases of sideroblastic anemia may represent mitochondrial mutations either at the germ cell or the somatic cell, and the most sensitive strategy of screening for both would be the study of mitochondrial DNA from circulating erythrocytes. It seems likely that such studies would extend the understanding of mitochondrial function and disease.
Myelodysplastic transformation of polycythemia vera: Case report and review of the literature
Authors: Shamdas Glenn J. , Spier Catherine M. , List Alan F.
Published: February 2007

We report a case of refractory anemia with excess blasts (RAEB) developing in a 67‐year old man with a history of polycythemia vera; results of cytogenetic and immunophenotyping studies are described. In this report the clinical, cytogenetic and hematologic features of myelodysplasia complicating polycythemia vera are reviewed. Results of immunophenotyping and cytogenetic studies, and the preponderance of cases developing after myelosuppressive therapy suggest that in the majority of cases myelodysplasia is treatment‐related.
Simultaneous occurrence of factor VIIIC inhibitor and antinuclear antibody in postpartum period
Authors: Marwaha Neelam , Sarode Ravindra , Chauhan A. P. , Joseph  , Varma S. , Dash S.
Published: February 2007

We are describing a rare case of acquired factor VIIIC inhibitor in postpartum period who also had strongly positive antinuclear antibody. On immunosuppression with prednisolone and azathioprine, both antibodies disappeared after 4 months of therapy.
Recombinant human erythropoietin for a Jehovah's witness with anemia of thermal injury
Authors: Boshkov Lynn K. , Tredget Edward E. , Janowska‐Wieczorek Anna
Published: February 2007

We report the use of recombinant human erythropoietin (rh‐Ep) as an alternative to transfusion therapy in a burn victim who was a Jehovah's Witness and refused blood transfusion. Despite endogenous elevated erythropoietin levels, the patient was reticulocytopenic and administration of rh‐Ep was accompanied by a 10‐fold increase in reticulocyte response and a rise in hemoglobin from 7.4 to 10.4 g/dl over a 12‐day period. We suggest that the exogenously administered erythropoietin overcame a clinically inadequate endogenous erythropoietin response.