bluuebunny/crossref_metadata_2025 huggingface dataset:
Diminished lymphocyte and granulocyte γ‐glutamyltranspeptidase activity in acute lymphocytic leukemia and response to chemotherapy
Authors: Russo Sandra A. , Harris Michael B. , Greengard Olga
Published: February 2007

γ‐Glutamyltranspeptidase (GGT) acitivity (per mg protein) in blood lymphoid cells of 27 children with acute lymphoblastic leukemia (ALL) (1.05 ± 0.15) was significantly below that of controls (2.25 ± 0.30), became normalized during chemotherapy‐induced remission (2.47 ± 0.26), and was low again (1.59 ± 0.62) in relapsed subjects. Individual variations in the GGT activity of the blood lymphoid cell fraction (per mg protein) bore a significant inverse correlation to the number of white blood cells (WBC) as well as of blasts per ml blood. Blasts had minimal GGT activity; however, partial GGT deficiency was also exhibited by the microscopically normal circulatory lymphocytes of several patients prior to treatment and in relapsed subjects whose blood was still devoid of blasts.

Significantly diminished GGT activity (per mg protein) was found in the blood granulocytes of ALL subjects. This deficit, restored during remission and present again at relapse, varied in magnitude but showed no statistically significant correlation to the different patients' degree of neutropenia. In about one‐third of the newly diagnosed or relapsed pre‐B ALL children, the circulatory granulocytes' GGT activity was only 10–20% of normal. The results suggest that 1) the presence or absence of this sign of functional maldifferentiation in granulocytes is a factor in the heterogeneity of disease manifestation among subjects with apparently the same type of ALL and that 2) measurement of GGT in the circulatory granulocytes, as well lymphocytes, may be useful for monitoring the efficacy of chemotherapy.
Acute myelomonocytic leukemia (AML‐M4) and translocation t(6;9) (p23;q34): Two additional patients with prominent myelodysplasia
Authors: Horsman Douglas E. , Kalousek Dagmar K.
Published: February 2007

Two patients with acute myelomonocytic leukemia (AML‐M4) and a specific chromosomal translocation t(6;9)(p23;q34) are reported and compared to 21 AML patients with the same translocation collected from the literature. Our observations suggest that AML with t(6;9)(p23;q34) is characterized by myelodysplasia, basophilia, and a variety of blast cell morphologies (M1, M2, M4) with a greater proportion of the cases than previously appreciated being examples of acute myelomonocytic leukemia (AML‐M4). The consistent association of myelodysplasia provokes the proposal that this subtype of de novo AML is a result of an acute stem cell disorder. The poor outcome with standard AML chemotherapy experienced in this group of relatively young patients necessitates consideration of alternative therapeutic strategies such as early bone marrow transplantation.
Immunophenotyping of acute myeloid leukemia by immuno‐alkaline phosphatase (APAAP) labeling with a panel of antibodies
Authors: Davey Frederick R. , Erber Wendy N. , Gatter Kevin C. , Mason David Y.
Published: February 2007

A panel of eight antibodies was used by the alkaline‐phosphatase/anti‐alkaline phosphatase (APAAP) method to stain peripheral blood films, bone marrow smears, and cytocentrifuge preparations from 29 cases of acute myeloid leukemia. These findings were correlated with the French‐American‐British (FAB) classification. Leukemic cells from six cases of myeloblastic leukemia (FAB;M1) were predominantly labeled by the antimyeloperoxidase monoclonal antibody (MPO‐7). Leukemic cells from the majority of eight cases of myeloblastic leukemia with maturation (FAB;M2) and progranulocytic leukemia (FAB;M3) stained with monoclonal antibodies MPO‐7, NP57 (anti‐elastase), and EBM11 (antimonocyte/macrophage). Leukemic cells from six cases of myelomonocytic (FAB;M4) and five cases of monocytic (FAB;M5) leukemia were most often labeled with antibodies MPO‐7, NP57, and EBM11 as well as monoclonal antibodies Y1/82A (anti‐monocyte) and KB90 (against the p150, 95 molecule, CD11c; a monocyte/granulocyte marker), but not with monoclonal antibody C17 (antiglycoprotein IIb/IIIa) and/or monoclonal antibody Y2/51 (antiglycoprotein IIIa). Erythroblasts from a single case of erythroleukemia (FAB;M6) were not labeled with any of the antibodies from this panel. Leukemic cells from two cases of acute megakaryocytic leukemia (FAB;M7) stained strongly with the monoclonal antiglycoprotein IIIa/IIb antibody (C17) and antiglycoprotein IIIa antibody (Y2/51). Staining by the APAAP method with this panel of antibodies was easy to perform, required no expensive instrumentation, and provided useful information in the classification of acute myeloid leukemia.
Impaired antioxidant defense in hemoglobin E‐containing erythrocytes: A mechanism protective against malaria?
Authors: Lachant Neil A. , Tanaka Kouichi R.
Published: February 2007

Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E‐B+ thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% ± 18%; p < 0.001) compared to normal and thalassemic RBC (10% ± 2% and 11% ± 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3‐diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 ± 0.69 μmol/ml RBC as compared to normal (4.51 ± 0.77; p < 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.
Effect of heparin on platelet count and platelet aggregation
Authors: Shojania A. Majid , Turnbull Gail
Published: February 2007

The in vitro effect of heparin on platelet aggregation was studied in three groups: in 26 subjects recently treated with heparin, in 18 subjects on maintenance hemodialysis, and in 20 normal controls. With the aid of Technicon H6000, platelet counts and platelet aggregations were compared in whole blood samples collected in ethylenedi‐aminetetraacetic acid (EDTA) and in heparinized tubes. Although there was no significant difference between platelet count of heparinized and EDTA blood in the control group, the dialysis group and the group recently treated with heparin showed significantly lower platelet counts and more platelet aggregation in heparinized tubes than in EDTA tubes.

We speculate that the majority of subjects exposed to heparin develop an antibody or a proaggregator which can aggregate or agglutinate platelets in the presence of heparin and causes destruction of platelets; but only in a small percentage of subjects receiving heparin is this reaction severe enough to cause thrombocytopenia.
Carrier detection in the hemophilias
Authors: Lillicrap D. P. , White B. N. , Holden J. J. A. , Giles A. R.
Published: February 2007

The subject of carrier detection in the hemophilias has received new impetus in the past several years. Treatment complications arising from clotting factor concentrates have become more evident and earlier prenatal diagnosis and new genetic markers for the clotting factor genes have focused interest on this area. Until now, carrier diagnosis has relied upon standard pedigree analysis and clotting factor assays. The results obtained using these methods are probabilistic, and the coagulation tests are unavoidably influenced by the effects of random X chromosome inactivation and the inherent variability of the methods involved. With the cloning and characterization of both factor IX and factor VIII genes, has come the capability of using gene analysis to diagnose the carrier state. This usually involves the detection of restriction fragment length polymorphisms (RFLPs) and their use as linked markers for the defective clotting factor gene. In hemophilia A, the combined use of three intragenic RFLPs and two closely linked, highly polymorphic extragenic markers will make carrier information available to approximately 90% of kindred. In hemophilia B, phenotypic analysis has been complicated by the more heterogeneous expression of the gene defect. To date, five intragenic and one closely linked RFLP have been reported, as well as two protein polymorphisms detectable by monoclonal antibody immunoassays. With the combined use of these genetic markers it is likely that accurate carrier assignment will be available to more than 80% of hemophilia B families.
Evaluation of factor VII antigen in factor VII congenital deficiencies with a new ELISA assay
Authors: Tirindelli M. C. , Mariani G. , Mazzucconi M. G. , Iacopino G. , Carbonaro M. , Ghirardini A. , Motta M. , Mandelli F.
Published: February 2007

An evaluation of a new Enzyme Linked Immunosorbent Assay (ELISA) factor VII:Ag assay in factor VII congenital deficiencies was carried out. This assay was compared to factor VII:C assay and the Inhibitor Neutralization Assay (INA) for factor VII:Ag, both in normals and F VII‐deficient patients. The correlations between ELISA F VII:Ag and VII:C, as well as the one between INA F VII:Ag and VII:C, were good (r = .86 and .81, respectively). The correlation between the two immunologic methods of assay in normals was fairly good (r = 0.73, P < 0.001); whereas in mild F VII deficiencies (heterozygotes for F VII deficiencies), the two methods correlated very well (r = .96). In the severe deficiencies, ELISA F VII:Ag assay allowed the evaluation of F VII protein levels below 1 u/dl.

The sensitivities of the INA and ELISA assays were evaluated by creating artificially prepared plasmas containing serial amounts of purified F VII: INA was unable to pick up F VII protein levels lower than 75 ng/ml, whereas the ELISA assay could detect up to 5 ng of F VII.
Acquired factor XI inhibitors in congenitally deficient patients
Authors: Schnall S. F. , Duffy T. P. , Clyne L. P.
Published: February 2007

Four factor XI (F XI)‐deficient patients are described, all of whom formed circulating anticoagulants against F X1. In the three most severely affected patients (F XI 0%–6% activity), the anticoagulant appeared to have been stimulated by plasma infusion. However, in the milder case (25% F XI activity), no infusion had been documented. The findings in these cases emphasize the diversity of F XI inhibitors in congenitally deficient patients. Awareness of the potential development of these inhibitors will be helpful in both daily management and perioperative care of such patients.
Durable response to etoposide‐loaded platelets in refractory immune thrombocytopenic purpura: A case report
Authors: Wood Lucille , Jacobs Peter
Published: February 2007

A 23‐year‐old female presented with widespread purpura and ecchymoses as a result of immune thrombocytopenia which was refractory to corticosteroids, splenectomy, and immunosuppressive agents. In view of the extent and serious nature of her bleeding, salvage therapy with etoposide‐loaded platelets was undertaken, which was associated with a lasting complete remission.
Acute respiratory failure in hyperleukocytotic acute myeloid leukemia: The role of perfusion lung scintigraphy
Authors: Nagler A. , Brenner B. , Zuckerman E. , Hazani A. , Israel O.
Published: February 2007

A patient with acute hyperleukocytotic myelogenous leukemia who presented with acute respiratory distress is reported. Clinical manifestations included dyspnea, tachypnea, hyperventilation, and cyanosis. Blood gas analysis revealed hypoxemia, hypocapnia, and metabolic acidosis. Chest X‐ray and perfusion lung scanning were normal. Pulmonary leukostastis syndrome (PLS) was later confirmed at autopsy. In a patient with hyperleukocytosis from acute nonlymphocytic leukemia and respiratory distress, a normal perfusion lung scintigraph should make one consider the PLS.
Philadelphia‐positive acute myelomonocytic leukemia with inversion of chromosome 16 and eosinobasophils
Authors: Mecucci Cristina , Noens Lucien , Aventin Ana , Testoni Nicoletta , Berghe Herman Van Den
Published: February 2007

Cytogenetic studies in a case of acute nonlymphocytic leukemia, type M4‐FAB with eosinophilia, showed an acquired abnormal karyotype characterized by both a t(9;22) Philadelphia translocation and a pericentric Inversion of chromosome 16, inv(16)(p13q22). This unique case shows that the previously described association between inversion of chromosome 16 and myelomonocytic leukemia with bone marrow eosinophilia is true also in Philadelphia‐positive disorders.

The present findings are consistent with the existence of a group of chromosome anomalies, namely t(15;17) and inv(16), which are specifically associated with one single stage of morphological differentiation of myeloid leukemic cells.
Divalent cations induce protofibril gelation
Authors: Marx Gerard
Published: February 2007

Soluble fibrin oligomers (protofibrils) undergo phase change merely by adding 1–2 mM Ca2+ 25‐100 μM Zn2+. The cation‐induced “protofibrin” clots appear similar to normally formed fibrin gels. Maximal clot turbidity of protofibrin gels increases with cations in a concentration‐dependent manner. Magnesium (less than 0.5 mM) is ineffective in inducing protofibril gelation. Turbidity and degree of polymerization (DP) [indirectly expressed as AT (activation time)] appear to be positively correlated, regardless of whether the divalent cation is Ca2+ or Zn2+. Cross sections of Ca2+‐induced protofibrin fibers are ∼6–18‐fibrin‐monomers‐thick. With both Ca2+ and 40 μM Zn2+, fiber cross section increases to 30–50 monomers thick. Negatively stained Zn2+,‐ and Ca2+‐induced protofibrin gels exhibit banding periodicity of ∼ 240 Å, similar to that of normally generated fibrin gels. Regions of lateral merging of individual segments of the protofibrin leads to increased cross section of the fiber and forms a branch required for gelation. These findings indicate that the rate of coagulation and the ultimate thickness of the fibers both relate to lateral associative processes of protofibrils, which are augmented by physiologic concentrations of2+ and Zn2+.
Acute myeloblastic leukemia presenting as apparent acute otitis media
Authors: Bertrand Yves , Lefrère Jean‐Jacques , Leverger Guy , Bonnet Madeleine , Lacombe Hervé , Lasfargues Gérard
Published: February 2007

Three cases of acute myeloblastic leukemia of FAB‐M2 type revealed by an isolated otitis media are reported. This mean of revelation is valuable for early diagnosis and treatment of the disease. A karyotype was performed in two cases and showed an 8;21 translocation. As far as we know, these are the first acute myeloblastic leukemia cases with otitis media reported in which an 8;21 translocation was detected.
βS gene in sicily is in linkage disequilibrium with the benin haplotype: Implications for gene flow
Authors: Ragusa Angela , Lombardo Mario , Sortino Grazia , Lombardo Turi , Nagel Ronald L. , Labie Dominique
Published: February 2007

Hemoglobin β‐like gene cluster haplotypes defined by restriction enzyme polymorphic sites are useful in determining the origin of the βS gene found in several human populations. We present here evidence that the βS gene found among Sicilians is associated with the same haplotype observed among sickle cell anemia patients from Central West Africa. In addition, this haplotype is either nonexistent or very rare among normal Sicilian individuals. We conclude that the βS gene was introduced to Sicily from North Africa and that the gene flow originated in Central West Africa and traveled north through historically well‐defined trans‐Saharan commercial routes.
Adverse reactions to trimethoprim‐sulfamethoxazole in hemophiliacs
Authors: Nahum Kenneth , Saidi Parvin , Kim Hugh C. , Karp George I.
Published: February 2007

Adverse reactions to trimethoprim‐sulfamethoxazole are very prevalent in patients with acquired immunodeficiency syndrome (AIDS). Recently we have observed severe toxicities associated with trimethoprim‐sulfamethoxazole in three hemophiliacs, a group known to be at risk for developing AIDS. At the time of these reactions to the antibiotic, none of the patients had yet manifested any stigmata of AIDS per se. We advise caution in the use of trimethoprim‐sulfamethoxazole in hemophiliacs and other patients at high risk for the development of AIDS.
Prognostic factors in chronic myelodysplastic syndromes: A multivariate analysis in 107 cases
Authors: García Sonia , Sanz Miguel A. , Amigo Victoria , Colomina Pedro , Carrera M. Dolores , Lorenzo J. Ignacio , Sanz Guillermo F.
Published: February 2007

A retrospective multivariate analysis of 37 clinical, biochemical, and hematological data was performed in 107 cases of primary myelodisplastic syndromes (MDS) in order to recognize their prognostic significance. The most important individual variables, isolated in a previous univariate analysis, were placed in a multiple regression modeling procedure to identify major significant prognostic factors. Multivariate analysis tends to identify prognostic variables containing significant independent predictive information. Characteristics were examined on both continuous and binary bases. The FAB classification was the first parameter entered in regression equations on both models, followed by platelet count, hemoglobin level, and circulating erythroblasts in the binary model, and by hemoglobin level, systemic symptoms, platelet count, age, and dyserythropoiesis in the continuous model. Our analysis confirms FAB classification as the main prognostic factor in MDS, supports the previously noted predictive value of platelet count, hemoglobin level, and age, and recognises the importance of circulating erythroblasts, systemic symptoms, and dyserythropoiesis as prognostic characteristics in MDS.
Clonal trisomy 8 is associated with myeloid phenotype rather than the neoplastic transformation in acute leukemia
Authors: Cassano William F. , Hintz Marilyn S.
Published: February 2007

Our studies of an acute leukemia with a clonal t(1;11) marker have demonstrated a conversion from pre‐B cell to myelomonocytic phenotype associated with the acquisition of trisomy 8. This finding suggests that trisomy 8, a frequent clonal abnormality in acute myeloid leukemias, may be associated with the myeloid phenotype rather than the neoplastic transformation. A permanent myelomonocytic cell line, designated UF‐SK1, has been established from leukemic cells with a 47,XX, + 8,t(1;11) (p31;q25) karyotype and shown to have myelomonocytic characteristics, including phorbol ester‐induced differentiation to macrophages. This new cell line will be a valuable tool in the study of leukemogenesis and lineage commitment.
Possible cytogenetic distinction between lymphoid and myeloid blast crisis in chronic granulocytic leukemia
Authors: Diez‐Martin Jose L. , Dewald Gordon W. , Pierre Robert V.
Published: February 2007

This study consists of 25 patients with chronic granulocytic leukemia in blast crisis (BC) or with acute leukemia who had a Ph1 chromosome and one or more other chromosome abnormalities and who were investigated by cytochemistry and immunocytochemistry techniques to determine whether the predominant blasts were myeloid or lymphoid. The disorder was myeloid in 15 patients, lymphoid in 8, and mixed in 2. Among the 15 patients with myeloid disorders, 13 (86.6%) had an additional Ph1 chromosome, i(17q), +8 +19, or some combination of these abnormalities. None of the eight patients with a lymphoid disorder had +8, +19, or i(17q), but one had an additional Ph1 chromosome. Among the eight patients with lymphoid disorders, two had structural abnormalities of chromosome 7 and two were monosomy 7. None of the patients with myeloid disease had a structurally abnormal chromosome 7, but one was monosomy 7. Our findings suggest that the number of chromosomes in an abnormal clone may be unreliable for distinguishing between lymphoid and myeloid BC. Most patients with myeloid disease had only abnormal metaphases, whereas many patients with lymphoid disorders had both normal and abnormal metaphases. This finding may partially explain why many patients with lymphoid BC respond better to treatment than do those with myeloid BC.
Thrombotic thrombocytopenic purpura in human immunodeficiency (HIV)‐seropositive males
Authors: Meisenberg Barry R. , Robinson Warren L. , Mosley Coleman A. , Duke Mark S. , Rabetoy Gary M. , Kosty Michael P.
Published: February 2007

Two male patients with thrombotic thrombocytopenic purpura (TTP) were found to have antibodies to the human immunodeficiency virus (HIV). In one patient, platelet‐associated antibody levels were measured serially and were found to be initially elevated, but the levels decreased with initiation of successful therapy. The simultaneous occurrence of these two conditions in two of three patients admitted for TTP within the previous 2 years at this institution suggests an association between the two diseases. The precise nature of this association remains speculative inasmuch as the pathogenesis of TTP remains uncertain.
Elevated erythrocyte adenosine deaminase activity in a patient with primary acquired sideroblastic anemia
Authors: Kanno Hitoshi , Fujii Hisaichi , Tani Kenzaburo , Morisaki Takayuki , Takahashi Keisuke , Horiuchi Naomi , Kizaki Masahiro , Ogawa Tetsuhei , Miwa Shiro
Published: February 2007

We report a case of primary acquired sideroblastic anemia (PASA) associated with elevated erythrocyte adenosine deaminase (ADA) activity. The patient was an 85‐year‐old Japanese male. Analysis of the peripheral blood revealed pancytopenia, and the bone marrow findings showed marked ringed sideroblasts and chromosomal deletion (46XY, 11q‐). The erythrocyte ADA activity was 17 times higher than that of normal control, the leukocyte ADA activity was within the normal range, and the plasma ADA activity was 2 times higher than the normal mean. The adenine nucleotides in the patient's erythrocytes were within normal range. According to starch gel electrophoresis, ADA isozyme of the patient was ADA 1. Western blotting showed an increased amount of ADA protein in the patient's erythrocytes. Southern blotting revealed no gene amplification or large structural change. Dot blot analysis of the reticulocyte mRNA showed no increase in the amount of ADA mRNA in the patient's reticulocytes compared with those of reticulocyte‐rich controls. We considered that the mechanism of elevated ADA activity in this acquired defect was similar to that found in hereditary hemolytic anemia associated with ADA overproduction.
Leukocytosis due to adrenal metastases from malignant melanoma: Reversal after bilateral adrenalectomy with long‐term survival
Authors: Carey Robert W. , Kunz Victoria S.
Published: February 2007

Leukocytosis has been noted in association with many non‐hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases.
The first report of familial adult T‐cell leukemia lymphoma in the United States
Authors: Denic Srdjan , Abramson Jonathan , Anandakrishnan Ravi , Krishnamurthy Muthuswamy , Dosik Harvey
Published: February 2007

Two patients, a daughter and her father, developed the acute type of adult T‐cell leukemia/lymphoma (ATLL) within a 3‐month period. Antibodies against HTLV‐I have been found in both wives of the father. The second wife acquired the infection from her husband within 3 years of marriage. The patients described represent the first cases of familial ATLL in the United States. ATLL continues to be frequently misdiagnosed in the United States. A positive family history consistent with this disease in a patient with a lymphoid malignancy may be a helpful clue for earlier diagnosis.
Hypereosinophilic syndrome with multiple organ dysfunction treated by allogeneic bone marrow transplantation
Authors: Archimbaud Eric , Guyotat Denis , Guillaume Christian , Godard Jean , Fiere Denis
Published: February 2007

A 26‐year‐old man with hypereosinophilic syndrome who had initial neurologic, cardiac, and pulmonary dysfunction, high eosinophil count, thrombocytopenla, and bone marrow fibrosis had only a transient response to conventional treatment with corticosteroids and hydroxyurea. He therefore received human lymphocyte antigen‐identical allogeneic bone marrow transplantation (BMT) after conditioning with cytoxan and fractionated total body irradiation. Hematologic recovery was prompt, with normalization of blood counts and bone marrow. The patient died less than 3 months after transplantation from diffuse cytomegalovirus infection. Potential interest of BMT in patients with resistant hypereosinophilic syndrome and features of poor prognosis is discussed.
Random donor platelet crossmatching: Comparison of four platelet antibody detection methods
Authors: Freedman J. , Garvey M. B. , Hornstein A. , De Friedberg Z. Salomon , Blanchette V.
Published: February 2007

The standard lymphocytotoxicity assay (LCT), a biotin‐avidin enzyme immunoassay (ELISA), platelet suspension immunofluorescence test (PSIFT), and platelet radioactive antiglobulin test (PRAT) were examined in prospective crossmatching for selection of compatible random donor platelets for refractory patients. One hundred seven episodes of pooled random donor platelet transfusions were evaluated in 26 patients. There was good reproducibility of results by individual techniques. Concordance of results by the different methods was 40–60%. One‐hour and 24 hr posttransfusion corrected count increments (CCI) were compared as parameters for assessing success or failure of the transfusion. Using a rank scoring system, the relative efficiency of predictiveness for all transfusions was PRAT > LCT > PSIFT > ELISA. Combination of PRAT and LCT afforded the best predictability and sensitivity was higher than for either PRAT or LCT alone (93 vs. 79 and 62%, respectively). Mean posttransfusion CCI (x 108/L) following PRAT‐compatible platelets was 13.9 ± 12.7 at 1 hr and 7.3 ± 6.9 at 24 hr; following PRAT‐incompatible 5.7 ± 7.8 (1 hr) and 2.1 ± 4.1 (24 hr). Results were similar for LCT‐tested platelets. A radioimmunofiltration modification of the PRAT developed and used in selected cases was simple, fast, efficient, and inexpensive. The study indicated that the techniques evaluated are practical and feasible for routine use in the provision of compatible random donor platelets to the refractory patient who has no other cause for increased platelet destruction.
Undetectable bcr‐abl rearrangements in some CML patients are due to a deletion mutation in the bcr gene
Authors: Hirosawa Shinsaku , Aoki Nobuo , Matsushime Hitoshi , Shibuya Masabumi
Published: February 2007

Most patients with chronic myelogenous leukemia (CML) have Philadelphia (Ph) chromosome. Breakpoints on chromosome 22 in CML occur in a small region designated as the breakpoint cluster region (bcr). More than 90 percent of CML patients have breakpoints in the bcr; the remaining patients had no detectable rearrangement. In our study, a commercially available 1.2 kb Hindlll‐Bglll (1.2 HBg) bcr probe was used to locate breakpoints in the bcr, which were found in 22 of 24 patients. Furthermore, using a probe upstream from the 1.2 HBg probe, rearranged bands were clearly detected in the two patients in whom no extra bands had been found with the 1.2 HBg probe. These results strongly susggest that these two patients carry a deletion at the acr‐abl recombination point encompassing the area of the 1.2 HBg probe. Therefore, in our series, all CML patients eventually had breakpoints in the bcr, and the involvement of rearrangement was demonstrated to be highly specific for CML. Our data indicate that hybridization of CML cellular DNA with several bcr probes is important in examining accurately the frequency of bcr‐abl rearrangements in CML, as some cases contain a deletion within the region.
The variant fetal hemoglobin F Texas I is abnormally acetylated
Authors: Keitt Alan S. , Jones Richard T.
Published: February 2007

Two related infants with indistinct slow‐moving minor hemoglobin bands were detected by electrophoretic cord blood screening. The variant separated into a major and a minor band on isoelectric focusing (IEF), anion exchange chromatography (AEC), and high‐performance liquid chromatography (HPLC). Analysis of the products of tryptic hydrolysis of the abnormal chain revealed a truncated AγT‐l peptide containing a glu→lys substitution at position 5, identifying the variant as Hb F Texas 1. Microsequencing of the major early peak from AEC confirmed the substitution. However, γ chains from the minor peak resisted Edman degradation and were shown to be acetylated by fast atom bombardment mass spectrometry (FABMS). Acetylation of HbF Texas I was nearly three times that of normal HbF measured in the same hemolysate, and this ratio remained constant for over 1 year in the proband. This represents the first demonstration of increased Nα‐acetylation of a variant fetal hemoglobin.
Acute leukemia following treatment of polycythemia vera and essential thrombocythemia with uracil mustard
Authors: Toh Ban T. , Gregory Stephanie A. , Knospe William H.
Published: February 2007

Transformation to acute leukemia (AL) is known to occur in polycythemia Vera (PV) and essential thrombocythemia (ET). Myelosuppressive therapy with agents such as 32P and alkylating agents increase this risk in both disorders. The alkylating agent, uracil mustard (UM), which is an effective agent for controlling thrombocytosis, has not been reported to be leukemogenic. We have treated 29 patients with UM (9 treated continuously and 20 treated intermittently): II with PV, 16 with ET, and 2 with myelofibrosis (MF). Three patients developed AL, two after continuous therapy. These two patients with PV had received the fourth highest and highest total dose of UM, and their duration of treatment was the third and fourth longest among the nine patients treated continuously, respectively. One out of 20 patients treated intermittently with UM developed AL. This patient (3) with ET had received the highest total dose of UM, and her duration of treatment was the longest among the 20 patients treated intermittently.
Characterization of a new glucose‐6‐phosphate dehydrogenase variant: GGPD central city
Authors: Csepreghy Magdolena , Yeilding Allen , Lilly Michael , Hall Kelley , Scott C. W. , Prchal Josef T.
Published: February 2007

Glucose‐6‐phosphate‐dehydrogenase deficiency is the most common disease‐producing enzyme deficiency in man. This paper describes a new glucose‐6‐phosphate‐dehy‐drogenase variant discovered during the evaluation of an episode of acute hemolytic anemia in a 62‐year‐old black male, which was temporally related to the ingestion of Tolbutamide. The hemolysis resolved within 10 days despite continuation of Tolbutamide. The erythrocyte glucose‐6‐phosphate‐dehydrogenase activity was significantly decreased, and its electrophoretic mobility was indistinguishable from wild type enzyme, though faster on starch gel with tris, borate, and phosphate buffers. The enzyme had a biphasic pH optimum reduced Km for G‐6‐P and NADP, decreased utilization of deamino‐NADP, and reduced Ki for NADPH. Because the kinetic properties of this enzyme were unique, we have designated it as G6PD Central City.
Absence of circulating natural killer (NK) cells in a child with erythrophagocytic lymphohistiocytosis lacking NK cell activity
Authors: Kawai Hiroshi , Komiyama Atsushi , Aoyama Kohki , Miyagawa Yukiaki , Akabane Taro
Published: February 2007

A 5‐year‐old girl who was diagnosed as having erythrophagocytic lymphohistiocytosis died at age 9 years. Peripheral lymphocytes from the patient persistently lacked natural killer (NK) cell activity during the 4‐year observation period: the percent lysis values as measured by a 4‐hr 51 Cr release assay at a 40:1 effector:target ratio were below 1.0% against K562 and Molt‐4 cells as compared with the normal lymphocyte value (mean ± SD) of 46.2% ± 5.8% and 43.9% ± 6.7%, respectively. The patient's lymphocytes never developed NK cell activity by their incubation with target cells for longer time periods or by their stimulation with interferon‐α, interleukin‐2, or polyinosinic‐polycytidilic acid. Single cell‐in‐agarose assay showed the absence of target‐binding cells (TBCs): TBC numbers were below 0.3% as compared with the normal lymphocyte value of 8.1% ± 1.3% (mean ± SD). Flow cytometry showed a marked decrease in Leu‐7+ cells (1.7%) and the absence of Leu‐11+cells (0.4%) in the peripheral blood. These results first demonstrate a case of erythrophagocytic lymphohistiocytosis in which there is the lack of NK cell activity due to the absence of circulating NK cells.
Coagulation defects in cyclosporine a treated allogeneic bone marrow transplant patients
Authors: Smith Roy E. , Berg Dale D.
Published: February 2007

CSA toxicity includes renal impairment, microangiopathic hemolytic anemia (MAHA), thrombocytopenia and consumptive coagulopathy (CC). We report five BMT patients who developed CSA‐associated hematological toxicity. All were conditioned with Ara‐C, Cyclophosphamide, Methylprednisolone, TBI, and in two cases busulfan. IV CSA was started the day after marrow infusion and, when practicable, changed to the enteral route. Five patients developed MAHA and T resulting in significantly increased transfusion requirements. All patients had renal impairment and red cell fragmentation. In all patients fragmentation was noted before renal impairment. All developed disproportionate increases in BUN relative to serum creatinine consistent with decreased renal perfusion. Hypertension followed renal impairment in four cases and occurred at the same time as the renal impairment in one case. Two developed CC, prolongation in APTT, and marked decreases in plasma fibrinogen. All patients improved on reduction of the CSA dose. BMT recipients receiving CSA at variable doses may develop evidence of a TTP‐like syndrome and/or CC.
Hemostatic effects of hormonal stimulation in patients with metastatic prostate cancer
Authors: Al‐Mondhiry Hamid , Manni Andrea , Owen John , Gordon Robert
Published: February 2007

Hemostatic abnormalities are common in patients with metastatic malignancy and are attributed, in part, to materials secreted by tumor cells. Tumor stimulation might therefore cause further perturbation of hemostasis. This article reports observations on the effects of androgen stimulation on multiple hemostatic parameters in patients with metastatic prostate cancer. Testosterone was given before chemotherapy in an experimental protocol designed to increase tumor sensitivity to cytotoxic agents. The following parameters were measured on day 0 (before) and days 2 and 4 of fluoxymesterone administration: PT, APTT, platelet count, plasma betathromboglobulin (BTG), platelet factor 4 (PF4), fibrinogen, fibrin(ogen) split products (FSP), factor VIII coagulant activity (VIII C), von Willebrand factor antigen (vWF Ag), fibrinopeptide A (FPA), antithrombin III (AT III), and protein C antigen (PC). Ten patients were studied during 17 cycles of hormonal stimulation. Baseline levels of BTG, PF4, fibrinogen, FSP, factor VIII C, vWF Ag, and FPA were significantly elevated compared with normal control. Although androgen stimulation resulted in elevation of BTG, FPA, and FSP levels by day 4 in many patients, the changes for the entire group were not statistically significant. Other parameters remained unchanged or were only slightly elevated. Two patients developed laboratory evidence of disseminated intravascular coagulation (DIC) but were clinically unaffected. Our data suggest that most patients with metastatic prostate cancer show evidence of ongoing activation of platelets, coagulation, and fibrinolysis. In a few individual patients, androgen stimulation of this hormonally dependent tumor may cause further activation of platelets, coagulation, and fibrinolysis.
Progression of a human B cell chronic lymphocytic leukemia line in nude mice
Authors: Ghose T. , Lee C. L. Y. , Faulkner G. , Fernandez L. A. , Lee S. H. S.
Published: February 2007

Subcutaneous (s.c.) inoculation of the 85‐4LN subline, derived from a lymph nodal metastasis of the Epstein‐Barr virus (EBV) transformed human chronic lymphocytic leukemia (CLL) B cell line, EBV‐CLL (1), produced progressively growing lethal tumors in 31/35 nonirradiated (88.6%) and 22/25 (88%) of whole‐body irradiated (440 rad) nude mice. In contrast, EBV‐CLL(1) could produce progressive tumors only in irradiated nude mice. All 85‐4LN cells had Epstein‐Barr virus nuclear antigen and reacted with pan B and anti‐la antibodies. The morphology and ultrastructural features was consistent with the lymphoblastoid nature of the cells. In all s.c tumor bearing mice, there was enlargement of the spleen and draining lymph nodes. Karyological studies revealed human cells in the spleen and draining nodes in all the mice investigated. Metastases in nonlymphoid organs were seen in 1/8 irradiated and 8/12 nonirradiated mice. The subline contained 77% cells with 47,XY,+ 12 and 23% cells with 4,XY karyotype. The clone with trisomy 12 did not have any growth advantage either in s.c. transplants or in splenic/lymph nodal metastases. Treatment with the maximum permissible doses of methotrexate (MTX) or chlorambucil (CBL) revealed xenografts to be more sensitive to MTX than CBL. A clone with a 1g+ marker, i.e., 46,XY,Dup (1) (q11→q32) appeared to be associated with resistance to CBL. We have not seen any previous report on the growth and dissemination of human CLL B cells in nonirradiated nude mice. The 85‐4LN subline, thus, provides a model for studying the progression, dissemination and therapeutic response of human CLL‐B cells.
A modified method of DNA extraction from peripheral blood and bone marrow specimens
Authors: Hanson Curtis A. , Kersey John H.
Published: February 2007

We have outlined a modified method of DNA extraction from blood and bone marrow that can be used for gene rearrangement studies of leukemia and lymphoma and can consistently give excellent yields of DNA from as little as 1 × 106 cells. The method is based on the use of small sample vessels, a marked reduction in solution volume and minimal handling of the specimen. By using known cell numbers from eight leukemic bone marrow samples and four leukemic call lines, the modified extraction procedure consistently had better yields of DNA, compared with a standard procedure. These findings were confirmed by further comparisons of DNA yields from 14 hypocellular clinical specimens that had been divided into two equal parts for side‐by‐side DNA extraction with both methods. The quality of the DNA from the modified extraction method was similar to standard methods on subsequent Southern blot analysis and hybridization with immunoglobulin and/or T‐cell receptor gene probes. This modified DNA extraction method is a procedure that complements standard extraction methods and expands the number and type of specimens that can be evaluated by the clinical molecular genetics laboratory.
Amsacrine is safe in patients with ventricular ectopy
Authors: Puccio Carmelo A. , Feldman Eric J. , Arlin Zalmen A.
Published: February 2007

Amsacrine is an active antileukemic agent known to induce cardiac arrhythmias, although the incidence of these cardiac events is low. Rhythm abnormalities associated with amsacrine use include the development of fatal tachyarrhythmias, but this risk can be minimized by ensuring a normal serum potassium level prior to drug administration. Even though amsacrine has been given safely to patients with pre‐existing supraventricular arrhythmias, its safety in patients with ventricular ectopy has not been addressed. We describe two patients who underwent treatment with amsacrine without developing life‐threatening dysrhythmias and show that ventricular ectopy does not contraindicate therapy with this agent.
Fetal lamb coagulation system during birth asphyxia
Authors: Andrew M. , O'Brodovich H. , Mitchell L.
Published: February 2007

Levels of many coagulation factors are low in the healthy infant and even lower in the asphyxiated premature infant. We investigated whether a brief exposure to asphyxia at the time of birth causes the activation and consumption of coagulation factors. Following delivery by caesarian section, premature lambs were asphyxiated by occluding the endotracheal tube for 10 min and then resuscitated. Blood was obtained prior to and following birth for measurement of blood gases and the coagulation system. Birth asphyxia in the premature lamb resulted in thrombin generation and rapid consumption of specific coagulation factors.
Lymphocyte and complement abnormalities in splenectomized patients with hematologic disorders
Authors: Wang Winfred C. , Herrod Henry G. , Valenski William R. , Watt Robert J.
Published: February 2007

Twenty‐two patients, splenectomized 1 to 26 years earlier for hematologic disorders, were studied to determine possible defects in immunologic function or complement levels. Quantitation of B cells and T‐cell subsets revealed slight decreases in the proportions of CD3 and CD4 cells but normal or increased absolute numbers of all cell populations. IgM synthesis in vitro by peripheral blood mononuclear cells was markedly diminished, but IgG synthesis was normal. Fractionation studies, in which various B‐cell‐ and T‐cell‐enriched populations from controls and patients were combined, demonstrated diminished B‐cell function in the patients. Sickle cell patients, who were functionally asplenic, showed similar deficits. Complement levels in splenectomized and sickle cell patients in both the classical and alternative pathways were generally normal. A modest decrease in component H in the alternative pathway in splenectomized and sickle cell patients probably was not clinically significant. In summary, splenectomized patients have a diminished capacity for IgM synthesis that can be attributed primarily to defective B‐cell function. This may be partially responsible for their increased susceptibility to infection by encapsulated organisms.
Chemotherapy With cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) for hodgkin disease: Fourteen‐year follow‐up results
Authors: Dusenbery Kathryn E. , Peterson Bruce A. , Bloomfield Clara D.
Published: February 2007

Thirty‐eight patients with advanced Hodgkin disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) from 1970 to 1973 and followed prospectively. Long‐term results after a median follow‐up of 14 years are reported. Seventeen of the 28 complete responders (61%) survived more than 10 years from the initiation of chemotherapy. At the current time, 12 of the 28 patients (43%) are continuously disease‐free 12.8 to 15.3 years after completing induction chemotherapy. Two additional patients are alive in third and fifth remissions. All relapses occurred within 5.5 years of completing induction chemotherapy. Late complications included sterility, aseptic osteonecrosis, severe pulmonary fibrosis, and chronic uveitis. Four of the complete responders (14%) developed second neoplasms, including acute myelogenous leukemia, non‐Hodgkin lymphoma and small cell carcinoma of the lung. All second malignancies were fatal and developed 5‐13 years after initiation of induction chemotherapy. Our data confirm that cure is possible with alternative regimens to MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone).
Multiple myeloma: Relationship between light chain isotype suppression, labelling index of plasma cells, and CD38 expression on peripheral blood lymphocytes
Authors: Joshua Douglas E. , Ioannidis Rosemary , Brown Ross , Francis Susan E. , Gibson John , Kronenberg Harry
Published: February 2007

In this study we have investigated the relationship between the labelling index of plasma cells, the expression of CD38 positive lymphocytes in the peripheral blood, and light chain isotype suppression. This study confirms the relationship between plateau‐phase disease and light chain isotype suppression (LCIS) and documents an inverse relationship between LCIS and CD38 positive lymphocytes (.001 < P < .01), which is similar to the relationship we have described with the expression of CD10 positive lymphocytes. PCA‐1 is rarely expressed in the peripheral blood of patients with myeloma and does not fulfill a role as a marker of active vs. stable disease. There is no relationship between the labelling index of plasma cells and LCIS, because many patients can enter a stage of progressive disease and yet have a labelling index of <1% at that time, although a labelling index <1% is present in the majority of patients with LCIS. β‐2‐microglobulin (β2M) also fails to differentiate these two phases of disease in myeloma and does not have a relationship with LCIS, CD38 expression, or CD10 expression. These data suggest that myeloma, like chronic granulocytic leukemia (CGL), can be considered as having two phases of disease: a stable or chronic phase disease, as identified by the presence of LCIS, the absence of CD10 and CD38 positive lymphocytes in the peripheral blood, and a low labelling index, and progressive disease, which is associated with the loss of LCIS and of, CD10 and CD38 positive lymphocytes in the peripheral blood and a high labelling index, although in many cases of progressive disease, the labelling index may also be low. β2M does not differentiate between these states.
Phenotypic heterogeneity of erythroblasts in erythroblastic leukemia revealed by monoclonal antibodies
Authors: Gupta Amar Das , Dhond Subodh R.
Published: February 2007

Eight cases each of erythroleukemia (AML‐M6) and erythroblastic crisis of chronic granulocytic leukemia (CGLBC‐E) were immunophenotyped with the help of a panel of lineage‐associated monoclonal antibodies (McAbs). The latter included those reactive with erythroid progenitor (BFU‐E and CFU‐E) and erythroid precursors at different stages of maturation. In six of eight cases of AML‐M6, erythroblasts revealed an immature phenotype, as evident from reactivity of the blast cells with McAbs directed against the earlier stages of erythroid maturation. One case had the phenotype of CFU‐E, and in the remaining case of AML‐M6 the erythroblasts showed a “mature” surface antigenic profile. This immunophenotypic spectrum was unrelated to the morphologic maturity of the erythroblasts.

In two cases of CGLBC‐E, an early erythroblastic phenotype was observed, while in as many cases a “mature” phenotype was present. Four of eight cases, however, revealed a mixed, erythroid plus myeloid phenotype. In one of the four cases, two separate blast populations, which represented erythroblasts and myeloblasts, could be identified. In the remaining three cases the blasts were morphologically homogeneous and undifferentiated. High incidence of HLA‐DR positivity in the latter three cases suggests the primitive nature of blasts cells and their closeness to the putative “bipotent” myeloid stem cell. Our study has shown phenotypic heterogeneity of blast cells in AML‐M6 and CGLBC‐E.