bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative thrombocytopenia in type IIB von Willebrand disease
Authors: Hultin Mae B. , Sussman Ira I.
Published: February 2007

We report studies of a large kindred with type IIb von Willebrand disease and manifestations of thrombocytopenia. While only one member of the family was thrombocytopenic routinely, three members of the family who underwent various surgical procedures demonstrated thrombocytopenia and platelet clumping postoperatively. Platelet clumps were found on peripheral blood smear only in the immediate postoperative specimens and did not appear to be a technical artifact. In the one patient who received no preoperative prophylactic therapy, postoperative plasma specimens showed the transient appearance of high molecular weight von Willebrand factor multimers. These results support the hypothesis that surgery, or some related aspect such as stress, led to the release of high molecular weight multimers, resulting in platelet clumping and removal from the circulation, and subsequent thrombocytopenia. Thrombocytopenia under conditions of stress may be a more common manifestation of type IIb vWd than is currently appreciated.
Transformation of refractory anemia with excess of blasts into acute myelogenous leukemia with Ph‐negative chronic myelogenous leukemia‐like characteristics
Authors: Yamauchi Kunihiko , Arimori Shigeru , Nagao Tadami
Published: February 2007

We report a 56 year old patient with acute myelogenous leukemia (FAB classification: M2), in whom the number of mature myeloid cells similar to those seen in Ph‐negative chronic myelogenous leukemia increased markedly 2 months after the diagnosis of refractory anemia with excess of blasts (RAEB). This is a rare case of leukemic evolution as a terminal event of RAEB.
B‐cell surface phenotypes of proliferating myeloma cells: Target antigens for immunotherapy
Authors: Chan Clara S. P. , Wormsley Susan B. , Pierce Lawrence E. , Peter James B. , Schechter Geraldine P.
Published: February 2007

Dual‐parameter flow cytometric analysis of B‐cell antigens and DNA content was used to determine the phenotypes of proliferating tumor cells (S‐phase cells) from 30 patients with multiple myeloma. B4 (CD19), J5 (CALLA, CD10), B1 (CD20), and monotypic surface immunoglobulin (Sig) were expressed heterogeneously in 24 patients. J5 and monotypic Slg were found most frequently but were always expressed on a significantly lower percentage of cells than the antigens typically associated with plasma cells, cytoplasmic immunoglobulin (Clg) and T10 (CD38). S‐phase cells were found in each antigen(+) subset. B antigen(+) cycling cells were demonstrated in 16 patients whose marrow or blood cells expressed B antigens exclusively in the hyperdiploid fraction and therefore were certainly part of the myeloma clone. Similar to the low level of proliferative activity of the T10(+), Clg(+), and PCA1(+) subsets, the percentages of cycling cells of the preplasma cell B‐antigen‐bearing myeloma subsets ranged from < 1% to 12%. The tumor cells of four patients were also studied with dual‐color surface antigen analysis and demonstrated independent expression of B antigens, with only rare coexpression of T10 and monotypic Slg, J5, or B4. These findings are consistent with the presence of distinct myeloma subsets bearing differing B phenotypes in the same tumor and provide evidence that the proliferation in myeloma is occurring at various developmental stages in the malignant B lineage. These antigens may be important targets for immunologic therapy aimed at eliminating the entire proliferating compartment of this B‐cell tumor.
Prognostic factors at relapse for adults with acute myeloid leukemia
Authors: Uhlman Dorothy L. , Bloomfield Clara D. , Hurd David D. , Peterson Bruce A.
Published: February 2007

To identify prognostic factors for patients with acute myeloid leukemia in first relapse we have analyzed the courses of 57 patients undergoing intensive reinduction therapy. The median duration of first remission was 9 months. A second complete remission was achieved by 31 patients (54%). The median duration of second remission was 5 months (range 1‐142 + months). Two patients are still disease‐free with 42 months and 142 months follow‐up. Clinical, laboratory, and treatment variables at the time of original diagnosis and at relapse were examined for possible associations with the outcome of reinduction chemotherapy. Only duration of first remission consistently correlated with ability to achieve a second remission, second remission duration, and overall survival from reinduction. The second complete remission rate was 69% for those with a first remission longer than 9 months but only 39% for those with a first remission less than 9 months (P < 0.05). The patients with longer first remissions also had longer second remissions (8 months median vs. 4 months, P = 0.02) and a longer median survival following reinduction chemotherapy (8 months vs. 5 months, P = 0.02). We conclude that the duration of a patient's first remission should be considered a useful prognostic factor both in treatment planning and in the interpretation of clinical trials of patients in relapse.
Detection of monosomy 7 in interphase cells of patients with myeloid disorders
Authors: Kolluri Rukmini V. , Manuelidis Laura , Sait Sheila , Cremer Thomas , Gezer Sefer , Raza Azra
Published: February 2007

Six patients, five with acute myeloid leukemia (AML) and one with a myelodysplastic syndrome (MDS), were found to have monosomy 7 by conventional cytogenetics at diagnosis. Repetitive DNA sequences from the heterochromatic region of human chromosomes 1 and 7 were used as probes for in situ hybridization experiments on interphase cells of these patients. A double hybridization protocol was used to reveal the particular chromosomes as distinct spots or clusters of signals within interphase nuclei. The chromosome 1 sequence served as an internal control. Simultaneous detection of the sequences showed the presence of two normal number 1 chromosomes and a missing 7 chromosome from individual cells. While cytogenetic preparations showed only −7 metaphases in 3 AML and 1 MDS patients, in situ hybridization of interphase cells showed many normal cells as well as the presence of ‐7 in fully mature granulocytes. One AML patient studied in remission showed only normal metaphases yet had 9% interphase cells with a missing 7 and relapsed within 3 months. We conclude that examination of interphase cells by in situ hybridization provides clinically useful data since every cell including mature granulocytes can be examined, the lineage of a cell can be determined, and efficacy of differentiation therapy can be evaluated.
Spectrin modifications in a heterozygous case of both hereditary elliptocytosis and β‐thalassemia
Authors: Streichman Sara , Herz Ethy , Tatarsky Ilana
Published: February 2007

The clinical and hematological parameters of a patient described here, who inherited the genes of both hereditary elliptocytosis (HE) and β‐thalassemia, seem to reflect a mutual enhancement of the two diseases. The coexistence of the two pathologies is probably also responsible for the observed changes in spectrin: the appearance of an extra spectrin band between tetramers and dimers on denaturing gel electrophoresis and the metabolic‐dependent reduction in spectrin amount. It is assumed that the instability of the skeletal network that results from the HE pathology caused increased exposure of the spectrin molecule to oxidative damage that usually occurs in thalassernic red cells. The products of such oxidation may have led to abnormal spectrin associations which finally resulted in the above changes.
Immunogenetic analysis of bone marrow aspirates in patients with non‐hodgkin lymphomas
Authors: Ellison Douglas J. , Hu Eddie , Zovich Dan , Pinter‐Brown Lauren , Pattengale Paul K.
Published: February 2007

The immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non‐Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy‐ and/or light‐chain or the T‐cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy‐ and light‐chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, by NHL while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B‐cell lineage, while the immunogenotype demonstrated a T‐cell lineage. IGA also demonstrated a clonal population in 1 case of T‐chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of patchy distribution.
Synergy of inhibition of DNA synthesis in human bone marrow by azidothymidine plus deficiency of folate and/or vitamin B12?
Authors: Herzlich Barry C. , Ranginwala Mohammad , Nawabi Ismat , Herbert Victor
Published: February 2007

The effect of azidothymidine (Zidovudine, AZT) on pyrimidine (thymidine, deoxyuridine, and thymidine triphosphate) incorporation into DNA in folate‐ and/or vitamin B12‐deficient and normal human bone marrow cells was studied to Investigate whether such vitamin deficiency affects susceptibility to AZT‐induced hematologic toxicity. Bone marrow cells from 12 patients were studied: 5 had folate and/or vitamin B12 deficiency; 7 controls included 5 with anemia related to chronic disease and 2 with iron deficiency.

At 0.2 μM AZT (3 hr, 37°C), the approximate pharmacologic serum trough level, pyrimidine incorporation into DNA was suppressed by 12 to 19% in folate‐ and/or vitamin B12‐deficient cells and by 16 to 23% in normal cells. At 2.0 μM AZT (3 hr, 37°C), the approximate pharmacologic serum peak level, this was suppressed by 15 to 40% in folate‐ and/or vitamin B12‐deficient cells and by 32 to 47% in controls. Deoxyuridine incorporation into DNA was inhibited signlficantly greater than thymidine at 2.0 μM AZT (3 hr, 37°C) in both groups. Inhibition of deoxyuridine incorporation was not reversed with methyltetrahydrofolate or vitamin B12. There tended to be less striking suppression by AZT of deoxyuridine incorporation into DNA in bone marrow cells from vitamin B12‐deficient patients, which was made more striking by adding vitamin B12. This suggests that some of what passes for “AZT damage” to bone marrow cells may in fact be coincident deficiency of vitamin B12.

AZT Inhibition of DNA synthesis in 3 hr bone marrow cultures is relatively consistent in a varlety of hematologic disorders. As approximately two‐thirds of AIDS patients appear to be in negative balance with respect to folate and/or vitamin B12, the fact that AZT‐induced inhibition of pyrimidine incorporation into DNA is occurring in cells which may be megaloblastic, i. e., In a state of Impaired DNA synthesis, suggests that these cells may be more susceptible to AZT toxicity. The data also support the notion that AZT inhibition results predominantly from termination of DNA chain elongation.

Whether folate or vitamin B12 supplementation may partially overcome apparent “AZT inhibition” of DNA synthesis (hematologic toxicity) and whether the benefit of such therapy exceeds the risk will require further study.
Effect of adherent cells on the regulation of BFU‐E in patients with myeloproliferative disease
Authors: Shabbad Evelyne , Cassel Aliza , Froom Paul , Aghai Esther
Published: February 2007

The interaction between adherent cells and red cell progenitors from peripheral blood of patients with polycythemia vera (PV), essential thrombocytosis (ET), and healthy controls was studied. Various combinations of adherent and nonadherent cells were co‐cultured in a semisolid system. Adherent cells from controls, when added at low concentrations, stimulated BFU‐E proliferation, whereas high concentrations (40% of total cells in the culture) caused a significant decrease in the number of BFU‐E colonies in 6/8 PV patients, 4/4 ET patients, and 8/12 controls. On the other hand, low and high concentrations of adherent cells from both patients with PV and ET caused a significant increase in BFU‐E from either patients or controls. Moreover, adherent cells from these patients induced endogenous BFU‐E proliferation (independent of erythropoietin) in nonadherent cells of 12/12 normal controls.

The results show that BFU‐E from patients with PV and ET are sensitive to suppression by normal adherent cells. On the other hand, adherent cells from these patients possess stimulatory activity on BFU‐E from peripheral blood at all concentrations and are devoid of the inhibitory activity. This suggests a possible defect in the functioning of adherent cells in PV and ET patients which may contribute to the abnormal regulation of hematopoiesis in these disorders.
Hematological abnormalities in hemophilic patients with human immunodeficiency virus infection
Authors: Bello Jose L. , Burgaleta Carmen , Magallon Manuel , Herruzo Rafael , Villar Jose M.
Published: February 2007

Hematological abnormalities are common in patients with AIDS or AIDS‐related complex. We studied cytological characteristics in peripheral blood and bone marrow samples of 33 hemophilic patients with HIV Infection and in six HIV negatives. The HIV‐positive patients presented leukopenia (60.6%), thrombocytopenia (69.9%), and anemia (57.5%). Bone marrow showed abnormalities of maturation in one or more cell lines similar to those described in other HIV‐infected groups of patients. These findings were more prominent in megacaryocytes and granulocytic series. Lymphocytosis, plasmocytosis, and increased hemophagocytosis were also common. These alterations do not appear in HIV‐negative patients and seem related to a direct effect of HIV on bone marrow cells or to alterations in T‐cell regulatory functions.
Platelet peroxidase‐like activity detected in mature erythroblasts from a patient with pernicious anemia
Authors: Kawaguchi Masato , Nakano Masaru , Enomoto Yasuhiro , Watanabe Younosuke , Toyama Keisuke
Published: February 2007

We report a case of pernicious anemia in which the possession of platelet peroxidase (PPO)‐like activity was proved in its erythroblasts. PPO‐positive cells were found in a distinct minor population of hemoglobinized (as a mean of differentiated) erythroid cells in the bone marrow before treatment, but these cells disappeared following therapy with vitamin B12. The present report is considered to be the first case to identify PPO‐like activity in mature erythroblasts from the nonmalignant clone. The existence of PPO in erythroid lineage in cases with pernicious anemia is discussed.
Familial macrothrombocytopenia associated with decreased glycosylation of platelet membrane glycoprotein IV
Authors: Yufu Yuji , Ideguchi Hiroshi , Narishige Takahiro , Suematsu Eiichi , Toyoda Kazunori , Nishimura Junji , Nawata Hajime , Oda Susumu
Published: February 2007

A case of hereditary thrombocytopenia with large platelets (familial macrothrombocytopenia, FM) is reported. Studies on the platelets from the propositus showed decreased glycosylation of platelet membrane glycoprotein IV, which would distinguish the case from other FM previously described.
Effects of 2′‐deoxycoformycin on hl‐60 cell differentiation, adenosine deaminase, and oligoadenylate synthetase
Authors: Triozzi Pierre L. , Vicstein Frederick
Published: February 2007

There is evidence that 2′‐deoxycoformycin (DCF) functions as a differentiating agent. We examined the effects of DCF on the differentiation of HL‐60 cells, a standard model of leukemic cell differentiation. DCF did not induce morphologic or histochemical evidence of differentiation, nor did it interact with retinoic acid, 1,25‐dihydroxyvitamin D3, or interferon‐gamma in inducing differentiation. Furthermore, DCF and agents that differentiated HL‐60 cells had opposing effects on adenosine deaminase and 2′, 5′‐oligoadenylate synthetase activity.
Pulmonary embolism and splenic infarction in a patient with sickle cell trait
Authors: Sugarman Jeremy , Samuelson Wayne M. , Wilkinson Robert H. , Rosse Wendell F.
Published: February 2007

A 43 year‐old black man with sickle cell trait documented by hemoglobin electrophoresis presented with severe pleuritic chest pain and hypoxemia three weeks after discharge following abdominal surgery. A pulmonary embolus was diagnosed by angiography and he was treated with heparin; the minimum arterial pO2 was 55 torr while O2 was being administered at a rate of 3 L/min. During this therapy, he developed abdominal pain. Computerized tomography suggested splenic infarction, which was documented by radionuclide liver‐spleen scan and magnetic resonance imaging (MRI); the patient's spleen had been normal at exploratory laparotomy three weeks previously. No source for emboli was identified in the deep venous system by MRI.

Although splenic infarction has been reported in patients with sickle cell trait at high altitude, this is the first reported case of splenic infarction secondary to the hypoxemia of pulmonary embolism in a patient with sickle cell trait. The spleen is subject to infarction in sickle cell trait because blood flow is slow through a hypoxemic and acidemic environment. The additional hypoxemia due to pulmonary embolism is presumed, in our patient, to have created a local splenic environment which permitted infarction to occur.
Cigarette smoking, blast crisis, and survival in chronic myeloid leukemia
Authors: Herr Ray , Ferguson Jan , Myers Nicole , Rovira Douglas , Robinson William A.
Published: February 2007

We reviewed the records of all patients with chronic myeloid leukemia (CML) seen in the CML Clinic of the University of Colorado Health Sciences Center between 1968 and 1987 for a history of cigarette smoking. Patients who smoked for five or more pack/years within the ten years preceding, or after the diagnosis of CML, were defined as smokers. Adequate smoking histories were obtained on 122 patients. Eighty‐seven of these were non‐smokers and 35 were smokers by the above criteria. The smoking group had a higher predominance of males, an older median age, and were diagnosed earlier in the course of the 20 year study. Seventy‐two patients had died at the time of analysis. All but one, a non‐smoker, died from the development of blast crisis. The overall median actuarial survival was significantly reduced for smokers (35 months) as compared to non‐smokers (47 months). This was particularly striking for patients who had succumbed to the disease, with a median survival of 30 months in smokers versus 46 months in non‐smokers. Although various explanations could explain the differences noted, we conclude that cigarette smoking has an adverse effect on the development of blast crisis and survival in chronic myeloid leukemia.
Rapid reduction of methemoglobin in rat bone marrow erythroid cells
Authors: Yubisui Toshitsugu , Takeshita Masazumi , Hultquist Donald E.
Published: February 2007

Methemoglobin reduction was shown to proceed much more rapidly in erythroid cells from rat bone marrow than in rat erythrocytes. Methemoglobin reduction in suspensions of intact, nitrite‐treated bone marrow cells does not depend on the presence of glucose in the incubation mixture, even after the cells have been stored in substrate‐free medium. 2‐Deoxyglucose and iodoacetate prevent the reduction from proceeding to completion. The results suggest that, relative to erythrocytes, immature erythroid cells more efficiently catalyze methemoglobin reduction and more effectively store metabolites which provide electrons for this reaction.
Effect of novel 1‐alkyl‐3‐hydroxy‐2‐methylpyrid‐4‐one chelators on uptake and release of iron from macrophages
Authors: Brock Jeremy H. , Licéaga Joan , Arthur Helen M. L. , Kontoghiorghes George J.
Published: February 2007

The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2‐dimethyl (L1) and 1‐ethyl‐2‐methyl (L1NEt) derivatives of 3‐hydroxypyrid‐4‐one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe‐transferrin‐antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic α‐ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine.
Myelodysplastic syndromes: A study of surface markers and in vitro growth patterns
Authors: Guyotat Denis , Campos Lydia , Thomas Xavier , Vila Liliana , Shi Zhi‐Hua , Charrin Christiane , Gentilhomme Odile , Fiere Denis
Published: February 2007

A study of surface markers and in vitro growth in semi‐solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB‐t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony‐forming cells were assessed by culture in semi‐solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB‐t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS.
Leukemic transformation in polycythemia vera: Analysis of risk factors
Authors: Nand Sucha , Messmore Harry , Fisher Susan Gross , Bird Mary Lourdes , Schulz William , Fisher Richard I.
Published: February 2007

Forty‐eight patients with polycythemia vera (PV) were retrospectively studied for incidence of acute leukemia over a 12 year period. Initial clinical features, hemogram, RBC mass, B12 levels, neutrophil alkaline phosphatase (NAP), and therapy given were studied for association with development of acute leukemia. There were 25 males and mean age at diagnosis was 61.4 years. Initial Hg was 18.38 ± 1.86 g/dl, WBC 16.44 ± 12.92 (× 1,000/mm3), platelets 632.94 ± 303.81 (×1,000/mm3), B12 1,030.93 ± 445.20 pg/ml, and neutrophil alkaline phosphatase (NAP) score 136.63 ± 55.14. Twenty‐three patients were treated with phlebotomy alone and 25 received additional myelosuppressive therapy as follows—2 received p32 alone, 4 alkylating agents alone, 8 hydroxyurea (HU) alone, and 11 received 2 or more (multiple) of these agents. None of those treated with phlebotomy alone but 6 of 25 (24%) patients given myelosuppressive therapy developed acute leukemia (P = .03) after a mean period of 46.8 months from start of myelosuppressive therapy. Four of the 11 patients (36%) receiving multiple agent therapy developed acute leukemia (P = .019). Initial hemoglobin levels, but not the other clinical parameters, were significantly higher in patients who developed acute leukemia (P = .002), and this difference persisted in various subgroups receiving myelosuppressive therapy. Thus, high initial hemoglobin and use of any myelosuppressive therapy are associated with an increased risk of leukemic transformation in polycythemia vera. This risk becomes substantial with the use of two or more myelosuppressive agents. Since myelosuppressive therapy does not prolong survival, its role in the management of polycythemia vera should be reexamined.
5′ nucleotidase in chronic b cell leukemias: A cytochemical and ultrastructural study
Authors: Invernizzi Rosangela , de Fazio Pasqualina , Fenoglio Carla , Ippoliti Giovanbattista , Zambelli Luisa M. , Razzano Monica , Ascari Edoardo
Published: February 2007

We studied by cytochemical means the distribution of 5′ nucleotidase (5′ NT), a purine degradative enzyme, in the circulating lymphocytes of 24 healthy donors and 41 cases of chronic lymphoid leukemias, classified according to morphological and immunological criteria. About half the normal circulating lymphocytes were 5′ NT positive and exhibited variable degrees of enzyme activity. Among chronic B lymphocytic leukemias we found high percentages of positive cells only in the phenotypically more mature cases. Moreover all cases of hairy cell, follicular cell, lymphoplasmacytic, and plasma cell leukemia showed moderate or weak 5′ NT reactivity. Also one case of chronic T lymphocytic leukemia, CD8 positive, was moderately positive, while another, with large granular lymphocyte morphology, was completely negative. Electron microscopy revealed a discontinuous, granular plasma membrane reaction pattern, varying in intensity from case to case. In conclusion, our results confirm the usefulness of the 5′ NT cytochemical reaction for identification of lymphoid populations at different stages of maturation in chronic B cell disorders.
Recurrent spleen enlargement during cyclic granulocyte‐macrophage colony‐stimulating factor therapy for myelodysplastic syndrome
Authors: Delmer A. , Karmochkine M. , Cadiou M. , Gerhartz H. , Zittoun R.
Published: February 2007

A 65‐year‐old woman with refractory anemia with excess of blasts received sequential courses of granulocyte‐macrophage colony‐stimulating factor therapy (GM‐CSF) and low‐dose cytosine arabinoside. Each course of GM‐CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen.
Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations
Authors: Lindenbaum John , Savage David G. , Stabler Sally P. , Allen Robert H.
Published: February 2007

The serum cobalamin level has been generally considered to be essentially 100% sensitive in the detection of the clinical disorders caused by cobalamin deficiency. We tested this hypothesis in two groups of patients. In patients with pernicious anemia or previous gastrectomy who received less than monthly maintenance therapy, early hematologic relapse was associated with elevation of the serum methylmalonic acid, total homocysteine, or both metabolites in 95% of instances, although the serum cobalamin was low in only 69%. In the absence of hematologic relapse, the methylmalonic acid was abnormal more than twice as frequently as the serum cobalamin. We also reviewed the records of 419 consecutive patients with recognized clinically significant cobalamin deficiency. Twelve patients were identified in whom deficiency was clearly present although the serum cobalamin was greater than 200 pg/ml. Anemia was usually absent or mild, but 5 had prominent neurological involvement that subsequently responded to cobalamin. Both the serum methylmalonic acid and total homocysteine were increased in each patient. The serum cobalamin was normal in 9 (5.2%) of 173 patients with recognized cobalamin deficiency seen in the last 5 years. Antibiotic treatment lowered the serum methylmalonic acid but not the total homocysteine level in two cobalamin‐deficient patients, suggesting that propionic acid generated by the anaerobic gut flora may be a precursor of methylmalonic acid in deficient patients. We conclude that the serum cobalamin is normal in a significant minority of patients with cobalamin deficiency and that the measurement of serum metabolite concentrations facilitates the identification of such patients.
Methylmalonic aciduria due to a new defect in adenosylcobalamin accumulation by cells
Authors: Cooper Bernard A. , Rosenblatt David S. , Watkins David
Published: February 2007

A child with methylmalonic aciduria due to failure to accumulate adocbl in mitochondria has a phenotype similar to cblA disease. Deficient utilization of labeled propionate by his fibroblasts is corrected by their fusion with those from cblA patients, indicating that he belongs to a different complementation class and probably is deficient in a different gene product. The defect appears not to be due to reduced affinity of enzymes for adocbl, or for ATP, and the minimal thiol required for adocbl synthesis is not different from that of extracts of normal cells.
Further characterization of prolymphocytic leukemia cells as a tumor of activated B cells
Authors: Berrebi Alain , Bassous‐Guedj Lucette , Vorst Eljakim , Dagan Shlomo , Shtalrid Mordechai , Freedman Arnold
Published: February 2007

Peripheral blood mononuclear cells from 24 patients with prolymphocytic leukemia (PLL) were isolated using a Ficoll‐Hypaque gradient and stained by indirect immunofluorescence using a wide panel of monoclonal antibodies against B cell restricted and associated antigens, including HLA DR (la), CD19, CD21 (C3dR) surface membrane immunoglobulin (Slg), CD10 (CALLA), C3b, B5, CD25 (TAC), PCA1, T9, and T10. The cells were also tested for the FMC7, defined previously on PLL cells and the RAB1, a newly described hairy cell leukemia antigen. Thirteen out of the 24 samples expressed with variable intensity all the above antigens.

While la, CD19, CD20, FMC7, and RAB1 were strongly or moderately expressed in all, the complement receptors (CD21 and C3b) were only weakly expressed in 12 cases; and the activation antigens B5, TAC, T9, T10, and PCA1 were found with variable intensity in two‐thirds of the cases. In 50% of the cases tested, the CD5 antigen (usually strongly expressed on B CLL cells) was weakly to moderately expressed. These findings (absence or weak expression of complement receptors with variable expression of activation antigens) suggest that the PLL cells are activated B cells. When stimulated in vitro by anti‐mu and TPA, (phorbol ester) tumor cells showed a decrease in CD21 and Slg and a stronger expression of CD25, T9, T10, and PCA1, with evidence of lg secretion in four out of the seven cases studied. This confirms that the PLL cells arrested at an advanced stage of differentiation progressed narrowly to more differentiated cells. In view of our findings, we believe that the term prolymphocytic leukemia is inaccurate to define the stage of cell differentiation, and we suggest calling the disease preplasmacytic leukemia.
Acute leukemia evolving from multiple myeloma and co‐expressing myeloid and plasma cell antigens
Authors: Stewart A. K. , Freedman J. , Garvey M. B.
Published: February 2007

This report describes the development of acute myeloblastic leukemia in a patient after long‐term alkylator therapy for multiple myeloma. Despite chromosome deletions −5, −7, the patient lacked the histochemistry and clinical findings characteristic of therapy‐induced leukemia. In double‐labeled surface marker studies by flow cytometry, the leukemic blast cells co‐expressed myeloid and plasma cell surface markers. The findings may support the hypothesis of a single stem cell abnormality's being responsible for both the malignant plasma cells and the myeloid leukemic cells.
Level and composition of fetal hemoglobin expression in normal newborn babies are not dependent on β cluster DNA haplotype
Authors: Rochette Jacques , Dodé Catherine , Leturcq France , Krishnamoorthy Rajagopal
Published: February 2007

Interindividual variations in the level and composition of fetal hemoglobin observed in 604 cord blood samples from normal white and nonwhite newborns, unlike those in adults, are not dependent on β gene cluster DNA haplotype. The data suggest that the mechanism(s) involved in the neonatal expression of Hb F is distinct from that at the adult stage.
CD4+ and CD56+ acute monoblastic leukemia
Authors: Tauchi Tetsuzo , Ohyashiki Kazuma , Ohyashiki Junko H. , Kawanishi Yoshikazu , Kimura Yukihiko , Saito Midori , Nakazawa Shinpei , Kawai Yoshikazu , Toyama Keisuke
Published: February 2007

We report here a patient with acute monoblastic leukemia whose leukemia cells had CD4 (T4) and CD56 (NKH‐1) antigens, in addition to CD36 (OKM5) antigen. The leukemia cells did not have NK or ADCC activities. They showed no rearrangements of immunoglobulin heavy (IgH) chain and T cell receptor (TCR)‐beta chain genes, indicating that the leukemia cells were nonlymphoid. The presence of this case suggests that leukemia cells could be orginated from monocytes with NK‐associated antigen without IgH or TCR rearrangements.
Variation in the level of fetal hemoglobin in (δβ)°‐thalassemia heterozygotes with different numbers of α‐globin genes
Authors: Öner C. , Gurgey A. , Altay C. , Kutlar F. , Huisman T. H. J.
Published: February 2007

The Sicilian type of (αβ)°‐thalassemia characterized by a ˜13 kb deletion, was present in a Turkish boy who is a homozygote and in his heterozygous parents who are first cousins. The father with ˜21% Hb F had five α‐globin genes (αα/ααα) and the mother with ˜10% Hb F had an α‐thal‐2 heterozygosity (αα/‐α). The difference in Hb F level is explained by a decreased formation of α2γ2 tetramers in the mother with an α‐chain deficiency while the extra α‐globin gene in the father will promote Hb F production.
Target cell of leukemic transformation in acute megakaryoblastic leukemia
Authors: Koike Tadashi , Urushiyama Masaru , Narita Miwako , Saitoh Hiroshi , Ishida Fumihiro , Imashuku Shinsaku , Morioka Yoshihito , Utsumi Jiroh , Ishizuka Toshie , Tsuruta Toshihisa , Takeuchi Yutaka , Kashimura Makoto , Shibata Akira
Published: February 2007

Acute megakaryoblastic leukemia (AMkL) is a newly defined acute leukemia in which the differentiation of proliferating blasts is arrested at the megakaryocytic precursor stage. In order to clarify whether a target cell of leukemic transformation in AMkL is a cell committed to megakaryocytic lineage, or a multipotential stem cell, we examined AMkL patients with regard to: a) the presence of myelodyplastic features in residual erythroid and granulocytic cells, b) coexistence of myeloperoxidase (MPO)‐positive blasts with megakaryoblasts, and c) the presence of the same chromosomal abnormality in erythroid and granuloid colony‐forming cells as seen in megakaryoblasts. Regarding the former two items, results were compared with those from megakaryoblastic crisis of chronic myelocytic leukemia (CML‐MkBC) and transient myeloproliferative disorder in Down syndrome (DS‐TMD), which are thought to be multipotential stem cell disorders. Among 18 patients with AMkL, three, all complicating myelofibrosis, had marked myelodysplastic changes of erythroid series and/or granulocytic series. In 4 out of 7 patients with CML‐MkBC, 5 out of 8 patients with DS‐TMD, and 7 out of 18 patients with AMkL, MPO‐positive blasts, even though rare, were observed in addition to PPO‐positive blasts. All except one of these patients with AMkL also showed complicating myelofibrosis. In one case of AMkL with myelofibrosis, chromosomal analysis of cultured cells of individual colonies revealed that all the analysable metaphases from both CFU‐GM and BFU‐E had the same chromosomal abnormality as megakaryoblasts. This study has clarified that a considerable proportion of AMkL cases, particularly those with complicating myelofibrosis or showing acute myelofibrosis, arise against the background of a multipotential stem cell disorder, even if blasts are exclusively megakaryocytic in phenotype.
Relationship of partially purified factor concentrates to immune tests and AIDS
Authors: Jason Janine , Holman Robert C. , Evatt Group Bruce L.
Published: February 2007

We evaluated those members of a cohort of 203 hemophilic men providing all necessary information at their 1984 and 1985 evaluations, to determine whether non‐heated or < 80°C dry heat‐treated partially purified factor products were associated with 1) the development of AIDS in human immunodeficiency virus (HIV)‐infected persons or 2) abnormal immune test results in participants seroconverting or remaining HIV seronegative. We found no relationship between type of factor (VIII vs. IX) (n = 162), frequency of usage (≧once a week vs. < once a week) (n = 141), or yearly doses of non‐heated or dry heat‐treated partially purified factor (n = 118) and the development of AIDS. Seroconverting participants using partially purified factor products ≧once a week in 1984 had lower T‐helper cell numbers in 1985 than those receiving factor less frequently (median 515 vs. 772/mm3, n = 9), as did those using factor ≧once a week in 1985 (median 515 vs. 726/mm3, n = 10). A similar relation was seen between 1984 frequency and 1985 T‐helper cell numbers of seronegative participants (median 741 vs. 1037/mm3, n = 31). The yearly dose of heat‐treated products was not associated with any immune test result or changes in results between years. These findings suggested that frequency of administration of partially purified factor materials may have had an effect upon the immune system, but that total yearly dose did not. Previously used partly purified, dry heat‐treated factor concentrates were not associated with the development of AIDS.
Specific identification of fibrin(ogen) degradation products in plasma and serum using blotting and peroxidase labeled antiserum
Authors: Proietti Anna B. , McGuire Maura , Bell William
Published: February 2007

We describe a method for identifying fibrinogen and fibrin split products using electrophoresis on agarose gel with sodium dodecyl sulfate (SDS) followed by blotting in nitrocellulose paper. Detection of these derivatives after blotting is accomplished with per‐oxidase‐conjugated rather than by isotopically labeled antibodies. This technique can detect diverse fibrinogen derivatives produced in vivo or in vitro by the combined action of thrombin, plasmin, and factor XIII. This methodology is applicable to plasma, serum, and other body fluids including urine and ascitic fluid. This sensitive and specific assay, distinguishing the products of cross‐linked fibrin from those of fibrinogen and detecting fibrin polymers in plasma, can be achieved without the use of radioactivity.
Idiopathic myelofibrosis: A clinical study of 80 patients
Authors: Hasselbalch Hans
Published: February 2007

A series of 122 consecutive patients with bone marrow fibrosis initially referred or categorized as idiopathic myelofibrosis is described. After a clinical and pathological review 14 patients were classified as postpolycythaemic myelofibrosis and 7 patients as a transitional myeloproliferative disorder. In 13 patients a diagnosis of hairy cell leukaemia was made, 3 patients had malignant tymphoma, 2 had malignant histiocytosis, and 1 patient had systemic lupus erythematosus with myelofibrosis. Two patients were excluded for further analysis owing to insufficient data.

In the remaining 80 patients a diagnosis of idiopathic myelofibrosis was made. The clinical and laboratory findings in this series of patients are presented and compared to those in previous series. Infectious, cardiovascular, thromboembolic, and haemorrhagic complications were frequent, being recorded in 63%, 50%, 40%, and 33% of the patients, respectively. Various autoimmune phenomena were found in a proportion of the patients, but none had clinical evidence of connective tissue disease. Fifteen patients (19%) had a syndrome of acute myelofibrosis. The diagnostic criteria for this disease entity and its place within the spectrum of myeloproliferative disorders are discussed. In the present series acute myelofibrosis was found to encompass various transitional stages toward the evolution of acute leukaemia. It is proposed that acute or malignant myelofibrosis is considered as an acute variant of idiopathic myelofibrosis. Within this syndrome the acute variant seems to be far more common than previously recognized, which may also explain the marked clinical heterogeneity of the myelofibrosis/osteomyelosclerosis syndrome in this and most previous series.
Prolymphocytic leukemia treated with natural and recombinant α‐interferon
Authors: Terashima Takeshi , Ohtake Ken‐Ichi , Ogawa Tetsuhei
Published: February 2007

The patient was a 65 year old woman with a massive splenomegaly and no lymphoadenopathy. An electron microscopic study of the peripheral blood cells revealed that these cells were prolymphocytes with a single large nucleolus. Treatment with native and recombinant α‐interferon has produced an impressive reduction in spleen size and in the count of prolymphocytes.
Type‐C virus‐like particles in a human B‐cell lymphoma cell line
Authors: Kubonishi Ichiro , Sawada Takashi , Yano Shoki , Eguchi Taisuke , Iwahara Yoshihito , Takeuchi Chise , Miyoshi Isao , Ohtsuki Yuji
Published: February 2007

Type‐C virus‐like particles (VLPs) were found in an Epstein‐Barr (EB) virus‐infected human B‐cell lymphoma cell line, SP‐50B, that was established from a patient with non‐Hodgkin lymphoma. The cell line continuously produces a small number of type‐C VLPs, 150–200 nm in diameter, over 1 year. SP‐50B cells were negative for HTLV‐I and HTLV‐II antigens and did not contain the HTLV‐I genome. In addition, two EB virus nuclear antigen (EBNA)‐positive B‐cell lines, SP‐54‐Cord and SP‐57‐CLL, were established from human cord blood and chronic lymphocytic leukemia (CLL), respectively, by coculture with lethally irradiated SP‐50B cells. Type‐C VLPs with the same morphology were also found in both cell lines.
Transformation of polycythemia vera to ph‐positive chronic myelogenous leukemia
Authors: Haq Amin U.
Published: February 2007

A patient with polycythemia vera (PV) developed chronic myelogenous leukemia (CML) 8 years after his initial presentation with erythrocytosis. The patient received a total of 3.5‐7 g of chlorambucil over an approximate period of 5 years. Transformation of PV to CML is very unusual; only three substantiated cases had been reported in literature until 1975, and none has been described since then. All patients received either 32P or chemotherapy for PV treatment, suggesting that irradiation and alkylating agents may have played a role in the transformation to CML.
Lack of response of bone marrow, in vitro, to growth factors in congenital neutropenia
Authors: Chang James , Coutinho L. H. , Dexter Michael , Craft Alan W. , Reid Michael M.
Published: February 2007

Severe congenital neutropenia has a poor outlook. In vitro clonogenic assays using recombinant growth factors may improve understanding of the underlying pathogenetic mechanisms and identify those in whom growth factors might be clinically useful. Marrow from a boy with congenital neutropenia was cultured with a variety of recombinant growth factors. The results show that the neutropenia did not result from a lack of myeloid progenitors but that these progenitors could not produce mature neutrophils. Bone marrow transplantation is being considered as the most likely approach to correct neutropenia.
Serum and red blood cell magnesium, copper, and zinc content in G6PD deficiency
Authors: Karunanithy R. , Ng S. E. , Saha N.
Published: February 2007

Sixty‐nine G6PD‐deficient and 67 normal non‐deficient Chinese adult males were investigated for blood hemoglobin concentration and for serum and red cell content of magnesium, copper, and zinc. There was no significant difference in blood hemoglobin content. Both the serum magnesium and copper content were found to be significantly lower in the G6PD‐deficient subjects compared to that in the non‐deficient control. Serum zinc content and red cell content of all the three metals were not significantly altered in G6PD deficiency.
Regulation of Tissue Plasminogen Activator in Sickle Cell Anemia
Authors: Phillips George , Hartman John , Keller V. Antoine , Santiago Manuel A. , Pizzo Salvatore
Published: February 2007

Evidence of activation of the clotting system in individuals with sickle cell anemia (SCA) has been observed by several investigators. It has been suggested that the clotting and fibrinolytic systems may play a role in the pathophysiology of vaso‐occlusion in SCA. We reported previously evidence of abnormal fibrinolytic activity as reflected in decreased releasable tissue plasminogen activator (t‐PA) using a functional assay. We have examined the mechanism of the decreased functional releasable t‐PA in individuals with SCA. We studied 12 patients with respect to releasable t‐PA, fast acting inhibitor to t‐PA (or PAI‐1), and immunoreactive or antigenic t‐PA. These SCA individuals were at their baseline states and not taking medications known to interfere with the fibrinolytic or clotting systems. We found that the mean releasable t‐PA for the SCA individuals was 0.01 IU/ml of plasma with a standard error of mean (SEM) of 0.01. The mean releasable t‐PA of 118 healthy normal controls was 0.70 IU/ml with SEM 0.10 (P < 0.001). The mean level of fast‐acting inhibitor to t‐PA in unoccluded circulation of the SCA patients' plasma was 16.5 IU/ml with SEM of 3.54. The mean plasma levels of fast‐acting inhibitor to t‐PA in 56 healthy controls was 2.56 IU/ml with SEM of 0.29 (P < 0.0001). The SCA patients had a mean baseline t‐PA antigen level of 5.98 ng/ml with SEM of 1.72. The mean level of t‐PA antigen of 78 healthy controls using the same technique was 4.3 ng/ml with SEM of 2.7 (not significant). The mean baseline functional t‐PA for SCA individuals was 0.15 IU/ml with SEM 0.01 and the mean baseline functional t‐PA for 118 controls was 0.17 IU/ml with SEM 0.10. These data suggest that the mechanism of decreased releasable t‐PA in sickle cell anemia is related to an elevation of fast‐acting inhibitor to t‐PA and that antigenically t‐PA is present in normal quantities in the baseline plasma in this population.
Neonatal alloimmune thrombocytopenic purpura associated with sensitization against the platelet‐specific antigen Yuka
Authors: Matsuda Tadashi , Yonaha Hisashi , Azuma Eiichi , Sakurai Minoru , Imai Shigemi
Published: February 2007

We report a Japanese newborn who developed alloimmune thrombocytopenia by the antibodies to the newly discovered platelet antigen Yuka. The infant recovered uneventfully in 10 days without specific treatment. Antiplatelet ailoantibodies in the patient were IgG class detected by mixed passive hemagglutination (MPHA). Family study showed that Yuka antigen was inherited as an autosomal dominant trait. Cases with Yuka‐associated alloimmune thrombocytopenia are reviewed.