bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of electron microscopy in the diagnosis of congenital dyserythropoietic anemia type I: Report of a case
Authors: Facon T. , Zandecki M. , Caulier M. T. , Mannessier L. , Fenaux P. , Jouet J. P. , Bauters F.
Published: February 2007

This report describes a case of congenital dyserythropoietic anemia (CDA) type I diagnosed in a 22‐year‐old woman with a two year history of macrocytic anemia. Light microscopy study of bone marrow disclosed only minor and nonspecific findings, without erythroid hyperplasia. Electron microscopy of bone marrow erythroblasts surprisingly showed most of the classical features of CDA type I. Electron microscopy may be an important tool for the diagnosis of macrocytic anemia of obscure origin, especially in young patients.
CD7 false‐positive acute myelogenous leukemia and promyelocytic leukemia cell line HL‐60: Characterization of CD7 epitopes by four monoclonal antibodies
Authors: Imamura Nobutaka , Ota Hiromi , Kuramoto Atsushi
Published: February 2007

Phenotypes of cells from 12 patients with acute myelogenous leukemia (AML) were analysed by means of a fluorescence‐activated cell sorter utilizing a panel of monoclonal antibodies (MAbs). A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD11, CD13, and CD33 but did not express the antigens against CD1, CD3, CD4, CD5, CDB, CD19, CD20, CD21, CD41 and 42, and glycophorin A. Three out of the 12 cases expressed CD7 antigen. However, one of them showed no reaction with Tp40 MAb, whereas the others showed reaction with Leu9 and T55. The discrepancy of reactivities between Leu9 and Tp40 MAbs prompted us to study the promyelocytic leukemia cell line HL‐60, which showed similar reactions against Leu9 and Tp40 MAbs. Leu9, OKT16, and T55 MAbs reacted strongly with HL60 cells, whereas Tp40 MAb, which reacted strongly with T‐cell leukemia cell line Jurkat, showed no reaction.

The reactivity of Leu9, OKT16, and T55 MAbs with HL‐60 cells was completely inhibited after preincubation with aggregated human immunoglobulin G (AHIG), which clearly shows the existence of nonspecific binding between these 3 MAbs and HL‐60 cells via FcγR.

On the basis of our experiments, we conclude that HL‐60 cells bind nonspecifically with Leu9, OKT16, and T55 MAbs via FcRI, and this is suggestive that de novo AML cells probably behave in the same fashion. Hence, we recommend that the utilization of murine IgG2a and IgG3 MAbs should be avoided especially in cell surface analysis of myeloid leukemic cells.
Occupational risk for hematological malignancies
Authors: Pasqualetti Paolo , Casale Raffaele , Colantonio Domenico , Collacciani Antonio
Published: February 2007

A case‐control study was conducted in 620 cases of hematological malignancies and in 1,240 age‐ and sex‐matched controls in order to verify the possible association between occupation, toxic substances exposure, and the risk of hematological neoplasias. The results demonstrate that farmers and industrial workers have a significant risk for hematological malignancies. Exposure to asbestos, aromatic hydrocarbons, fertilizers, mineral oils, pesticides, and radiations is associated with a significant increase in the risk for these malignant diseases. These data are in agreement with previously reported data, and require a confirmation in larger, prospective studies.
Hemoglobin redondo [β 92(F8) His → Asn]: An unstable hemoglobin variant associated with heme loss which occurs in two forms
Authors: Wajcman H. , Vasseur C. , Poyart C. , Blouquit Y. , Galacteros F. , Santo D. Esperito , Peres M. J. , Martins M. C.
Published: February 2007

Hb Redondo [β92(F8) His→Asn] illustrates how post‐translational structural modifications may modify the phenotypic expression of an unstable hemoglobin. This variant was found in a Portuguese patient suffering from a chronic hemolytic anemia. The electrophoretic pattern demonstrated that it occurred in two forms, both being semi‐hemoglobins: the fastest one migrating like HbS and the other like HbA2; after a few days of storage at 4°C the intensity of the slowest Hb fraction decreased while that of the other increased proportionally. In both cases, the RP‐HPLC analysis of the tryptic digest of the aminoethylated β chains demonstrated the presence of an abnormal βT10 peptide carrying a His→Asx substitution. Microsequence study of these two peptides demonstrated that the slowest abnormal Hb fraction had a β92 His → Asn substitution and the fastest a His → Asp at the same site.

All these results suggest that the β92 His → Asn variant loses readily its heme group and that a deamidation occurs rapidly in vitro, yielding a β92 Asp semi‐hemoglobin. The oxygen affinity of the patient's red blood cells was increased, leading to a stimulation of erythropoiesis and to a macrocytic hemolytic disease.
Induction of carbonic anhydrase I isozyme precedes the globin synthesis during erythropoiesis in K562 cells
Authors: Kondo Takahito , Isobe Hiroshi , Kawakami Yoshikazu , Sakai Masaharu , Nishi Shinzou , Taniguchi Naoyuki
Published: February 2007

Induction of carbonic anhydrase isozyme I (CA‐I) by erythropoietin or hemin was investigated using erythroleukemia (K562) cells. Immunological estimation and purification of carbonic anhydrases showed that untreated K562 cells contained only carbonic anhydrase isozyme II(CA‐II), while incubation of the cells with 2 units of erythropoietin (EP) per ml of the incubation medium or with 50 μM hemin resulted in the induction of CA‐I. The purified CA‐I induced in K562 cells was enzymatically and immunologically identical to that from mature erythrocytes. Flow cytometric analysis showed that incubation of K562 cells with EP as well as hemin induced CA‐I at the 3rd h, while α‐globin was detected at the 8th h. Northern blot analysis of CA‐I mRNA using a cloned genomic DNA as a probe showed that mRNA of CA‐I was induced by EP. These results suggest that induction of CA‐I is regulated at the transcriptional level during developmental changes of erythroid cells, and that CA‐I may play a physiologically important role during erythroid differentiation.
Pelger—Huet anomaly in an infant with multiple congenital anomalies
Authors: Fishbein Julie D. , Falletta John M.
Published: February 2007

We report a new case of Pelger‐Huet anomaly (PHA) evident from the first day of life in an infant with multiple congenital anomalies suggestive of Fryn syndrome. The infant's parents are not affected by PHA, raising the possibility that the PHA resulted from a spontaneous mutation.
Concurrent acute myeloid leukemia and systemic mastocytosis
Authors: Wong K. F. , Chan J. K. C. , Chow T. C. , Chan J. C. W. , Ma S. K. , Kwong Y. L.
Published: February 2007

A 51‐year‐old woman presented with concurrent systemic mastocytosis and acute myeloid leukemia associated with a clonal karyotypic anomaly of t(8;21). Cytochemical, histologic, and cytogenetic studies helped in the distinction from a recently described entity: acute myeloid leukemia with marrow basophilia. Although the leukemia responded well to aggressive chemotherapy, the mastocytosis component worsened, illustrating the inherent resistance of mastocytosis to chemotherapy.
Cardiac complications observed in elderly patients following 2′‐deoxycoformycin therapy
Authors: Grem Jean L. , King Susan A. , Chun Hoo G. , Grever Michael R.
Published: February 2007

Deoxycoformycin (dCF) is an investigational nucleoside with significant activity in hairy cell leukemia, cutaneous T‐cell lymphoma, and chronic lymphocytic leukemia. During a 4‐year period, 11 patients have experienced cardiac events as a complication of dCF therapy under NCI sponsorship. The cases are presented and recommendations for the administration of dCF to patients with pre‐existing heart disease are made.
Simple method for differentiating between HLA and platelet‐specific antibodies by flow cytometry
Authors: Freedman J. , Hornstein A.
Published: February 2007

Since platelets express both platelet‐specific and class I HLA antigens, serum antiplatelet reactivity assessed by most platelet antibody techniques could be due to antibodies with either or both specificities. Flow cytometric analysis of sera for detection of anti platelet antibody commonly employs a purified platelet preparation as target cells. A method is described for investigating sera for platelet antibodies by flow cytometry using a mixture of platelets and lymphocytes. The mixture of lymphocytes and platelets as target cells has the advantage of confirming the presence of the HLA antibodies in reactive sera. The concomitant use of platelets and lymphocytes treated with citric acid, pH3, or with chloroquine (to remove or alter surface HLA antigens without affecting platelet specific antigens) may further assist in identifying antiplatelet antibodies in alloimmunized patients. These techniques may also be useful in platelet crossmatching procedures.
Hemophagocytic syndrome associated with aggressive natural killer cell leukemia
Authors: Okuda Tsukasa , Sakamoto Shinichi , Deguchi Takeshi , Misawa Shinichi , Kashima Kei , Yoshihara Takao , Ikushima Satoshi , Hibi Shigeyoshi , Imashuku Shinsaku
Published: February 2007

We describe a patient who had aggressive natural killer cell leukemia with profound hemophagocytosis. This combination must be underscored as one of several hemophagocytic syndromes. Activated phagocytes in the bone marrow appeared morphologically normal and could possibly be proliferating in response to some cytokine(s) such as interferon‐gamma produced by leukemic cells, whose serum level was found to be extremely elevated in this case.
Aplastic anemia associated with systemic lupus erythematosus
Authors: Sumimoto Shin‐Ichi , Kawai Masahiko , Kasajima Yoshiki , Hamamoto Torata
Published: February 2007

Hematologic complications of systemic lupus erythematosus (SLE) usually involve peripheral destruction of blood cells. We report a case of aplastic anemia associated with SLE observed during the remission phase of SLE 3 months after the beginning of treatment. CD8+ T cells in the patient's bone marrow may have suppressed maturation of hematopoietic progenitor cells, which may have induced the aplastic anemia associated with SLE. Repeated therapy with high‐dose methylprednisolone resulted in lasting remission.
Detection of minimal residual disease in acute lymphoblastic leukemia by flow cytometry with monoclonal antibodies
Authors: Imamura Nobutaka , Kuramoto Atsushi
Published: February 2007

To detect more precisely the minimal residual disease in acute lymphoblastic leukemia (ALL), two‐color flow cytometric analysis for the detection of cell‐surface antigen (CD10; CALLA) and nuclear terminal deoxynucleotidyl transferase (TdT) was performed in the six patients with CALLA‐positive ALL coexpressing TdT. In all patients, the leukemic blasts coexpressed la (HLA‐DR), CD9, CD19, CD20, CD24, and CD10. Five of six patients achieved complete remission, but one has so far relapsed. No leukemic blasts (CD10+, TdT+) were detected at the time of complete remission. During maintenance chemotherapy, leukemic blasts coexpressed C10 and TdT were found 2.32% in the patient's peripheral blood by two‐color analysis, whereas no obvious leukemic cells were recognized morphologically. The patient relapsed leukemia with the same phenotype 4 weeks after the examination. On the basis of our findings, we suggest that two‐color flow cytometric analysis with the use of these antibodies is quite valuable to detect the minimal residual leukemic cells in a patient with ALL. The reduction of leukemic cells below the threshold of detection of methods currently available appears to be necessary to achieve a cure in ALL. Hence accurate diagnosis of ALLs with monoclonal antibodies (MAbs) should contribute substantially to the development of an effective form of therapy for their cure.
HLA antibodies—the cause of platelet alloimmunization in chinese
Authors: Chow Mo‐Ping , Yung Chien‐Hui , Hu Hui‐Yu , Tzeng Jaw‐Lin , Lin Jeong‐Shi , Lin Wen‐Mei , Lin Chung‐King
Published: February 2007

Lymphocytotoxicity test (LCT) and platelet suspension immunofluorescence test (PSIFT) were used together to screen platelet‐associated antibodies in patients who received long‐term platelet transfusion. Twenty‐four of 53 patients (45.3%) were immunized subsequently. Since the concordence of LCT and PSIFT was 100%, most of the platelet associated antibodies were of HLA specificity, and platelet specific antibody alone (in absence of HLA) was not detected. The identified antibodies were anti‐A2, A11, A24, B5, B46, B57, B60, and B62. The majority of them were against the high frequency HLA antigens in the Chinese population. The development of antibody could not be correlated with the number of platelet‐donors exposed, the time interval after the initiation of platelet transfusion, or the percentage of reactive lymphocytotoxic panels. HLA antibody was the major factor in causing platelet alloimmunization in the Chinese patients. However, some other unknown factors should be looked for. In addition, ABO incompatibility did not affect the posttransfusional increment while the platelet was compatible with LCT crossmatching.
Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation
Authors: Wada Hideo , Ohiwa Michiaki , Kaneko Toshihiro , Tamaki Shigehisa , Tanigawa Motoaki , Shirakawa Shigeru , Koyama Masato , Hayashi Tatsuya , Suzuki Koji
Published: February 2007

Plasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP.
Expression of high affinity binding sites for erythropoietin on L8057 cells, a mouse megakaryoblastic cell line, associated with cell differentiation
Authors: Yoshida Takeshi , Ishida Yoji , Sasaki Hideki , Inoue Tohru , Kaku Kohei , Kaneko Toshio
Published: February 2007

In this study, specific binding sites were examined for erythropoietin (EPO) on the mouse leukemic cell line, L8057. This cell line is megakaryoblastic in origin as evidenced by an enlargement of cell size, multinuclearity, intense activity of acetylcholinesterase, more expression of glycoprotein Ilb and IIIa antigen, and higher ploidy distribution after the treatment with 12‐o‐tetradecanoylphorbor‐13‐acetate (TPA). The original undifferentiated cells possessed a single class of low affinity binding sites for recombinant human (rh) EPO with a Kd of 3.5 nM. Following the treatment with TPA, high affinity binding sites (Kd; 440 pM) were expressed in addition to the low affinity sites. EPO stimulated the incorporation of 3H‐leucine into TPA‐treated L8057 cells, and the maximal effect of EPO was observed at the same order as the Kd value of high affinity sites.

The present data demonstrates that the expression of high affinity binding sites for EPO is associated with the differentiation of L8057 cells which have megakaryocytic characteristics. Furthermore, protein synthesis stimulated by EPO may be mediated through the high affinity sites.
CD45RA expression by CD4 T lymphocytes in tumors invaded by B‐cell non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)
Authors: Jacob Marie‐Christine , Favre Mireille , Lemarc'Hadour FrançOis , Sotto Marie‐France , Bonnefoix Thierry , Sotto Jean‐Jacques , Bensa Jean‐Claude
Published: February 2007

Little is known about the role of tumor infiltrating T lymphocytes (TIL‐T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved.

In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B‐cell non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 ± 15.0% in B‐cell NHL, and 37.4 ± 18.6% in HD) than in reactive hyperplasia (54.7 ± 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment.

A further heterogeneity in the relative proportion of naive and memory TIL‐T was also observed within lymphoma (range: 11 to 68% in B‐cell NHL, 5 to 69% in HD). In B‐cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P < .0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 ± 7.4%) than class 3 NHL, which are more aggressive (40.1 ± 16.1%). Among the monoclonal antibodies (mAb) defining the B‐cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (p = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL‐T, activated CD3 DR TIL‐T, or CD4 subset.
Desmopressin (d‐DAVP) effects on platelet rheology and von willebrand factor activities in uremia
Authors: Zeigler Zella R. , Megaludis Alexis , Fraley Donald S.
Published: February 2007

Bleeding times, von Willebrand activities, and platelet retentions were examined before and following d‐DAVP in 13 uremic patients. Shortening of the bleeding time from 16.6 ± 2.2 (SEM) to 6.8 ± 0.7 min was seen in six patients. However, bleeding times remained ± 20 min in the remaining seven individuals. The only baseline parameter that correlated with response to d‐DAVP was the amount of blood loss (mg/min) during the bleeding time test. Responders had normal blood loss values averaging 6.2 ± 1.5 mg/min. By contrast, these values were elevated in 6/7 of the non‐responders and averaged 28.4 ± 5.9 mg/min (P = 0.01). Von Willebrand activities increased following d‐DAVP in the responders but not in the non‐responders. Platelet retention was uniformly low in all patients and improved from 21.0 ± 7.0% to 75.0 ± 7.9% (P = <0.001) following d‐DAVP in responders but not non‐responders. To further define the retention abnormality in uremia, the two‐stage platelet retention assay was performed prior to d‐DAVP. Most of the patients (9/12) had both first‐ and second‐phase abnormalities. Therefore, the retention defect in uremia appears to be more complex than that seen in von Willebrand's disease (2nd phase abnormality only). Nevertheless, d‐DAVP seems to improve platelet rheology in uremic individuals whose von Willebrand activities increase with d‐DAVP.
Erythropoietin affects the maturation pattern of fetal G‐CSF‐responsive progenitors
Authors: Christensen Robert D. , Rothstein Gerald
Published: February 2007

A transient hyporegenerative neutropenia has been reported in neonates, but not in older children or adults, undergoing treatment with recombinant erythropoietin (epo). Monocytopenia has not been reported. We postulated that epo might selectively reduce the responsiveness of neonatal progenitors to Granulocyte Colony‐Stimulating Factor (G‐CSF), while not similarly affecting their responsiveness to Macrophage Colony‐Stimulating Factor (M‐CSF). To test this hypothesis two types of experiments were performed. First, progenitors of adult or fetal origin were pre‐incubated with epo (or control), then washed, and their responsiveness to G‐CSF and M‐CSF evaluated in clonogenic culture assays. Second, clonogenic maturation was initiated using either G‐CSF or M‐CSF, after which the effect of a late addition of epo to the developing clones was evaluated. Indeed, pre‐incubation with epo resulted in production of fewer neutrophils from fetal progenitors grown in G‐CSF (P<0.001), but it did not reduce the number of macrophages generated from progenitors grown in M‐CSF. Adding epo to the already‐developing G‐CSF‐responsive and M‐CSF‐responsive adult and fetal clones did not alter colony development. Thus, epo appears to have an action on G‐CSF‐responsive, but not‐M‐CSF‐responsive fetal progenitors, resulting in reduced production of neutrophils. This effect is no longer apparent, however, when progenitors have matured to the 8‐cell clone stage.
Erythromelalgia in thrombocythemia of various myeloproliferative disorders
Authors: Michiels Jan J. , ten Kate Fiebo J. W.
Published: February 2007

Erythromelalgia is caused by platelet‐mediated acral inflammation and arteriolar thrombosis in thrombocythemia in its primary form or associated with polycythemia vera. The prompt and lasting relief of burning pain by low‐dose aspirin is a prerequisite for the diagnosis of thrombocythemic erythromelalgia.

Here we extend observations on the occurrence of erythtromelalgia in thrombocythemia associated with primary myelofibrosis, Philadelphia‐chromosome positive micromegakaryocytic myelofibrosis, and myelodysplastic syndrome type II. It is concluded that erythromelalgia may occur in thrombocythemia of all variants of chronic myeloproliferative disease as well as myelodysplastic syndrome if platelet counts are sufficiently high.
Immunophenotype and DNA content of myeloma cells in primary plasma cell leukemia
Authors: Shimazaki Chihiro , Gotoh Hideo , Ashihara Eishi , Oku Naritoshi , Inaba Tohru , Murakami Satoshi , Itoh Kunihiko , Ura Yasuaki , Nakagawa Masao , Fujita Naohisa
Published: February 2007

To clarify the biological characteristics of the myeloma cells in primary plasma cell leukemia (PCL), we studied the immunological phenotype and DNA content of cells from five patients with primary PCL as compared to those from the patients with typical multiple myeloma (MM). In two of five patients with PCL myeloma cells had B‐cell‐associated antigens (B1, J5) and surface immunoglobulin in addition to plasma cell associated antigens, suggesting that these cells are immunologically immature as compared to mature plasma cells. Concerning the DNA content of myeloma cells, two of four patients had hypodiploid while two had diploid myeloma cells. In contrast, 24 of the 37 (65%) patients with typical MM had hyperdiploid and 1 had hypodiploid myeloma cells. These observations suggest that the myeloma cells in PCL are immunologically heterogenous. The increased incidence of hypodiploidy in PCL may explain its relatively poor prognosis as previously shown in those with typical MM and hypodiploid DNA content.
Polysaccharide encapsulated bacterial infection in sickle cell anemia: A thirty year epidemiologic experience
Authors: Wong Wing Yen , Powars Darleen R. , Chan Linda , Hiti Alan , Johnson Cage , Overturf Gary
Published: February 2007

Annual age‐specific incidence rates of Streptococcus pneumoniae or Haemophilus influenzae bacterial septicemia in sickle cell anemia (SS) were determined for the years of 1957 through 1989. Forty‐nine patients had 64 episodes of septicemia among a population of 786 SS patients observed for 8,138 person‐years. Peak frequency of infection occurred between 1968‐1971 and 1975‐1981 with a conspicuous absence of episodes in 1972, 1973, 1982‐1984, and 1986‐1987, thus demonstrating cycles of high and low attack rates. The annual age‐specific incidence rate of septicemia varied from 64.5 (1965) to 421.1 (1980) per 1,000 person‐years for those under 2 years of age and never exceeded 10.2 per 1,000 in those over 4 years of age. Following the introduction of pneumococcal polyvalent vaccine in 1978, incidence of infection decreased in SS children greater than 2 years of age. No modification of the risk of infection was observed in immunized children less than 2 years of age.

During these three decades, there has been a ten‐fold increase in the number of SS adults over 20 years of age. The relative risk of chronic sickle complications comparing the survivors of septicemia to the non‐infected patients was: subsequent death 1.76, retinopathy 4.06, avascular necrosis 1.95, symptomatic cholelithiasis 1.33, stroke 1.30, and priapsim 1.26. These data suggest that prognosis for lifetime severe SS is initially manifested as an increased risk of septicemia during childhood.
Increased levels of plasma thrombomodulin in chronic myelogenous leukemia
Authors: Morishita Eriko , Saito Masanori , Asakura Hidesaku , Jokaji Hiroshi , Uotani Chika , Kumabashiri Ichiro , Yamazaki Masahide , Matsuda Tamotsu
Published: February 2007

Circulating blood plasma contains proteinase‐degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzymelinked immunosorbent assay using a monoclonal antibody to protease‐degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 ± 6.2 ng/ml: means ± SD) compared with the levels in normal controls (8.0 ± 1.9 ng/ml, n = 20) (P < 0.001). Fibrin degradation products (D‐dimer), thrombin‐antithrombin III complex, and plasmin α2‐antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin‐mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase‐α1‐proteinase inhibitor (E‐α1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P < 0.0001). The plasma levels of thrombomodulin and E‐α1 PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti‐leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E‐α1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P < 0.001).

These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease‐degraded fragments of it into the circulation.
Hemolytic anemia in protoporphyria: Possible precipitating role of liver failure and photic stress
Authors: Key Nigel S. , Rank Jeffrey M. , Freese Deborah , Bloomer Joseph R. , Hammerschmidt Dale E.
Published: February 2007

Hemolytic anemia is not a common clinical feature in protoporphyria. In this report, we describe two patients in whom we have encountered severe hemolytic anemia. Both individuals had advanced hepatic disease as a complication of their porphyria and were undergoing orthoptic liver transplantation. The onset of hemolysis appeared to be related to the development of liver disease, and in both cases, the operative procedure acutely exacerbated the red cell destructive process. We suggest that liver involvement in protoporphyria may unmask hemolytic anemia, and that red cells in these individuals are hypersensitive to photooxidative stress, such as might occur during a prolonged operative procedure.
Application of immunocryoultramicrotomy to free cells: Ultrastructural localization of myeloperoxidase in neutrophils of human peripheral blood
Authors: Saito Nagahito , Takemori Nobuo , Hirai Katsuyuki , Kubota Noriko , Onodera Ryuichi , Namiki Masayoshi
Published: February 2007

Immunocryoultramicrotomy is generally considered the most suitable method for observing the immunostainings by monoclonal antibodies to intracellular antigens by electron microscopy. However, this procedure with the free cells such as peripheral blood cells or cultured cells is not widely used because of the difficulty in preparing ultrathin frozen sections. We report here a new technique for making ultrathin frozen sections of peripheral blood cells by positioning the cell in a semigelatinized medium for ultrasectioning. Monoclonal antibody against myeloperoxidase (MPO) was reacted with the ultrathin sections made with this new technique to observe the ultrastructural localization of intracellular MPO. MPO was observed in the primary granules of the neutrophils.
Human parvovirus B19 infection in hemophiliacs first infused with two high‐purity, virally attenuated factor Vlll concentrates
Authors: Azzi A. , Ciappi S. , Zakvrzewska K. , Morfini M. , Mariani G. , Mannucci P. M.
Published: February 2007

Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high‐purity concentrates re‐duces the risk of B19 transmission, we have prospectively evaluated the rate of anti‐B19 seroconversion in two groups of susceptible (anti‐B19 negative) hemophiliacs infused with high‐purity, heated (pasteurized) or solvent‐detergent‐treated factor Vlll concen‐ trates. Both products infected a relatively high proportion of patients (nine of 20).
Granulocyte fcγ receptor recognition of cell bound and aggregated IgG: Effect of γ‐interferon
Authors: Ruiz Pedro , Gomez Francisco , Lopez Rafaela , Chien Paul , Rossman Milton D. , Schreiber Alan D.
Published: February 2007

Granulocyte Fcγ receptors are important components in the recognition of IgG‐coated cells and immune complexes. Two proteins have been identified on resting human granulocytes which function as Fcγ receptors, Fcγ RII (CD32) and Fcγ RIII (CD16). A third protein, Fcγ RI (CD64), is not constitutively expressed on resting granulocytes, but can be induced by activation with γ‐interferon. We examined the role of these three Fcγ receptors on human granulocytes in the binding of both IgG‐sensitized erythrocytes and soluble oligomeric IgG. In these studies we employed anti‐Fcγ receptor antibodies which complete for the Fcγ RII and Fcγ RIII ligand binding sites. Preincubation of granulocytes with saturating concentrations of high‐affinity anti‐Fcγ RII monoclonal antibody did not alter the recognition of IgG sensitized human cells by granulocytes. Furthermore, ligand binding studies demonstrated that anti‐Fcγ RII antibody altered neither the number nor the affinity of granulocyte binding sites for human trimeric IgG. In contrast, Fab anti‐Fcγ RIII inhibited the binding of both IgG (anti‐D) sensitized human RBCs and IgG sensitized sheep RBCs. Similarly, a reduction in the expression of Fcγ RIII by treatment with phosphatidyl‐inositol specific phospholipase C reduced PMN recognition of IgG‐sensitized cells. Also, anti‐Fcγ RIII decreased the number of granulocyte binding sites for human IgG trimer without a change in receptor affinity. Fcγ RI, which was induced by γ‐IFN, increased granulocyte recognition of both IgG sensitized RBCs and IgG trimer. These data suggest that Fcγ RIII is the primary Fcγ receptor on granulocytes which recognizes IgG sensitized RBCs and low molecular weight complexes of IgG. With γ‐interferon activated granulocytes, Fcγ RI appears to enhance this recognition process.
Familial association of autoimmune thrombocytopenia and hyperthyroidism
Authors: Bizzaro Nicola
Published: February 2007

An association between thrombocytopenia and thyrotoxicosis in a single individual is well documented, and the theories for this event include a common immunologic cause or a thyrotoxic‐induced decrease in platelet survival.

We report the first description of the coexistence of autoimmune thrombocytopenic purpura (AITP) and Graves' disease in several members of the same family, in which four females were thrombocytopenic and two of these were also hyperthyroid. All four patients had high titers of antiplatelet antibodies, and the two hyperthyroid cases were positive for thyroid‐stimulating immunoglobulins (TSI).

The familial occurrence of two autoimmune disorders is very uncommon, and suggests a genetic etiology. The HLA phenotype was determined and the antigens B8 and DR3, which are reported with high frequency in both diseases, were present in three patients. Although the etiologic cause is still unknown, our findings further support the theory that a genetic predisposition underlies autoimmune disease.
Further evidence for recessive inheritance of von willebrand disease with abnormal binding of von willebrand factor to factor VIII
Authors: Lopez‐Fernandez M. F. , Blanco‐Lopez M. J. , Castiñeira M. P. , Batlle J.
Published: February 2007

A new family with a bleeding diathesis and FVIII deficiency secondary to abnormal binding of von Willebrand factor (vWF) to factor VIII (FVIII) is described. Two propositi of this family, an 18‐year‐old male and a 33‐year‐old female, both with a history of epistaxis, bruising, bleeding from the gums, epistaxis, hemarthrosis, and hematoma, were analyzed. Also additional members of the same family with no bleeding history were also studied. The propositi showed normal vWF activities, low FVIII activity; one of them had been diagnosed as having hemophilia A and the other was a hemophilia A carrier. Both showed a very poor response to treatment with FVIII concentrates and desmopressin (DDAVP) but a good clinical response to cryoprecipitate. APTT was prolonged and no inhibitory activity was noticeable in their plasmas. Thirty‐five units per kilogram body weight of Hemofil M was infused to both propositi and FVIII reached basal level within 60 minutes of the infusion. No FVIII response at all was observed in the female after intravenous DDAVP administration. However, the male who received the infusion of 35 U/kg body weight of Humate‐P achieved a normal FVIII level that was maintained for 12 hours. Multimeric analysis of vWF was normal in all the members studied. Von Willebrand factor domain for FVIII binding was assayed in the two propositi and in six other members of the same family by using a non‐isotopic and sensitive method, a modification of the one previously described, using the Hemofil M concentrate as exogenous FVIII. The data obtained showed that both propositi had similar binding to that observed by using plasma of a patient with severe von Willebrand disease. Furthermore, five siblings had a decreased binding of vWF to FVIII, when compared with plasma from normal individuals or patients with hemophilia A. We also observed that, for screening purpose, the ratio of bound FVIII/immobilized vWF (at saturation of the anti‐vWF and offering of 1 U/ml of exogenous FVIII) distinguished two levels of abnormality (normal range 0.70–1.15, propositi 0,004–0.007, and remaining members affected 0.25–0.42). The most probable explanation is that the propositi are homozygous or double heterozygous, the other five siblings affected being heterozygous for a recessive vWF defect. This more accessible assay presented here may be of help in routine analysis for diagnosing this type of von Willebrand disease, which has important implications for therapy and genetic counseling. © 1992 Wiley‐Liss, Inc.
μ‐heavy chain disease: Presentation as a benign monoclonal gammopathy
Authors: Wahner‐Roedler Dietlind L. , Kyle Robert A.
Published: February 2007

μ‐Heavy chain disease (HCD) is a rare monoclonal lymphoid disorder characterized by the failure to assemble a complete IgM immunoglobulin. The μ‐heavy chains analyzed to date revealed absence of the variable region and a shortened constant domain. We report the first case of μ‐HCD presenting as a benign monoclonal gammopathy. The literature on the 27 reported μ‐HCD cases is reviewed, and important clinical and laboratory findings are discussed. The ages of the patients ranged from 15 to 80 years (median, 57.5 years). Twenty‐two of 27 patients had an associated lymphoplasma cell proliferative disorder. A monoclonal spike on routine serum protein electrophoresis was found in only 8 of 19 patients. Fourteen of 22 patients had Bence Jones proteinuria, but μ‐HCD protein was reported in the urine of only two patients. The survival ranged from <1 month to 11 years (median, 24 months). © 1992 Wiley‐Liss, Inc.
Treatment of relapsed or refractory Hodgkin disease and non‐Hodgkin lymphoma with high‐dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue
Authors: Rapoport Aaron P. , Rowe Jacob M. , Heal Joanna M. , Tanner Martin A. , Dipersio John F.
Published: February 2007

Nine patients with relapsed or refractory Hodgkin disease or non‐Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 × 109/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 × 109/L and a platelet count of 50 × 109/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days post‐transplant. Two patients died of transplant‐related complications and one relapsed 250 days post‐transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution.

Although administration of cytotoxic therapy and granulocyte—macrophage colony‐stimulating factor (GM‐CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive “salvage” therapy. Additional follow‐up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants. © 1992 Wiley‐Liss, Inc.
Coincident Kaposi sarcoma and T‐cell lymphoma in a patient with the Wiskott‐Aldrich syndrome
Authors: Meropol Neal J. , Hicks David , Brooks John J. , Siminovitch Katherine A. , Fishman Neil O. , Kant Jeffrey A. , Bennett Joel S.
Published: February 2007

A 24 year old male with a history of eczema, recurrent mild infections, and thrombocytopenia consistent with the Wiskott‐Aldrich syndrome (WAS) presented with a mediastinal mass, generalized lymphadenopathy, splenomegaly, and severe thrombocytopenia. Studies of immune function including immunoglobulin levels and T‐cell subsets were normal. Furthermore, his T lymphocytes proliferated normally in response to phytohemagglutinin, concanavalin A, and the combination of neuraminidase/galactose oxidase. However, their proliferative responses to anti‐CD43 antibody and periodate were diminished, consistent with the clinical diagnosis of WAS. An initial inguinal lymph node biopsy surprisingly revealed Kaposi sarcoma. However, following splenctomy to increase the platelet count, biopsy of the mediastinal mass revealed T‐cell large cell lymphoma. Studies of biopsied tissue for the presence of Epstein‐Barr virus and cytomegalovirus were negative, as were studies of blood, including the polymerase chain reaction, for the presence of the human immunodeficiency virus (HIV). This is the first report of Kaposi sarcoma arising in a patient with a congenital immunodeficiency syndrome. Although Kaposi sarcoma can arise in the face of the severe immunosuppression that follows allograft transplantation and in patients infected with HIV, we postulate that longevity in the face of mild immunosuppression was the major factor in the development of Kaposi sarcoma in this patient. © 1992 Wiley‐Liss, Inc.
Plasma cytokine levels in thrombotic thrombocytopenic purpura
Authors: Wada Hideo , Kaneko Toshihiro , Ohiwa Michiaki , Tanigawa Motoaki , Tamaki Shigehisa , Minami Nobuyuki , Takahashi Hoyu , Deguchi Katsumi , Nakano Takeshi , Shirakawa Shigeru
Published: February 2007

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Auto‐antibodies, platelet‐associated immunoglobulin G, and platelet aggregating factor were detected in many of these patients and high‐molecular‐weight bands of von Willebrand factor multimers were reduced in 9 of 10 patients examined. Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)‐1β, IL‐6, and soluble IL‐2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL‐6 and soluble IL‐2 receptor levels. These findings suggest that immunological mechanisms, such as the activation of macrophage, are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels. © 1992 Wiley‐Liss, Inc.
Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HIV(+) hemophilic men
Authors: Ragni Margaret V. , Miller Barbara J. , Whalen Robert , Ptachcinski Richard
Published: February 2007

The use of ibuprofen (IBP) in hemophilic men for chronic hemophilic arthropathy is associated with transient coagulation abnormalities, but usually does not cause bleeding symptoms. However, when hemophilic men are treated with ibuprofen while also receiving zidovudine (ZDV), excess bleeding has occurred in some. In order to evaluate platelet function and pharmacokinetics of combination IBP and ZDV, we measured platelet aggregation, platelet adhesive index, bleeding time, and IBP and ZDV drug levels by high performance liquid chromatography on five patients receiving chronic oral IBP, 400 mg every 6 hr, and on ten patients receiving both IBP and ZDV, 100 or 200 mg every 4 hr five times daily. Samples were obtained at baseline (ZDV alone), acutely (IBP + ZDV acutely), and chronically (2 weeks on IBP and ZDV). Abnormal platelet aggregation with arachidonic acid occurred in four of five (80%) of those receiving IBP alone and in 7 of 10 (70%) at baseline, 9 of 10 (90%) at acute, and 8 of 10 (80%) at chronic IBP and ZDV treatment, most commonly at 2 hr following dosing, when peak IBP levels occurred, and persisting 4 hr in those on chronic dosing. Half or more of those on combination IBP + ZDV showed a lowered platelet adhesive index and/or prolonged bleeding time. Excess bleeding symptoms occurred in three on chronic combination IBP + ZDV, two with increased frequency of spontaneous hemorrhages, and one with prolonged traumatic bleeding. Bleeding tendency was unrelated to the degree of platelet function abnormality, to peak drug levels of IBP or ZDV, or degree of liver function abnormality (SGPT). The clearance of IBP alone and ZDV alone were not different from the clearance of combination IBP and ZDV. Caution is urged regarding potential enhanced bleeding tendency in hemophiliacs receiving both IBP and ZDV in combination. © 1992 Wiley‐Liss, Inc.
Morphologic characteristics of acute lymphoblastic leukemia (ALL) with abnormalities of chromosome 8, band q24
Authors: Davey F. R. , Lawrence D. , Maccallum J. , Varney J. , Hutchison R. , Wurster‐Hill D. , Schiffer C. , Sobol R. E. , Ciminelli N. , le Beau M. , Bloomfield C. D.
Published: February 2007

The CALGB prospectively studied 140 adult acute lymphoblastic leukemia (ALL) patients for cytogenetic abnormalities. Seven (5%) patients with adequate cytogenetic preparations had t(8;14)(q24;q32) or t(8;22)(q24;q11). Patients were compared with non‐8q24 patients for clinical and laboratory characteristics, response to therapy, and survival. The median age of patients with translocations involving 8q24 (71% males) was 40 years. Forty‐three percent had lymphadenopathy, 29% splenomegaly, and 29% hepatomegaly. None exhibited central nervous system (CNS), skin, or gum involvement. These features did not differ significantly from non‐8q24 ALLs. Patients with 8q24 translocations had higher hemoglobins (11.5 vs. 9.8 g/dl; P = 0.04) and lower percentage of blasts in the peripheral blood (8.5% vs. 69%; P = 0.007). Although all seven were finally categorized as ALL‐L3, a marked variation in the proportion of typical L3 blasts was observed that initially resulted in the diagnoses of ALL‐L2 in three cases and prolymphocytic leukemia in one. In five of five patients, the blasts typed as B cells (Slg+ and CD19+). Complete remission rates for patients with 8q24 translocations were 43%, whereas they were 68% for non‐8q24 ALLS (P = 0.22). Furthermore, patients with 8q24 abnormalities exhibited significantly shorter survival (4.8 vs. 18.4 mo; P < 0.001). We conclude that ALL with translocations of 8q24 in adults shows a mature B‐cell immunophenotype (Slg+), poor prognosis and morphology ranging from classical ALL‐L3 to ALL with a subpopulation of L3 cells. Thus, the diagnosis of ALL‐L3 should be made when blastic cells possess a mature B‐cell immunophenotype (SIg+) and an 8q24 translocation, even though the number of L3 cells is low. © 1992 Wiley‐Liss, Inc.
Role of splenectomy in the management of hemophilic patients with human immunodeficiency virus‐associated immunopathic thrombocytopenic purpura
Authors: Leissinger Cindy A. , Andes W. Abe
Published: February 2007

Immunopathic thrombocytopenic purpura (ITP) can be a life‐threatening complication of human immunodeficiency virus (HIV) infection in patients with hemophilia and can seriously compromise quality of life if not managed effectively. We report here complete response to splenectomy in four severe hemophiliacs with HIV‐associated ITP. All patients were symptomatic, had platelet counts less than 25,000/mm3, and had failed at least one non‐surgical therapy prior to splenectomy. All patients tolerated surgery well and obtained an immediate and durable complete response. In addition to our experience, a review of the literature shows that splenectomy is well tolerated and provides the most effective long‐term solution for hemophiliacs with HIV‐ITP. © 1992 Wiley‐Liss, Inc.
Phorbol ester‐induced hairy cell features on chronic lymphocytic leukemia cells in vitro
Authors: Ai‐Katib Ayad , Wang Chang Yi , McKenzie Susan , Clarkson Bayard D. , Koziner Benjamin
Published: February 2007

Leukemic cells from eight patients with chronic lymphocytic leukemia were isolated and cultured in the continuous presence of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) at a concentration of 1.6 × 10−9 M for 4–10 days. Aliquots of cells were then analyzed at intervals of 24–72 hr for changes in morphology, acid phosphatase staining (AP), and expression of two hairy cell‐associated surface antigens, HCL1 (CD22, Leu 14) and HCL3 (CD11c, Leu M5). All cases studied showed typical B‐CLL phenotype, and only a small proportion of cells expressed CD22 and CD11c (mean 7% and 4.9%, respectively). TPA treatment induced the coexpression of CD22 (mean 49%) and CD11c (mean 48%) and tartrate‐resistant acid phosphatase in seven of eight cases. Morphologically, cells in TPA cultures expressed hairy cell features that were evident in light and electron microscopic studies. Collectively these changes indicate that TPA can induce hairy cell features on CLL cells in vitro, suggesting the later maturational stage of HCL compared with CLL. © 1992 Wiley‐Liss, Inc.
Laboratory and clinical aspects of inherited thrombotic disorders
Authors: Rodgers George M. , Chandler Wayne L.
Published: February 2007

The laboratory evaluation of patients with recurrent thrombosis is frequently frustrating, with a low diagnostic yield obtained despite extensive testing. The likelihood of reaching a diagnosis in these patients can be increased by considering diagnostic possibilities usually overlooked and by using assays optimal for their detection. This review summarizes clinical and laboratory issues important in inherited thrombotic disease and discusses practical aspects and a strategy for laboratory testing. New information is provided on the fibrinolytic disorders that may be a common cause of recurrent thrombosis. © 1992 Wiley‐Liss, Inc.