bluuebunny/crossref_metadata_2025 huggingface dataset:
Hb South milwaukee [β105 (G7) leu → Phe]: A newly‐identified hemoglobin variant with high oxygen affinity
Authors: Honig George R. , Divgi Ajit B.
Published: February 2007

Fifteen individuals among four generations of a family of English ancestry demonstrated elevated hemoglobin levels accompanied by leftward‐shifted whole blood oxygen equilibrium curves. Five of the affected family members have required phlebotomies for relief of symptoms attributable to erythrocytosis. An abnormal hemoglobin or globin chain could not be isolated, but 43% of the β chains of the affected individuals contained a Leu → Phe substitution at position 105 (G7). Oxygen equilibrium curves demonstrated a normal Bohr effect but decreased cooperativity.
Acetylcholinesterase in the human erythron. III. Regulation of differentiation
Authors: Barr Ronald D. , Koekebakker Marijke
Published: February 2007

Acetylcholinesterase (AChE) is present in both primitive and mature erythroid cells, but a role for the enzyme in human hematopoiesis has not been defined. This prospect represented the primary objective of the following study. In clonal culture of normal human bone marrow cells, a “wave” of AChE activity was demonstrated, rising from undetectable levels to a peak (of 1.48 femto‐moles per min per cell) at 10 days in the course of progressive erythroid clonogenesis. At concentrations of enzyme inhibitor that clearly reduced AChE activity in a dose‐dependent fashion, there was no overall effect on erythropoiesis in vitro, but the clones were generally smaller and significantly more often multi‐focal than in control cultures. Furthermore, in the presence of AChE inhibitors, a concentration‐dependent increase in the myeloid‐erythroid ratios of the culture harvests was observed. Likewise, a clear reduction in hemoglobination was revealed, in cells of 10 day cultures, from a mean hemoglobin concentration of 35.0 pg per cell in controls to 20.1 pg per cell in the presence of the maximal concentration of the inhibitor (10−6M eserine). These data point to a role for AChE in the regulation of differentiation in the human erythron.
Micromethod for demonstrating increased platelet surface immunoglobulin G: Findings in acute, chronic, and human immunodeficiency virus‐1‐related immunologic thrombocytopenias
Authors: Sthoeger Dahlia , Nardi Michael , Travis Susan , Karpatkin Margaret , Karpatkin Simon
Published: February 2007

A method has been developed for the demonstration of increased platelet surface IgG that uses 1 ml of blood regardless of the platelet count. Platelets are gel filtered to remove plasma and contaminating lymphocytes. They are then reacted with fluorescein‐conjugated antihuman IgG and analysed by flow cytometry. Percent positive staining cells vary from 10% to 80% of total cells examined. A platelet antibody index is derived from the product of percent positive staining cells X mean fluorescence intensity of positive staining cells. All patients studied with chronic idiopathic thrombocytopenia purpura (IIP) or human immunodeficiency virus‐1 (HIV‐1)‐related thrombocytopenia had increased platelet surface IgG. Twelve acute children and 11 chronic children had indices averaging 3.5‐and 8.9‐fold greater than 12 normal children, respectively. Five of 12 children with acute ITP had normal platelet IgG. There was no linear correlation between the platelet antibody index and platelet count. Platelets of patients with acute, chronic, or HIV‐1‐related ITP displayed autofluorescence. In chronic ITP, the percentage of platelets displaying auto‐fluorescence had a significant negative correlation with the platelet count. This technique will be a valuable diagnostic tool in the pediatric population.
Malignant mastocytosis with circulating mast cells
Authors: Torrey Elizabeth , Simpson Karen , Wilbur Stephen , Munoz Phillip , Skikne Barry
Published: February 2007

A case of malignant mastocytosis with peripheral blood involvement is presented. The course of the patient's illness was complicated by recurrent hypotensive episodes, presumed to have been caused by mast cell degranulation. Treatment with hydroxyurea was associated with persistent hypotension which resulted in death. It has been proposed that the diagnosis of mast cell leukemia be given to patients presenting with greater than 10% atypical mast cells in the blood. However, review of 16 published cases of malignant mastocytosis with circulating mast cells reveals that the clinical manifestations, complications, and survival do not vary significantly with the percentage of peripheral blood mast cells. Patients with malignant mastocytosis with significant involvement by atypical mast cells in the bone marrow and peripheral blood should be considered as having an aggressive disease, regardless of the precentage of circulating mast cells.
Richter syndrome with two B cell clones possessing different surface immunoglobulins and immunoglobulin gene rearrangements
Authors: Tohda Shuji , Suzuki Toshiya , Nagata Kaoru , Kamiyama Takashi , Imai Yasufumi , Nara Nobuo , Aoki Nobuo , Morio Tomohiro
Published: February 2007

A patient with two populations of B cell malignancy in the bone marrow is reported. One population consisted of mature small lymphocytes, expressing surface IgM + D, λ and proliferating very slowly. The other population consisted of abnormal large lymphoid cells, expressing surface IgM, K and proliferating actively. We considered the former as chronic lymphocytic leukemia cells and the latter as malignant lymphoma cells. Therefore, this case was considered as Richter syndrome. The analysis of immunoglobulin heavy chain gene rearrangement showed the different patterns between the two populations. It suggested that the two populations arose from the different origins. We discussed the genetic relationship between the two clones of Richter syndrome referring to other reported cases.
Heparin‐like anticoagulant associated with systemic candidiasis
Authors: Horne McDonald K. , Chao Elizabeth S. , Wilson Olga J.
Published: February 2007

A 15 year old girl with aplastic anemia developed a heparin‐like anticoagulant during the course of systemic candidiasis. This was initially detected in the laboratory by an elevation of the thrombin clotting time which corrected with toluidine blue but not by mixing with normal plasma. In vivo and in vitro the anticoagulant was remarkably resistant to neutralization by protamine sulfate. Nevertheless, its heparin‐like nature was confirmed by its sensitivity to heparinase and its dependence on antithrombin III.
Hemostasis in malignancy
Authors: Nand Sucha , Messmore Harry
Published: February 2007

Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor‐bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet‐aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications.

Clinical complications occur in 9–15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor‐related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit.
Distribution of cell surface glycoprotein CD9 (P24) antigen on megakaryocyte lineage leukemias and cell lines
Authors: Imamura Nobutaka , Mtasiwa Deodatus M. , Ota Hiromi , Inada Tominari , Kuramoto Atsushi
Published: February 2007

We herein describe CD9 (p24) antigen as existing on the cell surface of megakaryocyte lineage leukemias as well as megakaryocytic leukemia cell lines, MEG‐01 and HEL, by means of fluorescence‐activated cell sorter (FACS IV) with a panel of monoclonal antibodies (Mabs).

We found CD9 antigen expression on the cell surface of megakaryoblastic leukemias as well as MEG‐01 and HEL cells. Furthermore, CD9 antigen expression increased while culturing these cells with phorbol esters, and was also found in the cytoplasm by means of indirect immunofluorescence test.

These findings clearly showed that CD9 antigen exists on the cell surface of megakaryocytic cells which are capable of synthesizing the CD9.
The persistence and heterogeneity of factor VIII:C inhibitors as demonstrated by preparative isofocusing
Authors: Coots Macie C. , Glueck Helen I.
Published: February 2007

The purpose of this study was to determine if factor VIII:C inhibitors completely disappear during remission and if they recur on exacerbation, are they similar to or different from the original inhibitors? To answer these questions, isofocusing, which separates proteins on the basis of their p/s, was utilized to recover inhibitors from the plasmas of six patients, five nonhemophiliacs with acquired VIII:C inhibitors and the sixth with classic hemophilia. Initially, all plasmas were studied during the presenting hemorrhagic episodes and, subsequently, following the disappearance or recurrence of the inhibitors. Following isofocusing, each fraction was tested for inhibitory activity. The method enabled us to determine that inhibitors to factor VIII:C persisted even when they could not be demonstrated by conventional methods. The inhibitory activity resulted from a composite of inhibitors, each of the group identified by its own p/. In many patients, some peaks persisted throughout the entire interval of study, whereas others disappeared and new ones appeared, suggesting that various groups of cells were capable of producing the inhibitors.
Treatment of relapsed and refractory acute myeloid leukemia with diaziquone and mitoxantrone: A CALGB phase I study
Authors: Amrein Philip C. , Davis Roger B. , Mayer Robert J. , Schiffer Charles A.
Published: February 2007

Twenty‐one patients with relapsed or refractory acute myeloid leukemia (AML) were treated with mitoxantrone (12 mg/m2/day, days 1–3) and diaziquone (continuous infusion days 1–5). The dosage of diaziquone was increased for sequential cohorts of seven patients from 20 mg/m2/day to 24 mg/m2/day, and finally to 28 mg/m2/day to determine the maximum tolerated dose for this chemotherapy combination. Myelosuppression was the dose‐limiting toxicity. The median time to recovery of blood counts was greater at the highest dose of diaziquone (48 days) than at the lower two doses (31 and 28 days). Other toxic effects were minimal. Overall, 9/21 (43%, 95% confidence interval, 0.22 to 0.66) patients achieved complete remission. We conclude that this combination of drugs shows sufficient antileukemic activity with acceptable toxicity to warrant further trials.
Detection of interleukin‐6 (IL‐6) in human bone marrow myeloma cells by light and electron microscopy
Authors: Ohtake Ken‐Ichi , Yano Takahiro , Kameda Kazuo , Ogawa Tetsuhei
Published: February 2007

We used an Avidin‐Biotin peroxidase complex (ABC) immunoperoxidase technique to evaluate the localization of IL‐6 of human bone marrow cells in multiple myeloma (MM). The cellular distribution of IL‐6 was determined at light and electron microscopic levels. The author's study indicated that cytoplasmic IL‐6 was detected only in the myeloma cells of bone marrow cells. Immunoelectron microscopic (immuno‐EM) study showed positive reactivity mainly in the perinuclear space (PNS), well‐developed rough endoplasmic reticulum (RER), and Golgi area.
Cytogenetic findings in 21 cases of peripheral T‐Cell lymphoma
Authors: Inwards David J. , Habermann Thomas M. , Colgan Joseph P. , Banks Peter M. , Dewald Gordon W.
Published: February 2007

Although numerous publications have described the chromosome abnormalities in B‐cell non‐Hodgkin lymphoma and their significance, sparse literature exists pertaining to the chromosome abnormalities in T‐cell lymphoma. We did cytogenetic analyses in 21 cases of peripheral T‐cell lymphoma (PTCL). Chromosomally abnormal clones were identified in 15 (71%) of the cases, including 7 of the 10 cases in which the histologic distinction between a malignant and benign process was difficult. Abnormalities of chromosome 1 were observed in 10 cases; a breakpoint at 1p36 was demonstrated in 5 of these cases. Chromosome abnormalities previously attributed to B‐cell malignancies were infrequent. These results suggest an association between 1p36 breakpoints and PTCL and emphasize the utility of cytogenetic analysis for documenting clonality among the histologically diverse groupings of PTCL.
In vitro endocytosis of benign and malignant human bone marrow plasma cells
Authors: Ohtake Ken‐Ichi , Yano Takahiro , Kameda Kazuo , Ogawa Tetsuhei
Published: February 2007

We report ultrastructural evidence of the phagocytic potential of plasma cells and myeloma cells. The incubation of plasma cells and myeloma cells in vitro with horseradish peroxidase (HRP) and cationized ferritin (CF) allows the tracing of fluid‐phase and receptor‐mediated pathways. Surface‐bound ligands (CF) and solutes (HRP) taken up in primary pinocytic vesicles are internalized to the endosomal compartment. After 1 hr of incubation, CF was found not only in plasma cells but also in myeloma cells. Reaction products of HRP were observed only in myeloma cells. In myeloma cells, however, HRP was located only in the lysosomal system, whereas CF was present within membrane cisternae as well as within lysosomes. These myeloma cells morphologically produced interleukin‐6 (IL‐6).
Hypertonic cryohemolysis: A diagnostic test for hereditary spherocytosis
Authors: Streichman S. , Gesheidt Y. , Tatarsky I.
Published: February 2007

Red blood cells of subjects with hereditary spherocytosis are specifically susceptible to temperature changes while suspended in hypertonic solutions. Based on this property, a new diagnostic test for hereditary spherocytosis is presented. The suggested method is 100% sensitive in the diagnosis of all patients, including asymptomatic obligate carriers with hereditary spherocytosis, and is very specific in different control groups. Unlike other methods designed for the diagnosis of hereditary spherocytosis, this test does not depend on the cells' surface‐ area‐to‐volume ratio. Normal red blood cells that were induced to become spherocytes by different means (i.e., vinblastine, lysophosphatidyl choline, and heat) and showed increased osmotic fragility did not become susceptible to the hypertonic cryohemolysis conditions.
Transformation of bilineal hybrid acute leukemia to acute lymphoid leukemia: A case report with serial analyses of cytogenetics and gene rearrangement
Authors: Jinnai I. , Kusumoto S. , Shiomi Z. , Bessho M. , Saitoh M. , Hirashima K. , Minamihisamatsu M. , Kamiyama T. , Takase K.
Published: February 2007

A 17‐year‐old male with bilineal hybrid acute leukemia is described. Two‐color flow cytometric analysis of blast surface phenotype revealed that there were two groups of blasts which showed either CD 10+ CD 19+ CD 13− CD 33− or CD 10− CD 19− CD 13+ CD 33+, but not both. He developed a complete remission by treatment with vincristine, prednisolone, adriamycin, and L‐asparaginase. After 8 months, however, leukemia relapsed and lymphoid blasts were dominant. Cytogenetic analysis at presentation showed 46, XY, t(3;9)(p21;p22), and at relapse it showed 46, XY, t(1;3;9)(1 pter→1 q32::3p25→3pter; 3qter→3p21::9p22→9pter;9qter→9p22::3p21→3p25::1q32→1qter), t(2;19)(p21;q13). Analysis of the heavy chain joining region at diagnosis showed three hybridizing bands, all rearranged, but at relapse only one rearranged band. Analysis of the constant region for the β T‐cell receptor gene (TCRβ) both at diagnosis and at relapse showed one rearranged and one germline band, suggesting that rearrangement of one allele of TCRβ of not only lymphoid but also myeloid blasts occurred. It is considered that the target cell of lymphoid leukemia cells and that of myeloid leukemia cells at diagnosis were the same, which differentiated to two lineages, and the clone which evolved from lymphoid lineage proliferated at relapse.
Chronic myelomonocytic leukemia: A test of a proposed staging system
Authors: Molica Stefano , Iannaccaro Piergiorgio , Alberti Antonio
Published: February 2007

In an attempt to characterize the prognostic significance of the main clinical and hematological features of chronic myelomonocytic leukemia (CMML), 30 such patients were allocated the “modified Bournemouth score”. The most significant separation of groups predictive of poorer survival was obtained by setting a cutoff at the median score value for the whole series (score,2). On this basis patients could be divided into two different groups whose survival probability as well as risk of acute transformation significantly differ each other (P < 0.05). In our opinion, this score could be of interest in treatment planning of CMML patients when the possibility of conservative or aggressive approach in envisaged.
Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with myeloproliferative disorders
Authors: Katoh Osamu , Kimura Akiro , Kuramoto Atsushi , Itoh Takuji
Published: February 2007

Platelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c‐sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patients.
Selective Reduction of Serotonin Storage and ATP Release in Chronic Renal Failure Patient Platelets
Authors: Soslau Gerald , Parker Janet , Brodsky Isadore , Putatunda Bhaben , Schwartz Allan B.
Published: February 2007

Hemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly (P < 0.001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co‐stored with ATP, is unaltered. Analysis of the CRF‐derived platelets reflects a selective acquired storage pool defect with significantly (P < 0.001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different (P < 0.02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times (P < 0.001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patients.
Diagnosis of pyruvate kinase deficiency in a transfusion‐dependent patient with severe hemolytic anemia
Authors: Rijksen Gert , Schipper‐Kester Gerda P. M. , Staal Gerard E. J. , Veerman Anjo J. P.
Published: February 2007

In a 2‐yr old girl a hemolytic anemia was present since birth requiring multiple blood transfusions. Pyruvate kinase deficiency was suspected on the basis of a marginal enzyme activity, but could not be established due to the presence of massive numbers of donor cells in her peripheral blood. However, by density fractionation we succeeded in the isolation of a small fraction of the patient's own cells, in which a severe pyruvate kinase deficiency could be detected. In contrast hexokinase and glucose‐6‐phosphate dehydrogenase activities were extremely high, which is indicative that a very immature cell population is present in this fraction.

In immunofluorescence studies a clear crossreaction was apparent with anti M2‐type pyruvate kinase antibodies, whereas only a faint reaction with anti L‐type could be detected. Despite the presence of a slight amount of L‐type immunoreactive material, the residual activity in the patient's cell fraction could only be attributed to M2‐type pyruvate kinase as was shown by cellulose acetate electrophoresis.
New treatment strategies for multiple myeloma
Authors: Alexanian Raymond , Barlogie Bart
Published: February 2007

During the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high‐dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high‐dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non‐cross‐resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early relapse.
FAB L3 Type of B‐cell acute lymphoblastic leukemia (B‐ALL) without chromosome abnormalities
Authors: Imamura Nobutaka , Mtasiwa Deodatus M. , Ota Hiromi , Inada Tominari , Kuramoto Atsushi
Published: February 2007

Acute lymphocytic leukemias (ALLs) are morphologically classified into L1, L2, and L3. The former two types are phenotypically constituted of quite heterogeneous ALLs.

In the present study, phenotypes of cells from five L3 type ALL were analysed in FACS‐IV using a panel of monoclonal antibodies (MAbs). The leukemic cells of all these patients coexpressed la (HLA‐DR), CD19, CD20, CD21, CD24, CD38, and surface immunoglobulins, whereas a negative reaction with MAbs CD1, CD2, CD3, CD4, CD7, CD8, and Ti (WT31), TiγA, δTCS 1, and anti TCR‐γ/δ was observed. Neither myeloid‐monocyte‐erythroid nor megakaryocyte related cell surface antigens were detected in these cases with L3 type ALL.

Chromosomal analysis of the ALL cells from two cases revealed a normoploid karyotype with specific translocation t(8;14)(q24;q32), whereas it was normal (46XY or 46XX) for the remaining three cases. Expression of myc oncogene was high in the former group, but low in the later one.

Basing from our findings, we conclude that L3 type ALL is heterogeneous with respect to immunophenotypes, cytogenetics and oncogene analysis.
Necrobiotic xanthogranuloma with IgA multiple myeloma: A case report and literature review
Authors: Valentine Elizabeth A. , Zamkoff Kenneth W. , Friedman Henry D. , Streeten Barbara W.
Published: February 2007

The association between necrobiotic xanthogranuloma of the dermis and paraproteinemia and/or B‐cell malignancy is best described in the ophthalmologic literature. We report a case which occurred in the eyelid and orbit of a 64 year old man that led to the diagnosis of an IgA multiple myeloma. To our knowledge, this is the first report of an IgA type paraproteinemia and IgA type multiple myeloma associated with necrobiotic xanthogranuloma.
Increased protein binding to a −530 mutation of the human β‐globin gene associated with decreased β‐globin synthesis
Authors: Berg Patricia E. , Mittelman Moshe , Elion Jacques , Labie Dominique , Schechter Alan N.
Published: February 2007

Although some cases of the syndrome of hereditary persistence of fetal hemoglobin (HPFH) have been correlated with mutations causing a change in the binding of trans‐acting factors to DNA sequences flanking the γ‐globin gene, this mechanism has not been described in β‐thalassemias upstream of the canonical promoter of the β‐globin gene. In this report we describe such a change in binding of a protein that may explain a silent carrier phenotype of β‐thalassemia. We have previously demonstrated the binding of a protein (BP1) derived from a nuclear extract of human K562 cells to DNA 5′ to the human β‐globin gene in a region having a negative regulatory function. The binding of BP1 in this region can be detected by DNAse I footprinting and by gel mobility shift analysis. We have now compared binding of BP1 to the normal sequence and a mutated sequence (+ATA/‐T at −530 bp from the cap site) from the silent carrier of β‐thalassemia. Using mobility shift assays we show that BP1 binds about nine times more strongly to the mutated sequence than the normal sequence. These results suggest the possibility that the decreased expression of the β‐globin gene exhibited by the carrier may be due, at least in part, to tighter binding of a protein which functions as a negative control element or represser.
Maternal and fetal iron measurements in a hemochromatotic pregnancy
Authors: Baynes Roy D. , Meyer Theo E. , Bothwell Thomas H. , Lamparelli Rosario D.
Published: February 2007

The findings in the cord blood sample of an infant from a treated hemochromatotic mother of a raised transferrin saturation (88%) and a raised ferritin concentration (250.2 μg/L) together with elevated maternal values (66% and 91.6 μg/L, respectively) yet a normal total placental iron content (26.9 mg) suggested that in common with gastrointestinal mucosal cells and reticuloendothelial cells in hemochromatosis, the placental cell may exhibit an abnormality of iron storage and transport.
Radiotherapy of pseudotumors of bone in hemophiliacs with circulating inhibitors to factor VIII
Authors: Castaneda Victoria L. , Parmley Richard T. , Bozzini Miguel , Feldmeier John J.
Published: February 2007

Pseudotumors of bone in two hemophiliacs with severe factor VIII deficiency and a high level of circulating inhibitors are reported. Both had favorable response to radiation therapy after unsuccessful treatment with factor concentrates and remain free of recurrence at 18‐62 months. A review of the literature of cases in which radiotherapy has been used is presented. Radiotherapy in the treatment of pseudotumors of bone in hemophiliacs should be strongly considered, particularly if coagulation factor inhibitors are present.
Antiphospholipid antibodies and adrenal hemorrhage
Authors: McCroskey Robert D. , Phillips Anthony , Mott Frank , Williams Eliot C.
Published: February 2007

We recently encountered two cases of massive bilateral adrenal hemorrhage in patients with antiphospholipid antibodies. A search of the records of this institution covering the past 15 years revealed two additional patients with massive adrenal hemorrhage associated with evidence of antiphospholipid antibodies. Three of these four patients were receiving anticoagulant drug therapy. The presence of the antiphospholipid antibodies may increase the risk of massive adrenal hemorrhage, particularly in patients who receive anticoagulant drugs.
Occurrence of high‐grade T‐Cell lymphoma in a patient with philadelphia chromosome‐negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: Case report and review of the literature
Authors: Djulbegovic Benjamin , Hadley Terence , Yen Frank
Published: February 2007

In this report, we describe a patient with Philadelphia chromosome‐negative chronic myelogenous leukemia (CML) with breakpoint cluster region gene rearrangement who developed T‐cell lymphoblastic lymphoma. The occurrence of T‐cell lymphoblastic lymphoma coincided with the appearance in the bone marrow of the cytogenetic abnormality, trisomy 22q11.2 22qter. This is the first report of high‐grade T‐cell lymphoma in a patient with documented CML.
H‐ras‐1 polymorphism in leukemia
Authors: Wadleigh Robert G. , Chan Clara S. , Cohen Martin H. , Krasnow Steven H. , Anderson Anita , Detera‐Wadleigh Sevilla D.
Published: February 2007

We have examined leukocyte DNAs obtained from 21 patients with various types of leukemia for the Sacl polymorphism of H‐ras‐1. The patients included ten with B‐lineage leukemia, two with T‐cell leukemia, and nine with acute myelogenous leukemia. Using a genomic probe for H‐ras‐1 in Southern hybridizations, we found that 78% of the DNA from leukemias of myeloid origin were heterozygous. In contrast, only three of ten B‐cell‐derived leukemias showed heterozygosity. This difference in the number of heterozygotes vs. homozygotes in the two patient samples studied is statistically significant (P = 0.04 by Fisher's exact test). These results suggest the possibility that the H‐ras‐1 allelic pattern that is associated with acute myelogenous leukemia is distinct from that found in B‐cell‐derived malignancies.
Erythrocyte folate levels: A clinical study
Authors: Jaffe Jeffrry P. , Schilling Robert F.
Published: February 2007

PURPOSE: 1) To determine if there are significant differences in laboratory parameters and patient characteristics between patients with low erythrocyte (RBC) folate levels and those with normal RBC folate levels; 2) to determine the correlation between serum and RBC folate levels; 3) to determine if the RBC folate level changed the diagnosis, treatment, and outcome of these patients if the serum folate level was available.

PATIENTS AND METHODS: The study is a retrospective review of all inpatients and outpatients at a public teaching hospital who had an RBC folate level >175 ng/ml (N = 57) over the study period (69 months) and a blindly selected group of patients with RBC folate levels >175 ng/ml (N = 53) during the same period.

RESULTS: Patients' with low RBC folate levels had higher mean corpuscular volume (MCV) and red cell distribution width (RDW) values and lower serum folate and B12 values than patients with normal RBC folate levels, but there was no difference in degree of anemia, presence of oval macrocytes and/or hypersegmented neutrophils on the peripheral blood smear, LDH, alcohol use, diet, or any other measured clinical parameter. Serum and RBC folate levels were highly correlated and a low RBC folate affected the clinical outcome of three patients (5% of the low RBC folate group).

CONCLUSIONS: Based upon these retrospective data and a review of the literature, we cannot define significant differences between patients with low RBC folate and randomly selected patients with normal RBC folate that could not have been equally well defined using serum folate values. The sensitivity and specificity of a low RBC folate level in the diagnosis of ill or healthy individuals are undefined, and until prospective studies utilizing some of the newer, more specific biochemical indicators of tissue folate are completed, the interpretation of low RBC folate levels will remain problematic.
Hemoglobin aggregation and pseudosickling in vitro of hemoglobin setif‐containing erythrocytes
Authors: Noguchi C. T. , Mohandas N. , Blanchette‐Mackie J. , Mackie S. , Raik E. , Charache S.
Published: February 2007

Erythrocytes from individuals heterozygous for hemoglobin Setif (α94 Asp→Tyr) sickle in vitro without deoxygenation when incubated in chloride buffer due to hemoglobin aggregation. We now report quantitative studies of hemoglobin polymerization and deformability in these cells. Hemoglobin polymer gradually increased in intact cells during a 24 h incubation period at 24°C. After 24 hr, about 80% of the cells in 290 mosm sodium chloride buffer contained polymer which appeared as short rods compared to >99% containing polymer at 450 mOsm. Similar proportions of cells were morphologically sickled. Deformability of erythrocytes with 40% hemoglobin Setif incubated in 290 mOsm buffer at 37°C decreased to 80% of normal by 210 min but in 450 mOsm decreased to 50% after only 30 min as measured by the ektacytometer. However, at 4°C deformability remained normal even in 450 mOsm buffer. The solubility of gelled hemolysate containing 40% hemoglobin Setif was 24 g/dl and 21 g/dl at 290 and 459 mOsm buffer respectively. The gel persisted at 4°C with a solubility of 25 g/dl, but melted when dialyzed into sodium phosphate or potassium phosphate buffer. These data suggest that hemoglobin polymerization, reduced deformability, and sickling of hemoglobin Setif‐containing erythrocytes are related to reduced hemoglobin solubility. The rate and extent of intracellular polymerization in vitro are considerably reduced (as in the case of sickle trait) compared with erythrocytes from individuals with sickle cell anemia. Hence, the slower kinetics of hemoglobin aggregation in hemoglobin Setif‐containing cells provide an alternate system for studying hemoglobin aggregation in hemoglobin Setif‐containing cells provide an alternate system for studying hemoglobin polymerization and abnormal rhelogy.
Therapy of aplastic anemia with sequential antithymocyte globulin and cyclosporin
Authors: Doolittle Gary C. , Bodensteiner David C. , Skikne Barry S. , Amare Mammo
Published: February 2007

Five consecutive patients with severe aplastic anemia were treated with antithymocyte globulin followed by cyclosporin A. All received antithymocyte globulin initially, and because of lack of response within a 4 week period, cyclosporin was administered subsequently. Hematologic improvement occurred within four months of initiation of cyclosporin. Four patients no longer require blood product support, while one remains transfusion‐dependent. In two patients, thrombocytopenia developed when the cyclosporin was tapered but re‐institution of the drug resulted in a prompt improvement of counts. These observations indicate that the sequential use of antithymocyte globulin and cyclosporin may be an effective therapeutic approach in the treatment of severe aplastic anemia.
Hemophagocytosis by small cell lung carcinoma
Authors: Molad Yair , Stark Pinhas , Prokocimer Miron , Joshua Henry , Pinkhas Jack , Sidi Yechezkel
Published: February 2007

A 60‐year‐old woman with disseminated small cell carcinoma of the lung and hemophagocytosis by the metastatic cells in the bone marrow is presented, it is the first clinicopathologic report on phagocytosis of erythrocytes by lung tumor cells in concordance with a recently described evidence of a macrophage origin of small cell carcinoma of the lung.
Changes in plasma levels of tissue‐plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation
Authors: Asakura Hidesaku , Jokaji Hiroshi , Saito Masanori , Uotani Chika , Kumabashiri Ichiro , Morishita Eriko , Yamazaki Masahide , Matsuda Tamotsu
Published: February 2007

Plasma levels of tissue‐plasminogen activator · plasminogen activator inhibitor (t‐PA · PAI) complex and active PAI were assayed in 58 cases of disseminated intravas‐cular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non‐Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t‐PA · PAI complex was observed in most cases of APL, t‐PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.
Edta‐dependent pseudothrombocytopenia: A clinical study of 18 patients and a review of the literature
Authors: Berkman Neville , Michaeli Yossef , Or Reuven , Eldor Amiram
Published: February 2007

EDTA‐dependent pseudothrombocytopenia (EDTA‐PTCP) is the phenomenon of a spurious low platelet count due to the appearance of antibodies that cause platelet agglutination in blood anticoagulated with EDTA. We review here the clinical features of 18 patients with EDTA‐PTCP treated in our hospital from 1984 to 1987 as well as those of 34 patients reported in the literature. This phenomenon appears more frequently in severely ill patients, in association with autoimmune, neoplastic, atherosclerosis‐related, and liver diseases. In the majority of our patients, EDTA‐PTCP appeared during hospitalization, indicating that the antibody is an acquired one. Neither splenomegaly nor the presence of autoimmune markers were features of this entity. Unlike true thrombocytopenias, EDTA‐PTCP is associated with a normal mean platelet volume. Awareness of this entity is essential since EDTA‐PTCP is frequently misdiagnosed and therefore incorrectly treated.
CD71 phenotype and the value of gallium imaging in lymphomas
Authors: Feremans Walter , Bujan Willem , Neve Pierre , Delville Jean‐Pierre , Schandene Liliane
Published: February 2007

Tumor cells of 14 cases of non‐Hodgkin lymphomas and 2 cases of Hodgkin disease were tested for the presence of the transferrin receptor (CD71) by flow cytofluorimetry before 67gallium imaging. It appeared that expression of CD71 phenotype was closely related to the positivity of gallium scan before therapy. We feel that this test is able to predict the avidity for 67gallium and the clinical implications are discussed.
Arsenic intoxication presenting as a myelodysplastic syndrome: A case report
Authors: Rezuke William N. , Anderson Crawford , Pastuszak William T. , Conway Stephen R. , Firshein Stephen I.
Published: February 2007

A case of arsenic intoxication presenting as a myelodysplastic syndrome is reported. A 41‐year‐old woman with a 6‐month history of gastrointestinal and neurological symptoms was noted to be pancytopenic at presentation. A bone marrow aspirate revealed dysmyelopoietic changes involving all three marrow cell lines. Subsequent analysis of urine for heavy metals demonstrated very high levels of arsenic. Treatment with British anti‐Lewisite (BAL) resulted in the resolution of gastrointestinal symptoms and hematologica abnormalities although the neurological complications progressed. This case emphasizes that heavy metal intoxication should be considered in the differential diagnosis of any individual presenting with the hematological features of myelodysplasia especially when accompanied by clinical features considered atypical for primary or secondary myelodysplasia.
Analysis of tumor‐specific immunoglobulin gene rearrangement in peripheral blood B‐cells of multiple myeloma patients
Authors: Baldini L. , Cro L. , Delia D. , Chiorboli O. , Neri A. , Maiolo A. T.
Published: February 2007

The search for bone marrow clone neoplastic precursors in the peripheral blood of multiple myeloma (MM) patients has been the subject of a number of studies which, using different methodological approaches, have led to conflicting results. With the aim of contributing toward resolving this controversy, immunoglobulin (lg) gene rearrangement in the bone marrow mononuclear cells (BMMC) and B‐lymphocyte enriched peripheral cells (BePBC) of 11 appropriately selected advanced MM patients was studied by means of Southern blotting.

Peripheral mononuclear cells (PBMC) and BePBC were studied immunophenotypically by evaluating the presence of cytoplasmic Ig positive cells (Cylg+) and CD19/PCA‐1 reactivity. A pattern of Ig gene rearrangement identical to that observed in the respective BMMC was found in only two patients who, moreover, had a significant number of Cylg+ cells. Ig gene rearrangement was not found in any of the remaining patients who showed no evidence of the presence of Cylg+ cells, although there were CD19/PCA‐1 positive cells. Consequently, the significance of the presence of malignant pre‐plasma cell peripheral B‐lymphocytes needs to be reconsidered and, in any case, these cells should be looked for in cell populations greatly enriched in B‐lymphocytes and, above all, completely lacking in plasma cells or Cylg+ cells.
Spontaneous endocytosis in human neonatal and adult red blood cells: Comparison to drug‐induced endocytosis and to receptor‐mediated endocytosis
Authors: Colin Francine C. , Schrier Stanley L.
Published: February 2007

Neonatal RBC contain many more spontaneous endocytic vacuoles than do adult RBC. It is not known if this difference is a result of an increase in production of vacuoles in the neonatal RBC (as is the case in drug‐induced endocytosis), or is the result of a less effective neonatal macrophagic “pitting” process.

Using an in vitro model of spontaneous endocytosis, we compared the rate and quantity of vacuoles and the shape of cord and adult RBC containing pits, visible by interference contrast microscopy (Nomarski method). The mechanism of the spontaneous endocytosis was explored using different inhibitors: sodium vanadate an inhibitor of ATPases, sodium fluoride which inhibits the generation of ATP and sodium cyanide a potent inhibitor of oxidative phosphorylation. We then compared spontaneous endocytosis with two other forms of RBC endocytosis: drug‐induced endocytosis and receptor‐mediated endocytosis.

Spontaneous endocytosis is in fact increased in neonatal RBC initially but the increase in number of RBC containing pits after 144 hr of incubation is almost the same in adult RBC and neonatal RBC. Comparing spontaneous endocytosis with drug‐induced endocytosis, it appears that their mechanisms are different in that spontaneous endocytosis is not preceded by stomatocytic shape change and is not inhibited by sodium vanadate or sodium fluoride as is the case for drug‐induced endocytosis. Spontaneous endocytosis is different than transferrin receptor‐mediated endocytosis because it occurs in many RBC, not only in the motile R1 reticulocytes and is not inhibited by sodium cyanide as is receptor‐mediated endocytosis.

Thus spontaneous endocytosis appears to be different than drug‐induced endocytosis and transferrin receptor‐mediated endocytosis. The increase in spontaneous endocytosis in cord RBC seen in vivo is probably a consequence of an immaturity of the neonatal macrophage pitting process.
Erythrocyte webb‐type glycophorin C variant lacks N‐glycosylation due to an asparagine to serine substitution
Authors: Telen Marilyn J. , Le Van Kim Caroline , Guizzo Mary Lou , Cartron Jean‐Pierre , Colin Yves
Published: February 2007

We have analyzed part of the sequence of the human glycophorin C (GPC) gene carried by a Webb blood‐group positive donor. Our results indicate that the lack of N‐glycosylation of the variant GPC associated with the Webb phenotype is due to a point mutation resulting in an asparagine to serine substitution at amino acid position 8.
Erythrocyte glycophorin B deficiency may occur by two distinct gene alterations
Authors: Rahuel Cecile , London Jacqueline , Vignal Alain , Ballas Samir K. , Cartron Jean‐Pierre
Published: February 2007

The genomic DNA from rare persons whose erythrocytes are deficient in glycophorin B (GPB) (S‐s‐U‐ phenotype), was examined by Southern hybridizations using glycophorin B probes and was subdivided into two main categories. In the type I variant (Fav., M.H., S.K.), we found that the S‐s‐U‐ condition is generated by a large gene deletion extending from exons B2 to B4 of glycophorin B gene. Conversely, in the type II variant (Del.), the entire gene is present, and its promoter is almost similar to common Glycophorin A(GPA) and GPB as well as to type I promoters, except for four‐point mutations, which do not occur in potential cis‐acting elements. We concluded that the same phenotypic glycophorin B deficiency may occur by different gene alterations, including either a gene deletion or a mutation that might alter transcription or translation of the gene.
Increased production of tumor necrosis factor‐α by peripheral blood mononuclear cells in the patients with aplastic anemia
Authors: Shinohara K. , Ayame H. , Tanaka M. , Matsuda M. , Ando S. , Tajiri M.
Published: February 2007

The activity of tumor necrosis factor‐α: (TNF‐α) in the supernatant of cultured peripheral blood mononuclear cells (PBMC) was measured in patients with aplastic anemia. It was significantly higher in patients with aplastic anemia than in normal controls, both when PBMC were unstimulated or when they were stimulated with PHA. Results from aplastic anemia patients were also significantly higher than patients who had received allogeneic bone marrow transplants. In aplastic anemia patients, the TNF‐α: value produced by PBMC upon stimulation and the platelet count were inversely correlated, as well those patients who had high TNF‐α values tended to have lower hemoglobin and leukocyte values although this was not significant statistically. These results suggest that the increased production of TNF‐α by PBMC plays a role in the severe suppression of hematopoiesis in aplastic anemia.
Granulocyte proteases do not process endothelial cell‐derived unusually large von willebrand factor multimers to plasma vWF in vivo
Authors: Phillips Martin D. , Vu Chau , Nolasco Leticia , Moake Joel L.
Published: February 2007

The unusually large von Willebrand factor (ULvWF) multimers present within endothelial cells and platelets are larger than the vWF multimers normally found in adult human plasma. Furthermore, ULvWF multimers are cleared rapidly from the circulation if they are released by intense endothelial cell stimulation. The mechanisms by which the ULvWF multimers are processed to large plasma vWF multimers are not known. It has been demonstrated that granulocyte proteases are capable of decreasing vWF multimer size in vitro, and that some patients with myeloproliferative syndromes have a relative absence of large plasma vWF multimers in sodium citrate‐anticoagulated plasma samples. In order to assess the influence of granulocyte proteases on vWF multimer size, we evaluated the vWF multimeric patterns in 94 plasma samples from 60 patients with neutrophil counts that were either considerably elevated or extremely reduced. In 83 of 94 plasma samples, the vWF multimeric patterns were normal. No patients with very low neutrophil counts had ULvWF multimers present. These observations suggest that granulocyte proteases are not likely to be involved in vivo in the processing of ULvWF multimers from endothelial cells to the smaller vWF forms in circulation.