bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythrocytes as carriers of chemotherapeutic agents for targeting the reticuloendothelial system
Authors: Lynch William E. , Sartiano George P. , Ghaffar Abdul
Published: February 2007

The object of this work was to define a model using hypotonically loaded erythrocytes as a vehicle to target drugs to the reticuloendothelial system (RES). The optimum hemolytic event was found to occur at 100 mOsm/kg using a 0.5‐min exposure at 0°C. Approximately one third of the total volume of the cells could be replaced with hypotonic drug solutions under these conditions. Although cytosine‐β‐D‐arabinofuranoside, ara C, is membrane permeable and could not be entrapped in the erythrocytes, phosphorylation of this nucleoside antimetabolite enabled it to be loaded efficiently. Actinomycin D could be loaded and retained within the cells at 0°C, but 90% of this loaded drug leaked out of the erythrocytes in 1 min at 37°C. Actinomycin D‐DNA complexes, however, could be loaded and retained for longer periods. In this case, 50% of the DNA‐bound drug was retained in the cells for one hour at 37°C. It was found that the glycopeptide antitumor antibiotic, bleomycin, could be entrapped and retained in the cells without appreciable leakage. It was possible to load a human therapeutic dose of this drug in 1–2 ml of packed cells. Furthermore, it was demonstrated that bleomycin entrapped in erythrocytes was significantly more effective than the same dose of free drug in suppressing the phagocytic function of the RES in Balb/C and C3H mice. The rationale is discussed for the possible use of these drugs, entrapped in erythrocytes, for the production of RES blockade in the treatment of disorders in man.
Hematological evaluation of patients with various combinations of α‐thalassemia
Authors: Altay C. , Gurgey A. , Tuncbilek E.
Published: February 2007

Six patients and their parents from five different families with Hb H have been evaluated clinically and hematologically. Previous studies using restriction endo‐nuclease mapping technique indicated that α‐thalassemia determinants in these cases are heterogeneous. Only one of the five cases have the usual genotype for Hb H, which is characterized by an α‐DNA‐specific fragment of 20 kb long by Eco RI digestion.

Three cases from two different families have Hb H disease with α‐specific DNA fragments of 22.5 kb/2.6 kb long; and the other two have α‐specific DNA fragments of 20 kb/2.6 kb long, in Eco RI digestion of the cellular DNA. The hematological examination of the parents suggests that the α‐thalassemia condition associated with the Eco RI fragment of α‐specific cellular DNA of approximately 22.5 kb long produces an α‐thal‐2‐like clinical condition, while the other α‐thalassemia determinant associated with a fragment 2.6 kb long results in an α‐thal‐1‐like clinical condition. The clinical and hematological findings of the cases with 22.5 kb/2.6 kb fragment patterns were more severe than the case with the 20 kb/2.6 kb combination. This study suggests that variation in the clinical and hematological findings among patients with Hb H disease may well reflect a heterogeneity of the genotypic combination.
Priapism complicating chronic granulocytic leukemia
Authors: Suri R. , Goldman J. M. , Catovsky D. , Johnson S. A. , Wiltshaw Eve , Galton D. A. G.
Published: February 2007

Since 1952 we have seen nine patients with priapism leading to a diagnosis of chronic granulocytic leukemia (CGL) and a tenth patient who gave a history of priapism when CGL was diagnosed as a result of other symptoms. Seven patients had had one or more transient episodes of prolonged erection before the diagnosis of CGL was established. All ten had high blood leukocyte counts (mean 380 × 109/liter, range 186‐782) in comparison with other newly diagnosed patients. We estimate the incidence of this complication at 1%–2% of all male patients presenting with CGL. Treatment of patients in this series varied greatly. Five patients were treated mainly by local measures with or without cytotoxic drugs at conventional dosage, three were treated by sapheno‐cavernous bypass operations and leukapheresis followed by cytotoxic drugs at high dosage, and two were treated initially by leukapheresis alone. In general, the prompt initiation of measures designed to reduce the leukocyte count seemed more valuable than the surgical procedures employed in these patients.
Characterization of lymphoid cells in the blood of healthy adults: Sequential immunological, cytochemical and cytokinetic studies
Authors: Hirt A. , Wagner H. P.
Published: February 2007

With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha‐naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg− cells were ANAE+ than E−sIg+ cells (70% vs. 11%). About half of the E+sIg− cells were ANAE+. By combining esterase and surface marker analyses eight subpopulations of lymphoid cells could be distinguished. The most common subpopulations were E+sIg− ANAE+ and E+sIg−ANAE− cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE− cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E−sIg+ cells. The overall labeling index of the lymphoid cells examined was ≦ 0.2%.
Prolymphocytic leukemia: Flow microfluorometric, immunologic, and cytogenetic observations
Authors: Diamond Lawrence W. , Bearman Robert M. , Berry Paula K. , Mills Bonnie J. , Nathwani Bharat N. , Weisenburger Dennis D. , Winberg Carl D. , Teplitz Raymond L. , Rappaport Henry
Published: February 2007

Cells isolated from four patients with prolymphocytic leukemia were evaluated by surface markers, cytogenetics, and flow microfluorometric analysis of cell size and DNA content. All four patients had B‐cell markers with a high density of IgM, kappa type, and Ia‐like antigen. Less intense staining for surface IgD was also observed. In each patient studied, chromosomal modes were in the hypodiploid or near‐diploid range. Despite the karyotypic abnormalities, the cellular DNA content, as determined by flow microfluorometry, was within normal limits in all cases. This suggests that the variability in chromosome numbers seen in these patients may reflect an abnormality in DNA packaging rather than differences in total DNA content. The modal electronic cell size of the prolymphocytes, determined by light scatter, was readily distinguishable from that of normal peripheral blood lymphocytes and the lymphocytes of chronic lymphocytic leukemia. Fewer than 4% of the peripheral prolymphocytes had S‐phase DNA content, a finding consistent with the chronic nature of this leukemia.
Terminal‐deoxynucleotidyl‐transferase immunofluorescence on bone marrow smears: Serial studies on 28 patients
Authors: Miller William M. , Stass Sanford A. , Schumacher Harold R. , Bollum Frederick J.
Published: February 2007

Terminal‐deoxynucleotidyl‐transferase (TdT) activity determinations, using the indirect immunofluorescence technique, were performed on 28 consecutive leukemia patients. Fifteen patients with acute lymphoblastic leukemia had 38 bone marrow smears examined. TdT‐positive cells were a good indicator of disease activity in acute lymphoblastic leukemia in that numbers were increased at the time of diagnosis, normal during remission, and increased during relapse. Ten patients with acute myeloid leukemias had 42 smears studied. The number of TdT‐positive cells did not reflect the activity of the disease, except for two patients with acute myelomonocytic leukemia in which TdT‐positive cells were mildly increased during relapse. Three patients with chronic myelogenous leukemia had eight smears studied. The number of positive cells seemed meaningful only in following the course of lymphoid blast crisis. It would therefore appear that TdT determinations seem to be of value in lymphoblastic leukemia, but of limited value in myeloid leukemias.
Hereditary pyruvate kinase abnormalities associated with erythrocytosis
Authors: Rosa Raymonde , Max‐Audit Isabelle , Izrael Victor , Beuzard Yves , Thillet Joélle , Rosa Jean
Published: February 2007

A familial erythrocytosis is described. The propositus is a 52‐year‐old man who was found, on routine testing, to have an erythrocytosis with a Hb level of 19.8 g/dl. Physical examination and laboratory findings revealed an associated hemolysis. The P50 of the stripped hemolysate was normal. The 2,3‐DPG level was reduced to 15% of normal but that of ATP was increased more than twofold. Red cell diphosphoglycerate mutase activity was normal as were the levels of all red cell glycolytic and hexose monophosphate shunt enzymes with the exception of pyruvate kinase (PK). The level of the latter was elevated to 24.5 U/g(normal:6.3 ± 1.1). The electrophoretic pattern of hemolysate PK was abnormal, showing three additional bands; one of these migrated as the M2 isozyme. The findings were similar in the propositus's daughter and her daughter and in one of the two brothers of the propositus. The second brother and the son of the first brother also exhibited erythrocytosis but their red cell 2,3‐DPG levels were normal. In addition, the level of their RBC PK was reduced to between 50% and 60% of normal and the abnormal electrophoretic bands were absent. The erythrocytosis appears to be inherited as an autosomal‐dominant trait. The relationship between the PK abnormalities appears complex.
Platelet dysfunction in myeloproliferative syndromes
Authors: Phadke Kiran , Dean Shirley , Pitney W. R.
Published: February 2007

The most common abnormality of the platelets in 43 patients with a variety of myeloproliferative syndromes was impaired or absent aggregation when stimulated with collagen and adrenaline. Eight unselected cases studied in more detail showed a normal prostaglandin synthesis pathway as evidenced by normal aggregation with arachidonic acid and the production of normal amounts of malonyldialdehyde. Mixing experiments with aspirin‐tested platelets showed correction of the abnormal adrenaline and collagen responses and confirmed that the nature of the defect was different from that induced by aspirin. Stimulation of “myeloproliferative” platelets with thrombin after blocking the prostaglandin pathway with aspirin resulted in reduced aggregation, indicating either a deficiency of the storage pool of adenine nucleotides in the platelets or an abnormality of a membrane receptor for thrombin.
A microimmunofluorescent assay to detect human granulocyte antigens and antibodies
Authors: Zaroulis Charles G. , Jaramillo Sylvia
Published: February 2007

Granulocyte antibodies are important in the pathogenesis of neonatal granulocytopenia, in some varieties of idiopathic granulocytopenia, and in transfusion reactions, particularly since the development of leukocyte transfusion therapy for granulocytopenic patients. Previous assays for the detection of granulocytespecific antigens and antibodies were cumbersome, complex, and unreliable. Thus we have now described a new microimmunofluorescent method to assay human granulocyte antigens and their antibodies. This sensitive and reliable technique allows for the preservation of human granulocyte antigenicity for at least 24 hours. The granulocyte‐specific antigens of a Caucasian population, residing in metropolitan New York, were studied by this microimmunofluorescent method. We report the distribution of granulocyte‐specific antigens in this population, together with the corresponding gene frequency. This microimmunofluorescent test should improve our understanding of antigenic systems restricted to single cell populations.
Pure erythrocytosis: Reappraisal of a study of 51 cases
Authors: Najean Y. , Triebel F. , Dresch C.
Published: February 2007

Fifty‐one cases of pure, primary erythrocytosis were identified and followed at Hǒpital Saint‐Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32P. The median duration of the first remission was greater than five years, the mean yearly dose of 32P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods to investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32P therapy.
Increased T‐cell reactivity to leukemic B cells in chronic lymphocytic leukemia with change of stable disease to its progressive form
Authors: Fernandez Louis A. , MacSween J. Michael , Langley G. Ross
Published: February 2007

Some patients with chronic lymphocytic leukemia (CLL) have a relatively stable clinical course without treatment, but many of these eventually develop progressive disease. We have followed 68 patients over 5½ years by employing conventional surface markers and lymphocyte reactivity, including that of separate enriched T cells to their own leukemic B cells, to phytohemagglutinin (PHA), and to normal allogeneic B cells; we have observed an unusual response in each of the seven patients who developed progressive disease over this period of time. During the stable phase of the disease the T cells from 27 leukemic subjects did not respond to their own leukemic B cells in culture. In the seven patients who developed progressive disease, a significant reactivity of their enriched T cells to their own leukemic B cells occurred. There was no consistent change in T‐cell reactivity to PHA or to allogeneic B cells, suggesting a change in the leukemic B‐cell populations that was not detected morphologically. The change in reactivity of T cells to leukemic B cells occurred prior to evidence of clinical or laboratory deterioration in one of the seven cases; there was increasing lymphocytosis and lymphadenopathy in six and two instances, respectively; and anemia and thrombocytopenia in the three and one cases, respectively.
Monocyte α‐naphtyl esterase deficiency in chronic granulomatous disease
Authors: Gougerot‐Pocidalo Marie‐Anne , Buriot Diego , Griscelli Claude , Hakim Jacques
Published: February 2007

Monocytes from five unrelated children (four boys and a girl) with chronic granulomatous disease were studied for their ability to reduce nitroblue tetrazolium dye after stimulation with zymosan, and for their α‐naphtyl butyrate esterase activity. As expected, monocytes ingested zymosan particles but failed to reduce nitroblue tetrazolium dye. However, monocytes from two boys out of the five patients were α‐naphtyl butyrate esterase‐negative, whereas both their neutrophils and monocytes were positive for granular naphtol AS‐D esterase activity.
The modification of human erythrocyte membrane structure by membrane stabilizers: An electron spin resonance study
Authors: Janoff Andrew S. , Mazorow D. L. , Coughlin R. T. , Bowdler A. J. , Haug A. , McGroarty E. J.
Published: February 2007

Membrane structure in intact human erythrocytes was analyzed by electron‐spin‐resonance (ESR) spectroscopy. The spin probes 5‐doxyl stearate and 5‐doxyl stearate methyl ester revealed thermally‐induced structural transitions in the membrane at 37°C and 15°C. The addition of propranolol, diazepam, chlorpromazine, or Pluronic F68 all caused a decrease in the temperature of the upper transition, but did not markedly alter the temperature of the lower transition. In addition, diazepam caused a significant decrease in the ordering or packing of the membrane‐lipid acyl chains. It is proposed here that the protection from hypotonic hemolysis that has been reported in the presence of these drugs is mediated by a structural rearrangement in the erythrocyte membrane involving a change in protein‐lipid interactions.
Chronic myelomonocytic leukemia in childhood
Authors: Thomas William J. , North Robert B. , Poplack David G. , Slease Robert B. , Duval‐Arnould Bertrand
Published: February 2007

A four‐year‐old child with recurrent infections and increasing hepatosplenomegaly over a three‐year period was evaluated. Increased numbers of myeloid precursors packed the bone marrow and infiltrated the peripheral blood. A diagnosis of chronic myelogenous leukemia (CML) was considered but could not be confirmed by laboratory studies appropriate for the types of CML usually observed in childhood. Examination of the patient's peripheral blood smears revealed many atypical monocytoid cells with unipolar hairy projections. Scanning electron microscopy showed these to be leukemic monoblasts with characteristic broad‐based ruffles on the cell surface. A population of myeloid precursors possessing narrow ridge‐like profiles was also observed. Progressive infiltration of the spleen caused hypersplenism which necessitated splenectomy. Subsequently, massive liver and bone marrow involvement led to the patient's death. Terminally, the proliferating blast cells were demonstrated to be leukemic monoblasts by analysis of cytochemical staining patterns, surface immunoglobulins, serum lysozyme levels, and monocyte‐mediated antibody‐dependent cellular cytotoxicity studies. The findings in this case are most compatible with a diagnosis of chronic myelomonocytic leukemia (CMML), a condition not previously described in childhood. Several myeloproliferative disorders with prolonged survival have been reported in children, but special studies were not performed to determine which cell lines were abnormally proliferating. The similarities between these children and our patient with CMML suggest that monocyte studies may be useful in the diagnosis of these unusual disorders, provide insights into their pathogenesis, and aid in the selection of appropriate therapy.
Factors affecting iron balance
Authors: Conrad Marcel E. , Barton James C.
Published: February 2007

The availability of radioisotopes of iron led to the performance of physiologic studies of the absorption, excretion, and kinetics of iron. The effects of dietary constituents and intestinal secretions upon iron absorption have been thoroughly explored and have permitted the development of tools for nutritional studies in various geographic areas of the world. The basic mechanisms for regulation of iron absorption are not fully understood. However, the isolation and characterization of newer iron‐binding proteins, the existence of mucosal receptors in which there is competition for iron‐binding sites with other metals, and the identification of a number of animal models with genetic abnormalities of iron absorption provide promise for development in the foreseeable future. The means by which the body informs the intestine to increase or decrease iron absorption is poorly understood, and the abnormality in hemochromatosis and iron overloading disorders remains unexplained. Much has been learned in recent years regarding the structure of iron‐containing proteins and the variations that exist in different species. Similar problems remain to be solved with regard to the intermediary metabolism of iron in red blood cell precursors and other cells in the body. It is postulated that the combined usage of physiologic, biochemical, and immunologic investigations will provide the basic information required.
Thirteen cases of pyruvate kinase deficiency found in Japan
Authors: Ishida Yoji , Miwa Shiro , Fujii Hisaichi , Fujinami Noboru , Takegawa Susumu , Yamato Kunio
Published: February 2007

Thirteen cases of pyruvate kinase (PK) deficiency, considered to be heterozygous for different PK mutants because of no consanguinities in their parents, were characterized by the International Committee for Standardization in Haematology (ICSH) recommended methods. These deficiency cases are named PK “Kagoshima,” PK “Kyoto,” PK “Takamatsu,” PK “Abeno,” PK “Kobe,” PK “Marugame,” PK “Hoenzaka,” PK “Osaka,” PK “Motomachi,” PK “Gifu,” PK “Hiroshima” PK “Matsumoto,” and PK “Tama.”

The characteristics of mutant PK enzymes suggest that the cause of chronic hemolysis depends mainly on decreased affinity for phosphoenolpyruvate, thermolability, increased inhibition by adenosine triphosphate, and low activation by fructose‐1, 6‐diphosphate.
Antigranulocyte antibodies and deranged immune function associated with phenytoin‐induced serum sickness
Authors: Menitove Jay E. , Rassiga Anne L. , McLaren Gordon D. , Daniel Thomas M. , Mahmoud Adel A. F.
Published: February 2007

A phenytoin‐associated serum‐sickness‐like syndrome was followed by severe pancytopenia in a 17‐year‐old female. Serum obtained during the acute phase of her illness contained antibodies against homologous eosinophils and neutrophils, antibodies against autologous neutrophils, and antibodies to phenytoin. The serum also inhibited bone marrow granulocyte colony formation in vitro. Lymphocyte transformation by pokeweed mitogen was impaired and, after recovery, the patient's lymphocytes were transformed in vitro by the addition of phenytoin. These data demonstrate that profound derangements of immunity can be associated with a phenytoin‐induced serum‐sickness‐like illness.
Freeze preservation of sickle erythrocytes
Authors: Castro Oswaldo , Hardy Kathryn Phillips , Winter William P. , Hornblower Marne , Meryman Harold T.
Published: February 2007

The effect of short‐term cryopreservation on metabolic, functional, and survival characteristics of erythrocytes from patients with sickle cell disease was examined. Post‐thaw hemolysis of glycerolized sickle (SS) erythrocytes was greater (mean 12.9%) than in hemoglobin‐AA cells (mean 4.7%). Freeze preservation had no apparent effect on red cell morphology, percent irreversibly sickled cells, and fetal hemoglobin content. There were modest reductions in ATP and 2,3‐diphosphoglycerate in thawed, washed sickle erythrocytes (12.7% and 29.7%, respectively). However, the autologous survival of 51 Cr‐labelled SS red cells was not shortened by cryopreservation. The safety and efficacy of autotransfusion of cryopreserved red cells in alloimmunized sickle cell disease patients with anemic episodes unrelated to sickling need to be determined.
Labile anticoagulant in a patient with lymphoma
Authors: Goldsmith G. H. , Saito H. , Muir W. A.
Published: February 2007

A patient with diffuse lymphocytic lymphoma and monoclonal IgM kappa immunoglobulin was found to have an unstable circulating anticoagulant. The anticoagulant inhibited phospholipid‐dependent plasma coagulation reactions. Unlike previously described anticoagulants of this type, this plasma inhibitor was neutralized in vitro by products of platelet lysis but not by exogenous addition of other phospholipids or by intact platelets. Inhibitory activity seemed dependent on the monoclonal immunoglobulin, but isolated immunoglobulin fractions lacked anticoagulant activity, suggesting that the inhibitory function was dependent on an easily disrupted macromolecular aggregate. Recognition and characterization of other similar anticoagulants may provide a means of studying the role of phospholipids in normal hemostasis.
Freeze‐drying of hemoglobin solutions without adjuvant and in presence of glucose, tris, and β‐alanine: A study by electron spin resonance of the oxidized compounds produced
Authors: Chaillot B. , Labrude P. , Vigneron C. , Simatos D.
Published: February 2007

Hemoglobin cannot be freeze‐dried without the presence of protective compounds. Carbohydrates are a well‐known example of such compounds, but we have shown that some amine buffers and amino acids are also very effective. The mechanism of action of all these molecules is unknown. We report here experimental data showing that the protective effect is not the result of a direct bond between iron and the protective compound added.
Platelet calcium‐dependent proteins: Identification and localization of the calcium‐dependent regulator, calmodulin, in platelets
Authors: White Gilbert C. , Levine Steven N. , Steiner Alton N.
Published: February 2007

The calcium‐dependent regulator protein, calmodulin, is a 17,000 molecular weight polypeptide which binds calcium and has been shown to confer calcium sensitivity on contractile and other proteins. In the present study, we have examined the presence and subcellular distribution of this protein in preparations of human platelets. Calmodulin was quantified using a two‐stage phosphodiesterase assay. Whole platelets contained 1.33 ± 0.06 units calmodulin per 106 platelets or 26.5 ± 3.4 fg calmodulin per platelet. The distribution of calmodulin in the platelet was predominantly soluble with over 80 percent of calmodulin activity in the soluble fraction of the cell. There was no apparent difference in the distribution of calmodulin between soluble and particulate compartments in recalcified platelet homogenates compared to homogenates in EDTA. Indirect immunofluorescent studies with monospecific antisera to dinitrophenylated calmodulin showed intense staining of platelets in a diffuse pattern. The identification of calmodulin in platelets raises the possibility that this protein may participate in calcium‐dependent reactions important in platelet aggregation and release.
pH dependency of potassium efflux from sickled red cells
Authors: Roth Eugene F. , Nagel Ronald L. , Bookchin Robert M.
Published: February 2007

Potassium efflux from deoxygenated, hemoglobin S‐containing red cells is often used as an “objective” in vitro measure of red cell sickling, particularly during tests with antisickling agents. Since varying pH is known to affect both the extent of sickling and passive K+‐flux across the red cell membrane, in opposite directions, we measured the sickling‐related K+‐efflux in sickle cell anemia (SS) and sickle cell trait (AS) red cells as a function of extracellular and intracellular pH. The sickling‐related K+‐efflux was found to show the same direction of pH dependence as normal red cells, so that as the extracellular pH was reduced below 7.6, sickling and K+‐efflux were increasingly dissociated. A similar dissociation was observed between sickling and K+‐efflux when the intracellular pH was lowered by increasing red cell organic phosphate levels. The sickling‐related K+‐efflux from osmotically shrunken AS cells (whose sickling tendency resembles that of SS cells) was similar in magnitude and pH dependency to that of the SS cells. The findings suggest that measurement of K+‐efflux may be an accurate estimate of the extent of intracellular polymerization in sickled red cells, provided that both the intracellular and extracellular pH levels are carefully controlled, and the experimental conditions produce no independent effects on K+ permeability.
Hepatocellular enzyme patterns and hepatitis b virus exposure in multitransfused young and very young hemophilia patients
Authors: Gomperts E. D. , Lazerson J. , Berg D. , Lockhart D. , Sergis‐Deavenport E.
Published: February 2007

Thirty‐eight children with severe hemophilia A, 11 years of age and under, were evaluated by initial and follow‐up liver function tests (LFTs) in relation to age of onset of transfusion therapy. Each child had at least two complete evaluations within one year for a follow‐up period of at least one year. The mean number of exposure days was 36 with a mean of 275 units of factor VIII per exposure day prior to initial LFTs. At initial testing, 30% of patients demonstrated antibody to HBsAg and 39–51% at least one abnormal serum enzyme level (AST, ALT, LDH). During an average follow‐up period of 34.8 months, two children developed HBsAg‐positive icteric hepatitis. Of those initially serologically negative for HBsAg or antibody, 44% became antibody‐positive. Intermittent abnormalities of at least one serum enzyme were observed in 79% of the patient group, with 13% and 8% being persistently normal and abnormal. Eleven children born after January 1976, receiving only third‐generation RIA‐tested products for HBsAg, constituted a subgroup. Although only one child at first assessment had evidence of hepatitis B virus exposure, 55% had elevated ALTs, indicating considerable frequency of non‐A, non‐B hepatitis in this very young group.
Serum concentrations of erythropoietin measured by radioimmunoassay in hematologic disorders and chronic renal failure
Authors: Zaroulis Charles G. , Hoffman Beth J. , Kourides Lone A.
Published: February 2007

Bioassays for human erythropoietin are cumbersome, time‐consuming, and insensitive. The purification of human erythropoietin (EP) has provided small quantities of highly bioactive EP (∼70,000 U/mg) required for the development of an EP radioimmunoassay (RIA). The RIA for EP described in this investigation, can detect 5 mU/ml of EP in the assay tube; the serum concentration of EP in normal individuals ranged from <18 to 81 mU/ml with a mean value of 29 mU/ml. In contrast, nine patients with severe aplastic anemia had markedly elevated serum EP concentrations with a mean value of 3,487 mU/ml, range 984–6,434 mU/ml. In this RIA, patients with Polycythemia vera had consistently undetectable EP concentrations, <18 mU/ml. Eleven patients with chronic renal failure had a higher mean serum EP concentration (40.5 mU/ml) than normal individuals, but the range (<18–115 mU/ml) overlapped that of normals. By immunologic and gel chromatographic criteria, EP measured in serum was similar to standard urinary EP. The EP immunoassay that we have developed has sufficient sensitivity and specificity not only to quantitate the elevated serum EP levels found in aplastic anemia but also to discriminate decreased from normal serum concentrations of EP in most circumstances. This simple, reliable RIA has provided the necessary framework upon which to increase our understanding of the importance of EP in hematopoiesis.
Double light‐chain production by leukemic cells of common clonal origin: A case report with review of pertinent literature
Authors: Choi Young Ja , Wong Martha S.
Published: February 2007

We are reporting the first case of acute lymphoblastic leukemia whose individual leukemic cells produced both K and λ light chains, without any heavy chains, as demonstrated by double immunofluorescent staining. This case together with cases of lympho‐plasmacytic neoplasia reported in the literature indicates that cells of a single clone are capable of producing more than a single class of light and/or heavy chains.
Hypereosinophilia in a monosomy 7 myeloproliferative disorder in childhood
Authors: Humphrey M. J. , Hutter J. J. , Tom W. W.
Published: February 2007

Hyperosinophilia in association with a monosomy 7 myeloproliferative disorder is described in an eight‐year‐old boy. Antileukemic treatment resulted in a decrease in the eosinophilia, but did not appear to affect the blast cell population or the presence of monosomy 7 cells in the bone marrow. These findings suggest that bone marrow karyotyping may be useful in differentiating pre‐malignant causes of eosinophilia from those with a more benign etiology.
Hemoglobin connecticut (β21(b3) Asp→Gly): A hemoglobin variant with low oxygen affinity
Authors: Moo‐Penn W. F. , McPhedran P. , Bobrow S. , Johnson M. H. , Jue D. L. , Olsen K. W.
Published: February 2007

Electrophoretic analysis of a hemolysate from a young man undergoing a routine physical examination revealed an abnormal hemoglobin with a mobility similar to Hb S on cellulose acetate (pH, 8.4). This new variant, designated Hb Connecticut, was found in three generations of a family of Polish descent. Several individuals possessing the variant exhibited mild anemia. Structural analysis of the abnormal β‐chain indicated that the amino acid substitution was at position 21(B3), and involved the replacement of aspartic acid with glycine. Oxygen dissociation studies revealed low oxygen affinity. The alkaline Bohr effect and the degree of cooperativity were unchanged. Analysis of the crystal structure of the variant suggested that the low oxygen affinity was due to the possible disruption of salt bridges between aspartic acid 21(B3) and lysines 61(E5) and 65(E9), changes that could lead to steric interference in oxygen binding.
The relationship between lymphocyte nuclear morphology and cell cycle stage in lymphoid neoplasia
Authors: Diamond Lawrence W. , Weisenburger Dennis D. , Rappaport Henry
Published: February 2007

A significant percentage of lymphoid cells isolated from three lymphoid neoplasms (nodular lymphoma mixed cell type, mycosis fungoides, and Sézary syndrome) had tetraploid or near‐tetraploid DNA content, as determined by flow cytometric analysis. In each case, a morphologically distinct population of cells with large, irregular nuclei was present, the percentage of which corresponded to the percentage of tetraploid cells. In a fourth case (diffuse “histiocytic” lymphoma), cells were sorted on the basis of DNA content from the G0‐G1 compartment and compared morphologically to cells sorted from the S‐G2(M) compartment. The G0‐G1 cells had clumped nuclear chromatin, lacked prominent nucleoli, and had a mean nuclear diameter of 10.18 ± 1.22 μm. The sorted cells with S‐G2(M) DNA content had one to several prominent nucleoli and less clumped nuclear chromatin, and they were significantly larger, with a mean nuclear diameter of 13.76 ± 1.59 μm (P < 0.00001). These preliminary results suggest that, in lymphoid malignancies, certain morphologic characteristics of individual lymphoid cells are related to their DNA content (level of ploidy) and/or the stage of the cell within its division cycle.
Successful allogeneic bone marrow transplantation after reversion to chronic phase of blast crisis in chronic myeloid leukemia
Authors: Vernant J. P. , Rodet M. , Rochant H. , Feuilhade F. , Thuran A. , Bierling P. , Lesc M. C. , Mannoni P. , Dreyfus B.
Published: February 2007

A female with chronic myeloid leukemia (XX Ph 1 +) in blast crisis (localized to pleura and lymph nodes) was treated by polychemotherapy. After reversion to the chronic phase, an allogeneic bone marrow transplantation (BMT) was performed. Sixteen months after BMT, no sign of the disease was present (XY Ph 1 ‐).
Complement‐fixing platelet autoantibodies in autoimmune thrombocytopenia
Authors: Kayser W. , Mueller‐Eckhardt C. , Budde U. , Schmidt R. E.
Published: February 2007

A 16‐year‐old male patient is described with chronic autoimmune thrombo‐cytopenic purpura and, after two years, “warm” autoimmune hemolytic anemia (Evans syndrome) who transiently developed complement‐fixing platelet autoantibodies. The autoreactivity of these antibodies was established by quantitative complement fixation as well as by absorption and elution studies using autologous platelets. We believe this to be the first documented case with this very rare and peculiar type of platelet autoantibody.
Prednisone‐responsive aplastic anemia associated with T‐lymphocyte proliferation
Authors: Bodner Sara , Cohen Harvey Jay
Published: February 2007

In some cases, bone marrow aplasia has been thought to result from immunologic abnormalities. Our patient had severe transfusion‐dependent aplastic anemia, which responded to treatment with prednisone on two occasions. The exacerbations of aplastic anemia were associated with lymphocytic proliferation which on one occasion had the characteristics of T‐cell chronic lymphocytic leukemia. Though he had had mild lymphoproliferation for a number of years, he ultimately died with progressive diffuse lymphoid infiltration of the bone marrow and other organs. The simultaneous occurrence of the T‐cell lymphoproliferation and aplastic anemia and their simultaneous response to therapy suggests that this may be a clinical example of T‐lymphocyte mediated suppression of erythropoiesis.
Opsonic activity of myeloma immuno‐globulins (mm‐lg)
Authors: Cheson Bruce D.
Published: February 2007

Patients with MM are at an increased risk for life‐threatening bacterial infections, primarily by organisms that require opsonization for interaction with granulocytes. In the present study we used a neutrophil chemiluminescence (CL) assay of opsonization to explore the opsonic activity of MM‐lg for zymosan particles. Particles were treated with serum lacking in Ig to explore the contribution of Ig to zymosan opsonization. This serum was found to have 69 ± 2.6% (X̄ ± SEM) of the opsonic activity of normal serum (P < .001). Normal serum concentrations of normal IgG, MM‐IgG, and MM‐IgA all lacked opsonic activity for zymosan. However, when particles were treated with Nl‐IgG, MM‐IgG, or MM‐IgA as well as complement, normal opsonic activity was generated. Increasing the concentration of the Ig to stimulate MM serum did not inhibit this opsonic activity. Thus both MM‐IgG and MM‐IgA can function as normal, nonspecific opsonins.
A neutrophil lysozyme leak in patients with familial mediterranean fever
Authors: Bar‐Eli Menashe , Territo Mary C. , Peters Robert S. , Schwabe Arthur D.
Published: February 2007

Polymorphonuclear cells derived from the peripheral blood of patients with Familial Mediterranean Fever release more lysozyme in response to high temperatures (42°, 46°C) than do control cells. No differences between the FMF and control cells were observed in the release of acid phosphatase, β‐glucuronidase, or lactoferrin. Colchicine treatment had no effect on the measurable release of the enzyme from PMNs derived from FMF patients. The increased release of lysozyme in response to high temperatures appears to be specific to FMF neutrophils, and was not found in PMNs from non‐FMF patients with febrile or inflammatory diseases, nor was it seen in monocytes derived from the FMF patients. It is suggested that the increased release of lysozyme from the neutrophils may be of importance in the pathogenesis of FMF.
Auer rod positive dysmyelopoietic syndrome
Authors: Weisdorf Daniel J. , Oken Martin M. , Johnson Gerhard J. , Rydell Robert E.
Published: February 2007

Twenty‐five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod‐positive group was 14 months (range 2–27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod‐negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod‐negative group. The clinical course of Auer rod‐positive RAEB, like that of Auer rod‐negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod‐positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod‐negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.
Intrasplenic pH in normal and phenylhydrazine‐induced anemic rats
Authors: Chen L. T. , Chiang P. K.
Published: February 2007

Direct measurement of the intrasplenic pH with a microcombination glass pH probe was performed in rats. The pH probe was inserted into the splenic pulp during measurements. In the normal rats, the pH was 7.21. However, in rats with hemolytic anemia induced by phenylhydrazine treatment, the pH decreased to 7.01. The level of lactic acid in the spleen was also determined. The lactic acid content in the spleen of anemic rats was found to be higher (1.20–1.44 μmoles/gm spleen) than that of normal rats (0.70–0.74 μmoles/gm spleen). The results suggest that the lower pH in the spleens of anemic rats may result from an increase in the lactic acid level in the spleen.
Methods of processing marrow samples may affect the frequency of detectable aneuploid cells
Authors: Waghray Manjula , Eques Celida , Rowley Janet D. , Martin Paulette , Testa Joseph R.
Published: February 2007

Karyotypes were analyzed from 14 patients with various myeloproliferative disorders who had marrow samples processed directly and cultured in various ways. Eleven patients had acute nonlymphocytic leukemia (ANLL) (seven patients) or a dysmyelopoietic syndrome (four patients). All of these patients were known to have an abnormal karyotype, and in each case, two samples of a bone marrow aspirate were available: one processed directly and another cultured for 24 hr. Five of the 11 patients had essentially the same proportion of abnormal cells in the direct and 24‐hr samples; in five other patients, the percentage of aneuploid cells in the sample cultured for 24 hr was higher than that in the direct preparation. A higher percentage of aneuploid cells was observed in the direct preparation in only one case.

In three other cases of ANLL, a marrow aspirate was cultured with methotrexate in addition to samples processed directly and after 24‐hr culture; only two of these had an abnormal clone in any sample. The results of karyotype analysis differed in these two patients. The proportion of aneuploid cells was substantially higher in the methotrexate culture than in the 24‐hr culture in one patient; in the other patinet, the 24‐hr culture contained aneuploid cells, whereas the methotrexate culture showed none.

Three of the 13 aneuploid patients would have been incorrectly classified as being karyotypically normal on the basis of the initial analysis of the direct preparation, since only a single abnormal cell was detected in each case.

The karyotypic pattern in untreated patients with ANLL has prognostic significance; therefore, the method of processing marrow aspirates may substantially influence the degree of correlation between the karyotype and survival reported by different laboratories.
Plasma fucosyltransferase as an indicator of imminent blastic crisis
Authors: Shah‐Reddy Ila , Kessel David H. , Chou Ta‐Hsu , Mirchandani Ila , Khilanani Urmilla
Published: February 2007

Plasma fucosyltransferase activity was evaluated as an indicator of an impending blastic transformation in 25 patients with chronic granulocytic leukemia (CGL). Fifteen age‐and sex‐matched controls were also studied. The level of enzyme activity was significantly higher in the plasma of patients with blastic transformation (1,630 ± 570 units) compared with steady state chronic granulocytic leukemia (509 ± 110 units) and normal controls (354 ± 57 units). In three patients with CGL, a rise in fucosyltransferase activity preceded any other clinical or laboratory parameter of blastic transformation by 16–20 weeks.
Human leukocyte interferon‐mediated granulopoietic differentiation arrest and its abrogation by lithium carbonate
Authors: Verma Dharmvir S. , Spitzer Gary , Gutterman Jordan U. , Beran Miloslav , Zander Axel R. , McCredie Kenneth B.
Published: February 2007

Interferon has been shown to inhibit erythropoietic and granulopoietic differentiation. Since lithium carbonate (Li) elevates granulocyte levels in a variety of neutropenic disorders, we investigated the effect of Li on human leukocyte interferon (HLIF)‐mediated inhibition of granulopoietic differentiation. Using an agar culture technique for cloning granulocyte‐macrophage progenitor cells (GM‐CFC), we demonstrated that Li blocks HLIF‐induced granulopoietic differentiation arrest in a dose‐dependent manner. Results of removal of T lymphocytes from marrow cells suggest that this Li effect is not mediated through marrow T lymphocytes.
A study of a female with congenital sideroblastic anemia
Authors: Manabe Yutaka , Seto Shiro , Furusho Kenshi , Aoki Yosuke
Published: February 2007

A female infant with congenital refractory sideroblastic anemia is described. A market reduction of δ‐aminolevulinic acid (ALA) synthetase activity of erythroblasts was noticed with and without treatment of pyridoxal phosphate. Mitochondrial neutral protease activity of erythroblasts, which inactivates specifically the apo form of ALA synthetase, was normal and the sensitivity of apo form of ALA synthetase to the neutral protease was also normal. It was speculated that the reduction of ALA synthetase activity is not due to the high speed of destruction, but rather due to the impairment in production of ALA synthetase, which could explain the unresponsiveness to pyridoxine therapy in this case.
Burkitt cell leukemia following therapy for hodgkin disease
Authors: Nassar Victor H. , Jacobs Julian , Mirra Suzanne S. , Pandya Kishan J. , Schwartz Sheldon , Bennett John M.
Published: February 2007

Two adults with advanced Hodgkin disease — one treated with combination chemotherapy, and one with chemotherapy and radiation therapy — developed Burkitt cell leukemia four and seven years after diagnosis, proved by cytochemical and ultrastructural study. Acute lymphocytic leukemia must be considered in the evaluation of therapy‐related leukemias.
Recovery of splenic function after gvhd‐associated functional asplenia
Authors: Demetrakopoulos George E. V. , Tsokos George C. , Levine Arthur S.
Published: February 2007

An adolescent male patient developed functional asplenia in the course of graft versus host disease (GVHD) after successful allogeneic bone marrow transplantation (BMT) for aplastic anemia. Coincident with the onset of the asplenia, amelioration of the ongoing GVHD was observed. Unexpectedly, after 34 months of functional asplenia, the organ regained its function without evidence of graft rejection or reactivation of GVHD.
Thalassemia: Recent insights into molecular mechanisms
Authors: Steinberg Martin H. , Adams Junius G.
Published: February 2007

Recent advances in defining the molecular basis for the thalassemia syndromes are discussed. We now realize that the causes of the thalassemia phenotype are diverse and include gene deletions, nuclear RNA processing defects, nonsense mutations, fusion genes, termination codon mutants, and unstable globin chains.
A human T‐cell antigen defined by xenoantiserum to sézary leukemic cells: Immunochemical and functional studies
Authors: Ogasawara Minoru , Ishii Yoshifumi , Kamiya Hirofumi , Kikuchi Kokichi
Published: February 2007

Xenoantiserum to Sézary cell leukemia cells (ASS) was developed by immunizing rabbits with those cells and was absorbed with human red cells, liver, tonsil B cells, and cultured Raji cells. This reagent reacted by immunofluorescence with virtually all human thymus and T cells. In the thymus, medullary cells reacted more strongly with ASS than did cortical thymocytes. When immunoprecipitates that formed between ASS and 125I‐labeled lymphocyte surface glycoproteins were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, it was found that ASS precipitated a 72K molecular weight (MW) glycoprotein from T cells but not from B cells. On the one hand, it was shown by functional studies that T cells sensitive to the cytotoxic effect of ASS contained T cells that could aid the immunoglobulin synthesis of B cells induced by pokeweed mitogen. On the other hand, suppressor T cells induced by concanavalin A resided in those cells rather resistant to its cytotoxic effect. These data support the idea that the 72K MW glycoprotein on human thymus and T cells might be homologous to mouse Lyt‐1 antigens.