bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major
Authors: Brittenham Gary M. , Cohen Alan R. , McLaren Christine E. , Martin Marie B. , Griffith Patricia M. , Nienhuis Arthur W. , Young Neal S. , Allen Christopher J. , Farrell David E. , Harris John W.
Published: February 2007

To examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75, P < 0.0001) and in those with thalassemia major (R = 0.76, P < 0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76, P < 0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only ∼57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores. © 1993 Wiley‐Liss, Inc.
Postnatal changes in the quantities of globin chains and hemoglobin types in two babies with Hb H disease
Authors: McKie K. M. , Gu L.‐H. , Gu Y.‐C. , Huisman T. H. J.
Published: February 2007

We have studied two babies with Hb H disease from birth to about six months of age and analyzed the changes in the relative quantities of the five globin chains (α, β, Gγ, Aγ) and the four hemoglobins (Hb F, Hb A, Hb Bart's, Hb H) using different high performance liquid chromatography procedures. The types of Hb H disease were —(SEA)/‐α (3.7 kb) and —(Fil)/‐α (3.7 kb); the larger—(Fil) deletion includes the functional 2‐globin gene, explaining the higher chain level in the baby with the —(SEA)/‐α (3.7 kb) type. The functional hemoglobin level at birth (Hb A + Hb F) was 11 to 12 g/dl with 3 to 4 g/dl Hb Bart's (γ4). Only 5% of the “fast‐moving” hemoglobin was Hb H (β4). The level of Hb F at birth was low (less than 50% of the total Hb A + Hb F). After birth, the α and γ chain production decreases rapidly resulting in a severe anemia (total functional hemoglobin ∼7 g/dl) at 30 to 60 days postnatally, improving gradually to 8.5–9.5 g/dl at age of three months. The preferential formation of Hb A over Hb F at birth, and presumably prenatally, has the advantage that the level of the highly unstable Hb H is kept low; it also results in low levels of Hb F impairing the oxygen transfer capability of the fetal blood. © 1993 Wiley‐Liss, Inc.
Adult and childhood acute lymphocytic leukemia: Are they different diseases?
Authors: Mauer Alvin M.
Published: February 2007

Age has long been recognized as an important factor in predicting response to treatment for acute lymphocytic leukemia (ALL). Specifically, the results of treatment of childhood ALL have been far superior to the treatment of what appears to be the same disease in adults. However, from an analysis of the clinical and biological prognostic factors known to be predictive in childhood ALL, there is a striking difference in their distribution in adults with ALL. It appears that there is a special form of ALL seen in children of some populations with a peak incidence of three to seven years. This treatment responsive leukemia appears to be different clinically, biologically, and epidemiologically from adult ALL. © 1993 Wiley‐Liss, Inc.
Plasminogen activators and their inhibitors in leukemic cell homogenates
Authors: Wada Hideo , Kumeda Yasurou , Ogasawara Zin , Ohiwa Michiaki , Kaneko Toshihiro , Tamaki Shigehisa , Ohno Toshiyuki , Kageyama Sinichi , Kobayashi Thoru , Deguchi Katsumi , Shirakawa Shigeru
Published: February 2007

Plasminogen activator (PA) and PA inhibitor (PAI) were measured in homogenates of leukemia cells. Both PA and PAI levels were higher in non‐lymphoblastic leukemia than in lymphoblastic leukemia. The levels were below the sensitivity of determination in chronic myelocytic leukemia (CML) but showed significant increases in blast crisis (CML, bc). The level of the tissue type PA (t‐PA) antigen was highest in acute myelobtestic leukemia (AML) and that of the urokinase type PA (u‐PA) was highest in acute promyeiocytic leukemia (APL). The PAH antigen showed no marked cell specificity, but the PAI‐II antigen was markedly increased in myelomonocytic leukemia and acute monocytic leukemia (AMoL). From these findings, various PAs and PAIs are considered to be present in leukemia cells and to be involved in hemostatic disorders, thus they are of diagnostic value in leukemia. © 1993 Wiley‐Liss, Inc.
Comparison of cytogenetic and restriction fragment length polymorphism analyses for the detection of loss of chromosome material in clonal hemopoietic disorders
Authors: Abrahamson Gail M. , Rack Katrina , Oscier David G. , Fitchett Margaret , Buckle Veronica J. , Wainscoat James S.
Published: February 2007

Loss of chromosome material, as manifested by monosomy or partial deletion, is commonly found in neoplastic cells. We have undertaken a systematic comparison of standard cytogenetic analysis and molecular analysis for the detection of such loss, using as a model loss of chromosome 7 in 72 patients with a clonal myeloid malignancy. A large number of probes was used to screen three regions of chromosome 7 for loss by restriction fragment length polymorphism (RFLP) analysis. There were nine cases in which loss of chromosome 7 was detected by both techniques, but seven in which loss was detected by only one of the methods, demonstrating the complementary nature of these two techniques. © 1993 Wiley‐Liss, Inc.
Tumor necrosis factor‐α overproduction in Fanconi's anemia
Authors: Schultz John C. , Shahidi Nasrollah T.
Published: February 2007

Various in vitro studies and clinical observations suggest that Fanconi's anemia (FA) patients are unable to detoxify adequately superoxide anions (O) released by activated phagocytes. Recent studies have shown that certain lymphokines such as tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) can significantly enhance O production by phagocytic cells. To ascertain lymphokine production in FA patients, we measured TNF‐α and IFN‐γ production in vivo and in vitro. TNF‐α was detected in the plasma of 16 of 18 FA patients with concentrations ranging from 6 to 131 pg/ml (mean 31 pg/ml). TNF‐α was detected in only one of 25 control (healthy donor) plasma, and the level was very low (7 pg/ml). IFN‐γ levels in normal and patient plasma were negligible. Spontaneous and phytohemagglutinin (PHA)‐induced production of IFN‐γ and TNF‐α by cultured peripheral blood mononuclear cells did not differ significantly between FA patients and normal controls. The significance of overproduction of TNF‐α in vivo in the pathophysiology of FA is discussed. © 1993 Wiley‐Liss, Inc.
Hemorrhagic pleural effusion and pleural thickening as a complication of chronic lymphocytic leukemia
Authors: Dhodapkar Madhav , Yale Steven H. , Hoagland H. C.
Published: February 2007

We report a case of pleural thickening and hemothorax in a 56‐year‐old male with B‐cell chronic lymphocytic leukemia (CLL). The association of this entity with CLL has not been previously reported. Awareness of this occurrence is essential to appropriate therapy for similar patients with CLL. © 1993 Wiley‐Liss, Inc.
Zinc abuse and sideroblastic anemia
Authors: Ramadurai Jayanthi , Shapiro Charles , Kozloff Mark , Telfer Margaret
Published: February 2007

We report the case of a young woman who presented with anemia and leukopenia. A bone marrow aspirate, revealed a marked excess of ringed sideroblasts. A detailed dietary history disclosed excessive zinc intake. High serum zinc and low serum copper concentrations were confirmed. After discontinuation of the zinc supplements, she made a complete hematologic recovery. This report emphasises the importance of trace metals and their rote in the development of hematologic abnormalities. © 1993 Wiley‐Liss, Inc.
Effect of warfarin on arterial thrombogenesis: Problems of monitoring
Authors: Kovacs Iren B. , Murphy M. , Barin E. , Rees G. M.
Published: February 2007

Platelet reactivity to shear stress and collagen and dynamic overall coagulation were measured in vitro from nonanticoagulated blood of 137 patients on warfarin. One hundred five matched, healthy subjects served as controls. Platelet reactivity to both stimuli and contribution of platelets to plasmatic coagulation were significantly inhibited in patients on warfarin. No correlation was found between platelet reactivity and the coagulation status assessed by the international normalized prothrombin time ratio (INR). Despite similar INR, platelet reactivity showed great individual variation. In 98 patients who were followed up for 3 months, measurement of platelet reactivity to shear stress could discriminate between those who had either bleeding or thromboembolic episodes. These findings suggest that monitored platelet function would help in individualizing oral anticoagulant regimens and hence would increase the benefit of therapy without the risk of bleeding complications. © 1993 Wiley‐Liss, Inc.
Selection of a new generation of orally active α‐ketohydroxypyridine iron chelators intended for use in the treatment of iron overload
Authors: Kontoghiorghes G. J. , Barr J. , Nortey P. , Sheppard L.
Published: February 2007

The prospect of selecting oral α‐ketohydroxypyridine chelators intended for clinical use in iron overload has been examined using several animal models of efficacy and toxicity. Studies using iron dextran‐loaded mice labelled with 59Fe have shown that only the 1‐substituted methyl, ethyl, (n)propyl, allyl, cyclopropyl, 2′‐methoxyethyl, 3′‐ethoxypropyl, or 2‐methyl‐ or 2‐ethyl‐ 3‐hydroxypyrid‐4‐one chelators were orally effective in increasing iron (59Fe) excretion by comparison to intraperitoneally administered desferrioxamine at the same dose (250 mg/kg). In contrast, chelators containing ‐H, mono‐ or dihydroxyalkyl and diethoxyethyl 1‐substituents caused very little or no increase in iron (59Fe) excretion by the oral or intraperitoneal routes. In vitro studies using ferritin and haemosiderin have shown that equivalent iron release took place with both groups of chelators irrespective of their in vivo effects. In most cases there was no correlation between the n‐octanol/water partition coefficient (Kpar) and iron removal efficacy but positive correlation between the lipophilicity and acute or subacute toxicity of these chelators in rats. The most toxic chelator in the chronic toxicity studies in rats was the lipophilic 1, 2‐diethyl‐3‐hydroxypyrid‐4‐one (EL1NEt). The most effective chelator in increasing iron excretion in mice and rabbits was 1‐allyl‐2‐methyl‐3‐hydroxypyrid‐4‐one (L1NAll), and the chelator with the highest safety margin in mice and rats was 1, 2‐dimethyl‐3‐hydroxypyrid‐4‐one (L1). Overall the oral effectiveness in increasing iron excretion by these chelators in animals does not appear to be related to their lipophilicity or their ability to mobilise polynuclear iron in vitro but rather to other properties possibly related to their rate of biotransformation and excretion. © 1993 Wiley‐Liss, Inc.
In vitro activity of chloroquine and quinine in combination with desferrioxamine against Plasmodium falciparum
Authors: Basco Leonardo K. , Bras Jacques Le
Published: February 2007

The activity of chloroquine and quinine, alone and in combination with desferrioxamine (7 μmol/liter), was evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum by a semimicroassay system. The addition of desferrioxamine had no effect on the activity of chloroquine against both clones. Desferrioxamine had no effect on the activity of quinine against the susceptible clone but had slightly enhanced quinine action against the resistant clone. Further development of desferrioxamine as an antimalarial drug may be of limited interest. © 1993 Wiley‐Liss, Inc.
High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia
Authors: Saikia Tapan K. , Dhabhar Boman , Iyer R. S. , Nanjangud Gauri , Gopal R. , Nair Chandrika N. , Nadkarni Kanchan S. , Ashokkumar M. S. , Dhond Subodh R. , Advani Suresh H.
Published: February 2007

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC‐CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia‐positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC‐CML patients developed meningeal leukemia within a median period of 6 months (range 2–11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC‐CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.
Elevated levels of heme oxygenase‐1 activity and mRNA in peripheral blood adherent cells of acquired immunodeficiency syndrome patients
Authors: Levere Richard D. , Staudinger Robert , Loewy Gabriel , Kappas Attallah , Shibahara Shigeki , Abraham Nader G.
Published: February 2007

Patients with the acquired immunodeficiency syndrome (AIDS) commonly develop hematological abnormalities, including anemia, leukopenia, and thrombocytopenia. Heme synthesis and heme degradation are critical to the maintenance of cellular heme homeostasis and to hematopoietic differentiation. We examined heme oxygenase activity and expression of the heme oxygenase gene in adherent cells (monocytes‐macrophages) obtained from the peripheral blood of AIDS patients and normal controls. Heme oxygenase activity in normal control cells was 43 ± 16 pmol bilirubin formed/4 × 105 cells/hr as compared to 133 ± 30 pmol bilirubin formed/4 × 105 cells/hr in the AIDS patients. Via blot hybridization analysis with human heme oxygenase cDNA, heme oxygenase mRNA levels in cells of the normal and the AIDS patients were compared. Total RNA from normal cells displayed only weak hybridization with the cDNA probe. In contrast, cells from peripheral blood of the AIDS patients displayed marked increases over normal levels in heme oxygenase mRNA. Heme oxygenase activity could be substantially suppressed by the competitive inhibitor of the enzyme, Sn‐mesoporphyrin. Elevated heme oxygenase activity in cells of AIDS patients could produce a decrease in cellular heme needed for transductional signalling for the growth factor network, which regulates the hematopoietic microenvironment, and for other metabolic purposes. Suppression of heme catabolism by inhibitors of this enzyme may thus be useful in potentiating erythropoietic responses in this disorder.
Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B‐cell lineage by seminested polymerase chain reaction gene amplification
Authors: Liang Raymond , Chan Vivian , Chan T. K. , Wong Thomas , Chiu Edmond , Lie Albert , Todd David
Published: February 2007

Seminested polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity‐determining region 3 of the immunoglobulin (Ig) gene heavy chain from the malignant cell specimens of patients with leukemias and lymphomas of B‐cell lineage. Two different pairs of primers were used sequentially. Twenty of the 27 (74%) acute lymphoblastic leukemia (ALL) patients, 14 of 19 (74%) chronic lymphocytic leukemia (CLL) patients and eight of 20 (40%) non‐Hodgkin's lymphoma (NHL) patients, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by the seminested PCR. False‐negative results appeared to occur more commonly in cases of lymphoma. The PCR analysis was also less likely to be positive if one‐stage PCR studies with either pair of primers were both negative. The seminested PCR technique was found to have a high sensitivity of detecting malignant cells at the level of 0.02%. The clinical application of this assay needs to be investigated further.
Linkage analysis of the hemoglobin F determinant(s) in an australian hemoglobin lepore (Boston) kindred
Authors: Motum Penelope I. , Donald Jennifer A. , Trent Ronald J.
Published: February 2007

Genetic determinants that influence the levels of fetal hemoglobin (Hb F) in a single Australian kindred with heterozygous Hb Lepore (Boston) were sought. There were 22 affected individuals, some of whom had high Hb F and others with Hb F levels within the normal range. Family members were typed for restriction fragment length polymorphisms (RFLPs) associated with the β‐globin gene complex and the nearby genetic markers D11S12, INS, HRAS, and PTH. Prior to linkage analysis, a cohort of 54 unrelated Hb Lepore heterozygotes was analyzed to establish the distribution of Hb F levels measured by alkaline denaturation (Hb FAD). An Hb F level of >2.0% was used as the cutoff point for linkage analysis of the putative hereditary persistence of fetal hemoglobin (HPFH) determinant(s) in this kindred. Positive peak lod scores were obtained for the entire pedigree between the HPFH determinant and Hb Lepore (Zm+1 = 2.35 at θ = 0.15) and the β‐globin cluster (HBBC) (Zm+1 = 2.38 at θ = 0.20) marker loci, indicating the possibility of an independent HPFH gene at some distance from the β‐globin gene cluster. However, most of these lod scores result from the non‐Hb Lepore members of the family who, with one exception, do not have high Hb F, and when only those affected with Hb Lepore were analyzed the lod score values at these loci fell to small positive values (<1.0). These data do not support an independent cosegregating HPFH determinant separate from the Hb Lepore locus in this pedigree. The results favor a pleiotropic effect of the Hb Lepore lesion itself influencing Hb F levels by genetic or environmental factors not yet elucidated.
Chronic lymphocytic leukemia associated with bone marrow fibrosis: Possible role of interleukin 1α in the pathogenesis
Authors: Kimura Akiro , Hyodo Hideo , Nakata Yoshio , Kuramoto Atsushi
Published: February 2007

B‐cell chronic lymphocytic leukemia (B‐CLL) associated with bone marrow fibrosis is described. The conditioned medium of the CLL cells contained a high quantity of interleukin 1α (IL‐1α), and showed growth promoting activity for marrow fibroblasts which was partially inhibited by anti IL‐1α antibody. In addition, the conditioned medium as well as IL‐1α stimulated the growth of marrow fibroblasts from the patient. These results strongly suggested the marrow fibrosis occurred by the secretion of IL‐1α from the CLL cells and its growth stimulation of marrow fibroblasts. As far as we know, this is the first case in which B‐CLL was associated with marrow fibrosis, and its mechanism was investigated.
Polycythemia associated with primary systemic amyloidosis: Elevated levels of hemopoietic factors and cytokines
Authors: Nagasawa Toshiro , Yanagisawa Hiromi , Hasegawa Yuichi , Kanma Hiroshi , Abe Tsukasa
Published: February 2007

A 60‐year‐old man was diagnosed to have primary systemic amyloidosis (AL type) and polycythemia (Hgb 19.1 g/dl, WBC 14,600/μl, and platelets 60.5 × 104/μl). In vitro colony assay for hemopoietic stem cells showed increased numbers of colony‐forming units (CFU)‐G, CFU‐GM, CFU‐E, and CFU‐Meg. Serum levels of erythropoietin (Epo), granulocyte colony‐stimulating factor (G‐CSF), interleukin (IL)‐3 and IL‐6 were elevated. The infiltration of amyloid fibrils into the hemopoietic factor‐producing tissues may stimulate abnormal secretion of hemopoietic factors and cytokines, resulting in increased numbers of hemopoietic stem cells and polycythemia in the peripheral blood.
Coagulation system activation and increase of D‐dimer levels in peripheral arterial occlusive disease
Authors: De Buyzere M. , Philippé J. , Duprez D. , Baele G. , Clement D. L.
Published: February 2007

The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin‐antithrombin III complexes (TAT), and D‐dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 ± 0.19 nmol/liter) and of TAT (3.34 ± 0.35 μg/liter) were significantly increased compared to those obtained in age‐ and sex‐matched healthy controls (0.68 ± 0.06 nmol/liter and 2.30 ± 0.33 μg/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D‐dimers (719 ± 99 ng/dl in PAOD vs. 229 ± 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 ± 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D‐dimers (r = −0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase‐type plasminogen activator (u‐PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u‐PA antigen levels accounts for the elevated D‐dimers. Treadmill exercise was unable to increase these parameters further.
Comparison of buffy coat preparation to direct method for the evaluation and interpretation of bone marrow aspirates
Authors: Izadi Parvin , Ortega Jorge A. , Coates Thomas D.
Published: February 2007

Bone marrow differential and French, American, British (FAB) classification of buffy coat preparation (BCP) was compared to direct method (DM) in 69 pediatric patients with various hematologic and oncologic disorders. The marrow evaluation differed significantly in 12 of 69 patients (17.4%). The differential counts were discordant in 9 out of 69 patients (13%), and the FAB classifications were discordant in 3 out of 25 patients (12%) with acute lymphoblastic leukemia (ALL). Underestimation of the percent blasts occurred with buffy coat preparation in patients with acute non‐lymphoblastic leukemia (ANLL). While buffy coat preparations can facilitate morphologic evaluation in marrow malignancies, significant errors can occur in determination of the differential count. Direct smear should be used in conjunction with buffy coat smears in the evaluation of bone marrow aspirates.
DNA diagnosis for the detection of sickle hemoglobinopathies
Authors: Steinberg Martin H.
Published: February 2007

At this time, the sole generally accepted use for DNA diagnosis in the hemoglobinopathies is for the prenatal detection of disease, which can be identified by these means early in the first trimester of pregnancy. By ascertaining genotype rather than phenotype, the confusion that results from diagnostic errors should be diminished. DNA diagnostics are the future of all genetic disease detection and this future will soon be upon us.
Lymphoproliferative disease of 'lak cell' precursor large granular lymphocytes in association with celiac disease
Authors: Lopez P. , Morris D. G. , Galbraith P. R. , Lillicrap D. P. , Pross H. F.
Published: February 2007

We have investigated a case of lymphoproliferative disease of large granular lymphocytes (LDGL) occurring in association with celiac disease, anemia, neutropenia, and carcinomas of the endometrium, breast, and skin. The large granular lymphocyte (LGL) proliferation was monoclonal, T cell in origin, with T cell receptor β‐chain gene rearrangement, and a CD3+, CD8+, CD16± phenotype. In spite of the high frequency of LGL, natural killer (NK) cell activity was absent. Stimulation with interleukin‐2 in vitro, however, resulted in high lymphokine‐activated killer (LAK) cell activity against NK‐resistant targets. The T‐cell nature of the LAK precursor cells is in contrast to the majority seen in normal peripheral blood. Therapeutic trials of cyclosporin A, low‐dose cyclophosphamide, and levamisole were unsuccessful in reducing transfusion requirements. This case is unique in the association of LDGL with celiac disease. It is also unique in that the patient had been followed for several years prior to the onset of the LDGL. The case extends the list of lymphoproliferative disorders documented to be associated with celiac disease and, conversely, adds to our knowledge of lymphoproliferative disorder of LGL and its 'dysimmune' manifestations.
Chronic myelogenous leukemia and acute lymphoblastic leukemia occurring in the course of polycythemia vera
Authors: Roth Arnaud D. , Oral Arsinur , Przepiorka Donna , Gollin Susanne M. , Chervenick Paul A.
Published: February 2007

We are reporting an unusual case of a 54‐year‐old woman with polycythemia vera (PV) who developed Ph chromosome positive chronic myelogenous leukemia (CML) 8 years after the initial diagnosis of PV, and terminating in acute lymphoblastic leukemia (ALL), 11 years after the initial diagnosis. Cytogenetic studies revealed a normal female karyotype at the time of diagnosis of PV and the presence of a Ph chromosome at the time of appearance of CML. Southern blot hybridization revealed a bcr rearrangement in both mononuclear cells and granulocytes. The diagnosis of ALL was established on the basis of morphology, positive TdT staining, and monoclonal antibody studies positive for I2, B4, and J5.

This case demonstrates the transition of PV into CML, followed by a blastic transformation into acute lymphocytic leukemia. At termination of her disease there were findings compatible with bi‐phenotypic leukemia. These findings would suggest that the disease arose in a primitive multipotential stem cell.
Hemostatic study before onset of disseminated intravascular coagulation
Authors: Wada Hideo , Minamikawa Kouzou , Wakita Yoshihiro , Nakase Tutomu , Kaneko Toshihiro , Ohiwa Michiaki , Tamaki Shigehisa , Deguchi Akira , Mori Yoshitaka , Deguchi Katsumi , Shirakawa Shigeru , Suzuki Koji
Published: February 2007

Early diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre‐DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre‐DIC), in 237 patients with DIC, and in 50 patients without DIC or pre‐DIC (non‐DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin‐antithrombin III complex (TAT), plasmin‐α2 plasmin inhibitor complex (PIC), and FDP‐D‐dimer levels were significantly higher before the onset of DIC compared to the non‐DIC patients.

Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP‐D‐dimer might be useful for the diagnosis of a pre‐DIC condition.
Comparison between interphase and metaphase cytogenetics in detecting chromosome 7 defects in hematological neoplasias
Authors: Zhao Lian , van Oort June , Cork Ann , Liang Jan C.
Published: February 2007

Monosomy 7 (–7) is one of the most common chromosomal abnormalities found in the leukemic cells of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Because patients with –7 have a poor prognosis, their identification is important for treatment planning. Conventionally, –7 is detected by the G‐banding technique. This study examines the use of fluorescent in situ hybridization (FISH) methodology to detect –7 cells in interphase nuclei and metaphase chromosomes. Fifteen AML or MDS patients whose leukemic cells were found to have –7 by G‐banding at disease presentation were studied. In 13 of these patients, –7 could be detected in interphase by FISH using a chromosome 7‐specific centromeric DNA probe. The two patients whose leukemic cells were not detectable by interphase FISH had –7 and t(1q;7p), which were detectable by FISH in metaphase using a chromosome 7‐specific painting probe. Metaphase FISH was particularly useful in further defining chromosome 7 defects in cells that contained aberrant or marker chromosomes. For example, in 6 patients, chromosome 7 sequences were detectable in aberrant or marker chromosomes by metaphase FISH, but not by G‐banding. These results suggest that metaphase FISH is an important adjunct to conventional cytogenetic methods for defining chromosome 7 abnormalities in AML and MDS patients. Furthermore, interphase FISH is useful for follow‐up studies in patients who are found informative for the FISH study at presentation.
Cell‐mediated immune‐pancytopenia complicating primary sjögren's syndrome
Authors: Seki Takeshi , Kiyosawa Kendo , Monno Satoshi , Imai Yasuharu , Furukawa Kenichi , Kumazawa Shigeyuki , Ota Masao , Saito Hiroshi , Furuta Seiichi , Nakahata Tatsutoshi
Published: February 2007

A 64‐year‐old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS‐A, and SS‐B. Impaired cell‐mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.
Measurement of red blood cell‐vitamin B12: A study of the correlation between intracellular B12 content and concentrations of plasma holotranscobalamin II
Authors: Tisman G. , Vu T. , Amin J. , Luszko G. , Brenner M. , Ramos M. , Flener V. , Cordts V. , Bateman R. , Malkin S. , Browder T.
Published: February 2007

We have recently reported a new and rapid assay to measure plasma holotranscobalamin II (holo TC II) as a means of exploring vitamin B12 status. In order to further evaluate the significance of plasma holo TC II in determining tissue cobalamin, we have chosen the red blood cell‐vitamin B12 (RBC‐B12) assay as a measure of tissue vitamin B12 content and studied the relationship between RBC‐B12 and plasma holo TC II levels. Plasma holo TC II and RBC‐B12 concentrations were concomitantly assayed in 20 hematologically normal controls and cancer patients. In our groups of controls, the mean value of RBC‐B12 was determined as 241 ± 51 pg/ml of packed erythrocytes (PE) with a range varying from 180 to 355 pg/ml PE. Preliminary results obtained in 32 cancer patients revealed lower holo TC II and RBC‐B12 levels than the control group and a required threshold value of 70 pg/ml of holo TC II in order to maintain a normal RBC‐B12 greater than 180 pg/ml PE.
Mechanism of autoimmune hemolytic anemia in chronic lymphocytic leukemia
Authors: Sthoeger Zev M. , Sthoeger Dalia , Shtalrid Mordechai , Sigler Erica , Geltner David , Berrebi Alain
Published: February 2007

Chronic lymphocytic leukemia (CLL) is a malignant clonal expansion of CD5+B lymphocytes. The CD5+B lymphocytes have been postulated to produce autoantibodies. CLL patients may demonstrate features of autoimmunity including autoimmune hemolytic anemia. However, the origin of the autoantibodies causing the hemolysis is not clear. The present studies were performed to determine whether these autoantibodies are the products of the neoplastic B‐CLL clones. Immunoglobulins (Ig) were eluted from washed red blood cells (RBC) obtained from two CLL patients at the time they had autoimmune (DAT‐direct antiglobulin test ‐ positive) hemolytic anemia. The light chain phenotypes of these eluted autoantibodies were determined and found to be monotypic with exact correlation to the light chain expressed on the surface of the B‐CLL clones. Elutions from RBC of DAT negative patients or normal volunteers failed to demonstrate measurable amounts of Ig. In contrast, Ig eluted from RBC obtained from SLE patients with DAT positive hemolytic anemia found to be polyclonal autoantibodies exhibiting both light chain types. Furthermore, CD5+B lymphocytes obtained from the same two CLL patients (DAT+) produce, in vitro understimulation with phorbal myristate acetate (PMA), monoclonal antibodies which react and bind to RBC. Thus these studies provide direct evidence demonstrating that the antibodies causing the autoimmune hemolytic anemia in our two CLL patients are the products of the B‐CLL neoplastic clones.
Mitoxantrone and 5‐azacytidine for refractory/relapsed ANLL or CML in blast crisis: A leukemia intergroup study
Authors: Goldberg Jack , Gryn Jeff , Raza Azra , Bennett John , Browman George , Bryant John , Grunwald Hans , Larson Richard , Vogler Ralph , Preisler Harvey
Published: February 2007

In an effort to determine if cell cycle active agents are augmented when given after non‐cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5‐azacytidine. Twenty‐seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5‐azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5‐azacytidine given after mitoxantrone increased the complete remission rate.
Sequential administration of cyclophosphamide and granulocyte‐colony stimulating factor relieves impaired myeloid maturation in felty's syndrome
Authors: Pixley John S. , Yoneda Ken Y. , Manalo Pacita B.
Published: February 2007

A patient with Felty's syndrome (FS) and persistent profound neutropenia developed recurrent infections and sepsis syndrome. No impairment of granulocyte‐macrophage colony development was observed in vitro. Marrow morphology revealed an absence of mature neutrophil forms despite administration of granulocyte‐colony stimulating factor (G‐CSF). However, pretreatment with bolus cyclophosphamide (CY) permitted the growth factor to relieve this impairment of late myeloid maturation and resulted in a brisk, albeit short, burst of neutrophilia. This suggests that immune interference in myelopoiesis can be overcome by growth factor administration if immune activity is adequately dampened by immunosuppressive therapy.
Direct demonstration that the AγT globin gene is linked to the 4 bp promoter deletion in the βA chromosome of sickle cell traits
Authors: Gilman John G. , Josifovska Olgica , Erlingsson Soili , Nagel Ronald L. , Milner Paul F.
Published: February 2007

In βP°‐thalassemia and sickle cell patients, a 4 bp deletion at –222 to –225 of the Aγ globin promoter was associated with low expression of the AγT variant (threonine at codon 75 of Aγ), whereas AγI (isoleucine at 75) had the normal Aγ promoter and higher expression. However, it has been reported that the βA chromosomes of sickle cell trait cases have the 4 bp deletion as a common polymorphism unlinked lo the AγT allele. We now present data demonstrating the association of the AγT allele with the 4 bp deletion in βA chromosomes of sickle cell traits.
Familial lupoid thrombocytopenia
Authors: Shimizu Kazuyuki , Katsuta Itsuro , Uchikawa Takashi
Published: February 2007

Familial lupoid thrombocytopenia affecting three subjects in three generations is reported. All subjects had antinuclear antibodies with or without antibodies to single‐stranded DNA, an increase in platelet‐associated IgG, and a family member with an autoimmune disease. These findings implicate a genetic contribution. All subjects shared a common HLA haplotype. © 1993 Wiley‐Liss, Inc.
Adoptive chemoimmunotherapy using Ex vivo activated memory T‐cells and cyclophosphamide: Tumor lysis syndrome of a metastatic soft tissue sarcoma
Authors: Gold Jay E. , Malamud Stephen C. , Larosa Felicia , Osband Michael E.
Published: February 2007

Adoptively transferred immune cells in combination with chemotherapeutic agents form the basis for adoptive chemoimmunotherapy (ACIT) of neoplastic disease. Autolympho‐cytes (ALT‐cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor‐bearing hosts (TBH) that consist primarily of tumor‐specific CD45RO+ (memory) T‐cells. These ALT‐cells combined with cimetidine (CIM) as autolymphocyte therapy (ALT), have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). We have previously described an effective ACIT protocol using ALT and cyclophosphamide (CY) for patients with relapsed and refractory non‐RCC solid tumors. We now report a case of a patient with a metastatic gastric leiomyosarcoma to the liver, who developed a clinical picture consistent with a tumor‐lysis syndrome (TLS), following salvage therapy for his tumor with ACIT using ALT and CY. TLS is a well‐known complication resulting from the treatment of rapidly proliferating hematopoietic tumors such as Burkitt's lymphoma and acute lymphocytic leukemia. TLS has also been rarely described in chronic lymphocytic leukemia, as well as certain solid tumors such as breast cancer, small cell lung cancer, and medulloblastoma. However, there have been no previous reports of TLS occurring either secondary to immunotherapy or in sarcomas. The nature of these unusual findings is discussed. © 1993 Wiley‐Liss, Inc.
Phosphatidylserine in the outer leaflet of red blood cells from β‐thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes
Authors: Yashar Vered Borenstain‐Ben , Barenholz Yechezkel , Hy‐Am Esther , Rachmilewitz Eliezer A. , Eldor Amiram
Published: February 2007

Investigation of red blood cells from β‐thalassemia patients by means of prothrombinase assay reveals phosphatidylserine in the outer leaflet of the plasma membrane. This might explain their elevated susceptibility to phagocytosis by macrophages and the chronic hypercoagulable state, frequent thrombotic events, and life‐long platelet activation that are found in thalassemic patients. © 1993 Wiley‐Liss, Inc.
Phase II trial of recombinant interferon alfa‐2 in the treatment of primary systemic amyloidosis
Authors: Gertz Morie A. , Kyle Robert A.
Published: February 2007

Primary systemic amyloidosis (AL) is a rare disorder characterized by production of an aberrant monoclonal light chain. This insoluble light chain, or a fragment thereof, deposits in tissues as amyloid and results in disruption of organ function and, ultimately, death. Although melphalan and prednisone were reported to benefit subsets of patients with the disease, many patients showed no benefit; the median survival with the disease is ∼2 years. There is a need to develop new agents for patients who fail to respond to a trial of cytotoxic chemotherapy. A study was undertaken of interferon alfa‐2 in the treatment of 15 patients with AL because of its reported benefits in the induction and maintenance therapy for patients with multiple myeloma, a disease that has many characteristics in common with AL. None of the patients showed any objective regression of their disease; the median survival of the entire group was 26.3 months. This survival is not superior to that reported with other agents used for this disease. We conclude that interferon alpha‐2 is not a valuable agent in the treatment of AL. © 1993 Wiley‐Liss, Inc.
Growth retardation in homozygous sickle cell disease: Role of calorie intake and possible gender‐related differences
Authors: Modebe Onyechi , Ifenu Stella A.
Published: February 2007

To evaluate the possible role of inadequate food intake in the pathogenesis of the growth retardation of patients with sickle cell anemia, we determined the daily intake of calories and macronutrients and measured several anthropometric indices in 20 patients with sickle cell anemia aged 17–35 years and in 15 of their normal siblings of similar age. Compared to the control groups, the male patients, but not the females, had a significantly lower mean weight, body mass index, midarm circumference, and triceps and subscapular skinfold thicknesses. Also, while the male patients consumed significantly less total calories, proteins, carbohydrates, and fats per day than their control group, no difference was noted between the daily intake of calories or macronutrients in the female patients and their control group. However, when the intake of calories and macronutrients was corrected for body weight, there was no statistically significant difference between the intake of nutrients in the male patients and their control subjects or between the female patients and their control group. These results suggest a sex‐related difference in the somatic growth of adolescent and adult patients with sickle cell anemia and also suggest that, although an inadequate food intake may be partly responsible for the impaired somatic growth in sickle cell anemia, other factors are also probably important. © 1993 Wiley‐Liss, Inc.
Tracing iron and transferrin in the macrophage by visual means
Authors: Haurani Farid I. , Ryter Antoinette
Published: February 2007

The purpose of the study was to investigate the movement of iron and transferrin in the macrophage using light and electron microscopy. First, depicted here are the phagocytosis of antibody sensitized murine red cells by the murine bone marrow derived macrophage and the formation of red cell phagosomes. Second, we show the fusion of the lysosomes with the red cell phagosome to form a lysophagosome and the lysis of the red cell using acid phosphatase as a lysosome marker. Third, by autoradiography, the presence of 55Fe silver grains in the phagocytosed red cells and its delivery to the organelles of the macrophage are demonstrated. Fourth a transferrin species is shown in red cells of all ages, in the phagocytosed as well as the non‐phagocytosed, and in the phagocytosed as well as the non‐phagocytosed, and in the macrophage itself. Transferrin was detected using immunogold and fluorescence labelling. These studies suggest that iron, using vesicles as means of transport, moves from the effete red cells inside the macrophage to the outside possibly bound to transferrin. © 1993 Wiley‐Liss, Inc.
Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia: Results in 73 patients
Authors: Flores Glenn , Cunningham‐Rundles Charlotte , Newland Adrian C. , Bussel James B.
Published: February 2007

To determine whether warm‐antibody autoimmune hemolytic anemia (AIHA) responds to treatment with intravenous gammaglobulin (IVGG), we conducted separate pilot studies at three institutions enrolling a total of 37 patients. We combined these results with a review of 36 cases of AIHA treated with IVGG reported in the literature. Sixteen clinical variables were examined to determine associations with response to IVGG. Overall, 29 of 73 patients (39.7%) responded to IVGG therapy. Two variables were strongly related to a good response to IVIG: the presence of hepatomegaly (with and without splenomegaly) and a low pre‐treatment hemoglobin. A trend towards a better response was observed in the 11 children. Overall, IVGG provided acute benefit in only 1/3 of patients and therefore cannot be recommended as standard therapy for AIHA. It may, however, be useful as adjunctive treatment in selected cases, such as in those with a pre‐treatment hemoglobin < 6–7 gm/dl or those with hepatomegaly, and in clinical settings where the toxicity of other treatments may be an important consideration. © 1993 Wiley‐Liss, Inc.
Decreased fibrinolytic potential in patients with idiopathic avascular necrosis and transient osteoporosis of the hip
Authors: Van Veldhuizen Peter J. , Neff James , Murphey Mark D. , Bodensteiner David , Skikne Barry S.
Published: February 2007

A thrombotic etiology has been suggested as the cause of idiopathic avascular necrosis of the hip, although the underlying pathophysiological mechanisms are unknown. Transient osteoporosis of the hip has also been suggested to represent bone marrow edema that may be related to ischemia. We evaluated four patients with idiopathic avascular necrosis and one patient with transient osteoporosis of the hip for thrombotic potential placing a special emphasis on the fibrinolytic system. All five patients had identifiable abnormalities of fibrinolysis. Four patients had elevated levels of plasminogen activator inhibitor (PAI‐1) and one patient had an inadequate increase in tissue plasminogen activator (tPA) post venous occlusion. Serum triglycerides were increased in three of the patients. These findings suggest an association between decreased fibrinolytic potential and the subsequent development of avascular necrosis and transient osteoporosis of the hip. These patients should have an evaluation of the fibrinolytic system with tPA and PAI‐1 levels as well as a lipid profile. © 1993 Wiley‐Liss, Inc.