bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of megakaryocyte colony forming cell numbers and ploidy by dideoxynucleosides in immunodeficient mice
Authors: Chow Fung‐Phing R. , Ordóñez José V. , Sutton Patricia A. , Hamburger Anne W.
Published: February 2007

We have recently demonstrated that azidothymidine (AZT) elevates the levels of circulating platelets in mice made immune deficient by infection with LP‐BM5 murine leukemia virus (MAIDS mice). In an attempt to elucidate the mechanisms of the AZT platelet elevating effect, we examined the number of splenic and bone marrow megakaryocyte colony‐forming cells (CFU‐mk) and the ploidy of megakaryocytes derived from CFU‐mk using fluorescence cytophotometric methods. Two other dideoxynucleosides (ddN) 2′3′‐dideoxyinosine (ddL) and 2′3′‐dideoxycytidine (ddC) were assessed to determine the specificity of the effect of AZT. MAIDS mice were given ddN in drinking water for 15 days. AZT was the only ddN that significantly increased circulating platelet levels in MAIDS mice. AZT significantly increased splenic CFU‐mk in MAIDS mice, but bone marrow CFU‐mk were not affected. ddL and ddC failed to change either platelet levels or the numbers of splenic or bone marrow CFU‐mk. The ploidy of megakaryocytes derived from splenic and bone marrow CFU‐mk were examined by first identifying CFU‐mk by staining for acetylcholinesterase, followed by nuclear staining with propidium iodide. The fluorescence of individual cells was then measured using a Perceptics image analysis system. Modal ploidy of CFU‐mk megakaryocytes derived from spleen cells of AZT‐treated immunodeficient mice was shifted upwards from 16N to 32N. Similarly, AZT treatment changed the modal ploidy number of colony megakaryocytes derived from bone marrows of immunodeficient mice from 16N to 32N. The ploidy distribution was also significantly shifted. ddL and ddC failed to significantly alter either modal ploidy number or distribution of megakaryocytes derived from splenic or bone marrow CFU‐mk. These findings suggest that AZT may affect physiological processes that lead to platelet formation. © 1993 Wiley‐Liss, Inc.
Characteristics of zinc binding to human red blood cell membranes
Authors: Brandão‐Néto José , Bell William R.
Published: February 2007

The objective of the present study was to standardize the analysis of zinc binding on human red blood cell (RBC) membranes in 20 normal adults. The displacement studies revealed that at the maximal stable zinc concentration tested (600 μM), 57% (mean) of the bound 85Zn was displaced and to displace half maximal 65Zn, the stable zinc concentration was 300 μM. Scatchard plots revealed two classes of binding sites for zinc on RBC membranes: one with higher affinity, Kd = 1.20 × 10−5 M (site I), and the other with lower affinity, Kd = 2.77 × M (site II). Binding sites occupancy was 97% means and 58.5% means for sites I and II, respectively. The displacement was affected by temperature, membrane protein concentration, freezing, thawing, and dialysis. Other metal cations, including Co+*, Fe++, and Mn++, had very little effect on 65Zn displacement, in contrast copper displaced 65Zn from its binding sites on RBC membranes. Zinc binding to RBC membranes was rapid and readily reversible in a dynamic equilibrium with its binding sites. It is anticipated that this method will be applicable to studies of a wide variety of diseases specifically related to zinc metabolism in humans as well as in animals. © 1994 Wiley‐Liss, Inc.
Direct evidence for systemic fibrinogenolysis in patients with acquired α2‐plasmin inhibitor deficiency
Authors: Okajima Kenji , Kohno Isao , Soe Gilbu , Okabe Hiroaki , Takatsuki Kiyoshi , Binder Bernd R.
Published: February 2007

To examine whether or not acquired α2‐plasmin inhibitor deficiency is associated with systemic fibrinogenolysis, we analyzed the fibrin and fibrinogen degradation products in eight patients with this condition in various disease states. The underlying disease was gastric cancer in three patients, metastatic prostatic cancer in two, acute promyelocytic leukemia in two, and abdominal aortic aneurysm in one patient. In all eight patients, the α2‐plasmin inhibitor level was reduced to less than 50% of normal, and plasmin‐α2,‐plasmin inhibitor complex levels were increased. Immunoblotting of serum using an anti‐fibrinogen antibody detected a 250 kDa protein (corresponding to fragments X or DY) in all eight patients. Fragment Y and D monomer were detected in seven of the eight patients, indicating the occurrence of systemic flbrinogenolysis. However, they were not detected in one patient with metastatic prostatic cancer. To determine whether or not fibrinogen degradation was also occurring in the patient without fragment Y, we characterized the 250 kDa protein in all eight patients. The protein was found to be fragment X in the metastatic prostatic cancer patient without fragment Y, while it was fragment DY in the other seven patients. Thus, systemic fibrinogenolysis was present in all eight patients. In the two patients with metastatic prostatic cancer, the level of α2‐plasmin inhibitor gradually increased with the reduction of tumor size by treatment. Fragment X, fragment Y, and D monomer were not detected when the α2‐plasmin inhibitor level exceeded 60% of normal in both patients. In the other six patients fragment Y and D monomer also disappeared when the α2‐plasmin inhibitor level exceeded 60% of normal.

These findings suggest that systemic fibrinogenolysis only occurs when the plasma levels of α2‐plasmin inhibitor falls below 60% of normal due to activation of the fibrinolytic system by various pathological conditions. © 1994 Wiley‐Liss, Inc.
Detection of tumor necrosis factor‐α in bone marrow plasma and peripheral blood plasma from patients with aplastic anemia
Authors: Schultz John C. , Shahidi Nasrollah T.
Published: February 2007

Plasma levels of interferon‐gamma (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α) were determined in healthy individuals and patients with aplastic anemia (ApAn). IFN‐γ was not detected in normal peripheral blood plasma (PBP) or bone marrow plasma (BMP) and was present in PBP from only 2 of 22 patients and in BMP from 1 of 14 patients and the levels were low (< 1.5 U/ml). Elevated levels of TNF‐α were present in BMP and PBP from patients but not in control (healthy donor) PBP and BMP. Eleven of twenty‐four patients had elevated levels of TNF‐α in their PBP and 6 of 13 patients had detectable levels of TNF‐α in their BMP. Only one of the 14 healthy control donors had detectable TNF‐α and the level was very low (7 pg/ml), while 13 of the 27 ApAn patients had detectable TNF‐α (P = .009, chi‐square test). Not surprisingly, the centers of the distributions of TNF‐α concentrations of the controls and ApAn patients differed significantly (P < .017 for control and patient PBP and P < .056 for control and patient BMP, Wilcoxon rank‐sum test). Spontaneous production of IFN‐γ and TNF‐α by cultured bone marrow mononuclear cells was observed in four of seven patients but not in the six healthy controls (P = 0.026). Spontaneous production of IFN‐γ and TNF‐α by cultured peripheral blood mononuclear cells from patients and controls was however similar. Phytohemagglutinin (PHA)‐induced production of IFN‐γ and TNF‐α by cultured mononuclear cells did not differ significantly between ApAn patients and normal controls. The significance of overproduction of TNF‐α in the pathophysiology of ApAn is discussed. © 1994 Wiley‐Liss, Inc.
Splenic lymphoma with circulating villous lymphocytes: Report of seven cases and review of the literature
Authors: Sun Tsieh , Susin Myron , Brody Judith , Dittmar Klaus , Teichberg Saul , Weiner Robert , Lin Jen H. , Felber Norbert
Published: February 2007

Splenic lymphoma with villous lymphocytes (SLVL) is a relatively new entity with only a few reports published. We report seven cases of SLVL with detailed clinicopathologic and comprehensive immunophenotypic studies to further characterize this lymphoma, which is frequently confused with hairy cell leukemia and other low‐grade B‐cell lymphoid neoplasms. The diagnostic criteria we used include 1) prominent splenomegaly, 2) insignificant or no lymphadenopathy, 3) lymphocytosis without leukopenia, 4) presence of circulating villous lymphocytes, 5) characteristic cytologic and histologic features, and 6) specific phenotypic and cytochemical findings. Our studies show that SLVL does not represent a pure entity but rather a morphologically heterogeneous group of low‐grade lymphomas with various cytologlc and histologic features. Although immunophenotyping is helpful in differential diagnosis, multiparameter studies are necessary to confirm the diagnosis. In our series, only two patients died of SLVL, who probably developed transformation to a higher‐grade lymphoma. © 1994 Wiley‐Liss, Inc.
Continuous infusion of monoclonal antibody‐purified factor VIII: Rational approach to serious hemorrhage in patients with allo‐/autoantibodies to factor VIII
Authors: Gordon Erlinda M. , Al‐Batniji Fatma , Goldsmith Jonathan C.
Published: February 2007

Hemorrhage in a patient with factor VIII inhibitor is associated with increased morbidity and mortality. Treatment with factor IX complex concentrates or recombinant factor VIIA (rVIIa) may not control bleeding and may induce thrombosis. In this study, continuous infusion of a monoclonal antibody‐purified factor VII concentrate (Monoclate‐P) was used successfully in two hemophilic patients with factor VIII alloantibodies and one nonhemophilic patient with a factor VIII autoantlbody. In two patients, hemorrhage was life‐threatening, and, in one, bleeding did not stop with repeated infusions of activated factor IX complex concentrates. The patients' ages ranged from 4 to 15 years, and the inhibitor levels from 6 to 300 Bethesda units/ml. Clinical hemostasis was excellent, and In vivo recovery of infused factor VIII was achieved. When an excess of monoclonal factor VIII was added to the inhibitor plasma in vitro, a stable level of residual factor VIII activity was noted after an initial rapid loss. This second‐order reaction occurs in plasmas of patients with type I factor VIII inhibitors. In one patlent, we showed that the saturation dose of the factor VIII inhibitor predicted in vivo recovery of factor VIII:C. These data emphasize the importance of characterizing the kinetic reactions of the factor VIII inhibitor. Furthermore, we confirm previous reports that continuous infusion of monoclonal factor VIII is a safe and effective treatment of patients with factor VIII inhibitors in whom hemorrhage Is either life‐threatening or refractory to standard treatment. © 1994 Wiley‐Liss, Inc.
Hypofibrinolysis: A common, major cause of osteonecrosis
Authors: Glueck Charles J. , Freiberg Richard , Glueck Helen J. , Henderson Clyde , Welch Michael , Tracy Trent , Stroop Davis , Hamer Tracey , Sosa Felix , Levy Mark
Published: February 2007

In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we assessed the role of hypofibrinolysis mediated by high levels of piasminogen activator inhibitor (PAI). We evaluated hypofibrinoiysis as a common, potentially reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18 patients with secondary osteonecrosis. PAI was normal, as was the ability to activate fibrinoiysis. Nine of the 12 patients with idiopathic osteonecrosis had exceptionally high PA1 levels and could not normally elevate tissue piasminogen activator (tPA‐Fx), the major stimulator of fibrinolysis, after 10 min of venous occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis, compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA‐Fx (1.92 vs. 7.6 IU/mi, P .001) and very high stimulated PAI‐Fx (70 vs. 7.6 U/mi, P ⩽ .01). Three of the 12 patients with idiopathic osteonecrosis had both normal PAI and normal Stimulated tPA‐Fx. These three patients and 14 of the 18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (>20 mg/dI). Mean Lp(a) was much higher (60 mg/dI) in the patients with secondary osteonecrosis than Lp(a) (16 mg/dI, P ⩽ .001) in the 12 patients with idiopathic osteonecrosis. These findings suggest that hypofibrinoiysis mediated by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may play an etiologic role in secondary osteonecrosis. Prospective studies of patients with high PA1 and/or high Lp(a) should be carried out to assess further their apparently causal roles in osteonecrosis. © 1994 Wiley‐Liss, Inc.
Primary amyloidosis associated with a novel heavy‐chain fragment (AH amyloidosis)
Authors: Solomon Alan , Weiss Deborah T. , Murphy Charles
Published: February 2007

Primary or AL amyloidosis occurs in patients with monoclonal plasma cell‐related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light‐chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain‐associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In this case, the renal and splenic amylold deposits consisted solely of the VH‐D‐encoded portion of the heavy polypeptide chain, in contrast to the first case, where the amyloid contained an immunoglobulin component composed of the entire heavy‐chain variable and third constant domains. In this respect, the chemical composition of the amyloid protein MAD differed not only from that of the first reported case of AH amyloidosis but from all other structurally abnormal components found in patients with heavy chain‐associated disease. The discovery that certain forms of heavy chains, as well as light chains, can form amyloid provides further information on the chemical basis of amyloidogenicity and the diverse nature of this disease. © 1994 Wiley‐Liss, Inc.
Effects of interleukin‐2 administration on platelet function in cancer patients
Authors: Oleksowicz Leslie , Zuckerman Dina , Mrowiec Zbigniew , Puszkin Elena , Dutcher Janice P.
Published: February 2007

Platelet function in 16 patients with metastatlc renal cell carcinoma and melanoma was studied sequentially over the first 96 hr of treatment with moderate and highdose inter‐leukin‐2 (IL‐2). During the first 96 hr of therapy, an increased ex vivo platelet maximal aggregation (MA) response to ADP, epinephrine, and arachidonlc acld was paralleled by a decrease In the peripheral platelet count. Plasma speclmens from patients receiving the moderate dose schedule showed a significant IL‐2 induced secretory response of the platelet α‐granule components β‐thromboglobulin (BTG) and platelet factor 4 (PF4) and the eicosanoid thromboxane B2 (TBX2) as measured by RIA. The increase in TXB2 was highly correlated with MA when analyzed by bivariate regression analysls, whereas the addition of PF4 to TXB2 in a multiple regression analysls further Increased their correlation to MA. The observed decrease In peripheral platelet count correlated significantly with MA and PF4 secretion. High‐dose IL‐2‐treated patlents showed a statistically significant increase in the percentage of large platelets exceeding 12 fl in diameter and platelet responsiveness to hypotonic shock. These observations suggest that IL‐2 therapy results in a reduced peripheral platelet pool, with an increased proportion of the remaining pool of platelets larger, more viable, and actlvated. © 1994 Wiley‐Liss, Inc.
Erythropoietin in the treatment of delayed immune hemolysis of a major ABO‐incompatible bone marrow transplant
Authors: López J. , Steegmann J. L. , Pérez G. , Otero M. J. , Berberana M. , Cámara R. , Lamana M. , Villalta M. J. Fernández , Fernández‐Rañada J. M.
Published: February 2007

Delayed immune hemolysls can be observed after major ABO‐incompatible bone marrow transplants (BMT). The management of these hemolytic eplsodes Includes transfuslofi of group O red blood cells and increases of immunosuppression. Here we report the case of a 25‐year‐old patient who developed overt immune hemolysis on day +50 after a HLA‐identical ABO‐incompatible BMT. To avoid added immunosuppression, erythropoietin was started: an Increase in reticulocytes sufficlent to maintain hemoglobin despite perslstent hemolysis was observed. We conclude that erythropoletin may have a role In the management of delayed‐onset hemolysis of major ABO‐incompatible BMT, especially when added Immunosuppresslon is undesirable. © 1994 Wiley‐Liss, Inc.
Pentosan polysulfate‐induced thrombocytopenia and thrombosis
Authors: Tardy‐Poncet Brigitte , Tardy Bernard , Grelac Françoise , Reynaud Jacqueline , Mismetti Patrick , Bertrand Jean Claude , Guyotat Denis
Published: February 2007

Pentosan polysulfate is a low‐molecular‐weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low‐molecular‐weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate‐induced thrombocytopenia, it seems that heparin or low‐molecular‐weight heparin should not be instituted during the acute phase even it platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycoaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question. © 1994 Wiley‐Liss, Inc.
Lineage determination of CD7+ CD5− CD2− and CD7+ CD5+ CD2− lymphoblasts: Studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3ϵ, and CD3δ
Authors: Yoneda Noriko , Tatsumi Eiji , Teshigawara Keisuke , Nagata Shigekazu , Nagano Takahiro , Kishimoto Yuji , Kimura Takashi , Yasunaga Koujiro , Yamaguchi Nobuo
Published: February 2007

The gene expression of myeloperoxldase (MPO), CD3ϵ and CD3δ molecules, the gene rearrangement of T‐cell receptor (TCR)δ, γ, and β and Immunoglobulin heavy (IgH) chain, and the expression of cell‐surface antlgens were investigated In seven cases of CD7+ CD5− CD2− and four cases of CD7+ CD5+ CD2− acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T‐lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5− CD2− blasts included four categories: Undifferentiated blasts without lineage commitment, T‐lineage blasts, T‐/myeloid lineage blasts, and cyMPO‐negative myeioblasts. The CD7+ CD5+ CD2− blasts included two categories; T‐lineage and T‐/myeloid lineage blasts.

The 11 cases were of the germ‐line gene (G) for TCRβ and IgH. Four cases were G for TCRδ and TCRγ. The others were of the monoclonally rearranged gene (R) for TCRδ and G for TCRγ or R for both TCRδ and TCRγ.

The expression or In vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed In all 11 CD7+ CD5− CD2−and CD7+ CD5+ CD2−, and some CD7+ CD5+ CD2+ (CD3− CD4− COB‐) cases, but not in CD3± CD4+ CD8+ or CD3+ CD4+ CD8− cases.

CD3ϵ mRNA, but not CD3δ mRNA, was detected in two CD7+ CD5− CD2− cases, while mRNA of neither of the two CD3 moleculea was detected In the other tested CD7+ CD5−CD2− cases. In contrast, mRNA of both CD3e and CD36 were detected in ail CD7+ CD5+ CD2− cases, indicating that CD7+ CD5+ CD2− blasts at least belong to T‐lineage.

The blasts of two CD7+ CD5− CD2− cases with entire germ‐line genes and without mRNA of the three molecules (MPO, CD3ϵ, and CD3δ) were regarded as being at an undifferentiated stage prior to their commitment to either T‐ or myelold‐lineage.

The co‐expression of the genes of MPO and CD3e In a CD7+ CD5− CD2− case or MPO, CD3ϵ, and CD3δ in a CD7+ CD5+ CD2− case suggested the presence of some overlapping phase for T‐ and myeloid‐lineage commitment during Immature stages of differentiation. This heips understand the conversion of some T‐ALL/LBL cases to acute myeloblastic leukemia (AML). The detection of CD3ϵ, but not CD3δ mRNA, in two CD7+ CD5− CD2−cases indicated that the gene expression of CD3ϵ occurs at a more immature stage of differentiation than that of the CD3δ chain. © 1994 Wiley‐Liss, Inc.
Myelomonocytic crisis with t(5;17) and a p53 mutation in a patient with chronic myelogenous leukemia
Authors: Nakagawa Hitoshi , Fujii Hiroshi , Nakai Hiroyuki , Inazawa Johji , Misawa Shinichi
Published: February 2007

We report a 64‐year‐old Japanese man with chronic myelogenous leukemia (CYL) who expired with myelomonocytlc crisis. Cytogenetic analyses of chronic phase (CP) and accelerated phase (AP) cells revealed a Philadelphia chromosome and an isochromosome for the long arm of chromosome 17, i(17q). This karyotype was replaced by another karyotype in blast crisis (BC), resulting in near triploidy with t(5;17) (p15;p11) and loss of chromosome 17pter→p11. Interphase fluorescent in situ hybridization studies with a chromosome 17 specific alpha satellite DNA probe confirmed the presence of a clonal change in BC. In addition, singie‐strand conformation polymorphism analysis and PCR‐direct sequencing of BC cells revealed a point mutation at codon 203 of the p53 gene, GAG to GAG (Val to Glu), and loss of the normal allele. In contrast, no alterations of the p53 gene were found in CP and AP cells. Therefore, progression of CML in this patient appeared to be related to loss of 17p, as well as a mutation in the p53 gene. © 1994 Wiley‐Liss, Inc.
Impact of reinduction regimens for relapsed and refractory acute lymphoblastic leukemia in adults
Authors: Welborn Jeanna L.
Published: February 2007

The clinical outlook for adults with acute lymphoblastic leukemia (ALL) has Improved with the use of intensive chemotherapy. Complete remissions (CR) are achieved in 80% of adults but the majority relapse on maintenance chemotherapy and a few exhibit primary resistance to induction therapy. This report compares the various salvage treatments and provides guidance in selecting a regimen with the optimum clinical outcome. Regimens using high‐dose ara‐C (HDAC) in combination with mltoxantrone, amsacrine, or idarublcin are superior to HDAC alone or with L‐asparaginase. The sequential administration of methotrexate and L‐asparaginase Is equally effective. The duration of second CR is short for all chemotherapeutic regimens. © 1994 Wiley‐Liss, Inc.
Erythropoiesis in primary (idiopathic) osteomyelofibrosis: Quantification, PCNA‐reactivity, and prognostic impact
Authors: Thiele Juergen , Windecker Roland , Kvasnicka Hans Michael , Titius Baerbel Ruth , Zankovich Rudolph , Fischer Robert
Published: February 2007

In 64 patients with primary (idiopathic) osteomyelofibrosis (OMF), a morphometric analysis has been performed on bone marrow trephine biopsies following sequential doubleimmunostaining with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and erythroid precursor cells (glycophorin C). The purpose of this study was to quantify erythropoiesis and its PCNA‐staining capacity and, further, to determine the impact of these parameters for the development of anemia and for prognosis. In comparison with a control group (15 patients), a significant reduction in the number of erythronormoblasts could be demonstrated, associated with an increase in PCNA‐labelling. Moreover, significant correlations between the amount of nucleated erythroid marrow cells and degree of anemia (hemoglobin level, hematocrit, erythrocyte count) and survival could be calculated. Adverse relationships were assessed between number of erythroid cells, thrombocyte count, and spleen size, and also argyrophilic (reticulin/collagen) fiber density. These interactions were thought to reflect the biological behaviour of the disease process, i.e., the progression or extent of myeloid metaplasia. Our findings support ferrokinetic studies suggesting erythroid hypoplasia as one of the major causes of anemia in OMF. The remarkable high PCNA‐labelling index of the macrocytic‐megaloblastoid appearing erythropoiesis is probably caused by an overexpression of this marker protein. A comparative evaluation of Ki‐67 antigen immunostaining in splenic tissue (myeloid metaplasia) and of the PCNA‐labelling in pernicious anemia lend support to the assumption of an undue prolongation of the S‐phase generated by secondary folate (hematinic) deficiency. © 1994 Wiley‐Liss, Inc.
Pure red cell aplasia after chemotherapy for Hodgkin's lymphoma: In vitro evidence for t cell mediated suppression of erythropoiesis and response to sequential cyclosporin and erythropoietin
Authors: Reid Thomas J. , Mullaney Mark , Burrell Linda M. , Redmond John , Mangan Kenneth F.
Published: February 2007

Acquired pure red cell aplasia (PRCA) has been associated with various lymphoproliferative conditions but its occurrence with Hodgkin's disease is rare. We report a case of PRCA occurring immediately following the completion of induction chemotherapy in a patient with Stage IIIB nodular sclerosing Hodgkin's disease. In vitro erythroid colony studies documented evidence for T cell mediated suppression of erythropoiesis and lack of a serum inhibitor. Addition of cyclosporin to the in vitro cultures stimulated erythroid colony growth. Following in vivo treatment with cyclosporin peripheral blood CD4/CD8 ratios returned to normal. However, serum erythropoietin levels were inappropriately low. Subsequent treatment with erythropoietin induced a reticulocytosis and transfusion independence. Since discontinuing the erythropoietin, the patient has been able to maintain a hemoglobin of 100 g/L. This case illustrates that red cell aplasia occurring in the setting of Hodgkin's disease may be due to T cell mediated suppression of erythropoiesis. A response to cyclosporin may be masked by inappropriately low erythropoietin levels. © 1994 Wiley‐Liss, Inc.
Spontaneous remission of polycythemia vera: Clinical and cell culture characteristics
Authors: Cowan D. H. , Messner H. A. , Jamal N. , Aye M. T. , Smiley R. K.
Published: February 2007

A 20‐year‐old woman presented with polycythemia vera and was treated with phlebotomy alone for eleven years, following which all clinical manifestations of the disease disappeared. The clinical remission with normal physical findings and normal peripheral blood counts has persisted for a further 11 years. Erythroid colony culture results have paralleled the clinical state. Initial bone marrow cultures revealed spontaneous growth of erythroid burst‐forming units (BFU‐E). Subsequent cultures of peripheral blood cells throughout most of the period of spontaneous clinical remission have revealed little or no spontaneous growth of BFU‐E. This suggests a suppression of the abnormal stem cell clone during the period of remission. © 1994 Wiley‐Liss, Inc.
Establishment of a human pro‐B cell line (JKB‐1) and its differentiation of preestablished bone marrow stromal cell layer
Authors: Urashima Mitsuyoshi , Hasegawa Notomi , Kamijo Makoto , Shishikura Akihiro , Kato Yoko , Hoshi Yasutaka , Akatsuka Jun‐Ichi , Maekawa Kihei
Published: February 2007

A human pro‐B cell line, named JKB‐1, was established from the bone marrow of a 16‐year‐old girl with acute lymphoblastic leukemia (ALL) in relapse. The origin of the JKB‐1 cell line was indicated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. This cell line has been growing for more than 14 months in suspension culture medium and had a doubling time of about 24 hours. JKB‐1 expressed terminal deoxynucleotide transferase (TdT) and early antigens (HLA‐DR, CD19, CD24) of B cells, with heavy chain gene rearrangement. However, it did not express late antigens (CD10, CD20, CD21, CD22, CD23) of B cells, light chain gene rearrangement, and cytoplasmic μ‐chain. These results suggested that JKB‐1 is at the stage of “pro‐B” cell or early B‐cell precursors.

This cell line was induced to differentiate after 7 days of co‐incubation with irradiated bone marrow stromal cells because of the expression of pre‐B cell antigens (CD10, CD20), cytoplasmic μ‐chain, light chain gene rearrangement, and disappearance of TdT. JKB‐1 cells adhered to a preestablished bone marrow stromal cell layer with string‐like processes under scanning electron microscope. When JKB‐1 cells were separated from the stromal layer by a cyclopore membrane with 0.45 μ pore size, they did not differentiate. Bone marrow stromal cell conditioned medium could not induce differentiation either. Thus it was suspected that direct contact between JKB‐1 cells and stromal cells was required for differentiation. In methylcellulose semisolid medium, the colony size and number of JKB‐1 cells were increased by stem cell factor (SCF), or interleukin (IL)‐3, or IL‐7, but they were decreased by IL‐6. Moreover, SCF synergized with IL‐3 or IL‐7 to stimulate the proliferation of JKB‐1 cells.

Because there are very few reproducible models for examing early stages of human B‐cell differentiation, the JKB‐1 cell line would be useful for studying the relationship between human B‐cell differentiation and bone marrow microenvironment, as well as leukemogenesis. © 1994 Wiley‐Liss, Inc.
Sporotrichosis as a presenting manifestation of hairy cell leukemia
Authors: Kumar Shimareet , Kumar Dhruv , Gourley William K. , Alperin Jack B.
Published: February 2007

An infectious episode is the presenting manifestation of hairy cell leukemia (HCL) in approximately 30% of cases. Most often this is bacterial and only rare cases of opportunistic fungal infection are described. We report a patient who presented with sporotrichal involvement of multiple cutaneous sites and lymph nodes. The lesions resolved following antifungal therapy, but persisting pancytopenia and splenomegaly necessitated further hematological evaluation. A diagnosis of HCL was suspected based on morphologically characteristic hairy cells in the peripheral blood that contained tartrate resistant acid phosphatase. A bone marrow biopsy specimen had a normocellular marrow with an increase in interstitial lymphoid cells that stained with L26, MB2, and LN2 antibodies. On flow cytometry these cells were positive for the leukocyte common antigen, B cell markers, and the CD11c antigen confirming the diagnosis of HCL. We believe that this is the first report of sporotrichosis infection as a presenting manifestation of HCL. © 1994 Wiley‐Liss, Inc.
Acquired yon Willebrand's syndrome in association with a lupus‐like anticoagulant corrected by intravenous immunoglobulin
Authors: Hanley Debra , Arkel Yale S. , Lynch Jean , Kamiyama Mikio
Published: February 2007

We are reporting on a 47‐year‐old man who presented with a prolongation of the activated partial thromboplastin time (APTT) prior to orthopedic surgery. An evaluation suggested an inhibitor when his plasma prolonged a normal control APTT upon 50:50 solution of patients with normal plasma. The platelet‐neutralizing procedure (PNP), anticardiolipin antibody, and antinuclear antibody (ANA) were positive. Further studies revealed decreased von Willebrand factor ristocetin cofactor (vWF:RCoF), von Willebrand factor antigen (vWF:Ag), an inhibitor to vWF, and absent high‐molecular‐weight vWF multimeters. Assays of FVIII:C, FIX, and FXI were nonparallel to the standard curve. Intravenous immunoglobulin (IVIG) corrected the APTT, multimeric pattern, and FVIII:C by the 7th day postinfusion. This case demonstrates the efficacy of IVIG for acquired von Willebrand's syndrome (vWS) and also represents a unique combination of a lupus‐like anticoagulant and acquired vWS in a patient without the full serological requirement for systemic lupus erythematosus (SLE). Whether patients with acquired vWS and lupus inhibitors are more or less susceptible to either a thrombotic complication or hemorrhage is not established. Prospective studies for the incidence of lupus inhibitor/antiphospholipid syndromes and vWF deficiencies are needed to assess this question. © 1994 Wiley‐Liss, Inc.
Connective tissue components in serum in multiple myeloma: Analyses of propeptides of type I and type III procollagens, type I collagen telopeptide, and hyaluronan
Authors: Abildgaard Niels , Nielsen Johan Lanng , Heickendorff Lene
Published: February 2007

The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C‐terminal propeptide of type I procollagen (PICP) and the C‐terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N‐terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex‐ and age‐matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 μg/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 μ/L; P < 0.01) and hyaluronan (median 122 vs. 45 μ/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum β2‐microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen‐derived peptides or β2‐microglobulin. The MM group was followed for 9–25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown. © 1994 Wiley‐Liss, Inc.
Recombinant tissue plasminogen activator (rt‐PA) for veno‐occlusive liver disease in pediatric autologous bone marrow transplant patients
Authors: Yu Lolie C. , Malkani Indrani , Regueira Oswaldo , Ode David L. , Warrier Raj P.
Published: February 2007

The pathogenesis of veno‐occlusive disease (VOD) of the liver appears to be secondary to endothelial damage of terminal hepatic venules, which leads to activation of the coagulation cascade, fibrin deposition, and eventual fibrous obliteration of the hepatic venules. Patients with VOD usually present with jaundice, hepatomegaly, weight gain, and ascites. This complication is usually associated with a high mortality rate.

We report here the frequency and treatment of VOD in our autologous bone marrow transplant (BMT) patient population. Three of 15 (20%) children (median age 9 years) developed VOD and were treated with recombinant tissue plasminogen activator (rt‐PA). Two of these three patients were prepared for BMT with busulfan (16 mg/kg) and cyclophosphamide (Cytoxan, 200 mg/kg), while the other child received cytosine arabinoside (ARA‐C 18 g/m2), Cytoxan (3,600 mg/m2) and total body irradiation (TBI, 1,400 r). VOD developed between days 7–24 posttransplant. Clotting studies obtained pretransplant and during VOD included prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin‐degradation product (FDP), proteins C and S, and platelet count. There was no correlation between the incidence of VOD and coagulation status. All patients had normal pretransplant clotting studies. However, protein C levels were noted to be consistently low for those patients at the time of VOD.

All three patients received rt‐PA at a dose of 0.25–0.5 mg/kg for 4 days. This dose produced increased levels of FDP but did not significantly prolong PT nor PTT. Two of the patients had dramatic responses and had complete resolution of VOD within 6–12 days from the start of therapy. The other patient died of fulminant hepatic failure. It seems that rt‐PA is effective in VOD of the liver, which may be associated with low protein C level. © 1994 Wiley‐Liss, Inc.
1‐deamino‐8‐D‐arginine vasopressin (DCAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass
Authors: Sloand Elaine M. , Alyono David , Klein Harvey G. , Chang Ping , Yu Monica , Lightfoot Fred G. , Kessler Craig
Published: February 2007

1‐deamino‐8‐D‐Arginine vasopressin (DDAVP) shortens the bleeding time in some patients with platelet dysfunction and decreases blood loss in some cardiopulmonary bypass patients. We studied platelet membrane glycoproteins in patients with von Willebrand disease (vWD), disorders of platelet function, and in cardiopulmonary bypass patients after infusion of 0.3 μg/kg of DDAVP. Platelets from 8 cardiopulmonary bypass patients, receiving DDAVP immediately after surgery, were compared to those of 14 patients not receiving DDAVP. We also studied 12 patients with vWD, and 8 patients with platelet dysfunction receiving DDAVP. Fixed platelets, stained with monoclonal fluorescein (FITC)‐labeled antibodies directed against GPIb (CD42b antigen), GPIb/IX, GPIIb/IIIa (CD41a antigen), CD63 antigen (a platelet activation protein), and P‐selectin (CD62 antigen) were studied by flow cytometry. Binding of CD42b monoclonal antibody (MoAb) and anti‐GPIb/IX to platelets from both groups of bypass patients increased during the 18–20 hr after surgery, but the group receiving DDAVP showed the greater increase (P = 0.032). Platelets from patients receiving DDAVP for vWD or for platelet dysfunction, had increases in CD42b MoAb and anti‐GPIb/IX binding (P < 0.01) that coincided with shortening of their bleeding time. No changes were seen in binding of other antibodies. When platelets from normal donors were incubated with DDAVP for 20 hr, there were increases in platelet surface CD42b MoAb binding, while immunogold‐stained transmission electron micrographs of permeabilized platelets demonstrated decreases in cytoplasmic CD42b MoAb binding. DDAVP increases platelet membrane GPIb expression in a variety of patients and may account for improvement in hemostasis seen in some studies. Redistribution of GPIb from the cytoplasm to the membrane may account for this increased expression. © 1994 Wiley‐Liss, Inc.
Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant
Authors: Berruyer M. , Francina A. , Ffrench P. , Negrier C. , Boneu B. , Dechavanne M.
Published: February 2007

Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [β 145 (HC2) Tyr → Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high‐affinity hemoglobin variant, which displayed an increase of blood viscosity. Four members combined both abnormalities. Three had thrombotic accidents before the age of 30. We suggest the combination of protein S deficiency and the presence of this hemoglobin variant can lead to a severe primary hypercoagulable state with pathological consequences compared to each genetic defect alone. © 1994 Wiley‐Liss, Inc.
Gray platelet syndrome with splenomegaly and signs of extramedullary hematopoiesis: A case report with review of the literature
Authors: Jantunen Esa , Hänninen Auli , Naukkarinen Anita , Vornanen Martine , Lahtinen Reino
Published: February 2007

Gray platelet syndrome (GPS) is a rare bleeding disorder characterized by thrombocytopenia, agranular gray platelets in blood films, and almost total absence of platelet alpha‐granules and their constituents. We describe here a rare case of GPS with myelofibrosis and splenomegaly indicating extramedullary hematopoiesis. Splenectomy was followed by normalization of platelet count but the bleeding diathesis continued. Based on a follow‐up of more than 15 years, the slight myelofibrosis in our patient seems to be non‐progressive. We also summarize the major clinical and laboratory features of previously published cases of GPS in order to obtain more comprehensive understanding of this rare disorder. From the clinical point of view, the bleeding tendency in this syndrome generally varies from mild to moderate, and no specific treatment is usually needed. Careful examination of peripheral blood films is necessary for the diagnosis of this rare syndrome. © 1994 Wiley‐Liss, Inc.
Promace day 1/MOPP day 8 chemotherapy for prolymphocytic leukemia: A case report of prolonged survival
Authors: Yuen Benjamin H. , Godwin John E.
Published: February 2007

The treatment result of a case of de novo B‐cell prolymphocytic leukemia (B‐PLL) is described. The diagnosis was established with histologic, ultrastructural and immunologic studies. The patient was treated with chemotherapy using a total of seven cycles of ProMACE Day 1/MOPP Day 8 lymphoma regimen. Complete remission was achieved after 5 cycles of chemotherapy. The patient remains disease free after a 7‐year follow up. This is the first case of PLL being treated with such a regimen and the only case reported achieved such prolonged survival. Results of other treatment modalities are reviewed. © 1994 Wiley‐Liss, Inc.
Hemoglobinopathies in the dogon country: Presence of βs, βc, and δa'genes
Authors: Ducrocq Rolande , Bennani Mohcine , Bellis Gil , Baby Mounirou , Traore Kader , Nagel Ronald L. , Krishnamoorthy Rajagopal , Chaventre Andre
Published: February 2007

The population of the Dogon, located in Mali, is divided in an endogamic Noble class and two endogamic servant castes (Tanners and Blacksmiths). We find that the polymorphic frequencies of βc, βs, and, unexpectedly, a mutation of the δ‐chain (δA'), are geographically (valley vs. plateau) as well as social status dependent. © 1994 Wiley‐Liss, Inc.
Karyotype in myelodysplastic syndromes: Relations to morphology, clinical evolution, and survival
Authors: Bernasconi P. , Alessandrino E. P. , Boni M. , Bonfichi M. , Morra E. , Lazzarino M. , Campagnoli C. , Astori C.
Published: February 2007

One hundred eighty‐eight unselected consecutive patients with “de novo” myelodysplastic syndrome (MDS) were studied cytogenetically. They were subclassified as 4 refractory anemia with ringed sideroblasts (RARS), 67 refractory anemia (RA), 58 refractory anemia with excess of blasts (RAEB), 40 RAEB in transformation (RAEB‐t), and 19 chronic myelomonocytic leukemia (CMML). The overall incidence of chromosome abnormalities was 69%. The RAEB and RAEB‐t patients showed karyotypic changes, more often than RA and CMML (76% and 100% vs. 56% and 42%, respectively). The most frequent single anomaly was del(5)(q13‐q22q33) (22 cases), followed by monosomy 7 or del 7q (11 cases), del(11) (q14q23) (8 cases), trisomy 8 (4 cases). Complex karyotypes (defined by the presence of three or more structural or numerical abnormalities) were detected in 33 patients. With regard to the FAB classification, del (5)(q13q33) was associated with RA, and complex rearrangements with RAEB and RAEB‐t. Leukemic transformation occurred in 66 patients (46%), none with a normal karyotype or del(11)(q14q23) as single abnormality. In patients carrying 5q‐ alone, acute evolution correlated with proximal breakpoint localization, being found in no case with del(5)(q13q33) but in three out of four cases with del(5)(q22q33). Acute leukemia (AL) progression happened in all cases with complex rearrangements and monosomy 7 or del(7q). Two of the four trisomy eight patients evolved in AL. By using the Cox proportional hazard regression analysis it was demonstrated that the karyotype abnormality was a significant predictor of leukemic transformation (P < 0.001). Patients with abnormal karyotypes without complex abnormalities had a survival (median survival 12 months) shorter than that of cases with only normal metaphases (median 83 months) (P < 0.001); patients with a mixture of normal/abnormal metaphases had a median survival of 31 months. The median survival for complex karyotypes was 7 months. Among cases with single defects, del(5)(q13q33) showed the best survival (64 months), mono‐ somy 7 and del (7q) the worst (7 months) (P < 0.001). © 1994 Wiley‐Liss, Inc.
Hepatitis C virus infection in patients with leukemia
Authors: Fujii Yasuhiko , Kaku Kohei , Tanaka Masahisa , Yosizaki Miki , Kaneko Toshio , Matumoto Noboru
Published: February 2007

We have studied 30 patients with acute leukemia by the second‐generation assay for antibodies to hepatitis C virus (HCV) to determine the incidence of HCV infection and the impact of anti‐HCV positivity on liver disease. After a complete remission, 21/30 (70%) patients were anti‐HCV‐positive. During chemotherapy the anti‐HCV‐positive patients had more severe liver disease than the anti‐HCV‐negative patients, and they had a higher incidence of chronic hepatitis (13/21; 62% vs. 1/9; 11%, P < 0.01). During subsequent follow‐up, 15/30 (50%) patients relapsed and 15/30 (50%) patients completed the chemotherapy protocols. After a relapse 12/15 (80%) patients were anti‐HCV‐positive and they had more severe liver disease than the anti‐HCV‐negative patients. Among the patients who completed chemotherapy (n = 15), biochemical evidence of chronic hepatitis was found in 9/9 (100%) anti‐HCV‐positive, and 2/6 (33%) anti‐HCV‐negative cases during off‐therapy follow‐up after therapy‐withdrawal (P < 0.05). These results indicate that HCV plays an important role in the etiology of chronic hepatitis which could worsen the final prognosis of successfully treated patients with leukemia. © 1994 Wiley‐Liss, Inc.
Increased natural antibody activity in sera of patients with malignant non‐Hodgkin's lymphomas containing paraproteins
Authors: Kourtis Athena P. , Boussiotis Vassiliki A. , Lymberi Pigi , Pangalis Gerassimos A.
Published: February 2007

In view of the frequent association between malignant lymphoproliferative diseases and autoimmunity, we studied by ELISA the presence, lsotype, and specificity of natural antibodies in sera from 60 patients with malignant non‐Hodgkin's lymphomas and 70 healthy controls. The antigens selected were actin, tubulin, myosin, troponin, tropomyosin, keratin, thyroglobulin, single stranded DNA, and the hapten trinitrophenyl. The results of this study were compared with the presence of oligoclonal immunoglobulins in the same sera, as previously detected by lsoelectric Focusing and Immunoblotting.

Our results showed that 1) there is a high proportion of autoreactive NHL sera: 28 (46.6%) exhibited high IgG natural antibody activity (Nab) against one or more panel antigens, mostly against keratin, myosin, and tropomyosin, 26 (43.3%) had high IgA Nab activity, mainly against myosin, keratin, and ssDNA, whereas 17 (28.3%) displayed a high IgM Nab activity. The great majority (>80%) of positive sera was polyspecific, i.e., reacted with at least two panel antigens. 2) A strong correlation exists between the high serum Nab activity and the presence of paraproteins: of the 28 sera exhibiting high IgG Nab activity, 16 (57%) contained oligoclonal IgG, and of the 17 sera exhibiting high IgM Nab activity, 13 (76.4%) contained oligoclonal IgM. The Nabs detected had frequently the same heavy and light chain as the paraproteins. No relationship between the presence of paraproteins with Nab activity and the stage of disease or grade of malignancy was found. We conclude that the high incidence of clonal immunoglobulins of different isotypes with various autoantibody specifities suggests an oligoclonal lymphocyte activation involving Nab producing cells. The significance of such autoreactive clones in NHL patients remains to be elucidated. © 1994 Wiley‐Liss, Inc.