bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous remission of multilobated non‐Hodgkin lymphoma
Authors: Grigg Andrew P. , Gray George R. , Shepherd John D.
Published: February 2007

A 67‐year‐old previously well man was admitted with hypercalcemia after a 7‐day history of fever, night sweats, and back pain. The blood showed 5% multilobated lymphoid cells. A multilobated non‐Hodgkin lymphoma associated with marked reticulin fibrosis was diagnosed on a bone marrow biopsy. During the next 7 days, in the absence of specific therapy, his symptoms disappeared. Three weeks after admission his biochemical abnormalities had resolved and after 9 weeks his bone marrow examination was normal. He remains in clinical and laboratory remission 16 months after presentation. © 1992 Wiley‐Liss, Inc.
Clonal remission in aplastic anemia after treatment with antithymocyte globulin
Authors: Wun Theodore , Lewis Jerry P.
Published: February 2007

Aplastic anemia includes a group of disorders characterized by peripheral blood pancytopenia and marrow hypocellularity. The current report describes a patient who is an apparent constitutional mosaic and presented with marrow aplasia. Using cytogenetic analysis of bone marrow, skin, and peripheral T lymphocytes, we demonstrate the clonal nature of this patient's aplastic marrow, and, in addition, identify clonal evolution. The patient was treated with antithymocyte globulin (ATG) and achieved a complete remission, with disappearance of an abnormal evolved clone. This case illustrates that clonal cytogenetic abnormalities do not preclude a response to ATG and that aplastic anemia may be a nonmalignant clonal disorder with clonal evolution. © 1992 Wiley‐Liss, Inc.
Frequent rearrangements of retinoic acid receptor alpha gene and myl gene, and rare mutations of RAS and FMS genes in acute promyelocytic leukemia
Authors: Yamamoto Koh , Hirosawa Shinsaku , Sakamaki Hisashi , Aoki Nobuo
Published: February 2007

To investigate leukemogenesis of acute promyelocytic leukemia (APL), we studied the involvements of retinoic acid receptor alpha (RARα) and myl genes, and also the frequency of N‐RAS, K‐RAS, H‐RAS, and FMS point mutations in sixteen patients with APL. By Southern blot analysis, the rearrangements of RARα gene were detected in 13 patients (81.2%), and myl gene in 14 (87.5%). Either RARα or myl gene rearrangements were found in all patients including one with normal karyotype. Breakpoints of both genes were clustered. By direct sequencing, no point mutations were found at codons 12, 13, and 61 of N‐, K‐, and H‐RAS genes, and at codons 301 and 969 of FMS gene. These data indicate that myl‐RARα translocation occurs frequently in APL, whereas RAS and FMS mutations are rare in APL. It may be suggested that leukemogenesis of APL is different from other subtypes of acute myelogenous leukemia, and multistep leukemogenesis may not be a prevalent feature in APL. © 1992 Wiley‐Liss, Inc.
Effects of normal and sickle erythrocytes on prostacyclin release by perfused human umbilical cord veins
Authors: Sowemimo‐Coker Samuel O. , Haywood L. Julian , Meiselman Herbert J. , Francis Robert B.
Published: February 2007

We compared the effects of normal (AA) and sickle (SS) erythrocytes (RBC) on endothelial cell release of prostacyclin by perfused human umbilical cord veins. Two equal‐length segments of fresh umbilical cords were perfused first with serum‐free Dulbecco's modified Eagle's medium (DMEM) to establish the basal prostacyclin production rate for each segment; then one segment was perfused with SS RBC and/or plasma, while the other segment was simultaneously perfused with AA RBC and/or plasma. Aliquots of perfusate were removed at intervals for measurement of the stable prostacyclin metabolite 6‐ketoprostaglandin F1α (6‐keto‐PGF). Basal prostacyclin production by segments from the same cord was very similar, but it varied considerably among segments from different cords. Therefore, the ratio of prostacyclin release with RBC and/or plasma to basal prostacyclin release for each segment was used to compare prostacyclin release among segments from different cords. Mean prostacyclin release was significantly higher from segments perfused with SS RBC in autologous plasma than from segments perfused with AA RBC in autologous plasma at 15, 30, and 60 min. However, no significant differences in mean prostacyclin production were observed between segments perfused with SS vs. AA RBC in DMEM or between segments perfused with SS vs. AA plasma alone. No significant correlations were observed between prostacyclin production and either the viscosity of SS and AA RBC in autologous plasma or DMEM or the adhesiveness of SS and AA RBC to cultured human umbilical vein endothelial cells. We conclude that SS RBC in autologous plasma cause increased prostacyclin release from perfused human umbilical cord veins. The perfused human umbilical cord vein system may be a useful model for comparing the response of vascular endothelium to SS and AA RBC and plasma under controlled‐flow conditions. © 1992 Wiley‐Liss, Inc.
New variant of cytochrome b5 reductase deficiency (b5RKurashiki) in red cells, platelets, lymphocytes, and cultured fibroblasts with congenital methemoglobinemia, mental and neurological retardation, and skeletal anomalies
Authors: Yawata Yoshihito , Ding Lily , Tanishima Kiyoh , Tomoda Akio
Published: February 2007

A Japanese man with cytochrome b5 reductase (b5R) deficiency in various blood cell lineages (red cells, platelets, and lymphocytes) and in cultured fibroblasts demonstrated congenital methemoglobinemia associated with mental and neurological retardation, and various skeletal anomalies, such as spondylosis deformans and finger joint deformations, which have never been described in association with this enzyme deficiency. Cytochrome b5 reductase deficiency was most severe in red cells (0.3–4%) and less marked in platelets (13–27%), lymphocytes (18–31%), and fibroblasts (50%). The present case appears to be a new variant of cytochrome b5 reductase deficiency (b5RKurashiki). © 1992 Wiley‐Liss, Inc.
Presence of an African β‐globin gene cluster haplotype in normal chromosomes in sicily
Authors: Ragusa A. , Frontini V. , Lombardo M. , Amata S. , Lombardo T. , Labie D. , Krishnamoorthy R. , Nagel R. L.
Published: February 2007

African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The Taql polymorphism in the intervening sequences between the two γ genes is informative. We have found only two instances of this African marker (Taql(‐)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought. © 1992 Wiley‐Liss, Inc.
Splenectomy vs. alpha interferon: A randomized study in patients with previously untreated hairy cell leukemia
Authors: Smalley Richard V. , Anderson Susan , Connors Joseph , Tuttle Richard L. , Whisnant John K. , Robinson William
Published: February 2007

Twenty patients with previously untreated hairy cell leukemia were randomized to undergo either splenectomy or to receive interferon alfa‐N1, a highly purified natural alpha interferon, as primary therapy. A response in the peripheral blood elements to a hemoglobin greater than 110 gm/l, a granulocyte count greater than 1 × 109/l, and a platelet count greater than 100 × 109/l (Catovsky criteria) was noted in all ten patients receiving alpha interferon but in only three of the patients undergoing splenectomy (P = < .01). Median time to response was longer in the ten interferon patients (153 days) than in the three splenectomy responders (20 days). Median time to treatment failure was significantly greater in the alpha interferon patients (> 18 months) than in the splenectomy patients (< 1 month). Survival was no different since patients relapsing following splenectomy subsequently responded to alpha interferon. A significant decrease in leukemic bone marrow infiltration was observed in seven of ten patients receiving alpha interferon and in none of the patients undergoing splenectomy. Side effects, primarily infections, were more frequent in patients receiving interferon. Alpha interferon is preferable to splenectomy as initial treatment for hairy cell leukemia. © 1992 Wiley‐Liss, Inc.
Protein C survival during replacement therapy in homozygous protein C deficiency
Authors: Marlar Richard A. , Montgomery Robert R. , Madden Renee M. , Sills Richard H. , Groncy Paula K.
Published: February 2007

Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 ± 15 units/dl. PC is present in all PCC analyzed; however, a ten‐fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC‐deficient children, the PC levels obtained were ≦30 units/dl post‐ infusion and undetectable after 12‐18 hr. With infusions of PCC, plasma levels of PC obtained were 100‐145 units/dl and <10 units/dl after 48 hr. The percent recovery and half‐lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC‐rich material. Based on this information, a specific replacement protocol has been developed using a PC‐rich concentrate. However, several problems may arise with the „less pure”︁ PC‐rich concentrates: catheter‐tip thrombosis, related large vessel thrombosis and blood‐transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long‐term management/treatment of homozygous PC deficiency. © 1992 Wiley‐Liss, Inc.
Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation
Authors: Yau Jonathan C. , Huan Susan D. , Lemaistre Charles F. , Meneghetti Carole M. , Andersson Borje S. , Wallerstein Ralph O. , Woo Shiao Y. , Brunner Lane J. , Dimopoulos Meletios A. , Jagannath Sundar , Deisseroth Albert B. , Spitzer Gary , Spencer Verneeda , Spinolo Jorge A. , Dicke Karel A. , Giralt Sergio
Published: February 2007

Forty‐three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty‐eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day –8, cyclophosphamide 60 mg/kg/day intravenously on days –7 and –6, and total body irradiation at 170 cGy twice a day on days –3, –2, and –1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease. © 1992 Wiley‐Liss, Inc.
Elevated neutrophil function in chronic neutrophilic leukemia
Authors: Ohtsuki Tetsuya , Mizukami Hiroaki , Kimura Fumihiko , Ohnishi Mayumi , Nagata Naokazu , Motoyoshi Kazuo , Katsura Yoshiya , Matsu‐ura Yoshifusa
Published: February 2007

A 65‐year‐old man with marked leukocytosis was admitted for diagnosis and treatment. His peripheral blood leukocyte count was 37,500/μI and the leukocytes consisted of mature neutrophil‐like cells. A high neutrophil alkaline phosphatase score and a normal bone marrow cell karyotype suggested that the patient had chronic neutrophilic leukemia rather than chronic myeloid leukemia. Several neutrophil functions, such as superoxide production, nitroblue tetrazolium reduction activity, and phagocytosis, were elevated. These data and the morphological features (toxic granules and Döhle bodies) indicated that the patient's neutrophils were in an activated stage. © 1992 Wiley‐Liss, Inc.
Role of endothelin in disseminated intravascular coagulation
Authors: Asakura H. , Jokaji H. , Uotani M. Saito C. , Kumabashiri I. , Morishita E. , Yamazaki M. , Matsuda T.
Published: February 2007

We examined the changes in plasma levels of endothelin‐1 (ET‐1), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET‐1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET‐1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non‐Hodgkin lymphoma. Plasma levels of ET‐1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET‐1 were decreased or remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET‐1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders. © 1992 Wiley‐Liss, Inc.
5‐Aminolevulinate synthase in sideroblastic anemias: mRNA and enzyme activity levels in bone marrow cells
Authors: Bottomley Sylvia S. , Brandenburg Mark A. , Healy Helen M. , May Brian K.
Published: February 2007

To examine the role of 5‐aminolevulinate synthase (ALAS) in the pathogenesis of sideroblastic anemias, levels of mRNAs for erythroid and housekeeping ALAS isozymes were examined, and total ALAS activity was assessed in bone marrow cells. In two patients with X‐linked sideroblastic anemia the levels of mRNA for erythroid ALAS as well as for α and β globin appear to be decreased while levels of mRNA for glycophorin A in both patients were the same as in normal individuals. However, amounts of housekeeping ALAS mRNA were increased two‐ to threefold in these patients. Total ALAS activity was also increased two‐ or threefold, perhaps reflecting increased transcription of the housekeeping gene in response to diminished cellular heme in erythroid cells and/or enhanced translation of the erythroid isoform in response to iron accumulation. In a third patient with X‐linked sideroblastic anemia ALAS activity was low but increased to twice the normal value after pyridoxine administration, suggesting a structural defect of the enzyme. In a fourth patient, with isolated congenital, pyridoxine‐responsive sideroblastic anemia, the erythroid ALAS mRNA was normal and a low enzyme activity was strikingly enhanced by pyridoxal‐phosphate albeit to subnormal levels. In idiopathic acquired sideroblastic anemia, ALAS mRNA for both isozymes was normal and enzyme activity was slightly elevated. These observations thus reflect heterogeneous aberrations of erythroid heme synthesis in the various types of sideroblastic anemia and suggest that defects involving erythroid ALAS underlie at least some of them. © 1992 Wiley‐Liss, Inc.
Procoagulant activity of endotoxin or tumor necrosis factor activated monocytes is enhanced by IgG from patients with lupus anticoagulant
Authors: Schved Jean‐Fraņois , Gris Jean‐Christophe , Ollivier ValéRie , Wautier Jean‐Luc , Tobelem GÉRard , Caen Jacques
Published: February 2007

The effect of lupus anticoagulant (LA) positive plasma on the expression of human monocyte procoagulant activity (PCA) was studied. LA positive plasma were able to enhance the endotoxin or TNF alpha induced monocyte associated PCA. The monocyte PCA had the characteristic of tissue factor activity (factor VII, factor × dependence). The enhancement of monocyte PCA could be confirmed using purified LA positive IgG. The stimulating effect was supported by the F(ab')2 fragments. © 1992 Wiley‐Liss, Inc.
Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B‐Cell malignant lymphoma patients
Authors: Nagasu Masaya , Aizawa Shin , Hojo Hitoshi , Tsuda Akemi , Yaguchi Makoto , Nakano Masaru , Toyama Keisuke
Published: February 2007

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B‐cell‐type non‐Hodgkin lymphoma (B‐NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF). Each patient received only chemotherapy in the first course, and rhG‐CSF (1 βg/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG‐CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte–macrophage precursor cells (CFU‐GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU‐E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG‐CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa–lambda imaging (KLI) analysis was performed to detect the malignant B‐cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs. © 1992 Wiley‐Liss, Inc.
Malignant tγ/δ lymphoproliferative disease with natural killer lytic activity
Authors: Falcão Roberto P. , Voltarelli Julio C. , Simões Belinda P. , Pestana Denise N. R. , Zago Marco A. , Figueiredo Mauro S.
Published: February 2007

A 17‐year‐old girl presented with a lymphoproliferative disease involving the bone marrow, peripheral blood, and liver associated with reactive hyperplasia of the spleen. Neoplastic cells were atypical medium‐sized lymphoblasts with convoluted nuclei and nucleoli without features of large granular lymphocytes (LGL). The phenotype was CD3+CD4‐CD8‐, TCRα/β‐, TCRγ/δ+, δTCS1‐. and CD16+, and these cells exhibited spontaneous natural killer (NK) activity. DNA analysis showed rearrangement of the TCRγ gene but not of TCRβ or of lg μ genes. This unusual lymphoproliferative disease may represent the neoplastic expansion of a minor subset of normal Tγ/δ cells with NK activity. © 1992 Wiley‐Liss, Inc.
Accessory spleen in recurrent chronic immune thrombocytopenic purpura
Authors: Facon T. , Caulier M. T. , Fenaux P. , Plantier L. , Marchandise X. , Ribet M. , Jouet J. P. , Bauters F.
Published: February 2007

From 1969 to 1985 we discovered accessory spleens in 8 patients with chronic immune thrombocytopenic purpura (ITP) who relapsed or failed after splenectomy. Imaging of accessory spleen used a liver spleen scintigraphy with heat‐treated RBC labeled with Tc‐99m. Platelet kinetic studies with 51Cr or 111In, including sequestration index, were performed. Five patients had accessory splenectomy. Disappearance of bleeding symptoms was achieved in the 5 splenectomized patients but with only partial response of platelet counts. These results are discussed in the context of diagnosis and therapeutic management of accessory spleens in patients with chronic immune thrombocytopenic purpura who relapsed or failed afler splenectomy. © 1992 Wiley‐Liss, Inc.
Molecular basis of beta thalassemia in the south of thailand
Authors: Laosombat V. , Fucharoen S‐P. , Panich V. , Fucharoen G. , Wongchanchailert M. , Sriroongrueng W. , Nopparatana C. , Kenpitak K. , Maipang M. , Fukumaki Y.
Published: February 2007

A total of 103 beta thalassemia genes from 78 children (45 with Hb E/beta thalassemia, 8 with beta thalassemia heterozygotes, and 25 with homozygous beta thalassemia) were analyzed using dot‐blot hybridization of the polymerase chain reaction‐amplified DNA and direct DNA sequencing. Nine mutations were characterized in 98/103 (95%) of beta thalassemia alleles, of which six (a 4 bp deletion in codons 41–42, a G‐C transition at position 5 of IVS‐1, A‐G transition at codon 19, an A‐T transition at codon 17, an A‐G transition at position –28 upstream of the beta globin gene, a G‐T transition at position 1 of IVS‐1), accounted for 92%. The spectrum of beta thalassemia mutations in Chinese Thai is similar to that reported among the Chinese from other parts of the world. The distribution of beta thalassemia mutations in Muslim Thai is similar to that reported among Malaysians. The most common beta thalassemia mutation in Thai and Chinese Thai patients is the frameshift mutation at codons 41–42, in comparison with the Muslim Thai in whom the G‐C transition at position 5 of the IVS‐1 mutation predominates. The heterogeneity of molecular defects causing beta thalassemia should aid in the planning of a prenatal diagnosis program for beta thalassemia in the South of Thailand. © 1992 Wiley‐Liss, Inc.
Cytogenetic characterization of primary refractory anemia
Authors: Gyger Martin , d'Angelo Giovanni , Bélanger Robert , Forest Lorraine , Lussier Pauline , Busque Lambert , Perreault Claude , Boileau Jacques , Bonny Yvette , Lavallée René , Lacombe Michel , Roy Denis‐Claude
Published: February 2007

Refractory anemia (RA) is the only myelodysplastic syndrome (MDS) devoid of quantitative marrow diagnostic criteria. The diagnosis rests mainly on the subjective identification of qualitative abnormalities according to the French‐American‐British criteria (FAB) involving one or more bone marrow hematopoietic cell lineages. The occurrence of nonrandom chromosome abnormalities remains the hallmark of the disease and the only means of investigation which confirms the disease objectively. With the purpose in mind to further characterize RA among MDS, we have undertaken a prospective high resolution banding chromosome analyses of bone marrow cells in patients with primary refractory anemia (PRA) with the aim of defining a cytogenetic phenotype and of assessing the clinical relevance of clonal abnormalities at initial diagnosis. Of 39 patients consecutively referred for chromosome analyses with a diagnosis of RA according to the FAB criteria, 27 patients had PRA and fulfilled our criteria for adequate chromosome analyses. Median age was 68 years. Fourteen of 27 patients (52%) had clonal chromosomal abnormalities at diagnosis. None of the patients showed a complex karyotype; 9/14 (64%) had a mixture of normal and abnormal cells. Interstitial or terminal deletions, involving chromosomes 5, 6, 7, 9, 11, 12, and 20, were found in 11/14 (79%) of the patients. Comparison of survival between patients with and without abnormalities showed no difference. The presence of clonal abnormalities did not predict transformation to acute myeloblastic leukemia (AML) nor was it associated with poor survival. In this study, patients with PRA were found to have a predominant pseudodiploid karyotypic pattern characterized by interstitial and/or terminal deletions as opposed to derivatives, specific and non‐specific balanced translocations, or other structural and numerical abnormalities. We were unable to reveal any prognostic significance to the presence of these clonal abnormalities at initial diagnosis. © 1992 Wiley‐Liss, Inc.
Clinical, hematological, and molecular features in sicilians with Hb S‐β‐thalassemia
Authors: Schiliro' G. , Samperi P. , Testa R. , Gupta R. B. , Gu L.‐H. , Huisman T. H. J.
Published: February 2007

The clinical, hematological, and molecular features of 81 patients with Hb S‐β‐thalassemia and relatives from 76 unrelated families are reported. We analyzed the β‐thalassemia mutations and the βS haplotypes in all patients and detected 6 different β‐thalassemia alleles: codon 39 (C→T) (39 cases), IVS‐I‐1 (G→A) (12 cases), IVS‐II‐1 (G→A) (4 cases), IVS‐l‐6 (T→C) (6 cases), IVS‐I‐110 (G→A) (14 cases), and IVS‐II‐745 (G→C) (6 cases). Eighty patients had haplotype #19 or the Benin type and one had haplotype #17 or the Cameroon type. The type of β‐thalassemia allele had the greatest influence on the phenotypic expression; this was observed for patients with Hb S‐β‐thalassemia and for simple β‐thalassemia heterozygotes. The mild IVS‐I‐6 (T→C) mutation produced borderline abnormal erythrocytic indices and Hb A2 levels in heterozygotes. Overall, there was a milder expression in βSβ+ patients (only 7.7% presented severe disease) than in those with the βSβ° condition (22.6% had the severe form of the disease). © 1992 Wiley‐Liss, Inc.
Adult T‐cell leukemia developing during immunosuppressive treatment in a renal transplant recipient
Authors: Tsurumi Hisashi , Tani Kenzaburo , Tsuruta Toshihisa , Shirato Risa , Matsudaira Tadahiro , Tojo Arinobu , Wada Chikashi , Uchida Hisanori , Ozawa Keiya , Asano Shigetaka
Published: February 2007

We report a case of a 32‐year‐old male, an asymptomatic carrier of human T‐cell leukemia virus type 1 (HTLV‐1), who underwent a renal transplantation and developed adult T‐cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl‐prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV‐1 infection to overt ATL. A careful approach is required with HTLV‐1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment. © 1992 Wiley‐Liss, Inc.
Methemoglobinemia
Authors: Mansouri Ali , Lurie Aubrey A.
Published: February 2007

The ferrous iron of hemoglobin is exposed continuously to high concentrations of oxygen and, thereby, is oxidized slowly to methemoglobin, a protein unable to carry oxygen. To restore hemoglobin function, methemoglobin (ferrihemoglobin) must be reduced to hemoglobin (ferrohemoglobin). Under physiological conditions, methemoglobin reduction is accomplished mainly by red cell NADH‐cytochrome b5 reductase (NADH‐methemoglobin reductase) so efficiently that there is insignificant amounts of methemoglobin in the circulating blood. However, should methemoglobin formation be increased—e.g., due to the presence of oxidant drugs, or an abnormal methemoglobin not amenable to reduction (hemoglobin M), or a deficiency in red cell cytochrome b5 reductase—methemoglobinemia will result. Most methemoglobinemias have no adverse clinical consequences and need not be treated. Under certain conditions, such as exposure to large amounts of oxidant or in young infants, rapid treatment is necessary. In hereditary cytochrome b5 deficiency, treatment is often directed at improving the poor cosmetic effect of persistent cyanosis with the minimum amount of drugs to give satisfactory clinical results. © 1993 Wiley‐Liss, Inc.
Fetal hemoglobin reactivation in baboon and man: A short perspective
Authors: Lavelle Donald , Desimone Joseph , Heller Paul
Published: February 2007

Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5‐azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating γ‐chain synthesis. © 1993 Wiley‐Liss, Inc.
Band 3 peptides inhibit deoxy S polymerization: Viscosity studies
Authors: Danish Elizabeth H. , Lundgren David W. , Harris John W.
Published: February 2007

We have previously obtained evidence that N‐terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1‐15AA fragment binds to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror‐image peptide, corresponding to two N:1‐8AA + lysine (K) linked by coupler, binds to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary complexes” incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol‐gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror‐image peptide was a more effective inhibitor than the N:1‐15AA peptide. When the mirror‐image peptide was present in peptide:hemoglobin molar ratios of 0.25‐1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15–25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror‐image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 peptides. © 1993 Wiley‐Liss, Inc.
Evaluation of bone marrow iron stores in anemia associated with chronic disease: A comparative study of serum and red cell ferritin
Authors: Balaban Edward P. , Sheehan Richard G. , Demian Saba E. , Cox John V. , Frenkel Eugene P.
Published: February 2007

The serum ferritin (SERFER) may be elevated and misleading in the setting of chronic disease (chronic inflammation, liver disease, and neoplasm). The red cell ferritin (RBCFER) may be more stable in clinical situations that affect the SERFER. We compared the ability of SERFER and RBCFER to assess iron stores in these settings. Iron stores were defined by bone marrow aspirate staining. We studied 120 anemic (Hb < 14 g/dl) male patients. Twenty‐eight (23%) were iron deficient based on the absence of marrow iron. The SERFER correlation with marrow iron stores (r = 0.58; P < 0.001) was better than the RBCFER (r = 0.36; P < 0.001). Cutoff values for the diagnosis of iron deficiency were determined by chi‐square analysis (SERFER < 70 ng/ml; RBCFER ± 4 ag/RBC). The sensitivity for detecting iron deficiency with SERFER (0.60) was less than RBCFER (0.82). The specificity of SERFER (0.90) was slightly better than RBCFER (0.83). Neither difference reached statistical significance (P > 0.05). The positive predictive value between the two assays was the same (SERFER 0.65 vs. RBCFER 0.59). The combination of SERFER <70 ng/ml with RBCFER ≤ 4 ag/RBC was more specific (0.97) when compared with the SERFER alone (0.90) (P = 0.04). In addition, the potential of this combination to predict iron deficiency (0.82) was higher than that seen with either SERFER (0.65) or the RBCFER (0.59). Our findings show that the RBCFER as a single assay is not anymore accurate than the SERFER. However, we find that the RBCFER can effectively complement the SERFER to either predict iron depletion or confirm the presence of bone marrow iron. © 1993 Wiley‐Liss, Inc.
Platelet activation in patients with thrombotic thrombocytopenic purpura
Authors: Hoffman Maureane , Monroe Dougald M. , Roberts Harold R.
Published: February 2007

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology. It is characterized by platelet microthrombi in small vessels, which results in tissue dysfunction and a microangiopathic hemolytic anemia. Activation of coagulation is not a prominent feature of TTP. It is not known whether the process which results in platelet aggregate formation might also activate platelets. Using GMP‐140 as a marker of activation, we examined the activation state of circulating platelets in seven TTP patients and three normal controls, as well as the ability of purified platelets from three TTP patients and three controls to be activated in vitro. There was no statistically significant difference in the percentage of activated platelets circulating in patients and controls (4% vs. 2%). Both TTP and control platelets increased GMP‐140 expression and procoagulant activity after stimulation with thrombin or the calcium ionophore A23187. Thus, we conclude that TTP patients do not have a significantly increased proportion of circulating activated platelets, and their platelets can be activated normally by thrombin or a calcium ionophore. © 1993 Wiley‐Liss, Inc.
GγAγ(β+) hereditary persistence of fetal hemoglobin: The Gγ – 158 C → T mutation in cis to the − 175 T → C mutation of the Aγ‐globin gene results in increased Gγ‐globin synthesis
Authors: Coleman M. B. , Adams J. G. , Steinberg M. H. , Plonczynski M. W. , Harrell A. H. , Castro O. , Winter W. P.
Published: February 2007

Hereditary persistence of fetal hemoglobin (HPFH) can be generally classified into deletional and nondeletional forms. The family described in the present study has characteristics of both types of HPFH. The proband is a healthy 30‐year‐old black woman. Analysis of her hemoglobin revealed 40.4% HbS, 40.9% HbF (Gγ/Aγ ratio 0.53), 16.8% HbA, and 1.9% HbA2. All of her hematologic indices were normal, and the distribution of HbF in her red cells was pancellular. Family studies demonstrated that the proband has one chromosome 11 bearing the βs‐globin gene and the other bearing a GγAγ(β+) HPFH determinant in cis to the βA‐globin gene. Gene mapping studies of the region between the Gγ‐ and β‐globin genes were normal. However, when the Aγ and Gγ promoters were amplified by polymerase chain reaction (PCR) and sequenced, the Aγ promoter was found to have the T→C mutation at −175, and the Gγ promoter region was found to have the C→T mutation at −158. The −158 C→T mutation has been associated with elevated Gγ levels and high HbF in hemolysis, although its role in causing these effects is unclear. The present study suggests that this mutation can also enhance Gγ‐globin expression in cis to the −175 T→C mutation in the absence of hemolysis. We suggest that the alteration of the Aγ gene octamer binding site by the −175 mutation, as well as the loss of a putative Gγ “silencer” caused by the −158 mutation may account for this phenotype. We propose calling these linked mutations the GγAγ(β+) HPFH. © 1993 Wiley‐Liss, Inc.
Improved or fatal acute disseminated intravascular coagulation in systemic lupus erythematosus
Authors: Shimamoto Yoshinori , Ohta Akihide , Sano Masayuki , Suga Kenji , Yamaguchi Masaya
Published: February 2007

To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC. © 1993 Wiley‐Liss, Inc.
A mild type of Hb S‐β+‐thalassemia [‐92(C→T)] in a sicilian family
Authors: Divoky V. , Baysal E. , Schiliro G. , Dibenedetto S. P. , Huisman T. H. J.
Published: February 2007

Hematological data are presented for an adult Sicilian patient with a mild Hb S‐β+‐thalassemia caused by a C→T mutation at position −92 of the β promoter. This mutation was identified by sequencing of amplified DNA and was confirmed by dot‐blot analysis with specific probes. A comparison of levels of Hb S and Hb A in Hb S‐β‐thalassemia patients with different β‐thalassemia alleles showed great variations; the highest level of Hb A (45%) was recorded in the patient with Hb S‐β+‐thalassemia [‐92(C→T)] and the lowest (∼13%) in patients with Hb S‐β+‐thalassemia [IVS‐II‐745 (C→G)]. Clinical severity is directly related to the level of Hb A present. © 1993 Wiley‐Liss, Inc.
Long‐term high‐level expression of human β‐globin occurs following transplantation of transgenic marrow into irradiated mice
Authors: Himelstein Andrew , Ward Maureen , Podda Silvio , de la Flor Weiss Eduardo , Costantini Frank , Bank Arthur
Published: February 2007

When the human β‐globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human β‐globin into irradiated recipients. We demonstrate that long‐term high level expression of the human β‐globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human β‐globin transgene expression to endogenous mouse β‐globin gene expression in donor‐derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human β‐globin gene in mouse bone marrow cells following marrow transplantation. © 1993 Wiley‐Liss, Inc.
Discordant LFA‐1/ICAM‐1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma
Authors: Tsutani Hiroshi , Sugiyama Taeko , Shimizu Shiro , Iwasaki Hiromichi , Ueda Takanori , Ozaki Kenji , Konda Susumu , Nakamura Toru
Published: February 2007

We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72‐year‐old woman after she had completed 9 months of chemotherapy for IgG k multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM‐1 (CD54) but negative for LFA‐1 α (CD11a) and LFA‐1 β (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA‐1 α and LFA‐1 β but negative for ICAM‐1. In addition, intermingling capillary endothelial cells were positive for ICAM‐1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA‐1/ICAM‐1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA‐1 α+, LFA‐1 β+ leukemic cells to ICAM‐1 endothelial cells. © 1993 Wiley‐Liss, Inc.
Spleen in sickle cell anemia: Comparative studies of Nigerian and U.S. patients
Authors: Adekile A. D. , McKie K. M. , Adeodu O. O. , Sulzer A. J. , Liu J.‐S. , McKie V. C. , Kutlar F. , Ramachandran M. , Kaine W. , Akenzua G. I. , Okolo A. A. , Asindi A. A. , Obinyan E. A. , Ogala W. N. , Ibrahim M. , Huisman T. H. J.
Published: February 2007

Anecdotal reports have attributed persistent splenomegaly in African sickle cell anemia (SS) patients to the effects of malaria. However, no comparative studies of patients in malarial and nonmalarial regions have been conducted, and few studies of malaria antibody titers have been reported. In the present study, age‐ and sex‐matched Nigerian and U.S. steady‐state SS patients were compared. Splenomegaly was found in 22.3% of Nigerian patients (n = 310), while it was found only in 8% of U.S. patients (n = 100) from Georgia. There was significant linear correlation between spleen size and Hb levels and with serum immunoglobulins in the Nigerian group. However, serum complement levels (C3 and C4) were not affected by spleen size. In both groups, patients with splenomegaly had fewer circulating pitted red cells than their counterparts without splenomegaly. The mean ± SE of IgG‐specific malaria antibody titer among the Nigerian patients without palpable spleens was 9,386 ± 2,036; 9,334 ± 2,980 in those with spleens between 1 and 5 cm, 16,201 ± 4,502 in those with spleens between 6 and 10 cm, and 22,445 ± 8,456 in those with spleens above 10 cm. Coexistent α‐thalassemia did not influence the prevalence of splenomegaly among the Nigerian SS patients. This study provides additional evidence that malaria plays a significant role in the persistence of splenomegaly in African patients. © 1993 Wiley‐Liss, Inc.
Interleukin‐5 mRNA in three T‐cell lymphomas with eosinophilia
Authors: Samoszuk Michael , Ramzi Eiman , Cooper Dennis L.
Published: February 2007

The objective of this controlled pilot study was to determine if mRNA coding for interleukin‐5 (IL‐5), a cytokine that promotes eosinophil differentiation, growth, and migration, could be detected in three T‐cell lymphomas that were infiltrated extensively by eosinophils. To detect mRNA coding for IL‐5, we performed an RNA polymerase chain reaction on mRNA extracted from three T‐cell lymphomas with eosinophilia and from 29 positive and negative validation controls. Using this procedure, we detected a 293‐base pair, IL‐5‐specific amplification product in the three cases of T‐cell lymphoma with eosinophilia and in 11 of 12 positive validation controls, including 10 cases of Hodgkin's disease with eosinophilia. IL‐5 mRNA was not detectable in the 17 negative validation controls. This preliminary study suggests that IL‐5 mRNA is detectable by polymerase chain reaction in three cases of T‐cell lymphoma with eosinophilia. © 1993 Wiley‐Liss, Inc.
Pilot study of ascorbic acid for the treatment of refractory immune thrombocytopenic purpura
Authors: Jubelirer Steven J.
Published: February 2007

The treatment of corticosteroid‐ and/or splenectomy‐refractory Immune thrombocytopenic purpura (ITP) includes vinca alkaloids, immunosuppressives, Danazol, intravenous gammaglobulin, and α‐interferon. However, these treatments have often been associated with toxic side effects. Brox et al. (Br J Haematol 70:341–344, 1988) reported the efficacy of ascorbic acid in the treatment of ITP; the platelet count normalized in seven of 11 patients studied, and tolerance was excellent. However, other investigators have reported less impressive results. These conflicting reports prompted a pilot study of ascorbic acid in 12 patients with refractory ITP. Patients were given 2 g every morning for at least 10 weeks. All have received glucocorticoids, three had undergone splenectomy, and six received other treatments. The maximal increase in platelet count above baseline (i.e., the prestudy platelet count) achieved was <20,000 in 11 patients and 25,000 in one patient. Therapy was well tolerated, with only two patients complaining of dyspepsia. The results of this study suggest that ascorbic acid is not very effective in patients with refractory ITP.
Hematologic remission and cytogenetic improvement after treatment of stable‐phase chronic myelogenous leukemia with continuous infusion of low‐dose cytarabine
Authors: Robertson Michael J. , Tantravahi Ramana , Griffin James D. , Canellos George P. , Cannistra Stephen A.
Published: February 2007

Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15–30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)‐positive cells. Five patients demonstrating >90% Ph‐positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery‐operated syringe pump until the total leukocyte count reached 2500/μl or the platelet count reached 75,000/μl. A new cycle was begun when the total leukocyte count exceeded 4,000/μl and the platelet count exceeded 100,000/μl. The median duration of cytarabine administration per cycle was 29 days (range 15–72 days). Leukocytosis was readily controlled by low‐dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Phpositive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8–8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph‐positive marrow metaphases (range 10–53%) over 32 months. Cytarabine therapy was generally well‐tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low‐dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effects of this treatment on duration of stable phase and overall survival.