bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of carryover contamination in the detection of βS and βC genes by polymerase chain reaction
Authors: Wang Xiuhua , Chen Timothy , Kim David , Piomelli Sergio
Published: February 2007

As the polymerase chain reaction (PCR) process becomes a common tool in genetic diagnostic laboratories, prevention of carryover contamination from previous PCR amplifications has become an urgent topic. A PCR carryover prevention technique, utilizing deoxyuridine triphosphate (dUTP) and uracil DNA glycosylase (UDG), has been described recently. We report on its adaptation to a diagnostic system for detecting hemoglobin SS and SC diseases. Excellent amplification was achieved by increasing the dUTP and MgCl2 concentrations. dU‐containing DNA could be analyzed by restriction endonucleases to distinguish the βS from βA gene using Ddel, but two other restriction enzymes, Bsu36l (replacement for Mstll by the manufacturer) and Cvnl, can no longer be used. The dU‐containing PCR products retained their hybridization specificity with allele‐specific oligonucleotide (ASO) probes for the βA, βS, and βC genes. The PCR carryover prevention technique is easy to use and takes only 20 additional minutes. It should be extremely useful to genetic diagnostic laboratories where PCR is repeated daily and carryover contamination may thus lead to misdiagnoses. © 1992 Wiley‐Liss, Inc.
Clonality of cold agglutinins in patients with hemolytic anemia: An analysis by high‐resolution two‐dimensional gel electrophoresis
Authors: Tissot Jean‐Daniel , Clément François , Schifferli Jüirg A. , Frei Philippe C. , Hochstrasser Denis F. , Schneider Philippe
Published: February 2007

High‐resolution two‐dimensional gel electrophoresis (2‐DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B‐cell disorder. The electrophoretograms of their plasma showed evident alterations of the “normal” protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2‐DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from “parainfectious” CA. © 1992 Wiley‐Liss, Inc.
Coincidental finding of May‐Hegglin anomaly in a patient with end‐stage renal failure
Authors: Nel N. , van Rensburg B. W. J , Plessis Lizette Du , Potgieter C. D. , Stevens K.
Published: February 2007

We present two cases of May‐Hegglin anomaly incidentally discovered in a patient and his brother during investigation of the patient for end‐stage renal failure and workup for renal transplantation. Routine laboratory tests were performed and included a basically normal clotting profile. Ultrastructural studies of the May‐Hegglin inclusions proved diagnostic, findings were compared with those of two similar granulocyte inclusion bodies, and nomenclature discrepancies that still exist in most references are again emphasized. The finding of the May‐Hegglin anomaly in our patient appears to be incidental to the underlying renal disease. A successful renal transplant has been carried out in this patient.

We now report on a patient and his brother in which the MHA was discovered during workup of the patient for end‐stage renal failure and renal transplantation. No association between the underlying renal disease and the MHA could be demonstrated. © 1992 Wiley‐Liss, Inc.
Ifosfamide in plasma cell leukemia: A report of two cases and review of the literature
Authors: Malhotra Hemant , Dhabhar Boman N. , Saikia Tapan K. , Gopal Ramkrishnan , Nadkarni Kanchan S. , Nair Chandrika N. , Advani Suresh H.
Published: February 2007

We report two patients with primary plasma cell leukemia (PCL) treated with a single agent, ifosfamide. One patient had a total disappearance of plasma cells (PC) from the peripheral blood and the bone marrow and disappearance of the myeloma protein, is disease free 8 months after completion of treatment, and alive 14 months after diagnosis. The second patient had a partial response with persistence of plasma cells in the bone marrow lasting 7 months, after which she had a frank relapse of the disease. We suggest that ifosfamide may be an active agent in plasma cell malignancies and needs further evaluation in multiple myeloma. © 1992 Wiley‐Liss, Inc.
Secondary T‐cell lymphoma in the setting of nodular lymphocyte predominance Hodgkin's disease
Authors: Tefferi A. , Wiltsie J. C. , Kurtin P. J.
Published: February 2007

Lymphocyte predominance Hodgkin's disease (LPHD) can be histogically subdivided into a nodular and diffuse variety. The two subtypes differ in immunophenotypic characteristics but have a similar long‐term clinical outcome. Nodular LPHD has immunophenotypic and histological characteristics suggestive of a B‐cell derived neoplastic process. Nodular LPHD is associated with an increased risk of secondary large cell lymphoma (LCL). Gene rearrangement studies in some of these cases have revealed a B‐cell clonal process, further supporting the association between nodular LPHD and the B‐cell system. In addition, it has been suggested that the apparent secondary LCL, at least in some cases, may represent a histologic progression of nodular LPHD. We report a unique case of T‐cell lymphoma, confirmed by T‐cell receptor gene rearrangement studies, which developed in the setting of nodular LPHD. Our observation demonstrates that the association of nodular LPHD and LCL is complex and that LCL developing in the context of nodular LPHD may be an independent secondary process sometimes involving T‐cell lymphomas. © 1992 Wiley‐Liss, Inc.
Cyclosporine and prednisone therapy for pure red cell aplasia in patients with chronic lymphocytic leukemia
Authors: Chikkappa G. , Pasquale D. , Zarrabi M. H. , Weiler R. J. , Divakara M. , Tsan M. F.
Published: February 2007

We describe the characteristics of response to treatment with cyclosporine (CYA) plus prednisone in seven episodes of pure red cell aplasia (PRCA) in four patients with B cell chronic lymphocytic leukemia (CLL). Fourteen episodes of PRCA occurred in four patients with CLL. Eleven episodes were treated with conventional therapies which included an alkylating agent and prednisone. Four episodes that failed to respond to conventional therapies and an additional three episodes were treated with CYA and prednisone. Six of the seven episodes, including three of four which had failed conventional therapies, responded to CYA plus prednisone compared with six of eleven episodes treated with conventional therapies. Response to CYA and prednisone occurred without a reduction in leukemic mass. In contrast, PRCA remission did not occur until after leukemic mass reduction in three of four patients treated successfully with conventional therapies. Time to response was shorter (14 ± 3 days) with CYA plus prednisone than with conventional therapies (154 ± 97 days) in three of four patients. These results indicate that CYA plus prednisone is an effective therapy for the induction of remission from PRCA in patients with CLL. © 1992 Wiley‐Liss, Inc.
Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the united states: Comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood‐transfusion recipients with AIDS
Authors: Holman Robert C. , Clarke Matthew J. , Evatt Bruce L. , Chorba Terence L.
Published: February 2007

From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and ≧30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS. © 1992 Wiley‐Liss, Inc.
Recombinant interferon‐α2A as maintenance treatment for patients with advanced stage chronic lymphocytic leukemia responding to chemotherapy
Authors: Ferrara Felicetto , Rametta Vincenzo , Mele Giuseppina , Antinolfi Iolanda , Mettivier Vincenzo , Cimino Renato
Published: February 2007

Forty‐five patients suffering from advanced B‐CLL were randomized to receive interferon‐α (IFNα) or no treatment after achieving complete remission or partial response, following a chemotherapy protocol called MINa. The two groups were fully comparable in terms of clinical characteristics and level of response obtained by chemotherapy. IFNα was given at a dose of 3 megaunits three times a week intramuscularly for 1 year. The IFN‐treated patient group showed a significantly longer duration of response and a less frequent incidence of infections as compared to the no treatment group. A minority of patients who had had partial response to chemotherapy obtained complete remission while on therapy with IFNα. Toxicity was mild and patient compliance was excellent. We conclude that IFNα may have a role as maintenance therapy in CLL for patients responding to chemotherapy. © 1992 Wiley‐Liss, Inc.
Coexistence of congenital afibrinogenemia and protein c deficiency in a patient
Authors: Hanano Masaharu , Takahashi Hoyu , Shibata Akira , Itoh Masakazu
Published: February 2007

A rare association of congenital afibrinogenemia and hereditary protein C deficiency is described in a 37‐year‐old female who suffered from ischemic necrosis in the left first toe. The diagnosis of afibrinogenemia was assessed by the absence of fibrinogen in clotting and immunological assays. The diagnosis of hereditary heterozygous type I protein C deficiency was based on the evidence of proportional decreases of activity and antigen of plasma protein C in the propositus, her mother, and two maternal aunts. © 1992 Wiley‐Liss, Inc.
Inefficacy of extracorporeal photochemotherapy in the treatment of B‐Cell chronic lymphocytic leukemia: Preliminary results
Authors: Wieselthier Janet S. , Japowicz Mary C. , Rothstein Thomas L. , Yu Thomas L. , Anderson Tom , Koh Howard K.
Published: February 2007

Because extracorporeal photopheresis has been shown to be clinically effective in Sezary syndrome, a disease characterized by a circulating malignant clone, we initiated a pilot study of its use in B‐cell chronic lymphocytic leukemia (B‐CLL) to see if it could be similarly effective. We treated three patients with Rai stage III and IV B‐CLL with photopheresis (3 consecutive days a week every 3 weeks) and followed serial clinical and immunologic parameters. While we noted no major toxicity, there was neither clinical response to treatment nor marked improvement in white counts or mitogen assays. We conclude that photopheresis was not effective in inducing remission in this pilot study of advanced stage B‐CLL patients. © 1992 Wiley‐Liss, Inc.
Effectiveness of high‐dose intravenous immunoglobulin in a case of acquired von willebrand syndrome with chronic melena not responsive to desmopressin and factor VIII concentrate
Authors: Castaman Giancarlo , Tosetto Alberto , Rodeghiero Francesco
Published: February 2007

A patient with benign monoclonal lgG lambda paraproteinemia, acquired von Willebrand syndrome (AVWS), and chronic melena successfully responding to high‐dose intravenous immunoglobulin (lvlg) is reported. Coagulation parameters at admission were APTT (ratio) 1.68; VIII:C 11 IU/dL; vWF:Ag 7 IU/dL: Ricof <3 IU/dl. RIPA was >1.8 mg/ml, and bleeding time (BT) was prolonged (18 min). No evidence for an in vitro inhibitor against the VIII/vWF complex was observed. VIII/vWF measurements showed a short‐lived increase after both DDAVP and Hemate P, and BT was transiently normalized. After intravenous lg (1 g/kg for 2 days), VIII/vWF measurements, hemostatic parameters and multimeric pattern were completely corrected (VIII/C 106 IU/dl, vWF:Ag 168 IU/dl, RiC of 147 IU/dl, APTT ratio 0.89, BT 5′), with a return to pre‐infusion values after 15 days. Hemoccult test became negative and packed red cell transfusions, of which 130 units were administered during the last year, were no longer required. After 18 months the patient is on maintenance treatment with repeated courses of Ig, at 3 to 4‐week intervals based on VIII/vWF and BT monitoring. © 1992 Wiley‐Liss, Inc.
Dyserythropoiesis in iron‐deficiency anemia: Ultrastructural reassessment
Authors: Rozman Maria , Masat Teresa , Feliu Evarist , Rozman Ciril
Published: February 2007

Iron deficiency is usually included among the causes of acquired dyserythropoiesis. This concept was derived mainly from light microscopic studies. To reassess such a notion at ultrastructural level, a transmission electron microscopic evaluation of bone marrow was performed in seven patients with iron‐deficiency anemia. In contrast to the widely accepted concept, derived from light microscopic studies, only a small proportion (2–4%, not different from controls) of erythroblasts displayed some of the features of nuclear dyserythropoiesis. On the contrary, when examining the cytoplasm, we found a significantly increased number of void ropheocytotic vesicles in the majority of late erythroblasts as compared to controls (P < 0.001). This feature may be considered as an ultrastructural marker of iron deficiency and is consistent with the present knowledge on transferrin‐mediated delivery of iron to the cell. © 1992 Wiley‐Liss, Inc.
Human Lyb‐2 homolog CD72 is a marker for progenitor B‐cell leukemias
Authors: Schwarting Roland , Castello Roberto , Moldenhauer Gerhard , Pezzutto Antonio , Dörken Bernd , Hoegen Llka Von , Parnes Jane R. , Ludwig Wolf‐Dieter
Published: February 2007

S‐HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb‐2). Under nonreducing conditions, S‐HCL 2 monoclonal antibody (mAb) precipitates a glycoprotein of 80–86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa, with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal and malignant tissues is different from expression of all other previously described human B‐cell antigens. In peripheral blood and bone marrow, the antigen appears to be present on all B lymphocytes, with the exception of plasma cells. In tissue, immunohistochemical staining revealed positivity for all known B‐cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also. Among 83 malignant non‐Hodgkin's lymphomas examined by immunohistochemistry (alkaline phosphatase anti‐alkaline phosphatase technique), all 54 B‐cell lymphomas, including precursor B‐cell lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic leukemias, and hairy cell leukemias, were CD72 positive, but no T‐cell lymphomas were. Flow cytometry study of more than 80 mainly acute leukemias (52 B‐cell leukemias) showed reactivity with S‐HCL 2 mAb over the full range of B‐cell differentiation. In particular, very early B cells in cytoplasmic Ig (clg)‐negative, CD19‐positive prepre‐B‐cell leukemias and hybrid leukemias (mixed myeloid and B‐cell type) were consistently positive for CD72 on the cell surface. Therefore, CD72 may become an important marker for progenitor B‐cell leukemias. © 1992 Wiley‐Liss, Inc.
Pseudoxanthoma elasticum‐like skin lesions and angioid streaks in β‐thalassemia
Authors: Aessopos Athanasios , Savvides Panayotis , Stamatelos George , Tassiopoulos Thomas , Kaklamanis Phaedon , Fessas Phaedon , Rombos Loannis , Karagiorga Markisia
Published: February 2007

One hundred patients with homozygous or doubly heterozygous β‐thalassemia (62 with the major form and 38 with β‐thalassemia intermedia) were examined for signs of Pseudoxanthoma elasticum (PXE). Diagnostic skin lesions were found in 16 patients with either form of the basic disease. Twenty percent of all patients had angioid streaks (AS); both PXE skin lesions and AS were found in 10% of the patients; in all, 26% had either one or both of these manifestations. A positive correlation was found between the presence of one or both types of lesion and age of the patients (P = 0.032); there were no differences as regards ferritin and hematocrit levels, number of transfused units, chelation therapy, and splenic status between patients with PXE/AS findings and those without. The pathogenesis of these connective tissue manifestations at such a high frequency in β‐thalassemia is not clear; the possibilities of it's being acquired or inherited are discussed, the former being considered to be the more economical interpretation. © 1992 Wiley‐Liss, Inc.
IgD myeloma presenting as a testicular tumor: Establishment and characterization of an IgD‐secreting myeloma cell line
Authors: Ishii Kazuyoshi , Yamato Kenji , Kubonishi Ichiro , Taguchi Hirokuni , Ohtsuki Yuji , Miyoshi Isao
Published: February 2007

A 72‐year‐old man presented with a left testicular tumor and underwent orchiectomy. The tumor was massively infiltrated with myeloma cells bearing monoclonal cytoplasmic IgDλ. Three months after orchiectomy, he developed huge abdominal masses and subsequently ascites containing numerous myeloma cells. An IgD‐secreting myeloma cell line, designated delta‐47, was established from the ascites. This cell line expressed CD4 and CD38, but lacked Fc and complement receptors, surface immunoglobulin, CD19, HLA‐DR, and PCA‐1. CD30 was detected on the cultured cells but not on the ascites tumor cells. Delta‐47 cells secreted the same immunoglobulin (IgDλ) as was found in the patient's serum. The light chain had a molecular weight of 35 kD which was larger than that of the normal light chain. Chromosome analysis of delta‐47 revealed an aneuploid karyotype with complex abnormalities including 1q+, 2p+, and 14q+. To our knowledge, this is the only IgD‐secreting myeloma cell line and would provide a useful tool for the study of IgD production and IgD myeloma. © 1992 Wiley‐Liss, Inc.
Relationship of plasma alpha tocopherol to index of clinical severity in individuals with sickle cell anemia
Authors: Phillips George , Tangney Christine C.
Published: February 2007

Several parameters of micronutrition related to antioxidant activity are reduced in individuals with sickle cell anemia (SCA). The data presented here suggest that vitamin E, specifically alpha tocopherol, has a significant correlation (r = –0.38,P< 0.04) with a retrospective survey of clinical events and a significant correlation with a prospective survey of clinical events (r = –0.42,P< 0.03). The survey of clinical events score takes into account important vaso‐occlusive manifestations in SCA. Differences in plasma vitamin E levels explained about 15% of the variability in the clinical manifestations of SCA in the population studied. Previously reported data from our lab suggests that the differences in alpha tocopherol levels are not related to dietary intake. Vitamin E may play an important role in modulating the ability of sickle hemoglobin containing erythrocytes to produce vaso‐occlusion. Alternatively, it may simply be a marker of disease activity. Studies are ongoing at our center to determine if the relationship of alpha tocopherol to clinical events is causal. © 1992 Wiley‐Liss, Inc.
Essential thrombocythemia in pregnancy: Platelet count and pregnancy outcome
Authors: Chow Eudora Y. , Haley Lawrence P. , Vickars Linda M.
Published: February 2007

We report our experience of 4 successful pregnancies (including a pair of twins) in 3 women who have essential thrombocythemia (ET). All of the patients had a significant fall in platelet count (>20% of non‐pregnant state) during the course of the pregnancy. A review of the literature and our own experience suggests that the degree of platelet count reduction may be correlated with pregnancy outcome. Close monitoring of the platelet count is useful in the management of these cases. © 1992 Wiley‐Liss, Inc.
Interleukin‐2 production by primary adult T cell leukemia tumor cells is macrophage dependent
Authors: Arima Naomichi , Daitoku Yasuhisa , Hidakia Shiroh , Matsushita Kakushi , Ohtsubo Hideo , Fukumori Junko , Tanaka Hiromitsu , Yamamoto Yusei , Fujimoto Kouji , Onoue Kaoru
Published: February 2007

We have investigated the cellular requirements for IL‐2 production by autocrine proliferating tumor cells from four patients with adult T cell leukemia (ATL). Cultures of these ATL cells both produced endogenous IL‐2 protein in the absence of added mitogen and proliferated at higher levels when exogenous recombinant IL‐2 was added. Depletion of macrophages in the tumor cell cultures resulted in a sharp decline in tumor cell IL‐2 production, while re‐addition of macrophages reconstituted this response. Macrophage‐derived factors including IL‐6 and IL‐1 also reconstituted IL‐2 production in these macrophage depleted cultures. These results raise the possibility that macrophages may play a central role in HTLV‐I mediated immortalization of T cells. © 1992 Wiley‐Liss, Inc.
Clinical course and molecular characterization of a compound heterozygote for sickle hemoglobin and hemoglobin kenya
Authors: Waye John S. , Chui David H. K. , Cai Shi‐Ping , Eng Barry , Francombe William H.
Published: February 2007

We describe a 25‐year‐old black woman who presented with a long history of anemia requiring transfusions during childhood and adolescence. Molecular analysis revealed her to be a compound heterozygote for the sickle mutation and the ∼22.7 kb deletion associated with hemoglobin Kenya. This patient's clinical course was more severe than previously reported for the Hb S/Hb Kenya genotype, a probable consequence of concomitant iron deficiency. © 1992 Wiley‐Liss, Inc.
Defining the architecture of the red blood cell membrane: Newer biophysical approaches
Authors: Shohet Stephen B. , Bicknese Stephen E.
Published: February 2007

For many years the red cell membrane has served as an extraordinarily valuable model for membrane structure and function. During the past 2 decades, the biochemical concept of the membrane skeleton was established, and, with the help of electron microscopy, a partial depiction of this structure evolved. Newer biophysical approaches designed to measure distances between various components of membrane skeleton as well as distances between the membrane skeleton and the overlying bilayer should now help to define this structure more realistically. Fluorescence resonance energy transfer, single photon radioluminescence, and total internal reflectance are three biophysical techniques that will enable us to measure such distances over a substantial range, which extends from a few Angstroms to ∼2 μm. The ability to make such measurements in intact cells and in fully hydrated, undenatured membrane preparations should add a new dimension to our understanding of the structure of the red cell membrane. © 1993 Wiley‐Liss, Inc.
Mechanism of red blood cell aging: Relationship of cell density and cell age
Authors: Piomelli Sergio , Seaman Carol
Published: February 2007

The human red cell has a life span of 120 days. The mechanism that determines cell removal from the circulation with such precision remains unknown. Most studies of red cell aging have been based on analysis of cells of progressively increasing age separated by density. The relationship between red cell age and density has been recently challenged, and the hypothesis has been put forward that cell death is not the result of a progressive deterioration of essential cell constituents. This theory was based on preliminary observations in transient erythroblastopenia of childhood, which could not later be confirmed. When the relationship between cell aging and increasing density is critically reviewed, it appears to be based on firm experimental evidence, confirmed by in vivo demonstration of decreasing survival of cells of increasing age. Analysis of studies using buoyant density gradients reveals that this technique can easily distinguish the single exponential slope of decline for those cell components that change progressively throughout the red cell life span from the biphasic decline of those that decrease drastically at the reticulocyte‐mature red cell transition. The view that the aging of the red cell and its removal from the circulation result from a progressive series of events during the 120 days of its life span appears to be the most consistent with the available data. Density separation, validated by much experimental evidence, remains a most useful technique for the study of the mechanism of aging of the red cell. © 1993 Wiley‐Liss, Inc.
Cobalamin absorption and hematologic status after two types of gastric surgery for obesity
Authors: Yale Charles E. , Gohdes Paul N. , Schilling Robert F.
Published: February 2007

A series of morbidly obese patients was treated surgically with a gastric bypass, and a subsequent series received a vertical banded gastroplasty.

To compare some of the nutritional effects of these two procedures we measured serum vitamin B12 levels, absorption of food vitamin B12, frequency of microcytosis of erythrocytes, and frequency of anemia at one or more years after surgery.

Patients with a gastric bypass showed greater weight loss, a greater frequency of microcytosis and anemia, more frequent subnormal serum levels of vitamin B12, and impressive failure to absorb food vitamin B12. Boiling the food containing vitamin B12 led to increased absorption. © 1993 Wiley‐Liss, Inc.
Some properties of hemoglobin A2
Authors: Ranney Helen M. , Lam Ruby , Rosenberg Gwen
Published: February 2007

While no significant physiologic function of hemoglobin A2 (Hb A2), the minor basic component of human hemoglobin, has been recognized, only its oxygen equilibria have been studied in detail. Since hemoglobin A2 and its oxidative denaturation product, hemichrome A2, bind to the red cell membrane, particularly to band 3, to a greater extent than do Hb A or hemichrome A, some of the properties of Hb A2 that might influence hemoglobin‐membrane association were examined. Hemoglobin A2 exhibited slightly increased susceptibility to autoxidation to methemoglobin. No differences were noted between methemoglobins A and A2, including the rates of enzymatic reduction and stability of the heme‐globin linkage. Oxyhemoglobin A2 had a slightly lower solubility in phosphate buffer than did hemoglobin A. While the hemichromes (prepared with phenylhydrazine) of hemoglobins A2 and A had the same optical spectra, the A2 hemichrome exhibited greater stability. It is suggested that the differences in products of oxidative denaturation may provide the basis for functional differences between hemoglobins A2 and A. © 1993 Wiley‐Liss, Inc.
Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia
Authors: Raza Azra , Preisler Harvey , Lampkin Beatrice , Lykins Joseph , Kukla Cathy , Gartside Peter , Sheikh Yasin , Yousuf Naveed , White Michael , Barcos Maurice , Bennett John , Browman George , Goldberg Jack , Grunwald Hans , Larson Richard , Vardiman James , Vogler Ralph
Published: February 2007

Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S‐phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti‐BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1–10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff‐) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3–4+ Diff+ as compared to Diff‐ (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long‐term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation. © 1993 Wiley‐Liss, Inc.
New assay for the rapid determination of plasma holotranscobalamin II levels: Preliminary evaluation in cancer patients
Authors: Vu Thu , Amin Jyoti , Ramos Mercedita , Flener Victoria , Vanyo Lori , Tisman Glenn
Published: February 2007

We describe a new and rapid assay for the measurement of plasma B12 bound to transco‐balamin II (holotranscobalamin II) using the property of adsorption of the polypeptides of apotranscobalamin II and holotranscobalamin II to the hydrophobic surface of microfine glass particles. Acid‐washed microfine glass was used to separate vitamin B12 bound to the glycoproteins transcobalamin I and transcobalamin III (haptocorrin or R binder) from that bound to transcobalamin II. Sephadex gel filtration separation of 57Co‐labelled vitamin B12 binders confirmed that >90% of holotranscobalamin II can be removed from plasma holohaptocorrin by adsorption to microfine glass particles. Since only holotrans‐cobalamin II is capable of delivering vitamin B12 to metabolizing cells, plasma holotrans‐cobalamin II content reflects the availability of B12 to cells. Use of this test in cancer patients undergoing either chemotherapy or radiation therapy revealed evidence of early negative B12 balance that in some instances was induced by the treatment itself. © 1993 Wiley‐Liss, Inc.
Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: Differences in cellular DNA content
Authors: Widell S. , Auer G. , Hast R. , Reizenstein P.
Published: February 2007

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS‐AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feul‐gen‐stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS‐AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; Dl) in each cell population was determined using a digital video‐based imageanalyzing system (CAS‐100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS‐AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit Dl was found both in immature and mature bone marrow cells. Patients with MDS‐AML had those of Dl values similar to normal controls. In consequence, a significantly reduced mean Dl was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS‐AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA‐DR expression, these data suggest biological differences between the two diseases. © 1993 Wiley‐Liss, Inc.
Successful bone marrow transplantation in children with severe aplastic anemia using HLA‐partially matched family donors
Authors: Locatelli Franco , Porta Fulvio , Zecca Marco , Pedrazzoli Paolo , Maccario Rita , Giani Simona , Vitale Vito , Martinetti Myriam , Mazzolari Evelina , Lanfranchi Arnalda , Nespoli Luigi , Bacigalupo Andrea , Severi Francesca
Published: February 2007

Bone marrow transplantation (BMT) using HLA‐partially matched family donors has produced disappointing results (25–30% of long‐term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA‐partially matched family donor. Both cases presented 2 first class HLA‐antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine‐arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine‐A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long‐lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA‐identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA‐identical donor. © 1993 Wiley‐Liss, Inc.
Three cases of familial hairy cell leukemia
Authors: Gramatovici Mirela , Bennett John M. , Hiscock Jeffrey G. , Grewal Kuljit S.
Published: February 2007

In a 10‐year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a “specific HLA antigen” and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia.

We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH: Cancer 65:319–321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR: Leuk Res 11:1027–1028, 1987). Based on these observations, we may conclude that a “specific HLA type,” A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia. © 1993 Wiley‐Liss, Inc.
Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia
Authors: Raza Azra , Preisler Harvey D. , Li Ya Qin , Larson Richard A. , Goldberg Jack , Browman George , Bennett John , Grunwald Hans , Vogler Ralph , Kukla Cathi
Published: February 2007

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)‐sensitive patients. Expression of c‐fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley‐Liss, Inc.
Antiphospholipid antibodies in sickle cell disease
Authors: Kucuk O. , Gilman‐Sachs A. , Beaman K. , Lis L. J. , Westerman M. P.
Published: February 2007

Antiphospholipid antibody formation can be induced in mice by phospholipid in a hexagonal II phase but not by phospholipid in a bilayer phase. Since sickle red cell membranes have increased hexagonal II phase content, we have measured serum antiphospholipid antibody levels in 25 patients with sickle cell disease to determine whether anti‐phospho‐lipid antibody may similarly be induced in these patients. Seventeen of the 25 patients (68%) had increased levels of antiphospholipid antibodies. Eleven patients (65%) had IgG and six each (35%) had IgM and IgA isotypes. Antiphosphatidylethanolamine, antiphos‐phatidylserine, antiphosphatidylinositol, and antiphosphatidic acid were the most frequently increased antibodies. The finding of increased antiphospholipid antibodies in these patients is compatible with the concept that antiphospholipid antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in the red cells of patients with sickle cell disease. © 1993 Wiley‐Liss, Inc.
Factor V inhibitor in thrombosis
Authors: Kapur Ashok , Kelsey Paul R. , Isaacs Peter E. T.
Published: February 2007

A 68‐year‐old previously well woman developed sudden onset of limb gangrene in association with liver dysfunction. An immediately acting inhibitor to factor V with some of the features of lupus anticoagulant was demonstrated. The patient required limb amputation within 2 weeks and activity of the anticoagulant seemed to be on the decline 6 months later. © 1993 Wiley‐Liss, Inc.
Acquired immunodeficiency syndrome presenting as marrow cryptococcosis
Authors: Wong K. F. , Ma S. K. , Chan J. K. C. , Lam K. W.
Published: February 2007

Disseminated cryptococcal infection is an uncommon initial manifestation in patients with the acquired immunodeficiency syndrome. The most common sites of involvement by cryptococci are the central nervous system and the lungs, and involvement of the marrow is rare. There are few descriptions in the literature on the cytologic findings of marrow cryptococcosis. We report a patient with disseminated cryptococcosis in which cytologic examination of the marrow provides the first clue to the diagnosis. © 1993 Wiley‐Liss, Inc.
Dysfunctional platelet glycoprotein IIb/IIIa associated with a platelet release defect: A family study
Authors: Kamiyama Mikio , Arkel Yale S. , Lynch Jean , Chen Karen , Kunicki Jan
Published: February 2007

We are reporting on a 36‐year‐old white female with a bleeding history attributed to dysfunctional platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and a coexisting platelet release defect. Platelet aggregation studies (PAS) revealed markedly diminished to absent responses to ADP, epinephrine, collagen and arachidonic acid; the ristocetin response was normal. ATP content was normal with poor release to the agonists as measured by luminescent technique. DDAVP infusion shortened bleeding time from 13.5 min to 8.0 and 12 min (at 1 and 2 hours). Flow cytometry and immunoblotting revealed normal amounts of GPIIb and diminished GPIIIa (50% of control). Using a previously reported ELISA which measures the binding of GPIIb/IIIa to immobilized fibrinogen, the patient's platelet extract showed no binding to fibrinogen. Both the father and mother were found to have decreased PAS responses and normal amounts of GPIIb/IIIa determined by both Western blot and flow cytometry. However, the ELISA showed decreased binding of their GPIIb/IIIa to fibrinogen (71% and 62% as compared to controls, respectively). The patient's dysfunctional fibrinogen receptor was clearly demonstrated by the ELISA. The parents had moderately reduced GPIIb/IIIa function in this assay, but they did not demonstrate a reduced GPIIIa as was noted in the patient. The parents' PAS indicated a platelet release defect. These findings suggest an inherited platelet release defect and a dysfunctional GPIIIa. The partial response to DDAVP would be compatible with the presence of a platelet release defect. © 1993 Wiley‐Liss, Inc.
New translocation involving homologous chromosome 3 in acute myelogenous leukemia (M2)
Authors: Verma Ram S. , da Costa Maria , Gogineni Swarna K. , Palermo Giuseppe
Published: February 2007

An apparent balanced translocation involving the long arms of homologous chromosomes is described for the first time in a patient with acute myelogenous leukemia (AML) (M2), i.e., 46, XY, t(3;3) (q21;q26). After reviewing the literature, it was noted that a breakpoint involving band 3q26 is a frequent anomaly in other translocations. Thus, we are tempted to hypothesize that 3q26 band may also play an important role in the pathogenesis of AML (M2). © 1993 Wiley‐Liss, Inc.
Serum levels of 2′, 5 oligoadenylate synthetase during interferon therapy in patients with B‐cell chronic lymphocytic leukemia
Authors: Musolino C. , Grosso P. , Alonci A. , Allegra A. , Orlando A. , Cincotta M. , Buda G. , Squadrito G.
Published: February 2007

We assayed 2′, 5 Oligoadenylate synthetase (2′5‐AS) activity in the serum of eight patients with B‐cell chronic lymphocytic leukemia (B‐CLL) who were undergoing therapy with alpha interferon (IFN). Mean pretreatment levels of 2′5‐AS were normal, but upon treatment the levels rose to higher than normal values. Moreover, the degree of enzyme induction in serum was significantly higher in CLL responders (P < 0.003) whereas no difference was found in non‐responders. The lack of serum 2′5‐AS induction in non‐responder patients might be related to unresponsiveness to treatment with IFN. These results seem to show that the measurement of serum levels of 2′5‐AS activity may be a useful tool in monitoring IFN treatment.
Desmopressin‐induced thrombocytopenia in type i platelet discordant von willebrand disease
Authors: Castaman Giancarlo , Rodeghiero Francesco , Lattuada Antonella , Mannucci Pier Mannuccio
Published: February 2007

Thrombocytopenia after desmopressin (DDAVP) infusion is usually observed in patients with type IIB von Willebrand disease (vWD). No other subtypes of vWD with thrombocytopenia after DDAVP have been reported so far. We describe here the occurrence of thrombocytopenia after DDAVP in a 39 year old male and his son with phenotypic characteristics of type I vWD, 'platelet discordant subtype.' After DDAVP, the abnormal ristocetin cofactor/von Willebrand factor antigen ratio in plasma was not corrected and the bleeding time remained markedly prolonged. Platelet count dropped 30 min after DDAVP (from 279 to 96 × 103/μL in the propositus and from 298 to 116 × 103/μL in his affected son) and returned to normal at 60 min. Platelet clumping was evident on peripheral blood smears obtained after infusion. These cases indicate that after DDAVP thrombocytopenia can occur in vWD other than type IIB.
Transfusion‐associated graft‐versus‐host disease in an immunocompetent patient following accidental injury
Authors: Kobayashi Hikaru , Kitano Kiyoshi , Kishi Etsuo , Hara Kenichi , Ishida Fumihiro , Saito Hiroshi , Ota Masao , Furuta Seiichi
Published: February 2007

We report a case of transfusion‐associated graft‐vs.‐host disease (TA‐GVHD) in a previously healthy, 58 year old Japanese man following an accidental injury. Despite intensive treatment, the patient died 22 days after the transfusion. Although many cases of fatal TA‐GVHD have been reported in immunocompetent patients, only two are known to have developed this disorder unrelated to a surgical procedure. This is the first such case to be confirmed by HLA typing. Our report suggests that TA‐GVHD can occur even in a healthy, immunocompetent recipient. Thus, it seems necessary to establish guidelines for the irradiation of cellular blood products before transfusion.
Acute thrombocytopenic purpura in an infant with cushing's syndrome: A case report
Authors: Magbool Gady M.
Published: February 2007

This paper describes the case of a female child who presented with severe thrombocytopenia and Cushing's syndrome. The underlying cause was found to be an adrenal cortical adenoma, removal of which was followed by complete recovery of both conditions. The pathogenesis of both presenting features in relation to the adrenal tumor is discussed.
Ph1‐chromosome positive acute lymphoblastic leukemia: Is t(9;22) the initial abnormality?
Authors: Aurer Igor , Sparkes Robert S. , Schiller Gary , Gale Robert Peter
Published: February 2007

We report a case of pre‐B‐cell acute lymphoblastic leukemia (ALL) with the Ph1‐chromosome, t(9;22) translocation and P190 associated BCR/ABL rearrangement. One cell with the Ph1‐chromosome and t(9;22) also had del(5q). Interestingly, another diploid cell with iso(17q) lacked the Ph1‐chromosome and t(9;22). This finding, similar to one reported in chronic myelogenous leukemia, is consistent with the possibility that abnormality manifest as chromosome instability antedates the Ph1‐chromosome and t(9;22) in some cases of Ph1‐chromosome positive acute leukemia.
Hypereosinophilic syndrome treated with α‐interferon and granulocyte colony‐stimulating factor but complicated by nephrotoxicity
Authors: Hansen Per Boye , Johnsen Hans E. , Hippe Erik
Published: February 2007

A 34‐year‐old male with hypereosinophilic syndrome (HES) and cardiac complications was treated with recombinant human α‐interferon (rhIFN) and recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) in the attempt to suppress the eosinophilic cell clones and stimulate the neutrophil myelopoiesis in the bone marrow, respectively. After 1 month of pretreatment with rhIFN, rhG‐CSF was administered daily for 22 days. Within a few days the combined treatment with rhIFN and rhG‐CSF was followed by a marked increase in absolute neutrophil count but complicated by abdominal pain and an increase in plasma creatinine and blood urea nitrogen. The renal failure persisted when rhIFN therapy was stopped but resolved after discontinuing rhG‐CSF. The pathogenesis of this reversible renal involvement needs further investigation. In that hematological improvement in vivo as well as in vitro followed the administration of rhIFN and rhG‐CSF, a role for combined therapy with these cytokines may be advocated. However, caution with regard to kidney function should be taken with this combination therapy.