bluuebunny/crossref_metadata_2025 huggingface dataset:
The infusion of anti‐rho‐(D) opsonized erythrocytes may be useful in the treatment of patients, splenectomized or not, with chronic, refractory autoimmune thrombocytopenic purpura—a prospective study
Authors: Ruiz‐Argüelles Guillermo J. , Apreza‐Molina Maria Guadalupe , Pérez‐Romano Beatriz , Ruiz‐Argüelles Alejandro
Published: February 2007

Six patients with chronic refractory autoimmune thrombocytopenic purpura (ATP) were treated with five doses of autologous red blood cells (RBCs) opsonized ex vivo with anti‐RhO‐(D) IgG. Increases in platelet counts were observed in all cases; complete responses requiring no further treatment—for periods of 8–72 months—were recorded in four patients, three of them splenectomized. The cost of the procedure was significantly lower than other 'Fc receptor (FcR) blockade' treatments.
Heterogeneous proliferative effect of tumor necrosis factor‐α and lymphotoxin on mitogen‐activated B cells from B‐chronic lymphocytic leukemia
Authors: Alvarez‐Mon M. , Garcia‐Suarez J. , Prieto A. , Manzano L. , Reyes E. , Lorences C. , Peraile G. , Jorda J. , Durantez A.
Published: February 2007

The proliferative effect of tumor necrosis factor‐α (TNF‐α) and lymphotoxin on B cells from patients with B‐chronic lymphocytic leukemia (B‐CLL) was studied. Fresh purified B‐CLL lymphocytes showed no proliferative response to either recombinant (r) TNF‐α or r‐lymphotoxin. However, after 'in vitro' activation of B‐CLL lymphocytes for 2 days with Staphylococcus aureus Cowan 1 (SAC), four of seven patients showed enhanced blastogenic response in the presence of either rTNF‐α or r‐Iymphotoxin. We also found that the proliferative response of SAC‐activated B‐CLL lymphocytes to the two cytokines was independent of that found in the presence of interleukin‐2. These results demonstrate that TNF‐α and lymphotoxin can heterogeneously support the proliferation of in vitro activated B cells from B‐CLL patients and may reflect the biological heterogeneity of B‐CLL disease.
Increase of hemoglobin A2 in human immunodeficiency virus‐1‐infected patients treated with zidovudine
Authors: Routy Jean‐Pierre , Monte Marc , Beaulieu Raymond , Toma Emil , St‐Pierre Line , Dumont Marc
Published: February 2007

We observed increased hemoglobin A2 (HbA2) levels in an asymptomatic human immunodeficiency virus‐1 (HIV1) patient with no previous history of β‐thalassemia. He was treated only with zidovudine (AZT). In an attempt to understand this observation, a retrospective study was initiated to determine whether mean HbA2 levels are higher in AZT‐treated patients than in subjects not receiving this drug and to assess if other hematologic alterations are associated with elevated HbA2. One hundred fifty‐one HIV‐positive cases were investigated; AZT was administered to 81 of them. The mean value of HbA2 was 0.032 (SD ±0.005) for the treated group vs. 0.027 (SD ±0.004) for the controls. This difference was highly significant (P < 0.001). Twenty‐four patients (31%) in the treated group had elevated HbA2 levels vs. none in the controls. Bone marrow toxicity seemed to be more significant in patients with heightened HbA2 values, and HbA2 levels did not increase with CDC clinical stage. We conclude that AZT may be linked to high HbA2 levels in some patients.
A simple, practical model for reducing alloimmunization in patients with sickle cell disease
Authors: Sosler Steven D. , Jilly Bernard J. , Saporito Catherine , Koshy Mabel
Published: February 2007

Patients with sickle cell disease (SCD) form immune alloantibodies more frequently than other transfused populations because red cells (RBCs) from white donors (with a higher incidence of certain Rh, Duffy, Kell, and Kidd blood group antigens) are transfused to black patients often lacking these antigens. We propose a model to reduce alloimmunization in patients with SCD by providing them with blood from only black random donors. Rationale is shown by examining calculations based on the phenotype E–, C–, Fy(a–), K–, and Jk(b–). There is a 7% probability that this phenotype belongs to a white donor, while there is a 93% probability that this phenotype belongs to a black donor. The probability of selecting blood from a black donor identical with the above phenotype for black recipients from an all black population and from a typical urban blood inventory population (90% white, 10% black) is 1/4 and 1/33, respectively. Therefore, an 8‐fold greater chance of selecting antigen non‐identical blood occurs if blood is obtained from a typical urban donor population as compared to a black population. Based on these calculations, alloimmunization can be reduced prospectively in patients with SCD by meeting their transfusion requirements with blood selected from random black blood donors.
Reactivation and dissemination of blastomycosis complicating hodgkin's disease: A case report and review of the literature
Authors: Winquist Eric W. , Walmsley Sharon L. , Berinstein Neil L.
Published: February 2007

Patients presenting with Hodgkin's disease (HD) may show lung involvement characterized by contiguous spread from ipsilateral hilar lymph nodes. Lung consolidation or noncontiguous pulmonary involvement makes an alternative diagnosis more likely. This report describes a patient with HD in whom concurrent pulmonary blastomycosis was recognized only after chemotherapy had started and dissemination had occurred. Although Blastomyces dermatitidis may behave as an opportunitist pathogen, there are no previous reports of blastomycosis in patients with HD. Undiagnosed active opportunistic infection at the time of diagnosis of HD may complicate staging as well as treatment. Biopsy of lung lesions with stain and culture for opportunistic pathogens should be considered in patients with newly diagnosed HD disease and atypical patterns of lung involvement.
Terminal acute myelogenous leukemia in a patient with congenital agranulocytosis
Authors: Wong Wing‐Yen , Williams Donald , Slovak Marilyn L. , Charak Bishan , Mazumder Amitabha , Snyder David , Powars Darleen R. , Brynes Russell K.
Published: February 2007

Congenital agranulocytosis terminating in acute myelogenous leukemia has been previously reported in only two cases of adolescent males. We describe the clinical and laboratory features of a 13‐year‐old male with congenital agranulocytosis, treated with G‐CSF with initial good neutrophil response, who subsequently developed acute myeloid leukemia. This rare complication may define a preleukemic subset of patients for whom G‐CSF therapy is ineffective. The diagnostic challenges of this case are presented.
A new α‐thalassemia‐2 deletion resulting in microcytosis and hypochromia and in vitro chain imbalance in the heterozygote
Authors: Indrak K. , Gu Y.‐C. , Novotny J. , Huisman T. H. J.
Published: February 2007

We have detected a novel α‐thalassemia‐2 with a large (18+ kb) deletion involving the α1‐and θ‐globin genes and the 3′ hypervariable region sequence. Unexpectedly, the heterozygote had a mild anemia with a marked microcytosis and hypochromia, and an in vitro α/β chain synthesis ratio of 0.62‐0.66. It is suggested that the deletion includes a sequence that is involved in the in cis regulation of the α2‐globin gene.
Ultrastructure of neutrophilic phagosome of autologous platelet in vivo in specific granule deficiency
Authors: Sakura Tohru , Murakami Hirokazu , Matsushima Takafumi , Tamura Jun'Ichi , Sawamura Morio , Tsuchiya Jun
Published: February 2007

The ultrastructure of neutrophilic phagosomes containing autologous platelets in vivo from a woman with specific granule deficiency is described. This phagosome formation was observed only when she had developed pneumonia due to Staphylococcus aureus. Therefore, the phenomenon might be induced by severe bacterial infection under an abnormal neutrophilic condition accompanied by specific granule deficiency.
Decreased erythropoietin responsiveness to iron deficiency anemia in the elderly
Authors: Nafziger Joëlle , Pailla Karine , Luciani Liliane , Andreux Jean‐Paul , Saint‐Jean Olivier , Casadevall Nicole
Published: February 2007

The prevalence of anemia in the elderly raises the question of an inappropriate secretion of erythropoietin in response to increased demands. Therefore, the serum erythropoietin concentration of elderly patients (74–95 years) with iron deficiency anemia was measured and compared to that of iron deficiency anemic adults (25–60 years). A lowered erythropoietin secretion in response to anemia was observed in elderly patients in comparison with adults. However, the serum erythropoietin of the anemic elderly was inversely correlated with hemoglobin levels as shown for the anemic adults. The progressive reduction of the renal function observed with aging could explain the decreased capacity of erythropoietin secretion in elderly patients.
Decreased affinity and number of transferrin receptors on erythroblasts in the anemia of rheumatoid arthritis
Authors: Feelders R. A. , Vreugdenhil G. , Van Dijk J. P. , Swaak A. J. G. , Van Eijk H. G.
Published: February 2007

In anemia of chronic disease (ACD) in rheumatoid arthritis (RA) a decreased iron uptake and transferrin binding by erythroblasts are postulated to play a pathophysiological role. To examine whether this is related to changes in transferrin receptor expression by erythroblasts, we studied bone marrow from 5 healthy controls, 5 nonanemic RA patients, and 9 RA patients with ACD. Bone marrow mononuclear cells were incubated with increasing concentrations of125I‐transferrin and specific binding data were analyzed by the method of Scatchard. The number of transferrin receptors on erythroblasts from RA patients with ACD was significantly lower as compared to nonanemic RA patients (P< .05) and controls (P< .02). The affinity of the transferrin receptor tended to be lower in ACD. These preliminary data may indicate that transferrin receptor expression by erythroblasts is impaired in ACD. Since the rate of erythroid iron uptake is mainly determined by the number of transferrin binding sites, this may explain a decrease in erythroblast iron availability in ACD in RA.
Azidothymidine(AZT)‐induced siderosis
Authors: Pollack Simeon , Weaver Janet
Published: February 2007

Azidothymidine(AZT) interferes with heme synthesis. This should upregulate the synthesis of transferrin receptors and increase the amount of iron taken up by the cell. We found a 50% increase in the iron content of liver and a 20% increase in the iron content of macrophages in AZT‐treated mice.
Megakaryoblastic transformation of polycythemia vera associated with hypercalcemia
Authors: Wong K. F. , Chan J. K. C. , Ma S. K. , Chu Y. C.
Published: February 2007

Leukemic transformation is not uncommon in polycythemia vera, particularly after treatment with chemotherapeutic agents. The leukemias that supervene are mostly of myeloid type but megakaryoblastic transformation is distinctly uncommon. We report a case of polycythemia vera terminating in megakaryoblastic leukemia with associated hypercalcemia.
Acute lymphoid leukemias following either a previous chronic myelogenous leukemia or myelodysplastic syndrome: Phenotypic and genomic differences
Authors: Hernández J. M. , Sánchez I. , González M. , Orfao A. , González‐Sarmiento R. , San Miguel J. F.
Published: February 2007

We have analyzed the immunological and genomic characteristics of the lymphoid blast cells present in secondary lymphoid leukemias following either a previous chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). Twenty‐one of 107 secondary leukemias analyzed displayed a lymphoid phenotype (15 after a CML and 6 after a MDS). Most of the lymphoid blast crises of CML (73%) correspond to pure lymphoid transformation, all of them having a common acute lymphoblastic leukemia (ALL) phenotype (CD10+). By contrast, in all MDS cases, lymphoid blast cells coexisted with another myeloid component (hybrid leukemias) and showed an early B phenotype. IgH and TCR‐γ gene rearrangements were detected in the CML‐lymphoid blast crisis (86% of cases) more frequently than in the MDS transformations (33%). The TCR‐β gene was in germ line configuration in all cases while TCR‐δ gene rearrangements were detected in four cases, all of them corresponding to a previous diagnosis of CML. These results show the existence of both immunophenotypic and genomic differences between the lymphoid transformations of either CML or MDS, which could reflect differences at the stage of maturation of the target cell in these transformations.
Relief of intractable pruritus in polycythemia vera with recombinant interferon alfa
Authors: Finelli Carlo , Gugliotta Luigi , Gamberi Barbara , Vianelli Nicola , Visani Giuseppe , Tura Sante
Published: February 2007

Following reports that recombinant interferon alfa (rIFNα), besides inducing clinical and hematologic remission in polycythemia Vera (PV), can also resolve intractable pruritus, we used rIFNα to treat 13 PV patients complaining of severe pruritus refractory to conventional treatment (venesection and/or cytostatics). rFNα was administered intramuscularly three times a week at a dosage of 3.0 × 106 U. Eight patients (61.5%) reported a ± 50% reduction of pruritus, which occurred within 2–8 weeks from the start of rIFNα treatment, leading to a substantial improvement in their quality of life. Three patients had to stop rIFNα within the first month of therapy because of unacceptable side effects. Thus rIFNα seems to be capable of providing considerable relief of otherwise intractable pruritus in a good proportion of PV patients.
Malignant lymphoma originating from the earliest T‐lineage precursor cell
Authors: Hashimoto Yoshie , Yasukawa Masaki , Takada Kiyonori , Hato Takaaki , Fujita Shigeru
Published: February 2007

The earliest T‐lineage precursor cells with a CD3–CD4+CDB– phenotype and germlinestate T‐cell receptor (TCR) genes have recently been identified in the murine thymus. We report a case of malignant lymphoma that was considered to originate from the human counterpart of this newly defined murine T‐cell population. The surface phenotype of the lymphoma cells was CD2+CD3–CD4+CD8–CD25–CD34+CD44+HLA‐DR+. TCR‐β, ‐γ, ‐δ chain genes and immunoglobulin heavy and light chain genes were all in a germline state. These characteristics were markedly similar to those of the murine earliest T‐lineage precursor cells. The present case thus strongly suggests the presence of the human counterpart of this novel murine T‐cell population.
T lymphocytes from autoimmune thrombocytopenic purpura show a defective activation and proliferation after cytoplasmic membrane and intracytoplasmic mitogenic signals
Authors: Garcia‐Suarez J. , Prieto A. , Manzano L. , Reyes E. , Molto L. , Alvarez‐Mon M.
Published: February 2007

T lymphocyte activation and proliferation are complex cellular processes involving membrane and cytoplasmatic molecules as well as the secretion and response to cytokines, mainly interleukin 2. There is increasing evidence that autoimmune thrombocytopenic purpura (ATP) is associated with an alteration of the regulation of the immune system. The blastogenic response of purified T lymphocytes to mitogens that interact with membrane molecules (phytohemaglutinin, anti‐CD3 monoclonal antibody) and with intracytoplasmic protein kinase C (phorbol myristate acetate) has been investigated in 22 ATP patients and 18 healthy controls. After the signal given by the three different mitogens [3H]‐thymidine uptake in T lymphocytes from ATP patients was found to be significantly decreased with respect to that found in healthy controls under similar experimental conditions (P < 0.05). Analysis of the cell cycle progression in these T lymphocytes from ATP patients, showed a significantly diminished percentage of cells in S‐phase after PHA stimulation (P < 0.05). The percentage of CD3+ cells in the CD2+ lymphocyte preparations was significantly decreased in ATP patients relative to healthy controls (P < 0.05). But there was no significant correlation between this percentage and the blastogenic response to PHA in the CD2+ cellular preparations from both groups of subjects. No significant differences were found in the percentages of CD4+ and CD8+ cells. These data indicate that the impaired blastogenic response of T lymphocytes from ATP patients may be ascribed to an intrinsic defect in these T cells. This defective proliferative response of T lymphocytes from ATP patients cannot be ascribed to either defective interleukin 2 production or receptor expression which were both similar to those of healthy controls (P > 0.05). And, the presence of saturating amounts of exogenous interleukin 2 did not normalize the defective proliferative response the mitogenic signals on the part of T lymphocytes from ATP patients. We conclude that T lymphocytes from ATP patients have a defective proliferative response to membrane and intracytoplasmatic mitogenic signals. © 1993 Wiley‐Liss, Inc.
Significant hyponatremia following DDAVP administration in a healthy adult
Authors: Humphries John E. , Siragy Helmy
Published: February 2007

We report the development of significant hyponatremia (121 mEq/L) following three daily intravenous doses of desmopressin acetate (DDAVP; 18 μg; 0.3 μg/kg) in a healthy adult with moderate von Willebrand's disease. Previous reports suggest that clinically important hyponatremia due to DDAVP administration only occurs in the very young, those receiving hypotonic intravenous fluids or those given multiple frequent (e.g., every 8–12 hours) doses of DDAVP. None of these conditions was present in this case. Consideration should be given to monitoring serum sodium levels and fluid balance in patients receiving more than a single dose of DDAVP, even in the absence of previously reported risk factors for the development of hyponatremia. © 1993 Wiley‐Liss, Inc.
Detection of the (–SEA) double α‐globin gene deletion by a simple immunologic assay for embryonic ζ‐globin chains
Authors: Ireland James H. , Luo Hong‐Yuan , Chui David H. K. , Chu Berbie , Yuen Juliet , Hsia Y. Edward
Published: February 2007

Homozygous α‐thalassemia [α‐thal‐1], with loss of all four α‐globin genes, causes lethal hydrops fetalis. The most common mutation producing this syndrome is the Southeast Asian (–SEA) double α‐globin gene deletion. Erythrocytes from adults heterozygous for the (–SEA) deletion have minute amounts of embryonic ζ‐globin chains detectable by anti‐ζ‐globin monoclonal antibodies.

Among 225 peripheral blood samples tested by a simple anti‐ζ‐immunobinding tetra‐zolium dye test, 81 were positive and 144 were negative. The majority of subjects were of Filipino, Chinese, or Laotian ancestry. All 81 positive samples were confirmed by Bam HI digests and a ζ‐cDNA probe to have the (–SEA) mutation. The (–SEA) double α‐deletion was the only abnormality in 58. In the others, it was combined with α‐globin or β‐globin mutations, or coincidental iron deficiency. Four other samples from (–SEA) heterozygotes were negative by this immunologic assay.

Anti‐ζ negative samples included 78 deletions of the total α‐globin region, (–Tot), 23 single α‐globin deletions, and a variety of β‐globin mutations; 16 normocytic samples with normal α‐genes were also negative. Ten anti‐ζ positive and 25 anti‐ζ negative samples had benign triplicated ζ‐globin genes.

In this population, the sensitivity of this test was 95%; and specificity for the (–SEA) mutation was 100%. Anti‐ζ immunobinding testing provides rapid, simple, and reliable screening for the (–SEA) double α‐globin deletion, although it does not detect the (–Tot) total α‐deletions. © 1993 Wiley‐Liss, Inc.
106 depletion of WBC with CF‐2, a new leukocyte removal filter
Authors: Endo Yoshihiro , Tani Tohru , Yokota Tohru , Tsutamoto Yoshihiro , Kodama Masashi
Published: February 2007

A new leukocyte removal filter, Nipro CF‐2, was evaluated. A non‐woven polyester filter, gravity flow device that does not require priming and rinsing after use was developed to remove white blood cells from 400 ml of whole blood or concentrates of 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low WBC counts. To evaluate the efficiency of this filter, leukocyte counts were measured by flow cytometry using a Coulter EPICS‐C cytometer. After filtration through a CF‐2 filter, more than 99.9999% of WBCs were depleted from 6 of 17 samples. The mean value of WBC depletion was 99.9994%. The CF‐2 filter achieved nearly a million‐fold depletion of WBCs from whole blood concentrates. © 1993 Wiley‐Liss, Inc.
Simultaneous demonstration of the Philadelphia chromosome in T, B, and myeloid cells
Authors: Mackinney Archie A. , Clark Steven S. , Borcherding Wayne , Fizzotti Marco , Hong Richard
Published: February 2007

A patient presented with lymphoblastic lymphoma in lymph‐nodes and chronic myeloge‐nous leukemia (CML) in marrow and peripheral blood. All marrow and unstimulated peripheral blood cells contained the Philadelphia chromosome{t(9:22)}. Lymphoma cells were analyzed by flow cytometry and were identified as T cells (CD2+CD5+CD7+CD34+). All fresh lymphoma cells contained the t(9:22) translocation. Cultures of purified peripheral blood T and B cells and specifically stimulated NK cells revealed that 59% of the B cells, 10% of the NK cells, and none of the normal T cells contained the translocation. The lack of translocation in normal peripheral T cells is attributed to their long lifespan. No rearrangement of immunoglobulin or T cell receptor beta or gamma genes was found in either the leukemia or lymphoma cells. Analysis of the DNA from cryopreserved lymphoma biopsy showed clonal rearrangement within the common breakpoint cluster region of the bcr gene identical to the bcr rearrangement in DNA from leukemia blood cells. The data support the concept that T and B cells originate in the patient's totipotent stem cell from which the CML is also derived. © 1993 Wiley‐Liss, Inc.
Effects of sCD23 on proliferation of leukemic cells from a patient with chronic myelogenous leukemia during blast crisis
Authors: Morel F. , Delwail V. , Brizard A. , Meseri A. , Guilhot F. , Goube de Laforest P. , Lecron J. C.
Published: February 2007

The present study has attempted to further delineate the growth factor requirements of peripheral blasts of a patient with CML in acute phase. Phenotypic analysis of leukemic blasts from this patient before culture has shown a homogenous population of CD34+ cells at the onset of blast crisis. In the second and third samples the percentage of CD34+ DR+ blast cells decreased slightly and up to 32% of cells in the third sample expressed the CD19 antigen. Optimal proliferation of cells derived from the first sample required the presence of exogenous sCD23 and to a lesser extent IL7. The stimulatory effects of sCD23 and IL7 were clearly reduced 4 months later and no longer detected after 6 months. This variability in growth factor response along with disease progression may be related to phenotypic differentiation. There was no evidence for lymphoid or myeloid maturation after 4 days of liquid culture. Our results in conjunction with previous studies are in agreement with sCD23‐involvement in the complex control of proliferative processes at both normal and leukemic stages, demonstrating that cytokines are critical in determining CML cell proliferation. © 1993 Wiley‐Liss, Inc.
Amegakaryocytic thrombocytopenia with a positive direct Coombs' test
Authors: Koduri Prasad Rao
Published: February 2007

A 50‐year‐old previously well woman developed a sudden onset of ecchymoses and petechiae over the trunk and extremities and gum bleeding. There was no history of alcohol use or drug ingestion. Physical examination was normal except for the ecchymoses, purpuric rash, and gum bleeding. Complete blood count showed Hb 8.0 g/dl, leucocytes 10.9 × 109/L with a normal differential, platelets 8 × 109/L and reticulocytes, 4%. The bone marrow was normocellular and showed absence of megakaryocytes; there was normoblastic erythroid hyperplasia and the myelopoiesis was normal. The direct Coombs test result was positive. There was poor response to treatment with prednisone and bolus doses of vincristine. Therapy with danazol resulted in the complete normalization of the blood counts, and the patient remains well 32 months after diagnosis and is currently taking 100 mg danazol daily. © 1993 Wiley‐Liss, Inc.
Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia
Authors: Kamiyama Mikio , Yoshimura Yuichi , Chen Karen , Arkel Yale S.
Published: February 2007

We previously described an ELISA to measure the inhibition of platelet glycoprotein llb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti‐platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV‐related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV‐related ITP, whereas in non‐HIV ITP, inhibition was only partially due to CIC; anti‐platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV‐related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV‐seronegative ITP patients, the decrease or disappearance of anti‐platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti‐platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti‐platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti‐idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV‐seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count. © 1993 Wiley‐Liss, Inc.
Increased vascular endothelial cell markers in patients with disseminated intravascular coagulation
Authors: Wada Hideo , Minamikawa Kouzou , Wakita Yoshihiro , Nakase Tutomu , Kaneko Toshihiro , Ohiwa Michiaki , Tamaki Shigehisa , Deguchi Katsumi , Shirakawa Shigeru , Hayashi Tatsuya , Suzuki Koji
Published: February 2007

We examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor‐l (PAI‐I), tissue plasminogen activator (t‐PA), and von Willebrand factor, in 80 patients with disseminated intravascular coagulation (DIC). The levels of thrombin‐antithrombin III complex (TAT), plasmin‐α2 plasmin inhibitor complex (PIC) and FDP‐D‐dimer were significantly increased both before and after the onset of DIC, but were not correlated with organ failure or prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis than in those with good prognosis, and it was also lower in those with organ failure than in those without. Plasma TM, PAI‐I, and t‐PA levels were increased in DIC patients with organ failure or poor outcome, but were not significantly increased before the onset of DIC. We consider that the prognosis of patients with DIC might be related to organ failure or endothelial cell damage and that plasma levels of TM, PAI‐I, and t‐PA might be useful in the detection of these disorders and in assessing prognosis. A hypofibrinolytic state might enhance organ failure in patients with DIC. © 1993 Wiley‐Liss, Inc.
Phenotypic and genotypic characterization of Hodgkin's disease
Authors: Koduru P. R. K. , Susin M. , Schulman P. , Catell D. , Goh J. C. , Karp L. , Broome J. D.
Published: February 2007

Although a few studies have reported clonal cytogenetic changes in Hodgkin's disease (HD), their correlation with histologic groups is poorly defined. This is because of insufficient numbers of clonally abnormal cases ascertained in each of these studies, an inherent problem associated with the cytogenetic studies of HD. In this report we present results of pathologic, phenotypic, and genetic studies on 29 HD tumors consecutively ascertained by us and the results of a comprehensive analysis of the cytogenetic data available in the literature. In our series 75% of the tumors were positive for Epstein‐Barr virus (EBV) by polymerase chain reaction (PCR) assay. A higher frequency of EBV‐positive tumors showed clonal karyotypic abnormalities than the EBV‐negative tumors. Unlike the case in the previous reports, none of the 24 tumors studied by PCR showed the presence of t(14;18) (q32;q21)‐carrying cells. From the comprehensive analysis of the literature, we identified recurring nonrandom numerical changes, deletions, and chromosome breaks in HD. Some of these are associated either with nodular sclerosis or with mixed cellular histologies. A comparison of the pattern of these nonrandom cytogenetic changes in HD and those reported for non‐Hodgkin's lymphomas (NHL) identified common deletions and breaks between them. These common genetic lesions probably play a role in disease evolution. © 1993 Wiley‐Liss, Inc.
Anticoagulant activity of an anti‐β2‐glycoprotein I antibody is depentent on the presence of β2‐glycoprotein I
Authors: Matsuda Juzo , Gohchi Kengo , Tsukamoto Miyo , Saitoh Noriko , Asami Katsuhisa , Hashimoto Masakatsu
Published: February 2007

We studied whether or not an anti‐β2‐glycoprotein I antibody (aGPI) had lupus anticoagulant‐like activity, employing the diluted Russel viper venom time (dRVVT) and kaolin clotting time (KCT) as indices. aGPI prolonged the dRVVT and KCT of β2‐glycoprotein I (GPI)‐depleted normal plasma in the presence of extrinsic GPI. This prolongation of the dRVVT and KCT occurred immediately after the addition of aGPI and GPI, and was subsequently enhanced further in a time‐dependent manner. The GPI/aGPI combinaion was judged to have lupus anticoagulant‐like activity by the dRVVT‐platelet neutralization test, but this was not confirmed by a lupus anticoagulant‐specific test, i.e., the activated partial prothrombin time (APTT) using hexagonal phospholipid. From these findings, it can be concluded that aGPI has lupus anticoagulant‐like activity in the presence of GPI, but may be a partially or considerably different antiphospholipid antibody from lupus anticoagulant. Further investigations may be needed to clarify this point. © 1993 Wiley‐Liss, Inc.
Hemoglobin sickle‐lepore: Report of two siblings and review of the literature
Authors: Seward Daniel P. , Ware Russell E. , Kinney Thomas R.
Published: February 2007

Hemoglobin Lepore is composed of two normal α‐globin chains and two δ‐β fusion globin chains that result from nonhomologous crossing over of genetic material during meiosis. The doubly heterozygous condition of sickle hemoglobin with Lepore hemoglobin (Hb S‐Lepore) is rare, having been described previously in only nine patients. We report two siblings with Hb S‐Lepore who have similar hematologic characteristics but a marked difference in clinical severity. © 1993 Wiley‐Liss, Inc.
Recombinant human granulocyte‐macrophage colony‐stimulating factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes
Authors: Hansen Per Boye , Johnsen Hans E. , Hippe Erik , Hellström‐Lindberg Eva , Ralfkiaer Elisabeth
Published: February 2007

The purpose of this study was to improve erythropoiesis in patients with anemia due to myelodysplastic syndromes (MDS). We treated 13 patients first with recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) for 6 weeks, then with recombinant human erythropoietin (rhEpo) and rhGM‐CSF for the next 12 weeks. Five patients had refractory anemia (RA), 3 refractory anemia with ringed sideroblasts (RAS), and 5 refractory anemia with excess of blasts (RAEB). Ten patients were transfusion‐dependent at the time of inclusion. Eleven patients completed this phase II study. Five responded with an increase in hemoglobin level (3 patients) or a reduction in transfusion requirement (2 patients). We registered no response in the remaining 6 patients during treatment. Patients responding to combined treatment had relatively low concentrations of plasma Epo and plasma ferritin before treatment with rhEpo and a normal karyotype throughout the study. Long‐term bone marrow cultures did not predict the response. Still, responders seemed to have a higher number of colony‐forming progenitors than non‐responders. In conclusion, combined therapy with rhGM‐CSF and rhEpo may stimulate hematopoiesis and correct or improve anemia in some patients with MDS. © 1993 Wiley‐Liss, Inc.
Multimeric pattern of plasma and platelet von willebrand factor is normal in uremic patients
Authors: Castaman Giancarlo , Rodeghiero Francesco , Lattuada Antonella , La Greca Giuseppe , Mannucci Pier Mannuccio
Published: February 2007

Several studies have reported increased von Willebrand factor (vWF) levels in plasma of uremic patients, with a normal multimeric pattern. Two recent studies, however, have shown a reduction of the larger multimers of plasma vWF and one has also found low levels of platelet vWF in uremic patients with prolonged bleeding time (BT). We have measured plasma and platelet vWF and analyzed its multimeric pattern in 20 uremic patients, 11 with a prolonged BT and 9 with a normal BT. For Plasma vWF, no difference for vWF:Ag, RiCof, and ristocetin‐induced platelet agglutination was found between the two groups with normal and prolonged BT. The multimeric pattern of plasma vWF, as evaluated by densitometric scanning of the electrophoretic gels, was normal in both groups. For platelet vWF, vWF:Ag and RiCof content was similar in the two groups. The multimeric pattern was indistinguishable from that of normal platelets. In conclusion, our study does not confirm the presence of a structural defect of plasma vWF and the reduction of platelet vWF content in uremia. © 1993 Wiley‐Liss, Inc.
Hb adana or α259(E8)Gly→Aspβ2, A severely unstable α1‐globin variant, observed in combination with the ‐(α)20.5 KB α‐thal‐1 deletion in two Turkish patients
Authors: Çürük M. A. , Dimovski A. J. , Baysal E. , Gu L‐H. , Kutlar F. , Molchanova T. P. , Webber B. B. , Altay Ç. , Gürgey A. , Huisman T. H. J.
Published: February 2007

We have identified a severely unstable hemoglobin variant through sequencing of amplified DNA involving the α1‐globin gene; the mutation is located in codon 59 (CCG CAG) andresults in a Gly—Asp replacement. This amino acid substitution concerns a glycine residue at an internal position in the E helix, which is in close contact with a glycine residue of the B helix; introduction of the larger and charged aspartic acid residue greatly affects the stability of the molecule. This variant was present in association with a common α‐thalassemia‐1 deletion [‐(α)20.5 kb] in two adults and caused a severe type of Hb H disease with anemia, low levels of Hb A2, increased → chain, and Hb Bart's. In vitro chain synthesis in reticulocytes showed a high specific activity of the variant α chain. Only a minute quantity of Hb H was present but instead about 10% of Hb Bart's was observed. The increased synthesis of γ chains was likely due to specific characteristics of a chromosome with haplotype #3, which was present in both patients. The same family was studied 18 years ago [1]; the improved methodology presently available has led to a corrected diagnosis for these patients. © 1993 Wiley‐Liss, Inc.
Hemostatic molecular markers in nephrotic syndrome
Authors: Chen Tsai‐Yun , Huang Chieng‐Chung , Tsao Chao‐Jung
Published: February 2007

Quantitative changes of hemostatic molecular markers were studied in patients with nephrotic syndrome. The plasma levels of fibrinopeptide A (FPA), thrombin‐antithrombin III complex (TAT), products of thrombin activation, and fragment F1 + 2 (F1 + 2), a product of prothrombin activation, were measured by enzyme immunoassay in 21 patients with nephrotic syndrome and in 16 normal controls. The mean value of FPA was 17.5 ± 7.5 ng/ml (mean ± SD) in nephrotic patients and 4.5 ± 0.3 ng/ml in normal controls (P < 0.02); F1 + 2 concentration was 1.4 ± 0.3 ng/ml in nephrotic patients and 0.5 ± 0.1 ng/ml in normal controls (P < 0.001); TAT level was 1.0 ± 0.3 μg/l in nephrotic patients and 0.2 ± 0.1 μg/l in normal controls (P < 0.05). These data indicated intravascular hemostasis activation. Based on these results, we propose that low antithrombin III level in nephrotic patients may be due to both urinary loss and intravascular consumption. © 1993 Wiley‐Liss, Inc.
Quantitative defect of glycoprotein ib in severe cirrhotic patients
Authors: Sánchez‐Roig María J. , Rivera José , Moraleda José M. , García Vicente Vicente
Published: February 2007

A decrease of platelet agglutination induced by ristocetin has been described in Cirrhotic patients. In order to investigate the relationship of such phenomenon with a putative defect on piatelet membrane glycoprotein Ib, we have studied the quantitative and functional status of Gp Ib in eleven severe alcoholic cirrhotic patients, and the ability of their formalin‐fixed platelets to agglutinate in the presence of normal plasma plus ristocetin. Interestingly, we found a significant decrease of immunoreactive GP Ib molecules (9,978 ± 1,534 vs. 17,064 ± 404 molecules per platelet) and ristocetin‐dependent binding of vWF (9,113 ± 1,338 vs. 13,992 ± 1,968 molecules per platelet) (P < 0.01) in comparison to the levels found in a control group of healthy subjects. Immunoblotting analysis of platelet lysates confirmed the reduction of GP Ib level in cirrhotic patients, but showed no modification on the precipitation pattern of this glycoprotein. The ristocetin‐induced platelet agglutination (light transmission %) was also significantly lower in patients with Cirrhosis (48 ± 7.6 vs. 92 ± 3.6, P < 0.01), and correlated with the binding of normal vWF (r = 0.863, P = 0.0013). Patients with bleeding times longer than 7 min and/or clinical history of bleeding episodes showed the lowest values of platelet agglutination and GP Ib level. In conclusion, our present results indicate that llver cirrhosis is associated with a relevant decrease of functional GP Ib molecules on the platelet surface. This reduction might be related to the prolongation of bleeding time and to the bleeding diathesis observed in cirrhotic patients. © 1994 Wiley‐Liss, Inc.
Dyshematopoiesis in combined immune deficiency with congenital neutropenia
Authors: Gasparetto Cristina , Smith Clay , Firpo Meri , Dennig Dieter , Small Trudy , Gillio Alfred P. , Lichtenberg Robert , O'Reilly Richard J. , Moore Malcolm A. S.
Published: February 2007

This report describes a patient with combined immune deficiency associated with congenital neutropenla (CID/CN) and reports a partial characterization of his hematopoletic abnormalities. The CID/CN syndrome described is characterized by neutropenla and by deficiencies in B‐lymphoid and T‐lymphoid cell number and function. Red cell and platelet counts were normal. In vitro assays indicate that the myeioid lineage was developmentally arrested at the level of the committed monocyte/granulocyte progenitor (CFU‐GM), while precursors to the CFU‐GM progenitor were normal. In vitro studies showed that the defect in myeiold development was not corrected with G‐CSF or GM‐CSF. However, combinations of cytokines present in conditioned media from the T‐cell lines MO or C5MJ, or defined multiple cytokine combinations containing IL‐1, IL‐3, GM‐CSF, kit ligand, IL‐6, and IL‐9, restored myelopoiesis in‐vitro. In contrast, CBMJ‐conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnormalities in the production of G‐CSF, GM‐CSF, M‐CSF, or IL‐1 from the patient could be identified to account for the defects in myelopoiesis orimmune function. © 1994 Wiley‐Liss, Inc.
A novel mediterranean “δβ‐thalassemia” determinant containing the δ+27 and β°39 point mutations in cis
Authors: Oggiano Lina , Guiso Luciana , Frogheri Laura , Loudianos Georgios , Pistidda Paola , Rimini Elena , Pirastu Mario , Cao Antonio , Longinotti Maurizio
Published: February 2007

The term δβ‐thalassemia with normal HbF has been recently proposed to define heterogenous δ and β globin gene molecular defects involving the same chromosome in cis. Here, we describe a Sardinian family in which three members showing microcytosis, border‐line HbA2 levels and normal HbF proved to be heterozygotes for δ +27 and β°39 point mutations in cis by allele specific oligonucleotyde hybridization as well as by ECO 0 109 I endonuclease digestion and electrophoresis. As some of these β‐thalassemia carriers shows normal HbA2 levels, knowledge of the molecular basis of this novel δβ‐thalassemia silent phenotype would be useful in thalassemia screening and genetic counselling. © 1994 Wiley‐Liss, Inc.
A new deletional α‐thalassemia detected in yemenites with hemoglobin H disease
Authors: Shalmon Lea , Kirschmann Chava , Zaizov Rina
Published: February 2007

A new large deletion from the human α‐giobin gene cluster is characterized. It involves at least 39 kb and includes the two α‐giobin genes, the ϑ 1‐gene, all the pseudogenes, and the two hypervariable regions (HVRs), interzeta‐HVR and α‐globin 3′HVR. The conserved ζ‐globin gene has been identified in various restriction fragments of abnormal size. The new deletion was found in four unrelated Israeli patients with Hb H disease, all orlginating in Yemen, and has been designated ‐ ‐YEM. It is the only two‐gene deletion identified in this ethnic group. © 1994 Wiley‐Liss, Inc.
Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation
Authors: Wada Hideo , Nakase Tsutomu , Nakaya Ryusuke , Minamikawa Kouzou , Wakita Yoshihiro , Kaneko Toshihiro , Ohiwa Michiaki , Deguchi Katsumi , Shirakawa Shigeru
Published: February 2007

The plasma tissue factor (TF) antigen level was measured in patients with disseminated intravascular coagulation (DIC). The plasma TF antigen was detected In normal volunteers, and it was significantly higher in DIC patients than in non‐DiC patients. However, in some patients with DiC, the plasma TF antigen level was within the normal range. The plasma TF antigen level in patients with DIC significantly decreased after therapy, but it was not correlated with organ failure or outcome. The plasma TF antigen level in patients with DIC was not correlated with other hemostatic markers. The plasma TF antigen level tended to be higher in DIC patients with nonlymphoid leukemia than in those with lymphoid tumor. TF might be implicated in the occurrence and progression of DIC. © 1994 Wiley‐Liss, Inc.
Spontaneous factor VIII inhibitor occurring in association with chronic graft‐versus‐host disease
Authors: Seidler Christopher W. , Mills Letha E. , Flowers Mary E. D. , Sullivan Keith M.
Published: February 2007

The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious hemorrhagic sequeiae. We report here the case of a patient who acquired a Factor VIII inhibitor two years after an allogeneic bone marrow transplant for CML. This occurred in association with a flare of chronic graft versus host dlsease (GVDH). He responded to corticosteroid therapy. A review of autoimmune phenomena associated with chronic GVDH and the treatment of Factor VIII Inhibitors is discussed. © 1994 Wiley‐Liss, Inc.
Thrombocytopenia following acute acetaminophen
Authors: Fischereder Michael , Jaffe Jeffrry P.
Published: February 2007

An unusual case of severe thrombocytopenia following acetaminophen overdose is pre sented along with a retrospective review of 174 patients with hospital admissions for acute acetaminophen toxicity. Thrombocytopenla occurred in 3.4% of these patients and strongly correlated with the degree of hepatotoxicity (as measured by peak AST values) but did not correlate with serum acetaminophen levels. The mechanism appears to be a transient direct toxic effect on platelets or megakaryocytes, and the finding of thrombocytopenia early in the course of acetaminophen overdose may identify a subset of patients at risk for significant hepatotoxicity. © 1994 Wiley‐Liss, Inc.
IgE plasma cell leukemia successfully treated with combination VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon‐α
Authors: Yamagata Noboru , Shimazaki Chihiro , Goto Hideo , Hirata Toshiyuki , Ashihara Eishi , Oku Naritoshi , Inaba Tohru , Fujita Naohisa , Nakagawa Masao
Published: February 2007

A 69‐year‐old woman with IgE/K plasma cell leukemia (PCL) was treated with a sequential combination of VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon‐α (IFNα). A complete remission was achieved for 14 months. Maintenance therapy with IFNα has continued for an additional 10 months. IgE PCL Is extremely rare. The biological characteristics of the myeloma cells, including surface marker, adhesion molecule, karyotype, DNA analysis, and the response to various cytokines, are presented. © 1994 Wiley‐Liss, Inc.
Autologous peripheral stem cell transplantation of the blastic phase of chronic myeloid leukemia following sequential high‐dose cytosine arabinoside and melphalan
Authors: Matulonis Ursula A. , Griffin James D. , Canellos George P.
Published: February 2007

Blast‐phase chronic myelogenous leukemia (CML) is the terminal phase in CML and is uniformly fatal. We treated 12 patients with blast‐phase CML with a program of high‐dose cytarabine 3.0 g/m2 and melphalan 140 mg/m2. followed by reinfusion of stem cells obtained from peripheral blood during the chronic phase.

Seven patients achieved either a partial or complete hematologic remission, while five patients showed no response to therapy. One petlent returned to chronic phase features with loss of a chromosomal abnormality acquired at blast phase, restoration of he matopolesis, and a decrease In the amount of bone marrow blasts to less than 10%. SIX patients cleared their peripheral blasts and showed recovery of their myelold and platelet lineages, but all six required treatment for acceleration within 3 months. Of the five nonresponding patients, three died with aplastlc bone marrow, one patient never cleared peripheral blasts after chemotherapy, and one patient had evidence of peripheral blasts 3 weeks after the autologous stem cell reinfuslon. None of the patients returned to a normal karyotype. The ablative regimen was effective in eradicating bone marrow blasts to <10% in 8 of 10 patients in whom interpretable bone marrow samples were performed following chemotherapy. Overall, the median survival for all patients from the time of stem cell reinfusion was 5.5 months.

We conclude that autotransplants with peripheral blood can successfully be used to support hematopoiesis during high‐dose therapy for CML blast crisis, however, has no role by itself in the curative therapy of blast crisis CML. A small number of patients can be restored to chronic phase features, and this may provide an opportunity to administer subsequent alternative treatments designed to eradicate the malignant stem cell population. Autotransplants with stem cells may also be used as therapy for patients without a histocompatible marrow donor. However, the autotransplant may be more effective when used during the chronic phase of CML, with the use of hematopoletlc growth factors, and with reinfusion of stem cells depleted of the malignant Philadelphia chromosomepositlve clone. © 1994 Wiley‐Liss, Inc.