bluuebunny/crossref_metadata_2025 huggingface dataset:
CD3+, CD4−, CD8− large granular T‐cell lymphoproliferative disorder
Authors: Sun Tsieh , Cohen Neil S. , Marino John , Koduru Prasad , Cuomo Joanne , Henshall Joan
Published: February 2007

Large granular T‐cell lymphoproliferative disorder (LGTLD) is a heterogeneous disorder covering a broad spectrum of diseases and requiring further subdivision. Most reported cases emphasized its suppressor phenotype (Tγ cell or CD8+), but we encountered two cases of CD3+, CD4−, CD8− LGTLD. Both cases had a benign clinical course and required no chemotherapy despite persistent lymphocytosis. This unique phenotype has been reported in a few cases of acute lymphoblastic leukemia expressing the T‐cell receptor (TcR) gamma chain gene and is considered the counterpart of thymocytes at the intermediate stage between early precursors and mature thymocytes. Our case 1 provides further evidence that the CD3+, CD4−, CD8− phenotype, indeed, expresses the TcR gamma chain gene. However, the negative reaction to terminal deoxynucleotidyl transferase in our case 1 indicates that this phenotype represents proliferation of peripheral T‐cells, in which about 2% bear the CD3+, CD4−, CD8− phenotype in the normal population. The selective use of CD3, CD4, CDS, HNK‐1 monoclonal antibodies and of cytochemical stains (acid phosphatase and alpha‐naphthyl butyrate esterase) for characterization of this disorder is discussed.
Platelet aggregation in Hyperapobetalipoproteinemia
Authors: Miller M. , Bell W. , Plano S. , Connors J. , Kennedy S. , Kwiterovich P.
Published: February 2007

Hyperapobetalipoproteinemia (HyperapoB) is a lipid disorder characterized by premature coronary disease, although the mechanisms have not been elucidated. Because abnormalities in platelet function may represent an enhanced susceptibility to coronary thrombosis, the aggregability of platelets was examined in hyperapoB subjects. Compared to controls, there were no significant differences in either platelet lipid composition or in aggregation to epinephrine, ADP, or collagen. In contrast to other dyslipidemias, platelet function does not appear to be abnormal in this well defined lipid disorder.
Isolated relapse of acute myelogenous leukemia presenting as a gastric ulcer
Authors: Roy Jean , Vercellotti Gregory , Fenderson Mary , Mulvahill Amy , Snover Dale , Weisdorf Daniel
Published: February 2007

Isolated gastrointestinal (GI) infiltrate is unusual at presentation or relapse of acute myelogenous leukemia (AML). We report a case of acute myelogenous leukemia (FAB‐M4) whose isolated relapse presented as a bleeding gastric ulcer. The patient was a 30‐year‐old male who had been diagnosed to have AML in June 1988. While in third complete remission, he underwent a sibling allogeneic HLA‐matched bone marrow transplant. Five months after transplantation, he was readmitted for pneumonia. While in the hospital, he had an episode of upper GI bleeding. The endoscopy revealed a leukemic gastric ulcer, with morphology and immunophenotyping identical to his initial AML. There was no evidence of leukemia in the blood or bone marrow. Although different types of leukemic infiltrates have been recognized at post‐mortem examination, our case is unique because AML presenting as an isolated malignant ulcer has not been described previously. We conclude that relapsing AML may present as an isolated gastric ulcer and suggest that any suspicious lesion on upper GI endoscopy should be biopsied after aggressive platelet support.
Stability of peripheral hematological parameters after chronic acetylcholinesterase inhibition in man
Authors: Moriearty Pamela L. , Womack Cindy L. , Dick Barrett W. , Colliver Jerry A. , Robbs Randall S. , Becker Robert E. W.
Published: February 2007

Acetylcholinesterase (AChE; EC 3.1.1.7) is present in both primitive and mature erythroid cells, and a role has been suggested for the enzyme in regulation of differentiation in the human erythron. AChE is also a major enzyme in the central nervous system; alteration of its activity has been proposed as a therapeutic strategy in Alzheimer disease. We recently treated 18 Alzheimer disease patients with metrifonate, a long‐acting AChE inhibitor, over periods up to 7 months, with resulting erythrocyte AChE inhibition as high as 82 per cent of baseline values. Despite chronic reduction of enzyme activity, no significant alterations were noted in erythrocyte, leukocyte or platelet characteristics or numbers that would suggest a deleterious effect of AChE inhibition on normal differentiation. Thus, any modification of developmental pathways appears to be compensated by other regulatory mechanisms in the intact organism.
Detection of rearrangement of immunoglobulin heavy chain and T‐cell receptor beta chain in leukemic cells by restricted polymerase chain reaction
Authors: Stole V. , Uhrmacher J. , Krause J. R.
Published: February 2007

Rearrangement of the immunoglobulin heavy chain and of the T‐cell receptor beta subunit was analyzed by using restricted polymerase chain reaction (PCR). To differentiate between the germline configuration and the rearranged genome in a DNA sample extracted from lymphocytes, we compared the ratio of the amplified products. The intensity of amplification of the intron region (JHF) upstream of the first joining region was compared to the intensity of joining region 6 of the immunoglobulin heavy chain. The number of the amplification cycles in the PCR was designated in such a way that the ratio of JHF/JH6 was less than one in the rearranged configuration. As the concentration of clonal B‐lymphocytes with the rearranged genome in the sample increased the amplification of the JHF intron proportionally decreased. We used the same approach for the two constant regions of the T‐cell receptor beta chain. As one of the intron regions of the constant sequence became depleted by rearrangement so the amplification of the particular region decreased. Therefore, the absence or decreased concentration of a particular product of amplification indicated deletion and thus rearrangement of the genome in the leukemic B‐ or T‐lymphocytes. The threshold of detection of cells with the rearranged genome on a photograph of agarose gel loaded with the particular amplified regions and staining with the ethidium bromide is less than 10% by densitometric tracing and 25–50% by visual evaluation.

This novel approach allows the detection of the rearranged DNA sequences in a 2 day span. Hence, it can serve as a diagnostic tool for the identification of clonal expansion of lymphocytes in acute leukemias and lymphomas in particular and for the detection of deleted genomic regions in general.
Molecular characterization of Hb S(C) β‐thalassemia in American blacks
Authors: Gonzalez‐Redondo J. M. , Kutlar A. , Kutlar F. , McKie V. C. , McKie K. M. , Baysal E. , Huisman T. H. J.
Published: February 2007

An extension of previous reports describing the molecular defects and hematological abnormalities in black patients with Hb S(C) β‐thalassemia living in the Southeastern United States is presented. As many as 58 patients with Hb S‐β+‐thalassemia, 16 with Hb C‐β+‐thalassemia and 12 with Hb S‐β°‐thalassemia have been studied. Patients with Hb S(C) β+‐thalassemia type 2 (high Hb A values) were most common; the thalassemia was due to mutations in the promoter of the β‐globin gene [−88 (C → T) and −29 (A → G)] or at the polyadenylation signal (T → C). Two patients with lower Hb A values (type 1) carried a mutation in the first intron of the β‐globin gene (IVS‐1‐5: G → T). The simultaneous presence of an α‐thalassemia −2( −αl) resulted in some modifications of the hematological parameters, but had a minimal effect on the clinical condition. Patients with Hb S‐β°‐thalassemia had lower hemoglobin values, lower number of red blood cells, and lower MCHC values and suffered more frequently from complications than the patients with Hb S‐β+ ‐thalassemia. A total of 17 different β‐thalassemia mutations were observed in 128 chromosomes; two mild β+ ‐thalassemia mutations [−88(C → T) and −29(A → G)] account for more than 80% of the thalassemic chromosomes.
A glycosaminoglycan inhibitor of thrombin: A new mechanism for abnormal hemostatic assays in cancer
Authors: Liebman Howard A. , Comenzo Raymond , Allen Suzanne T. , Dilorio Jere M.
Published: February 2007

The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin‐like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.
Transient reversal of bone marrow aplasia associated with lymphocyte depleted hodgkin's disease after combination chemotherapy
Authors: Johnston P. G. , Sullivan F. J. , Ruscetti F. W. , Longo D. L. , Connaghan D. G.
Published: February 2007

This report describes a patient with lymphocyte depleted Hodgkin's disease who presented with bone marrow aplasia. The aplastic marrow reverted to normal after initiation of MOPP chemotherapy; however, 4 months after completion of therapy, bone marrow aplasia recurred in the absence of recurrent Hodgkin's disease. The patient remains free of Hodgkin's disease 34 months after completion of chemotherapy. Bone marrow abnormalities in Hodgkin's disease are reviewed and the current understanding of the pathological mechanisms leading to aplastic anemia is discussed.
Ultrastructural evidence for the origin of mast cells in normal human bone marrow
Authors: Saito Nagahito , Takemori Nobuo , Tachibana Noriko , Hayashishita Naoyuki
Published: February 2007

Whether the origin of the progenitor of mast cells occurs in the basophil/mast cell system or the myeloid cell system of neutrophils and monocytes/macrophages remains controversial.

Lactoferrin or lysozyme is known to be present in the myeloid cell system. By electron microscopy, antibodies against lactoferrin and lysozyme were observed to stain the granules of normal bone marrow mast cells. This supports the proposal that the precursor cell of bone marrow mast cells is nearer to the myeloid cell system than the basophil/mast cell system.
Effect of estrogens and progesterone on human peripheral erythroid burst‐forming unit (BFU‐E) growth
Authors: De Feo T. M. , Cappellini M. D. , Fiorelli G.
Published: February 2007

Variations in the number of peripheral burst‐forming unit—erythroid (BFU‐E) of healthy women were observed during a prolonged period of observation. These differences were related to different phases of the menstrual cycle. A peak in the number of BFU‐E occurred on day 14 of the cycle corresponding to the serum 17‐β‐estradiol peak. The effect of estrogens and progesterone on the in vitro growth of peripheral BFU‐E of healthy women was assayed. Estrogens demonstrated a stimulatory and progesterone an inhibitory effect in total lymphomonocyte cultures, whereas neither hormone had an effect in monocyte‐depleted cultures. Prostaglandin E1 (PGE1) which is known to be secreted by monocytes, stimulated the in vitro growth of peripheral BFU‐E. These data suggest that estrogens and progesterone could have a role in the in vitro growth of peripheral BFU‐E, probably mediated by monocytes.
Primary non‐Hodgkin lymphoma of the spleen
Authors: Brox Alan , Bishinsky Jonathan I. , Berry Gerald
Published: February 2007

Primary splenic lymphoma is a relatively infrequent cause of splenomegaly, its reported incidence being less than 1%. Nonetheless, various series have reported on its occurrence and its unfavorable prognosis, but these series have reported data on heterogenous populations, including many patients with nodal or hepatic disease.

We report on a series of nine patients with primary splenic lymphoma. None of these patients had biopsy‐proven evidence of extrasplenic disease and were categorized as involving spleen only (stage 1) or spleen and splenic hilum (stage 2). In this series, classified by the recent N.C.I. working formulation, four patients had intermediate or high‐grade histology and five patients had low‐grade histology. There was no correlation between histological subtype and prognosis, nor could other factors be delineated to explain their favorable prognosis. The median survival in this group of patients was 7.48 years, and no evidence of relapse has been documented.

The data suggest that primary splenic lymphoma, treated by splenectomy alone or combination therapy, may be potentially curative. Further studies should address the question of aggressive accurate staging in hopes of obtaining homogenous patient populations so that appropriate treatment in primary splenic lymphoma can be better defined.
Circulating nucleated red blood cells following splenectomy in a patient with congenital dyserythropoietic anemia
Authors: Adams Christopher D. , Kessler John F.
Published: February 2007

A 24‐year‐old white female with a 10‐year history of juvenile rheumatoid arthritis and splenomegaly developed numerous circulating nucleated red blood cells (NRBC) following splenectomy for chronic abdominal pain. Subsequent evaluation revealed the presence of a congenital dyserythropoietic anemia (CDA) with atypical features. Circulating NRBCs have been reported following splenectomy in three other cases of CDA, each of which had atypical features and did not fit into the customary classification of types I–IV. Follow‐up of our patient at 4 years revealed no untoward consequences of persistent NRBCs in her circulation.
Thrombocytopenia associated with environmental exposure to polyurethane
Authors: Michelson Alan D.
Published: February 2007

Few chemicals in the environment have been implicated as causes of isolated thrombocytopenia, and the evidence is usually less than convincing because the patients were not rechallenged with the chemical in vivo. In the present paper, a child is reported with the onset of thrombocytopenia in temporal association with environmental exposure to polyurethane. Five years after the initial thrombocytopenia had resolved, an inadvertent in vivo rechallenge with environmental polyurethane resulted in recurrence of the thrombocytopenia. This recurrence, together with the fact that only 1–4% of cases of idiopathic thrombocytopenic purpura in children recur, provided strong evidence for a causal role for the polyurethane exposure in this patient's thrombocytopenia. In summary, environmental exposure to polyurethane should be considered in the differential diagnosis of acquired thrombocytopenia in childhood.
Sickle cell disease and hemochromatosis
Authors: Conrad Marcel E.
Published: February 2007

A 50 year‐old patient with sickle cell anemia was seen who had received only two units of blood during his lifetime. He had marked iron overloading, cirrhosis of the liver, arthralgia, and mild glucose intolerance. We believe the iron overloading was associated with hereditary hemochromatosis rather than sickle cell anemia because he had HLA‐A3 and B7 antigens, and hepatic iron deposits were primarily in parenchymal cells rather than Kupfer cells. The coexistence of either homozygous or heterozygous hemochromatosis should be suspected in sickle cell patients with organ damage from iron overloading.
Nutritional zinc increases platelet reactivity
Authors: Marx Gerard , Krugliak Judit , Shaklai Matityahu
Published: February 2007

After ingestion of 220 mg zinc sulfate, platelet aggregation was evaluated at various time intervals (i.e., T = 0, 1, and 3 hr) and the autologous plasma analyzed by atomic absorption analysis. The zinc levels increased maximally some 0.4 ± 0.2 μg/ml within 3 hr after ingestion, which tor the entire blood pool corresponds to only 5% of the ingested zinc. Aggregation responses of platelet rich plasma (PRP), instigated with suboptimal levels of thrombin (<0.2 U/ml), ADP (<2 μM), epinephrine (<2 μM), collagen (<2 μg/ml), or PAF (<50 ng/ml), show significant improvement to at least one aggregant. Mean ± SEM values for Δ% aggregation increase are as follows: thrombin, 51 ± 10%; epinephrine, 21 ± 6%; ADP, 31 ± 6%; collagen 23 ± 6%; and platelet aggregating factor (PAF), 56 ± 6%. For controls, the platelets from one individual with Glanzmann thrombasthenia as well as four undosed volunteers exhibited no significant changes in platelet responsiveness. Increased platelet responsiveness to agonists after zinc sulfate ingestion was observed in PRP from blood collected in either citrate or heparin. We demonstrate that within a relatively short time period, single bolus of nutritional zinc intake can significantly increase platelet reactivity. These findings show that nutritional zinc availability is relevant to hemostasis and may pertain to the viability of platelet concentrates in blood banks.
A p‐nitrophenylphosphatase activity associated with the human erythrocyte membrane
Authors: Brissette Renee E. , Swislocki Norbert I. , Cunningham Earlene Brown
Published: February 2007

A p‐nitrophenylphosphatase activity has been identified as a component of the human erythrocyte membrane. This activity is distinct from that associated with the cell's Na+ + K ‐dependent ATPase, Ca2+ ‐dependent ATPase, or spectrin phosphatase. The activity described here is stimulated by Mn2+ but not by Ca2+ with or without calmodulin. A potential erythrocyte membrane substrate for this activity is a 95 kDa phosphoprotein that can be shown to undergo Mn2+ ‐stimulated but not Mg2+ ‐stimulated dephosphorylation.
Origin of hematopoietic progenitor cells after bone marrow transplantation: Analysis by means of a Y‐chromosome specific DNA probe
Authors: Nakatsumi Tomoko , Nakao Shinji , Ohtaguro Mamiko , Chujo Tatsuya , Tsuchiya Haruo , Niki Takeo , Mori Takao , Matsuda Tamotsu , Shiobara Shintaro , Nagai Kozo
Published: February 2007

To characterize hematopoietic cells in mixed hematopoietic chimeras after allogeneic bone marrow transplantation (BMT), the authors examined the origin of progenies derived from hematopoietic progenitor cells of male recipients who received a marrow graft from female donors, by use of a Y‐chromosome specific DNA (YDNA) probe in combination with an in vitro colony assay. Host‐type hematopoietic cells were detected in cultured bone marrow mononuclear cells (BMMC) from 4 out of 6 patients studied, who were all in complete remission. In 2 patients of the mixed chimeras, the relative amount of host‐derived YDNA from BMMC increased after methyl cellulose cultures for 14 days. Analysis of individual colonies derived from granulocyte‐macrophage colony forming units (CFU‐GM) from these mixed chimeras, including 2 patients with chronic myelogenous leukemia (CML), revealed approximately 30% of total colonies were host‐type, although no evidence for the existence of residual Ph1 positive cells was obtained by using polymerase chain reaction for detecting bcr‐abl chimeric messenger RNA in the 2 CML patients. These findings provide direct evidence that considerable numbers of host‐derived normal hematopoietic progenitors survive and persist for a long term in a certain population of marrow recipients, after BMT following supralethal radiochemotherapy.
Continuous, low‐dose therapy with interferon‐α for human immunodeficiency virus (HIV)‐related immune thrombocytopenic purpura
Authors: Northfelt Donald W. , Kaplan Lawrence D. , Abrams Donald I.
Published: February 2007

A patient with HIV‐related immune thrombocytopenic purpura (HIV‐ITP) had a rapid rise in platelet count when treated with interferon‐α2b, 3 million units three times weekly. There were no significant toxicities with therapy. His platelet count fell to pretreatment levels when therapy was discontinued, then increased again when therapy was reinstituted at 1.5 million units three times weekly. Interferon‐α2b, administered continuously at low doses, is well tolerated, effective, and possibly less immunosuppressive than other treatments for HIV‐ITP.
Epirubicin and cytosine arabinoside for the induction therapy of childhood acute nonlymphocytic leukemia
Authors: Liang Der‐Cherng , Jiang Chang‐Jen
Published: February 2007

Epirubicin, a new anthracycline, was used in combination with cytosine arabinoside for the induction therapy of de novo acute nonlymphocytic leukemia in childhood. The treatment consisted of epirubicin 20 mg/m2/day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. The treatment could be repeated every 3 weeks. Remission induction rate was 80% (20/25). Moreover, in 13 patients, the remissions were obtained after a single course. In general, the side effects of epirubicin and cytosine arabinoside were tolerable. However, the main causes of all the three deaths were infections. Our study suggests that epirubicin is acceptable and effective for the induction therapy for de novo acute nonlymphocytic leukemia in childhood.
Characterization of novel platelet and endothelial cell target antigens in a family with genetic susceptibility to autoimmunity
Authors: Hashemi Sofia , Trudel Elise , Ganz Peter R. , Drouin Jeanne , Couture Roger , Page Denis , Aye M. T.
Published: February 2007

This report describes a French Canadian family whose members exhibit a high incidence of allo‐ and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, PIA1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.
The single ζ globin gene rearrangement: Hematologic phenotype and its frequent occurrence in polynesian niueans
Authors: Trent R. J. , Yakas J. , Rutherford J. , Mickleson K. N. P.
Published: February 2007

The single ζ globin gene rearrangement (−ζ/) is an unusual mutation associated with the α globin gene cluster on chromosome 16p13.3. It has been detected regularly among West Africans (gene frequency ˜0.05) and sporadically among other populations. DMA samples from 186 Polynesian Niueans living in Auckland, New Zealand, were studied. Eighteen (gene frequency 0.05) were shown to have the −ζ/ gene rearrangement, which results from loss of the Ψζ1 gene. Hematological phenotypes in six cord blood samples and 12 affected adults were normal. The high frequency for −ζ/ in Niueans may represent another example of genetic drift and a founder effect in Polynesians or may reflect a different founding population.
Disseminated toxoplasmosis in a severely immunodeficient patient: Demonstration of cysts in bone marrow smears
Authors: Soulier‐Lauper Mirella , Zulian Gilbert , Pizzolato Gianpaolo , Cox Jeremy , Helg Claudine , Beris Photis
Published: February 2007

A 30‐year‐old woman was treated with unrelated HLA‐compatible bone marrow transplantation for acute myeloid leukemia. Examination of her bone marrow smears because of fever and pancytopenia revealed the presence of Toxoplasma cysts. Although Toxoplasma cysts are rarely found in the bone marrow, bone marrow examination in the immunocompromised patient offers rapid diagnosis of systemic toxoplasmosis.
Molecular characterization of hemoglobin C in sicily
Authors: Travi M. , Cremonesi L. , Primignani P. , di Benedetto S. , Testa R. , Schilirò G. , Ferrari M.
Published: February 2007

Analysis of polymorphisms of the β‐globin gene cluster was performed on 12 families and on one unrelated individual of Sicilian origin who carried hemoglobin C (Hb C). Two different haplotypes were found in association with βc Sicilian alleles, corresponding to haplotypes I and II previously described in American blacks. In our population, the more frequent one (haplotype I) was linked to the lack of a polymorphic Hpal site 3′ to the β gene (13.0‐kb fragment), similarly to haplotype I in blacks, while the less frequent one was linked to a 7.0‐kb Hpal fragment attributable to a site that had never been previously described in linkage with βc alleles. In Italy, these two haplotypes have been found in rare cases in association with βA alleles. These findings provide new insights into the origin of Hb C present in Sicily, suggesting that (1) the βc mutation detected in Sicily derived from African black chromosomes and does not represent a new mutation; and (2) Hb C may have originated either by multiple mutational events on separate chromosomes or by mutation in the Hpal site 3′ to the β gene in a pre‐existing βc choromosome.
Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen‐induced platelet aggregation
Authors: Ryo Ryukichi , Yoshida Akinori , Sugano Wataru , Yasunaga Mutsumi , Nakayama Katsuji , Saigo Katsuyasu , Adachi Masashi , Yamaguchi Nobuo , Okuma Minoru
Published: February 2007

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen‐induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2, in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2‐loaded platelets. In contrast, thrombin caused TXB2, formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The lgG from the ITP‐patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPla/lla and thrombospondin were normally present. These results indicate that impaired collagen‐induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.
Low‐dose cytosine arabinoside for treating hypocellular acute leukemia in the elderly
Authors: Kanamori Heiwa , Maruta Atsuo , Miyashita Hiroko , Harano Hiroshi , Fukawa Hitoshi , Matsuzaki Michio , Motomura Shigeki , Mohri Hiroshi , Kodama Fumio , Okubo Takao
Published: February 2007

Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara‐C), 10 mg/m2 injected subcutaneously every 12 hours for 14‐28 days. Six patients achieved a complete remission (CR) for periods ranging for 6‐23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10‐24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low‐dose Ara‐C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug‐related deaths. These observations suggest that low‐dose Ara‐C is effective in treating elderly patients with hypocellular acute leukemia.
Low‐dose α‐interferon treatment of chronic myeloid leukemia
Authors: Sanchez Angel , Robinson William A. , Cohn Allen , Gonzalez Rene , Adlakha Arun
Published: February 2007

We treated 29 patients with chronic‐phase and accelerated chronic myeloid leukemia (CML) with α‐interferon in a dose of 2 mU/m2 given subcutaneously daily for 30 days and then three times per week. Most had received prior treatment. Three patients have had sustained hematologic and karyotypic remissions after a median of 22 months of treatment. Three further patients have had complete hematologic and partial karyotypic remissions. At a median follow‐up of 48 months, the median survival has not been reached. This dose of α‐interferon may induce sustained remissions even in pretreated patients and may prolong survival in CML.
Differential induction responses of δ‐aminolevulinate synthase mRNAs during erythroid differentiation: Use of nonradioactive in situ hybridization
Authors: Mitani Kinuko , Fujita Hiroyoshi , Hayashi Norio , Yamamoto Masayuki , Sassa Shigeru
Published: February 2007

Expression of mRNAs encoding the erythroid‐specific δ‐aminolevulinate synthase (ALAS‐E) and the nonspecific δ‐aminolevulinate synthase (ALAS‐N) were examined in murine Friend virus‐transformed erythroleukemia (MEL) cells using nonradioactive in situ hybridization. Following dimethyl sulfoxide (DMSO) treatment, ALAS‐E mRNA increased markedly, while ALAS‐N mRNA did not increase in wild‐type MEL cells. In contrast, in a DMSO‐resistant clone of MEL cells, ALAS‐E was not detectable before and after DMSO treatment. These findings suggest that ALAS‐E and ALAS‐N mRNAs are under separate controls and that the expression of ALAS‐E mRNA is a critical event in erythroid differentiation.
Cyclosporin A treatment for diamond‐blackfan anemia
Authors: Splain James , Berman Brian W.
Published: February 2007

Diamond‐Blackfan anemia (DBA) is characterized by a variable response to corticosteroid therapy. Patients poorly responsive to acceptable doses of steroid treatment require long‐term transfusion therapy. We have treated three patients with DBA with the immunosuppressive agent cyclosporin A with limited success. Patients 1 (DS) and 2 (LS), halfsiblings, were 13 and 9 years old, respectively, and remained transfusion independent for many years on steroid therapy. Both patients manifest steroid‐associated growth failure and osteopenia, with resultant orthopedic complications. Oral cyclosporin therapy sufficient to achieve trough serum levels of 100‐200 ng/ml was associated with a brisk 50‐100% increase in hematocrit within 1 month of initiation of treatment and allowed for a gradual tapering of prednisone dose to approximately 20% of prior established maintenance dose. After 7‐8 months, both patients developed progressive decline in hematocrit level requiring increased prednisone dose and, ultimately, transfusion support. Patient 3 (RD), a 5‐year‐old child with steroid refractory, transfusion‐dependent DBA, was entirely unresponsive to cyclosporin therapy. No cyclosporin‐associated toxicity occurred. Our observations indicate that cyclosporin A can transiently ameliorate the hematologic course of some patients with DBA. Further studies are in order to determine its mechanism of action and potential clinical utility in patients unresponsive to acceptable doses of steroid.
Nuclear localization and characterization of alkaline phosphatase in neutrophils from normal controls and pregnant women
Authors: Vergnes Henri A. , Brisson‐Lougarre Andrée , Grozdea Jean G. , Blum Claude J. , Kihn Y. , Sevely J.
Published: February 2007

There were controversial data concerning localization of alkaline phosphatase (AP) in neutrophil nuclei under physiological conditions. In this context, the AP pattern has been determined on nuclei preparations from normal human neutrophils. Blood cells were isolated from 10 healthy adults and from 3 women in the third trimester of an uncomplicated pregnancy. Purity of nuclear suspension was checked by electron microscopy and assay of organelle marker enzymes. Electron microscope cytochemistry and immunocytochemistry studies were carried out on WBC. Enzyme characterization was performed by the usual biochemical procedures. AP was found in nuclear preparations from four of ten normal controls. When present, AP was detected in approximately two‐thirds of the nuclei examined, representing an average of 20% of the total cell activity. Conversely, a large amount of nucleus‐bound enzyme (55% of total AP activity) was recognized in all pregnant women samples. Biochemical and immunological characteristics clearly differentiate AP forms in the two groups of subjects. Normal controls have an heterogeneous enzyme pattern. AP positive preparations contain a mixture of isoenzymes: a prominent heat labile form and a relatively heat stable minor component. The heat stable fraction displays some properties similar to those previously described in leukocyte AP. Pregnant women express a unique very heat labile isoenzyme identical in its main characteristics to the early placental type. © 1992 Wiley‐Liss, Inc.
Change of thyroid function in 50 patients with aplastic anemia
Authors: Cao Qingxue , Liu Jianbin
Published: February 2007

The serum thyroid hormones were measured in 50 patients with aplastic anemia (AA). Serum T3 and T4 levels were significantly lower, especially in the elderly and in those in chronic AA, while they were normal in acute AA. There was no obvious difference with thyroid‐stimulating hormone (TSH). It was suggested that the result may be caused by euthyroid sick syndrome, a protective adaptation that helps in classifying and evaluating the prognosis of the disease. © 1992 Wiley‐Liss, Inc.
Hereditary factor VII deficiency in pregnancy: Peripartum treatment with factor VII concentrate
Authors: Robertson L. E. , Wasserstrum Nathan , Banez Eugenio , Vasquez Maria , Sears David A.
Published: February 2007

This report describes pregnant sisters with severe factor VII deficiency and peripartum management with factor VII concentrate. In this family, two affected members had previously developed severe postpartum hemorrhage when managed with fresh frozen plasma. Therapy‐related complications owing to plasma infusion included viral disease transmission and pulmonary edema. Therefore, to lessen the risks of complications, specific factor therapy was initiated shortly before parturition in both patients. Factor VII concentrate was administered prior to delivery and every 6 hr for the next 72 hr to keep trough levels at approximately 10%. Based on peak and trough levels, the mean factor VII half‐lives were determined to be 3.6 and 5.7 hr. Use of the concentrate was associated with uncomplicated delivery and minimal postpartum bleeding. © 1992 Wiley‐Liss, Inc.
Activity of platelet‐activating factor acetylhydrolase exists in red cell membrane
Authors: Yoshida Hidemi , Satoh Kei , Imaizumi Tada‐Atsu
Published: February 2007

We have described the intracellular type of platelet‐activating factor acetylhydrolase (PAF‐AH) in the membrane extract of human red blood cells (RBCs). The enzymatic activity was inhibited by diisopropylfluorophosphate, trypsin or pronase E, but not affected by EDTA or the addition of 1‐O‐hexadecyl‐2‐hexadecanoyl‐rac‐glycero‐3‐phospho‐choline or 1‐O‐hexadecyl‐2‐[(cis)‐9‐octadecenoyl]‐rac‐glycero‐3‐phosphocholine. The activity in 10 healthy volunteers was 3.89 ± 3.26 pmol/109 RBCs/min (or 148 ± 73 nmol/g protein/min) (mean ± SD). Since PAF‐AH is also known to hydrolyze oxidized derivatives of phosphatidylcholine and since RBCs are not effector cells of PAF, the observed activity in RBC membranes may play a potential role in degrading oxidation products of membrane phospholipids. © 1992 Wiley‐Liss, Inc.
Recombinant alpha‐interferon inhibits colony formation of bone marrow fibroblast progenitor cells (CFU‐F)
Authors: Wang Jen C. , Lang Hong‐Dao , Liao Paul , Wong Albert
Published: February 2007

Alpha‐Interferon (IFN‐α) has been shown to inhibit colony formation of hematopoietic progenitor cells, including colony‐forming unit‐granulocyte, erythroid, macrophage, megakaryocyte (CFU‐GEMM), day 7 colony‐forming unit granulocyte‐macrophage (CFU‐GM), day 14 CFU‐GM, burst‐forming unit erythroid (BFU‐E), pluripotent stem cells (CFU‐S), and colony‐forming unit megakaryocyte (CFU‐MK). The present study was designed to see whether IFN‐α also has inhibitory effects on bone marrow fibroblast progenitors (CFU‐F). We found that IFN‐α exerted a significant inhibitory effect on both rabbit and human CFU‐F formation. Inhibition of human marrow CFU‐F formation by alpha interferon was unaffected by removal of 98% of monocytes/macrophages and T lymphocytes from light density marrow cells. This finding suggests that IFN‐α probably exerts a direct inhibitory effects. © 1992 Wiley‐Liss, Inc.
Differential expression of non‐major histocompatibility complex‐restricted cytotoxicity in patients with granular lymphocyte‐proliferative disorders associated with or unassociated with severe anemia
Authors: Oshimi Kazuo , Oshimi Yoko , Motoji Toshiko , Mizoguchi Hideaki
Published: February 2007

Of 27 patients with granular lymphocyte‐proliferative disorders (GLPD), 18 patients had CD3+ T‐cell‐lineage GLPD (T‐GLPD), and 9 patients had CD3−CD16+ natural killer (NK) cell‐lineage GLPD (NK‐GLPD). In 9 of the 18 patients with T‐GLPD, severe anemia of ≦7.5 g/dl hemoglobin (mean 5.4 g/dl) and erythroid hypoplasia in the bone marrow developed, while the remaining 9 patients with T‐GLPD and 9 patients with NK‐GLPD exhibited hemoglobin levels of ≧10.0 g/dl, and erythroid hypoplasia was not found. The number of leukocytes, neutrophils, lymphocytes or granular lymphocytes in the peripheral blood, or the percentage of lymphocytes in the bone marrow did not differ significantly between the patients with T‐GLPD associated with severe anemia and those with T‐GLPD not associated with severe anemia, and the immunophenotypes of peripheral blood mononuclear cells (PBMC) were not significantly different either. However, when non‐major histocom‐patibility complex (MHC)‐restricted cytotoxicity was assayed with PBMC, T‐GLPD patients with severe anemia and NK‐GLPD patients exhibited significantly higher levels of non‐MHC‐restricted cytotoxicity than T‐GLPD patients without severe anemia. Because PBMC obtained from T‐GLPD patients with severe anemia were shown not to lyse erythroblasts directly, the possibility that patient PBMC lyse erythroblasts in the bone marrow and thus cause anemia seems unlikely. The pathogenesis of anemia in GLPD was discussed. © 1992 Wiley‐Liss, Inc.
Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection: A report of three cases and review of the literature
Authors: Rarick Mark U. , Espina Byron , Mocharnuk Robert , Trilling Yvonne , Levine Alexandra M.
Published: February 2007

Three cases of thrombotic thrombocytopenic purpura (TTP) and coexistent human immunodeficiency virus (HIV) infection are presented with a review of 15 cases reported in the literature. Of the 18 total patients, one‐half presented with no symptoms of HIV infection while nine patients presented with symptomatic HIV disease before or simultaneous to the diagnosis. The presenting symptoms were similar to those with classic TTP and included fever in 75% and 40% with neurologic symptoms. Laboratory parameters reflected the microangiopathic hemolytic anemia typically seen in patients with TTP. The median hematocrit was 19.4%, while the median platelet count was 16,000/mm3. As with classic TTP, patients with HIV‐related TTP only had mild renal dysfunction (median creatinine of 1.2 mg/dl, range 0.8–4.8 mg/dl). Plasma exchange produced clinical remission in a majority of the patients. Importantly, approximately one‐third of the patients died prior to the initiation of therapy. We conclude that TTP is a rare but treatable condition in patients with HIV infection. A TTP diagnosis should be considered in patients with HIV infection who present with severe anemia and thrombocytopenia. Plasma exchange should be considered as initial therapy. The role of both antiplatelet therapy and aspirin is unknown. © 1992 Wiley‐Liss, Inc.
On laboratory problems in diagnosing mild von Willebrand's disease
Authors: Blombäck M. , Eneroth P. , Andersson O. , Anvret M.
Published: February 2007

By providing some examples of variations in the levels of von Willebrand factor antigen (vWF : Ag), ristocetin cofactor, and Factor VIII during one month, the authors wish to emphasize the difficulty of diagnosing mild forms of von Willebrand's disease (vWD), especially type I. In three of 15 normal female volunteers the vWF : Ag levels, on some sampling occasions, were so low (0.25–0.30 IU/mL, normal > 0.50 IU/mL) that the diagnosis of vWD type I might be made while on other occasions normal levels were obtained. The coefficients of variation (CV) for vWF : Ag in these three women were 12%, 25%, and 43%. However, CVs of similar magnitude were also observed for “non‐diseased” males and females. The ratio F VIII/vWF : Ag also varied greatly. In the three women with suspected vWD it was 36%, 15%, and 34%. A representative level for the entire cycle of vWF : Ag and ristocetin cofactor seems to have been obtained in the follicular phase and therefore it is suggested that in order to make the diagnosis of vWD type I, at least in females, blood samples should be taken in this phase. © 1992 Wiley‐Liss, Inc.
Cephalosporin‐induced hemolysis: A case report and review of the literature
Authors: Ehmann W. Christopher
Published: February 2007

Cephalosporins are commonly used drugs that interact with red blood cell membranes. They frequently cause a positive direct antiglobulin test but rarely cause hemolysis. A case of cefotetan‐induced hemolytic anemia is described in which two types of antibodies were detected. One reacted with red blood cells by a hapten mechanism, the other reacted with drug to form immune complexes. This case is compared with the 13 cases of cephalosporin‐induced hemolytic anemia reported to date. Understanding the interactions of red blood cells and cephalosporins is critical to the safe use of these commonly prescribed drugs. © 1992 Wiley‐Liss, Inc.
Effect of red blood cells from patients with sickle cell disease on platelet factor 3 release
Authors: Toumbis Constantine A. , Stadler Istvan , Ambrus Julian L.
Published: February 2007

Red cells from two SS genotype and two SA genotype patients were sampled. When the samples were deoxygenated and mixed with platelet‐rich plasma, they caused the release of platelet factor 3 as recorded in a coagulometer. This phenomenon was not present in control blood samples from normal individuals. Membrane changes in abnormal red cells during hypoxia may be responsible in part for platelet activation and its role in vasoocclusive crisis. Vasoocclusive crisis could be prevented by increasing the red cell membrane fluidity and inhibiting the platelet aggregation with pentoxifylline. © 1992 Wiley‐Liss, Inc.
Bound vitamin B12 absorption in patients with low serum B12 levels
Authors: Miller Aaron , Furlong David , Burrows Belton A. , Slingerland D. Ward
Published: February 2007

In many patients with low serum levels of vitamin B12, the absorption of the free vitamin has been normal. The present study, using a total body counter 57CoB12 absorption method that clearly separated those with intrinsic factor deficiency from controls, found that of 94 patients with low B12 levels and intact stomachs in whom the absorption of free and bound B12 was determined, 44 (47%) had normal absorption of both. However, 20 of the 94 (21%) with normal absorption of free B12 had low absorption of bound B12. The remainder (32%) had low absorption of both free and bound B12. All patients with high serum gastrin levels had low bound B12 absorption, but so did 21% of those patients with normal serum gastrin levels. © 1992 Wiley‐Liss, Inc.
A probable double heterozygous type II von Willebrand's disease with increased ristocetin induced platelet aggregation
Authors: Kinoshita Seiji , Yoshioka Keiichiro , Kasahara Motoko , Takamiya Osamu
Published: February 2007

We have identified a patient with von Willebrand's disease (vWD) resembling type IIB vWD, with increased ristocetin induced platelet aggregation (RIPA), the absence of the large multimers of von Willebrand factor (vWF) in plasma, and the presence of the large multimers in platelets in whom a family study indicated a probable double heterozygous inheritance pattern. The propositus was a 12‐year‐old boy with frequent epistaxis and bruising. Abnormal hemostatic findings included a prolonged bleeding time (BT), decreased levels of factor VIII coagulant activity (VIIIC), von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (RCof), and an increased RIPA. In the presence of ristocetin, binding of the patient's plasma vWF to normal platelets was increased but binding of normal vWF to his platelets was normal. SDS‐agarose gel (1.5%) electrophoresis revealed that plasma vWF lacked the large multimers, and 3.0% gel electrophoresis revealed that the multimers had a 5‐band pattern similar to normal. The above findings were consistent with type IIB vWD, but 1‐deamino[8‐D‐arginine]‐vasopressin (DDAVP) infusion resulted in a shortened BT and the transient appearance of large multimers without a decrease in the platelet count. Family studies revealed that his mother has mild bleeding symptoms, decreased VIIIC, vWF:Ag, and RCof levels and normal to slightly reduced RIPA with a multimer pattern consistent with type I vWD. In contrast, the father, sister, and paternal grandfather were asymptomatic, with a slightly decreased VIIIC level but a normal BT and vWF:Ag and RCof levels. Their RIPA and vWF binding to normal platelets were increased, but unlike the propositus their plasma contained large multimers. We concluded that the propositus is a type IIB‐like variant differing from previously reported IIB variants in two ways: 1) his response to DDAVP and 2) a possible double heterozygous mode of inheritance rather than the usual dominant route. © 1992 Wiley‐Liss, Inc.