bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstructive jaundice from hepatic amyloidosis in a patient with multiple myeloma
Authors: Calomeni James A. , Smith J. Robert
Published: February 2007

A patient with multiple myeloma is described who developed severe intrahepatic cholestasis secondary to hepatic deposition of amyloid. This is the first reported case of this complication's developing in a patient with multiple myeloma.
A case of agnogenic myeloid metaplasia evolving into acute myelogenous leukemia associated with the development of trisomy 11 in bone marrow cells
Authors: Dang Chi V. , Stein Peter H. , Gress Daryl R. , Dallabetta Gina A. , Bender Walter L.
Published: February 2007

An 83‐year‐old woman who had a 5‐year history of agnogenic myeloid metaplasia and a previous normal marrow cell karyotype presented with acute myelogenous leukemia (AML) associated with the development of trisomy 11 in 100% of cultured marrow cells. Isolated trisomy 11 in marrow cells has been reported previously in five cases of AML, suggesting that trisomy 11 is a nonrandom chromosomal aberration associated with AML.
Transformation of myeloma into Ph1‐negative CML with plasma cell antigens
Authors: Paletta Elisabeth , Goldstein Mervyn , Papenhausen Peter , Ciobanu Niculae , Wiernik Peter H.
Published: February 2007

We report a patient in whom Ph1‐negative chronic myelogenous leukemia (CML) developed 15 years after the diagnosis of myeloma. Combined staining of morphologically myeloid elements in the peripheral blood for myeloid and plasmacytoid antigens revealed double‐marker expression, suggesting that the two neoplasms arose from a common originator cell.
Molecular aspects of erythroenzymopathies associated with hereditary hemolytic anemia
Authors: Miwa Shiro , Fujii Hisaichi
Published: February 2007

Since the discovery of glucose 6‐phosphate dehydrogenase (G6PD) and of pyruvate kinase deficiences, erythroenzymopathies associated with hereditary hemolytic anemia have been extensively investigated. Kinetic and electrophoretic studies have shown that most, if not all, erythroenzymopathies are caused by the production of a mutant enzyme. Except for a few enzymes that are abundant in blood and tissues, it is difficult to obtain enough sample to study the functional and structural abnormalities of mutant enzymes associated with genetic disorders in man. The primary structures of only two normal red cell enzymes which can cause hereditary hemolytic anemia, phosphoglycerate kinase (PGK) and adenylate kinase, have been determined. Single amino acid substitutions of PGK variants have been found, and the identification of the exact molecular abnormalities of such variants has helped us to understand the accompanying functional abnormality. Gene cloning makes possible the identification of the DNA sequence that codes for enzyme proteins. Recently, human complementary DNA (cDNA) for aldolase, PGK, G6PD, and adenosine deaminase (ADA) have been isolated, and the nucleotide sequences for PGK and ADA determined. In the near future, human cDNA sequencing should permit identification of the gene alteration that gives rise to the mutant enzymes.
Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice
Authors: Boggs D. R. , Patrene K. D.
Published: February 2007

Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27‐28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43 % vs 49% (p < 0.001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20‐25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal‐appearing hair; the latter was subdivided into those weighing less (25‐26 g) or more (30‐34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild “dilutional” anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process.
Role of arachidonic acid metabolism in human platelet activation and irreversible aggregation
Authors: Rao Gundu H. R. , White James G.
Published: February 2007

Previous studies from our laboratory have demonstrated that the aggregation response of platelets inhibited by agents blocking cyclooxygenase activity could be restored to a normal state of sensitivity by prior stimulation of α‐adrenergic receptors. Since cyclooxygenase activity and thromboxane synthesis are not absolutely required for irreversible platelet aggregation, it is important to define precisely what role this pathway serves in platelet physiology. The present study has evaluated the influence of agents that selectively block arachidonic acid conversion at different steps of synthesis. Inhibition of peroxidase, cyclooxygenase, lipoxygenase, and thromboxane synthetase blocked the second wave response of platelets to several agonists, but did not cause dissociation of aggregates preformed by prior exposure to arachidonate (AA) or adenosine diphosphate. Phospholipase (A2/C) inhibitors, similar to prostaglandin inhibitors, blocked the second wave response of platelets to the action of agonists and, in addition, caused dissociation of aggregates induced by aggregating agents. Results of our study demonstrate that when single agonists are tested at threshold concentrations, products of arachidonate metabolism may play a role in the activation process. However, continued generation of these metabolites does not appear to be essential for the maintenance of irreversible aggregation. When a combination of agents or high concentration of physiological agonists are used, both activation and irreversible aggregation can be secured independent of prostaglandin synthesis or the release reaction.
Two arrangements of the human fetal globin genes may be responsible for high Gγ values in chinese newborns: ‐Gγ‐Gγ‐δ‐β and ‐Gγ‐AγGγ‐Aγ‐δ‐β
Authors: Harano T. , Hulsman T. H. J. , Zeng Y. T. , Huang S. Z.
Published: February 2007

High Gγ values (78% and higher) have been observed in about 3% of Chinese newborns from the Shanghai area. We describe here two arrangements different from the normal ‐Gγ‐Aγ‐δ‐β arrangement which have been characterized in the DNA from three of these babies. One baby was heterozygous for a chromosome with two linked Gγ globin genes (‐Gγ‐Gγ‐δ‐β), which has also been observed in Black newborns [Powers et al, Nucleic Acids Res 12: 7023, 1984], while the two other babies were heterozygous for a chromosome with triplicated γ globin genes, presumably of the ‐Gγ‐AγGγ‐Aγ‐δ‐β arrangement. A similar triplication has been observed in natives of the New Hebrides [Trent et al, Nucleic Acids Res 9: 6723, 1981].
Neonatal and maternal fibrinolysis: Activation at time of birth
Authors: Suarez Carlos R. , Walenga Jeanine , Mangogna Lynn C. , Fareed Jawed
Published: February 2007

Utilizing chromogenic synthetic substrate‐based methods, determination of the plasma concentration of plasminogen, α‐antiplasmin, α‐macroglobulin, and Bβ15‐42‐related peptides were made at the time of birth in both newborns and mothers. Plasminogen levels were increased in the maternal group (150 ± 26%), and markedly decreased in the newborn group (67 ± 14%). The major inhibitors of fibrinolysis, α2‐antiplasmin and α2‐macroglobulin, were within normal range in both groups. Determination of Bβ15‐42‐related peptide showed markedly increased levels in the maternal group above control values (115 ± 102, normal 29 ± 12); the newborn group showed values only mildly elevated above control values (39 ± 21). The results demonstrate increased fibrinolytic activity in both groups, though the degree of activation is significantly higher in the maternal group, as reflected by the higher levels of Bβ15‐42‐related peptides. Fibrinopeptide A levels confirm an activation of coagulation in both maternal and newborn groups (22 ± 4 ng/ml and 138 ± 22 ng/ml, respectively) with a significantly increased level in newborns (2‐5 ng/ml normal).
Multiple cerebral thrombosis in fletcher factor (prekallikrein) deficiency: A case report
Authors: Harris Margot G. , Exner Thomas , Rickard Kevin A. , Kronenberg Harry
Published: February 2007

Despite markedly prolonged activated partial thromboplastin times (APTT) patients with Fletcher factor (prekallikrein) deficiency do not clinically bleed. However, there is one reported case of myocardial infarction associated with prekallikrein deficiency. These clinical observations suggest that the contact mechanism has a minor role in normal in vivo hemostatic function. We report a further two cases of prekallikrein deficiency in Caucasian siblings. The propositus presented with multipie cerebral thrombosis. Cautious anticoagulation resulted in massive cerebral hemorrhage and death of this patient. The sibling was investigated in an attempt to establish a possible defective fibrinolytic pathway in vivo. New sensitive tests for fibrinolysis were used. These included radioimmunoassay of fibrin degradation product “D,” Bβ 15‐42, and in vitro 125I‐labelled fibrin lysis assays. The plasma half‐life of prekallikrein in this patient was calculated to be 58 hr. Family studies of heterozygotes were also performed. Prekallikrein deficiency is found not to be important in normal in vivo fibrinolysis, which possibly operates via tissue or vessel wall fibrinolytic activator release.
Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: Relation to duration of treatment
Authors: Pollack Shimon , Atias Dina , Yoffe Galina , Katz Rina , Shechter Yael , Tatarsky Ilana
Published: February 2007

Recently, abnormalities of cell‐mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia‐A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T‐helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T‐suppressor cells, Con A‐activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.
Acute nonlymphocytic leukemia in a glue sniffer
Authors: Caligiuri Michael A. , Early Amy P. , Marinello M. J. , Preisler Harvey D.
Published: February 2007

A 17‐year‐old while male with a past history of chronic inhalational abuse of plastic glue was referred to our institution for sore throat, cervical adenopathy, and an abnormal peripheral blood smear. A diagnosis of acute myelomonocytic leukemia was made and abnormalities in cytogenetic studies were demonstrated. Specific inquiry regarding this form of drug exposure should be pursued when searching for possible etiologies of malignant disease.
Human polymorphonuclear leukocytes of the bone marrow, circulation, and marginated pool: Function and granule protein content
Authors: Hetherington Seth V. , Quie Paul G.
Published: February 2007

Polymorphonuclear leukocytes (PMN) demonstrate altered function during acute infections and after administration of corticosteroids. We questioned whether or not such changes are due to population shifts from functionally different compartments of the granulocyte pool. Volunteers were given epinephrine to induce demargination or hydrocortisone (HC) to promote egress of PMN from the bone marrow. PMN obtained before and after drug administration were compared for adherence, chemotaxis, luminol‐enhanced chemiluminescence, and total content and release of lactoferrin (LF), myeloperoxidase (MPO), and β‐glucuronidase (β‐glu). Epinephrine induced a significant neutrophilia of mature PMN (segmented neutrophils), but there were no changes in function or granule protein content. HC induced a significant neutrophilia with segmented neutrophils and immature PMN (bands). Circulating PMN obtained 4 hr after HC administration demonstrated less adherence, increased chemiluminescence, increased MPO release, and decreased MPO content. Band neutrophils, however, were more adherent than segmented PMN and showed a similar decrease in adherence following HC in vivo. Thus alteration of PMN adherence following intravenous corticosteroids is not due to an influx of immature neutrophils. On the other hand, it is possible that MPO content and release and capacity for oxidative metabolism change as PMN mature.
B‐prolymphocytic leukemia cells that form rosettes with sheep red blood cells through monoclonal surface immunoglobulin
Authors: Maruta Atsuo , Motomura Shigeki , Ogawa Koji , Matsuzaki Michio , Asada Hiroko , Takahashi Kenichi , Fukumura Motonori , Sakurai Masako , Ita Akira , Ookubo Takao , Mouri Hiroshi , Watanabe Shinichiro
Published: February 2007

The neoplastic cells from a patient with B‐cell prolymphocytic leukemia exhibited sheep red blood cell (SRBC) rosette formation. Immunochemistries revealed no reactivity with T‐cell monoclonal antibodies OKT 3, 4, 8, and 11. However, the neoplastic cells expressed characteristics of B‐cells including surface IgM and IgD associated with lambda light chains, Ia‐like antigenicity, and reactivity to monoclonal antibodies against B‐cell antigens B1, B2, and B4. Inhibition procedures revealed that SRBC rosette formation was the result of binding activity of surface immunoglobulin to SRBC. Pretreatment of the leukemic cells with antihuman IgM or lambda antisera, or pronase or trypsin blocked rosette formation with SRBC. Circulating antibody to SRBC was also suspected by the fact that preincubation of SRBC with heat‐inactivated patient's serum resulted in agglutination of the SRBC.
Transient Passovoy defect during a febrile illness
Authors: Nand Sucha , Jordan James V. , Merchut Michael P. , O'Keefe J. Paul
Published: February 2007

The Passovoy defect is a recently characterized hemorrhagic diathesis. We describe a patient with a febrile illness, possibly from Epstein‐Barr (EB) virus, who acquired this defect transiently. Prothrombin time; assays for factors VIII, IX, XI, XII; and Fletcher (prekallikrein) and Fitzgerald (high molecular weight kininogen) factors were normal. No definite circulating inhibitor could be demonstrated. The transient Passovoy defect could possibly be ascribed to the infectious process or sulfisoxazole, which the patient had received.
Five adults with mild sickle cell anemia share a βs chromosome with the same haplotype
Authors: Bakioglu I. , Hattori Y. , Kutlar A. , Mathew C. , Huisman T. H. J.
Published: February 2007

Five adult SS patients from Qatar, Turkey, and South Africa with mild disease, had greatly elevated Hb F and specific patterns of polymorphic sites on their (βs chromosomes. One subject had an α‐thalassemia (–α/–α). The haplotypes were the common type # 19, associated with severe disease, and type # 31, not seen thus far in an SS patient (numbering system of Antonarakis et al [2]). The data suggest that modifications in the DNA of the βs # 31 chromosome promotes the synthesis of γ chains.
Determination of glucocorticoid receptors in leukemic myeloblasts by isoelectric focusing in polyacrylamide gel
Authors: Ogier Claudio , Humla Solveig , Nordenskjöld Bo , Skoog Lambert
Published: February 2007

We investigated the optimal conditions for measuring glucocorticoid receptor in blast cells from patients with acute nonlymphocytic leukemia.

Cytosol receptor measured with isoelectric focusing was saturated after 60 min of incubation at 0°C with 100 nM of either dexamethasone or triamcinolone. Saturation was achieved when cytosol from at least 7 × 106 cells was used for incubation. Trypsin treatment of the cytosol resulted in a sharpened peak of receptor focusing at pH 5.6 with no loss of receptor‐bound radioactivity.

The two physical forms of glucocorticoid receptor were isolated with DEAE cellulose chromatography. They were both found to focus at pH 5.6 during isoelectrc focusing.
Hypocellular bone marrow with increased blasts
Authors: Gladson Candece L. , Naeim Faramarz
Published: February 2007

Twenty patients with hypocellular bone marrow and increased blasts (HBMIB) were reviewed. The median age was 60 years with a male:female ratio of 17: 3. History of alcohol abuse was noted in 30%, potential exposure to toxic chemicals in 20%, second malignancies in 20%, and aplastic anemia in 25%. Pancytopenia with marrow hypocellularity and increased marrow blast cells were characteristic hematopathologic features. Marrow hypocellularity was moderate to severe (>25%) in over half of the cases and mild to moderate (>25, >35%) in the remainder. Blast cells were the predominant cellular elements in the marrow displaying scanty to moderate amounts of cytoplasm, round to oval nuclei, and one or more nucleoli. Special stains were performed in 19 cases. Blast cells morphologically displayed myeloid features, but Sudan black B and/or peroxidase positivity was noted in only ten patients. The overall mortality was high, especially in patients undergoing chemotherapy. At 1 year follow‐up, 11 patients had received chemotherapy and eight of these eleven were dead compared to three of nine patients dead in those not receiving chemotherapy. Only two patients developed „overt”︁ leukemia evidenced by hypercellular marrow and over 30% blast cells in the peripheral blood. HBMIB is a distinct clinicopathologic entity characterized by severe marrow failure and a low response rate to chemotherapy.
Thrombocytopenia in homosexual men
Authors: Goldsweig Howard G. , Grossman Ronald , William Daniel
Published: February 2007

The office records of two private practices with a preponderance of homosexual patients were reviewed for cases of males with unexplained thrombocytopenia. Twenty‐five patients meeting the selection criteria were found. The clinical and laboratory features of these patients were reviewed and compared to those characteristically seen in classic autoimmune thrombocytopenic purpura. The mean age of the group was 36.5 years. There was a high incidence of a history of sexually transmitted diseases. Sixty percent had another hematologic abnormality in addition to thrombocytopenia.

The clinical outcomes for these 25 patients were as follows: eight (32%) had a spontaneous increase in platelets; four (16%) had a stable count not requiring therapy; 12 (48%) received high‐dose prednisone; seven (28%) failed predinosone therapy and went on to splenectomy; two (8%) subsequently developed CDC‐defined AIDS.
Surface charge and hydrophobic properties of fresh and cryopreserved blood phagocytes as determined by partition in two‐phase aqueous polymer systems
Authors: Hill R. S. , Norris‐Jones R. , Still B. , Brooks D. E.
Published: February 2007

Cell partitioning in two‐phase aqueous polymer systems was used to examine hydrophobic and surface charge‐related membrane properties of fresh and cryopreserved human blood phagocytes. This technique is highly sensitive to cell surface characteristics, and the partition behavior depends exponentially on the membrane properties involved. The transition from fresh to cryopreserved and reconstituted cells was accompanied by a significant loss of net negative charge without detectable alteration in hydrophobic membrane properties as detected by the partition technique. The partition coefficient (PC), which is the proportion of cells partitioning into the upper phase, when measured for fresh cells mixed with dimethyl sulfoxide (Me2SO) and cryopreserved leukocytes. No difference was detected between the PCs of the total leukocytes and phagocytes as determined by differential leukocyte counts of the upper polymer phase. The significantly reduced PC of cells prepared by dextran (Dx) separation in both charge‐sensitive and ‐insensitive systems is attributable to the capacity of Dx to adsorb, in part irreversibly, to cells so that those carrying Dx tend to partition with Dx in the lower phase. These results serve to illustrate the utility of partitioning as a highly sensitive method to probe leukocyte surface membrane properties.
Thyroid Lymphoma with gastrointestinal involvement: Report of three cases
Authors: Stone C. W. , Slease R. B. , Brubaker Daniel , Fabian Carol , Grozea P. N.
Published: February 2007

Three elderly females are reported who presented with high‐grade lymphoma of the thyroid and subsequently were found to have extensive gastrointestinal (GI) lymphoma that dominated their clinical courses. One of the patients remains free of disease 30+ months after extensive resection of involved bowel and combination chemotherapy. Two died from disseminated lymphoma. Optimal delivery of therapy in both of the latter patients was impeded by massive gastrointestinal hemorrhage. A review of previously reported cases of thyroid lymphoma, plus those described here. suggests a predilection for these tumors to involve the GI tract independent of other organ metastases.
The level of Hb F‐sardinia (α2A γ275IIe→Thr) in the fetal hemoglobin of sardinian β‐thalassemic homozygotes determined by isoelectric focusing
Authors: Masala B. , Manca L. , Formato M. , Matera A.
Published: February 2007

A simple thin‐layer isoelectric focusing technique was used to separate Hb F‐Sardinia, containing the AγT‐globin chain, from the Hb F containing the γ‐ and the AγI‐ globin chains. The identity of the slow‐moving Hb F fraction as Hb F‐Sardinia was verified by PAGE. A negative correlation (R2 = 0.747, p < 0.001) was found between the percent Hb F‐Sardinia and percent Gγ‐chain in homozygotes for β‐thalassemia. Of 31 Sardinian β‐thalassemic patients studied, 21 were homozygous and eight heterozygous for the AγT polymorphism with a gene frequency of 0.823. The mean values of Hb F‐Sardinia were 39.1 ± 5.9% for the homozygotes and 17.1 ± 3.6% for the heterozygotes. The percentage of Hb F‐Sardinia found in β°‐thalassemic newborns was similar to that of corresponding normal newborns who also had the AγT poly‐morphism. No measurable differences in the percent Hb F‐Sardinia level were observed among β°‐thal patients who were polytransfused, β°‐thal patients studied before transfusion, and β°‐thal patients exhibiting the intermediate form of the disease who had never been transfused.
Autologous survival of cyanate‐treated cryopreserved sickle erythrocytes
Authors: Castro Oswaldo , Rana Sohall R. , Poillon William N.
Published: February 2007

The effects of carbamylation and frozen storage on the autologous 51Cr survival and metabolic features of sickle erythrocytes (S‐RBCs) were determined. Red cells from four patients with sickle hemoglobinopathies were treated with 50 mM sodium cyanate for 2 hr (37°C), glycerolized and frozen (−30°C) for 62‐153 days. The mean in vitro loss of S‐RBCs from the combination of cyanate treatment and cryopreservation was 23.6% (±3.5 SD). The 2, 3‐diphosphoglycerate content of the thawed cells did not change significantly. However, ATP levels decreased to about 50% of the corresponding values in fresh, untreated S‐RBCs. Despite this decrease in ATP, the mean intravascular survival of the frozen cyanated cells nearly doubled. At the high concentration of cyanate used, the oxygen affinity of S‐RBCs increased markedly: Their mean P50 was 13.1 mm Hg (± 1.9SD). The gelation of HbS at zero pO2 was also markedly inhibited in the one sample of cyanate‐treated S‐RBCs examined. Clinical studies to determine the efficacy of autologous transfusions with extensively carbamylated, cryopreserved S‐RBCs should be considered.
Increased bone marrow blood flow in rabbits with acute hemolytic anemia
Authors: Chen L. T. , Chen M. F. , Porter V. L.
Published: February 2007

The bone marrow blood flow in the femur of the rabbit with acute hemolytic anemia was measured by the radioactive microsphere method. Acute hemolytic anemia was induced by a single intraperitoneal injection of phenylhydrazine. An increase in the bone marrow blood flow was detected three days after the induction of anemia and continued for about one week. The bone marrow blood flow of the anemic rabbit (66 ml/min/100 g marrow) was about three times that of the control (20 ml/min/100 g marrow). The increased blood flow to the bone marrow appeared to be correlated to the increased erythropoietic activity.
Abnormal T cell function in early‐stage chronic lymphocytic leukemia (CLL) patients
Authors: Perri Robert T. , Kay Neil E.
Published: February 2007

Significant alterations in T cell subpopulations and function occur in chronic lymphocytic leukemia (CLL) patients. We studied whether abnormalities in peripheral blood T cell parameters were present in 15 untreated early stage CLL patients (ie, Rai stage 0, 1, 2). Seven of the nine patients showed decreased T helper support as compared to control T cells for pokeweed mitogen (PWM)‐induced control B cell proliferation (ie, patient 6,063 ± 1,434 cpm vs control 14,894 ± 121 cpm). All stage 0 and 1 patients showed a marked impairment of T helper activity for control B cell proliferation (patient T = 7,752 ± 1,137 cpm vs control T = 14,894 ± 121 cpm). In a separate assay system, six of nine CLL patients showed T suppressor activity for control B cell proliferation greater than control T cell suppressor activity. Four patients were stage 0 and 1. CLL patients demonstrated markedly impaired T cell support for control B cell immunoglobulin synthesis compared to control T cells (188 ± 28 vs 869 ± 56 hemolytic plaque‐forming cells (HePF)/culture, respectively). Control T cells showed increasing support for control B cell immunoglobulin synthesis with increasing T:B cell ratios (869 ± 56 vs 1,265 ± 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). In contrast, five of eight CLL patients' T cells showed no improvement in control B cell immunoglobulin synthesis with increasing T:B cell ratios (795 ± 56 vs 569 ± 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). There was no direct correlation with CLL T cellmediated suppression of B cell proliferation and suppression of B cell immunoglobulin synthesis. These studies suggest there is a complex array of abnormal immunoregulatory T cell function in early stage CLL. These include a prominent T helper dysfunction and more variable excessive suppressor activity. The relationship of these findings to the basic disease process remains to be elucidated.
T‐cell chronic lymphocytic leukemia with pure red cell aplasia: Laboratory demonstration of persistent leukemia in spite of apparent complete clinical remission
Authors: Hansen Richard M. , Lerner Neil , Abrams Ross A. , Patrick Catherine W. , Malik Mohammad I. , Keller Robert
Published: February 2007

A 40‐year‐old woman presented with splenomegaly, macrocytic anemia, and red cell aplasia. Although lymphocytosis was absent in the peripheral blood, large atypical lymphoid aggregates were present in the bone marrow. Splenectomy resulted in partial remission of red cell aplasia, but a gradual increase in the number of peripheral blood lymphocytes followed during the next 36 months. Flow cytometric analysis demonstrated that the majority of these peripheral blood lymphocytes had suppressor, natural killer T‐cell phenotye. No other treatment was given until red cell hypoplasia worsened 42 months after initial presentation. Repeat bone marrow evaluation again demonstrated severe erythroid hypoplasia and large abnormal lymphocytic infiltrates. Cyclophosphamide given for 8 months resulted in complete resolution of the red cell aplasia and complete clinical remission of CLL. However, flow cytometric analysis revealed persistent increase in bone marrow T‐cells, and bone marrow co–culture studies demonstrated residual ability of peripheral blood mononuclear cells to inhibit erythropoiesis in vitro, suggesting that residual, clinically undetectable leukemia persists in spite of complete clinical remission.
Conformational changes in von Willebrand's factor protein: Effects on the binding of factor VIII‐coagulant
Authors: Benson Roger E. , Jones Douglas W. , Dodds W. Jean
Published: February 2007

The effects of conformational changes in purified canine von Willebrand's factor (VWF) were investigated to explore the relationship between its factor VIII‐related antigen (VIIIR:AG) and ristocetin cofactor (RCoF) properties and the factor VIII‐coagulant (VIII:C) binding site(s). Binding of VIII:C from canine von Willebrand's disease (VWD) plasma by VWF was used to measure the combining reaction of these proteins. The VWF was denatured to varying degrees by exposure to temperature and pH extremes, low ionic strength, and 6 M urea. Various treatments resulted in three types of change: elimination of RCoF, VIIIR:Ag, and VIII:C binding, removal of RCoF activity alone; or elimination of RCoF and retarded elution of VIIIR:Ag and VIII:C. As long as VIIIR:Ag reactivity was maintained, binding of VIII:C could be demonstrated; but in the absence of VIIIR:Ag, neither RCoF activity nor VIII:C binding remained. These results suggest that VIII:C binding and RCoF sites are separate on VWF and that interaction between VIII:C and VWF is possible even after significant structural changes occur in VWF. Furthermore, RCoF is more vulnerable to denaturation than the antigenic site. The spectrum of conformational changes that affect the properties of VWF may parallel the various recognized subtypes of VWD.
Effect of IgG anti‐Rho(D) in adult patients with chronic autoimmune thrombocytopenia
Authors: Salama A. , Kiefel V. , Mueller‐Eckhardt C.
Published: February 2007

Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75–4.5 mg of IgG anti‐Rho(D) over a period of 1–5 days. Significant elevations of the platelet count (increments > 50 × 109/liter) resulted in 13 of 15 Rh‐positive patients but not in either of two Rh‐negative patients. Heat‐aggregated human albumin given to one of the Rh‐negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh‐positive patients after IgG anti‐Rho(D) administration was often transient (< 4 weeks), but long‐term benefit (> 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh‐positive patients studied increased from a usually undetectable value before to ∼ 700–1,700 IgG molecules/per RBC after anti‐RhoD) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51Cr‐labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient.

We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low‐grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP.
The effects of splenectomy on engraftment and platelet transfusion requirements in patients with chronic myelogenous leukemia undergoing marrow transplantation
Authors: Banaji Meera , Bearman Scott I. , Buckner C. Dean , Clift Reginald A. , Bensinger William I. , Petersen Finn B. , Slichter Sherrill J. , McGuffin Robert W. , Sanders Jean E. , Stewart Patricia S. , Hill Roger S. , Deeg H. Joachim , Storb Rainer , Thomas E. Donnall
Published: February 2007

Granulocyte and platelet recovery as well as platelet transfusion requirements following allogeneic marrow transplantation were analyzed in 67 patients with chronic myelogenous leukemia in the chronic phase. Twenty patients had splenectomy prior to transplantation. Forty‐seven patients were transplanted without splenectomy, 21 of whom had splenic enlargement by physical examination. There were no differences in the proportion of patients with granulocyte recovery, but the recovery of peripheral granulocytes to levels of 200, 500 and 1,000/mm3 occurred more rapidly in the splenectomy group than in the no‐splenectomy group. Patients with splenectomy received platelet transfusions for a mean of 10 (2–36) days as compared to 20 (3–82) days for patients without splenectomy (p < .001). Eighteen (90%) patients with splenectomy became platelet transfusion independent at a median of 16 (2–32) days after transplantation as compared to 40 (85%) patients without splenectomy who became transfusion independent at a median of 28 (15–86) days (p < .001). The proportion of patients achieving platelet levels of 50 and 100 × 103/mm3 did not differ between the two groups (p = .07), but patients in the splenectomy group achieved these levels more rapidly following transplant (p < .001). One of 17 evaluable patients in the splenectomy group and 31 of 46 in the no‐splenectomy group became refractory to random platelets (p < .001) and required platelets from family members or unrelated completely or partially HLA matched donors. In the no‐splenectomy group, splenic size did not affect the speed of granulocyte or platelet recovery or platelet transfusion requirements. There was no difference in the post‐transplant survival of patients with or without splenectomy.
Investigation of a case of subtype IIC von Willebrand disease: Characterization of the variability of this subtype
Authors: Mazurier Claudine , Mannucci Pier Mannuccio , Parquet‐Gernez Armelle , Goudemand Maurice , Meyer Dominique
Published: February 2007

A variant of von Willebrant disease (vWD) has been identified in a 19‐year‐old woman with a severe bleeding syndrome. She had a very prolonged bleeding time (over 20 min), 24 U/d1 factor VIII coagulant activity (F.VIII:C), 16 U/dl von Willebrand factor antigen (vWF:Ag), no ristocetin cofactor activity, and an anodal mobility of vWF:Ag on crossed immunoelectrophoresis (CIE). vWF:Ag was markedly reduced in her platelet lysate. In plasma and platelets, SDS‐agarose electrophoresis consistently demonstrated the absence of large multimers, a relatively increased concentration of the fastest‐moving multimer, and gross abnormalities of the internal structure of each vWF multimeric unit. Five members from the maternal side of the family had a double vWF:Ag peak by CIE and a relative increase of the fastest‐moving vWF multimer by SDS‐agarose electrophoresis; no quantitative or qualitative vWF defects were found in the paternal side of the family. The pattern of the findings in the propositus and her family is similar to those of type IIC vWD. However, there are some unique characteristics suggesting phenotypic variability in this subtype, such as low level of platelet vWF:Ag and the absence of increase of vWF after DDAVP administration.
T‐cell acute lymphoblastic leukemia with natural killer cell phenotype
Authors: Kaplan Joseph , Ravindranath Yaddanapudi , Inoue Susumu
Published: February 2007

To determine the type and proportion of cases within that type of acute lymphoblastic leukemia (ALL) that has a natural killer (NK) cell phenotype, we examined leukemic blasts from 31 children with ALL (14 with T‐ALL, 17 with non‐T‐ALL) for expression of antigens detected by NK‐specific monoclonal antibodies Leu 11b, Leu 7, and 1G2 (an antibody we have developed that cross‐reacts with Leu 7). None of the patients had leukemic blasts that reacted with Leu 11b. However, leukemic blasts from four T‐ALL patients were 1G2+ and/or Leu 7+. Blasts from two of these had spontaneous lytic activity against standard NK target cell line K562; blasts from one killed K562 only when incubated with interferon; blasts from the other had no lytic activity against K562 but did manifest antibody‐dependent cell‐mediated cytotoxicity against antibody‐coated cells from NK‐resistant cell line SB. Blasts from all four Leu 7+ patients had L2 morphology. In one, the leukemic blasts had azurophilic cytoplasmic granules similar to those found in NK‐enriched normal populations of large granular lymphocytes. These findings suggest that a significant proportion of T‐cell acute lymphoblastic leukemias may be malignancies of NK cell origin.
Comparative evaluation of bone marrow aspirate particle smears, biopsy imprints, and biopsy sections
Authors: Pasquale Donald , Chikkappa G.
Published: February 2007

Bone marrow aspirate particle smears, biopsy imprints, and biopsy sections were compared to determine the accuracy of the three samples in assessing for overall cellularity, differential cell count, megakaryocyte density, iron stores, and tumor infiltration. Aspirate particle smears and biopsy imprints were stained by Wright‐Giemsa method. Aspirate particle smears were also stained with Prussian‐blue. Biopsy sections were 1 1/2–2 μ thick and were prepared from non‐decalcified plastic embedded samples and stained with combined Prussian‐blue‐hematoxylin‐eosin, and Giemsa. One hundred‐eight sets of specimens from 99 patients were examined. In 20 cases, chi‐square analysis showed a comparable degree of cellularity (p < 0.001) and megakaryocyte density (p < 0.001) among the three preparations. Differential count comparison by regression analysis indicated that mean percentages of neutrophilic cells in the proliferation compartment were comparable in the three groups (p < 0.01). A better correlation was obtained among the three groups in the percent neutrophilic cells in the maturation‐storage compartment, normoblasts, eosinophils, and plasma cells (p < 0.001). Lymphocytes in the aspirate smears correlated with the biopsy imprints (p < 0.01) but not with the biopsy sections (p > 0.05). Monocytes did not correlate in any of the groups (p > 0.05). In 47 cases, chi‐square analysis of iron stores in the aspirate particle smears correlated well with those in the biopsy sections (p < 0.001). Fifty‐two marrows that were done for staging nonhematological malignancies revealed malignant cells in 21 cases, biopsy sections were positive in all, biopsy imprints were positive in 19 (90%), and aspirate particle smears were positive in 7 (33%). Thirty‐six marrows done for staging non‐Hodgkin's lymphoma showed malignant cells in 13 cases. Twelve (92%) biopsy sections, three (23%) biopsy imprints, and nine (69%) aspirate particle smears contained lymphoma cells. In conclusion, a satisfactory evaluation of marrow samples for diagnostic studies can be achieved by examination of biopsy sections along with aspirate particle smears or biopsy imprints. Any of the three marrow preparations alone is not sufficient for accurate diagnosis in all cases. The biopsy imprint is an accurate modality for identifying nonhematological tumor metastasis in the bone marrow.
Isolation of malignant cells from human bone marrow using a discontinuous percoll gradient
Authors: Macfarlane S. D. , Tauro G. P. , Rendall K. , Welch J. J. , Ekert H.
Published: February 2007

A technique for examining relatively large volumes of bone marrow for involvement by malignancy is described. The use of discontinuous Percoll gradients offers no advantage over conventional methods in the diagnosis of hematological malignancy. Its usefulness in detecting infiltration by solid tumor is uncertain. Complete exclusion of malignancy from the fraction containing hematologic stem cells in three patients raises the possibility that this technique is a useful adjunct to other methods of marrow purging before autologous marrow rescue in malignant disease.
Complex chromosomal abnormalities in a patient with lymphoid blast crisis of chronic myelogenous leukemia
Authors: Haubenstock A. , Kim H. J. , Zalusky R. , Malamud S. C. , Mernick M. H.
Published: February 2007

A 46‐year‐old Chinese man underwent lymphoid blast crisis (Ia+, CALLA+, TdT+) after 5 years of chronic phase, Philadelphia‐chromosome positive chronic myelogenous leukemia. Chromosome analysis revealed a hyperdiploid karyotype, including two Philadelphia chromosomes–‐55,XY,t(9;22) (q34;q11),+2,+5,+5,+6,+10,+18,+19,+21,+del(22)(qll→qter)–‐in the majority of the leukemic blasts. The constellation of a lymphoid blast crisis and complex chromosomal abnormalities usually associated with myeloid blast crisis as well as the clinical data are discussed.
TdT activity in acute myeloid leukemias defined by monoclonal antibodies
Authors: Miguel J. F. San , Gonzalez M. , Cañizo M. C. , Anta J. P. , Portero J. A. , Lopez‐Borrasca A.
Published: February 2007

Blast cells from eight out of 71 patients diagnosed with acute myeloid leukemia (AML) by morphological, cytochemical, and immunological criteria showed TdT activity. Their distribution according to the FAB classification was one M1, one M2, one M4, two M5a, one M5b, one M6, and one undifferentiated case. The TdT+ AML cases did not show major clinical and hematological differences when compared with the classical TdT− AML patients. Other phenotypical aberrations in the expression of membrane antigens, apart from the presence of nuclear TdT, were not observed in these TdT+ cases after study with a large panel of monoclonal antibodies.

A higher incidence of TdT+ cases was found among the monocytic variants of AML (M4 and M5)‐four cases‐than in the granulocytic variants (M1, M2, and M3)‐2 cases.

These TdT+ cases should be distinguished from mixed leukemias by double labeling techniques, assessing in the TdT+ AML the coexpression of TdT and myeloid markers in individual cells as shown in four of our cases.
Coexpression of p165 myeloid surface antigen and terminal deoxynucleotidyl transferase: A comparison of acute myeloid leukaemia and normal bone marrow cells
Authors: Bradstock Kenneth F. , Kerr Arna , Kabral Arnold , Favaloro Emmanuel J. , Hewson John W.
Published: February 2007

A double immunofluorescence technique, using antibodies to terminal transferase (TdT) and a 165‐kilodalton myeloid differentiation antigen (p165), has been used to investigate the phenomenon of TdT expression in cases of acute myeloid leukaemia (AML). Five cases of AML were shown to have significant (18‐90%) numbers of leukaemic cells that concurrently expressed both TdT and p165 myeloid surface antigen. Examination of nonleukaemic bone marrow cells showed that the vast majority of normal TdT+ cells are p165 negative. However, in 5 of the 11 samples analyzed, rare cells staining for both p165 and TdT were found. These results suggest that some cases of TdT + AML may arise from the clonal expansion of rare “biphenotypic” precursor cells existing in normal bone marrow.
Quantitation of the monoclonal plasma cell component in bone marrow from patients with serum paraproteinemia and nondiagnostic marrow morphology
Authors: Gordon Vanessa , Bezwoda Werner , Derman Dennis , Kramer Sydney , Mendelow Barry
Published: February 2007

Twenty‐one patients with serum monoclonal gammopathy but lacking acceptable morphological evidence of myelomatosis were studied with reference to the degree, if any, of monoclonal plasma cell expansion in aspirated marrow samples, enriched for plasma cells and analysed with respect to light chain distribution. Four of these patients had a biopsy‐proven plasmacytoma of bone. Bone marrow aspirated from sites distant to the tumor showed clear evidence of infiltration by monoclonal plasma cells in two of the cases studied; the other two patients had normal results. Of the 17 other cases, 14 showed evidence of a monoclonal plasma cell component qualitatively concordant with the serum paraprotein as one would expect. These cases could be subdivided into those with myeloma (six cases) and those with monoclonal gammopathy of undetermined significance (eight cases) on the basis of conventional biochemical and radiological criteria. Three of the 17 patients, however, did not show evidence of monoclonal plasma cell infiltration, despite the presence of lytic lesions. It is important to recognize this minority group that simulates myeloma but that may well reflect alternative pathology that has not been identified.
Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis
Authors: Fahey John L. , Rahbar Samuel , Farbstein Mark J. , Forman Stephen J. , Blume Karl G. , Beutler Ernest
Published: February 2007

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemaglobin values [MCV] <80 fl). Three patients had iron deficiency, and one had β‐thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal α‐to‐β‐globin chain ratios (1.0 ± 0.14). Seven patients with Hodgkin disease and MCV <80 fl had significantly lower α‐to‐β chain ratios (0.66 ± 0.05). Twelve normal controls and four with iron‐deficiency anemia and MCV <80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal α‐to‐β‐chain ratio was corrected along with the anemia.
High‐dose cytosine arabinoside in the treatment of preleukemic disorders: A leukemia intergroup study
Authors: Preisler H. D. , Raza A. , Barcos M. , Azarnia N. , Larson R. , Browman G. , Walker I. , Grunwald H. , D'Arrigo P. , Stein A. , Bloom M. , Goldberg J. , Gottlieb A. , Bennett J. , Kirshner J. , Priore R.
Published: February 2007

Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high‐dose cytosine arabinoside therapy. While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status. The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset.
Pyruvate kinase deficiency in dog and human erythrocytes: Effects of energy depletion on cation composition and cellular hydration
Authors: Muller‐Soyano Aixa , Platt Orah , Glader Bertil E.
Published: February 2007

Pyruvate kinase‐ (PK) deficient human reticulocytes incubated 4 hr under conditions where mitochondrial oxidative phosphorylation is inhibited become ATP‐depleted. Concomitantly, these energy‐depeleted red blood cells (RBC) lose massive amounts of potassium and water. PK‐deficient reticulocyte‐rich RBC from a Basenji dog, incubated under the same conditions, also manifest ATP‐depletion and K‐loss. In contrast to the cation changes in human cells, however, K‐loss in PK‐deficient dog reticulocyte‐rich RBC is balanced by an equivalent Na gain, and consequently these canine erythrocytes do not undergo any change in cellular hydration, Potassium depletion and dehydration, which may be related to membrane injury in human RBC, do not appear to be involved in the hemolysis of PK‐deficient dog erythrocytes.