bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful transfusion of platelets “mismatched” for HLA antigens to alloimmunized thrombocytopenic patients
Authors: Duquesnoy René J. , Filip Donald J. , Rodey Glenn E. , Rimm Alfred A. , Aster Richard H.
Published: February 2007

A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HL‐typed donors needed to procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered to 59 alloimmunized patients who were refractory to “random donor” platelets, it was found that platelets mismatched for 1 or 2 “cross‐reactive” HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded to platelets from donors selectively mismatched for non‐cross‐reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA‐A2 (13%) in comparison to the total patient population (49%). Use of donors whose HLA antigens are serologically cross‐reactive with those of alloimmunized patients provides approximately 10 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.
Differential in vitro sensitivity of marrow erythroid and granulocytic colony forming cells to chloramphenicol
Authors: Yunis Adel A. , Adamson John W.
Published: February 2007

The effects of chloramphenicol (CAP) and thiamphenicol (TAP) on mouse and human in vitro erythroid (CFU‐E) and granulocytic (CFU‐C) colony forming units have been studied. Both drugs inhibited CFU‐E growth in a concentration‐dependent, stereospecific, manner. Complete inhibition of human CFU‐E growth was observed at a CAP concentration of 10 μg/ml while a concentration over 50 μ/ml was required to inhibit CFU‐C growth. Furthermore, whereas the inhibition of CFU‐C growth could be blocked in vitro by high colony stimulating factor concentrations, inhibition of CFU‐E growth was not affected by increased erythropoietin (ESF) levels. The lack of protection by ESF may account for the apparent vulnerability of erythroid cells to CAP in vivo.
Inherited combined deficiency of factor V and factor VIII: Report of a case with normal factor VIII antigen and ristocetin‐induced platelet aggregation
Authors: Cimo P. L. , Moake J. L. , Gonzalez M. F. , Natelson E. A. , Fox K. R.
Published: February 2007

A patient with inherited combined deficiency of factor V and factor VIII is reported, who demonstrated normal levels of factor VIII antigen and plasma co‐factor for ristocetin‐induced platelet aggregation. The relationship of this condition to classical hemophilia and von Willebrand's disease is discussed. The data presented suggest that multiple loci on at least 2 chromosomes are necessary for the normal expression of factor VIII activity.
Deformability characteristics of sickle cells by microelastimetry
Authors: Havell Thomas C. , Hillman Diane , Lessin Lawrence S.
Published: February 2007

Deformability of normal and sickle erythrocytes was measured by means of micropipette elastimetry with determination of intrinsic membrane rigidity (P) and total cell deformability (Pt). In the elastimetric technique employed, negative pressure at the pipette tip was generated and measured continuously. Membrane rigidity is defined as the negative pressure, in mm H2O, required to induce a hemispherical projection of the cell surface into the micropipette, and total cell deformability as the negative pressure required to aspirate the entire cell into the pipette lumen. Membrane rigidity for oxygenated sickle discocytes was not statistically different from that of control normal discocytes, but Pt measurements were significantly higher for sickle than normal discocytes. Irreversibly sickled cells (ISCs) had markedly increased membrane rigidity and whole cell deformability when compared to control normal cells. Mildly deformed ISCs and severely deformed ISCs at ambient pO2, both showed significantly higher mean membrane rigidity values than sickle discocytes and reversibly sickled cells. Sickle and normal discocytes both showed membrane elasticity with reversion to original cell shape following release of the cell from its aspirated position at the pipette tip. ISCs, however, exhibited elastic deformation of the membrane. These studies provide further evidence of progressive alteration of the sickle cell membrane induced by the sickling‐unsickling process, culminating in formation of the ISC, and suggest a role for the ISC membrane abnormality in the pathologic rheology of sickle cell disease.
Platelet satellitism and phagocytosis by neutrophils: Association with antiplatelet antibodies and lymphoma
Authors: White Leonard A. , Brubaker Leonard H. , Aster Richard H. , Henry Patrick H. , Adelstein Edward H.
Published: February 2007

Satellitism and phagocytosis of platelets by neutrophils in EDTA anticoagulated blood have been considered in vitro phenomena without clinical significance. We observed these in a patient with acute, severe thrombocytopenic purpura who subsequently proved to have malignant lymphoma. Wide oscillations in the platelet count were noted and recurrent, severe gastrointestinal bleeding occurred even when the platelet count was normal. Platelet function was abnormal as shown by decreased platelet adhesion to glass beads, absence of a secondary wave of aggregation in response to ADP and epinephrine, and no aggregation with collagen. Suspension of control platelets in the patient's plasma induced similar aggregation defects in the control platelets. Combination chemotherapy resulted in regression of lymphadenopathy, but platelet abnormalities and bleeding persisted. Platelet satellitism and phagocytosis by neutrophils seen on peripheral blood films may be associated with true thrombocytopenia, abnormal platelet function and bleeding with an underlying systemic disease.
Methods for establishing a working immunoradiometric assay for serum ferritin
Authors: Ryan Sherry , Watson Lynn R. , Tavassoli Mehdi , Green Ralph , Crosby William H.
Published: February 2007

The two‐site immunoradiometric assay for measurement of serum ferritin requires purified human ferritin and an avid high‐titer antihuman ferritin antibody. Some of the antibody is radioiodinated following purification by immunoadsorption. All methods for preparation of these materials for the assay are described in minute detail. Performance of the assay itself and calculation of results are also described, and attention is drawn to several potential pitfalls. Adherence to these detailed descriptions will help to eliminate difficulties experienced by centers wishing to establish their own working serum ferritin assay.
Aplastic anemia associated with bone marrow suppressor T‐Cell hyperactivity: Successful treatment with antithymocyte globulin
Authors: Amare Mammo , Abdou Nabih I. , Robinson Maria G. , Abdou Nancy L.
Published: February 2007

In five patients with idiopathic aplastic anemia, the colony‐forming unit (CFU‐c) assay was used to quantitate stem cells and test the possible presence of supressor cells inhibiting bone marrow differentiation. All five marrows failed to form CFU‐c. In one out of the five cases tested, coculture of the patient's marrow with normal marrow suppressed the latter to form CFU‐c. Removal of T‐cells from the patient's bone marrow freed the aplastic marrow to produce more colonies and, in the coculture study, abrogated its inhibitory activity on the normal bone marrow. Treatment of the patient with horse antihuman thymocyte globulin (ATG), improved the peripheral blood count and myelopoiesis. Furthermore, the aplastic marrow increased its colony forming capacity from < 1% pre‐ATG to 46% post‐ATG of the normal control, and its inhibitory activity on the normal marrow was ablated. In selected cases of aplastic anemia, with evidence of T‐suppressor cell hyperactivity, treatment with ATG may offer an alternative approach to bone‐marrow transplantation.
Relapse Following Marrow Transplantation for Acute Leukemia
Authors: Harrison David T. , Flournoy Nancy , Ramberg Robert , Boyd Cheryl , Erne Kathy , Buckner C. Dean , Fefer Alexander , Sanders Jean E. , Storb Rainer , Thomas E. Donnall
Published: February 2007

One‐hundred‐thirty‐six patients who underwent marrow transplantation for endstage acute leukemia were studied with respect to factors that might predict failure to eradicate or recurrence of leukemia following transplantation. One‐hundred‐five patients were recipients of allogeneic and 31 recipients of syngeneic marrow. Sixty‐four patients had acute lymphoblastic leukemia (ALL) and 72 acute nonlymphoblastic leukemia (ANL). The frequency of persistence of leukemia and relapse was 35% for patients with ANL and 44% for those with ALL.

When all the patients are considered as one group pretransplant factors considered simultaneously through proportional hazards modeling showed only the WBC at admission for transplantation to be significant (P = 0.02). The presence of an enlarged spleen, either at diagnosis or at transplantation, was associated with an increased probability of relapse (P < 0.006) among patients with ANL. In patients with ANL. In patients with ALL, active central nervous system (CNS) disease at the time of transplantation significantly increased the risk of relapse in the CNS (P < 0.01). Patients with a white blood cell (WBC) count greater than 20, 000/mm3at admission for transplantation had an increased rate of relapse (P < 0.003). Patients whose leukemic cells showed a karyotypic abnormality on cytogenetic analysis had an increased probability of relapse as compared to those with karyotypically normal leukemic cells (P = 0.04). Following transplantation, the persistence of leukemic cells in the marrow one week after transplantation indicated an increased likelihood of failure to achieve remission and an increased likelihood of subsequent relapse in those who achieved a remission (P < 0.001).
Effect of a single ingestion of alcohol on iron absorption
Authors: Celada Antonio , Rudolf Hans , Donath Alfred
Published: February 2007

The effect of alcohol on inorganic and organic iron absorption was studied in 70 subjects, using a whole‐body counter technique. The mean iron absorption of a test dose was 24.44%, while in the presence of whisky, absorption fell to 9.73% (P < 0.0001). Absorption of a test dose in the presence of whisky without alcohol was 10.14% (P < 0.0001). The alcohol in whisky, therefore, was not responsible for the diminshed iron absorption (P > 0.20).

The absorption of the iron contained in wine with alcohol was 73.31 μg and wine without alcohol was 67.50 μg. The difference was not statistically significant (P > 0.20).

The absorption of inorganic iron contained in a test meal was 165.55 μg and was not changed in the presence of ethanol (151.35 μg) (P > 0.10). However, the presence of ethanol affected the absorption of heme iron: 538.68 μg compared with 442.41 μg with ethanol (P < 0.0001).

These studies show that the acute ingestion of ethanol does not influence the absorption of inorganic iron, while it does diminish the absorption of the organic form.
Spontaneous resolution of severe aplastic anemia associated with viral hepatitis a in a 6‐year‐old child
Authors: Smith Dean , Gribble T. John , Yeager Anne S. , Schwartz Herbert C. , Robinson William , Greenberg Harry B. , Purcell Robert H.
Published: February 2007

Recovery from acquired aplastic anemia associated with hepatitis is rare. This case of a 6‐year‐old boy with severe aplastic anemia is the first reported association of this disease with a hepatitis A infection. Antibody to hepatitis A (anti‐HA) was not detected on admission, but was detected three weeks later. Infection with hepatitis B virus, cytomegalovirus (CMV), and Epstein‐Barr virus (EBV) were excluded. The peak titer of anti‐HA was higher than would be expected for passive transfer of antibody resulting from transfusions. The persistence of antibody for more than 20 months after the last transfusion was not consistent with passive antibody, which would be expected to disappear over that time. This child had indications for allogeneic marrow transplant and a sibling donor who was histocompatible. However, the transplant was postponed because the prognosis was considered to be poor in the presence of active hepatitis. There was a spontaneous remission without the necessity of the transplantation procedure.
Red‐cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosis: Reversal with corticosteroid therapy
Authors: Cavalcant Jack , Shadduck Richard K. , Winkeistein Alan , Zeigler Zella , Mendelow Harvey
Published: February 2007

A 29‐year‐old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of eryihroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis.

The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.
Disseminated intravascular coagulation and related syndromes: Etiology, pathophysiology, diagnosis, and management
Authors: Bick Rodger L.
Published: February 2007

Disseminated intravascular coagulation (DIC) is being recognized with increased frequency and not only are newer diagnostic modilities becoming available for this syndrome, but newer, some controversial, methods of management are also being recognized and may prove to increase survival in DIC. In addition, several syndromes classically considered seprate, definitive disease entities, may actually share similar or identical pathophysiology to DIC. This review summarizes current, as well as controversial aspects of the etiology, pathophysiolog, clinical and laboratory diagnosis, and management of DIC. In addition, a brief discussion of syndromes which may share similar or identical pathophysiology to DIC is included.
Serial studies on in vitro colony formation in patients with acute leukemia in relation to the maintenance of remission
Authors: Kubota Kazuo , Mizoguchi Hideaki , Miura Yasusada , Chiyoda Shin , Muto Yoshitomo , Takaku Fumimaro
Published: February 2007

For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU‐C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU‐C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU‐C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensification therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU‐C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU‐C's are not reduced significantly should be treated intensively again within a short period.
Marrow adipose tissue: Response to erythropoiesis
Authors: Bathija Ambika , Davis Stephen , Trubowitz Sidney
Published: February 2007

A group of rabbits was treated chronically with phenylhydrazine to induce hemolysis and stimulate erythropoiesis. The mean volume of the marrow fat cell of a control group of hematologically normal rabbits was 54.8 pl; the mean volume of the perinephric fat cell was 549.5 pl, a volume ratio, perinephric/marrow of 10: 1. In the experimental animals the mean volume of the marrow fat cell fell to 25.9 pl; the volume of the perinephric fat cell was unchanged and the volume ratio, perinephric/marrow was 18: 1. Fat cell volume studies performed on rabbits subjected to chronic bleeding yielded comparable data. The l‐C14 palmitate uptake (esterification capacity) calculated on a cell basis was the same for both marrow and perinephric fat cells and was unaffected by phenylhydrazine treatment. The fatty acid composition shows higher content of unsaturated fatty acids in the marrow fat than in the perinephric fat of the control animal. In the experimental animal there appears to be a preferential release of the unsaturated fatty acid. The findings of the study suggest that increased hematopoiesis stimulates lipolysis of marrow fat cells, probably through the local release of a chemical substance. Marrow fat appears to be functionally related to hematopoiesis rather than to systemic fat storage. Marrow fat may be involved in the metabolic support of hematopoiesis.
Giant platelet granules in a child with the chediak‐higashi syndrome
Authors: Parmley R. T. , Poon M.‐C. , Crist W. M. , Malluh A.
Published: February 2007

Previous ultrastructural investigations have not identified abnormal lysosomes in platelets obtained from humans or animals with the Chediak‐Higashi Syndrome. We report here a patient whose megakaryocytes and platelets were found to contain giant granules when viewed by light and electron microscopy. The granules measured up to 1.5 μm in diameter, contained either homogeneous or heterogeneous material, were acid phosphatase positive, and were present in approximately 30% of bone marrow megakaryocytes and 5% of circulating platelets. A decrease was observed in serotonin containing dense granules, serotonin uptake and serotonin release as reported previously. Microtubules in platelets and megakaryocytes were intact and no other morphologic abnormalities were identified. No clinical evidence of bleeding was observed in this patient and platelet counts have been normal. The lack of giant platelet lysosomes in other reported cases of Chediak‐Higashi Syndrome attests to significant heterogeneity in this disease with a spectrum of clinical and laboratory findings.
Posttransfusion purpura: Therapeutic failure of PlAl‐negative platelet transfusion
Authors: Gerstner James B. , Smith Martin J. , Davis Kent D. , Cimo Philip L. , Aster Richard H.
Published: February 2007

The effect of platelet type‐specific transfusion in posttranfusion purpura is reported. Seven days after receiving 4 units of whole blood during total hip replacement a 69‐year‐old woman developed fulminant thrombocytopenic purpura. Her undiluted serum inhibited the clot retraction of PlAl‐positive, but not PlAl‐negative blood. Anti‐PlAl titer of her serum, determined by 51Cr platelet lysis technique, was 1:64. The serum had no lytic activity against platelet‐rich plasma from two PlAl‐negative donors. No anti‐HLA antibody was detectable in the serum by lymphocytotoxicity technique, and serum obtained prior to transfusions had no platelet lytic activity. Four units of PlAl‐negative platelet concentrate were administered, the first instance in which this treatment has been used. No rise in platelet count ensued, and the patient succumbed to purpura. Exchange transfusion or plasmapheresis remain the treatments of choice.
Heparin‐induced thrombocytopenia: Association with a platelet aggregating factor and arterial thromboses
Authors: Cimo Philip L. , Moake Joel L. , Weinger Ronald S. , Ben‐Menachem Yoram , Khalil Kamal G.
Published: February 2007

Eleven patients with heparin‐induced thrombocytopenia were studied. Thrombocytopenia appeared 3–16 days following the initiation of prophylactic or therapeutic doses of heparin. The mean lowest platelet count recorded was 48,000/mm3. When heparin was stopped, recovery from thrombocytopenia began within 24 hours and was complete by ten days. Two patients developed fatal thromboses, and two others had myocardial infarctions while thrombocytopenic. In the serum of seven patients, including three of the four with arterial thrombosis, a heparin‐dependent platelet aggregating factor was present. The factor caused release of platelet 14C serotonin but did not lyse platelets. It was present in the globulin fraction of all positive sera, and in one serum studied it was isolated in the IgG/IgA immunoglobulin fraction. The factor was not present in 16 normal sera or in the sera of 15 nonthrombocytopenic patients receiving heparin. Our observations suggest that heparin‐induced thrombocytopenia is common and that, in some patients it may be accompanied by severe arterial thrombosis. In vivo platelet aggregation is a possible explanation for the thrombocytopenia and the thrombosis in this disorder.
Bone marrow adipose tissue: Response to acute starvation
Authors: Bathija Ambika , Davis Stephen , Trubowitz Sidney
Published: February 2007

Adipose tissue is a major component of normal rabbit marrow. Its physiologic function has not been elucidated, but it is generally believed to be, essentially, a passive space filler. The response of marrow fat cells to lipolytic stimuli was studied by subjecting rabbits to acute starvation. Following 2 weeks of starvation and a weight loss of 28%, the mean marrow fat cell volume was 50.9 ± 9.6 pl (control, 42.8 ± 8.1 pl), and the mean volume of the perinephric fat cell 134.3 ± 87.8 picoliter (pl) (control, 318 ± 89.7 pl). Esterification capacity for labeled palmitate of the marrow fat cells did not change from control; the esterification capacity of the perinephric fat cells fell by about 60%. After 3 weeks of starvation and further weight loss to 34% of initial weight, the perinephric fat cells decreased their mean cell volume to 50.2 ± 33.6 pl. The marrow fat cell volume remained essentially unchanged from control. Esterification capacity of the marrow fat cells again did not differ from that of the control animals, but the esterification capacity of the perinephric fat cells fell further to 19% of that of the marrow fat cells. Despite the urgent energy requirements of the starved animals, the marrow fat cells did not yield their stored fat and continued to esterify free fatty acids at an unaltered rate. Drastic weight loss produced no change in volume, in esterification capacity, or in number of fat cells in the femoral marrow of the rabbit. Marrow adipocytes are metabolically active cells that are involved in the hematopoietic process rather than involved with the total energy needs of the animal.
Nonspecific serum iron in thalassemia: Quantitation and chemical reactivity
Authors: Graham Gary , Bates George W. , Rachmilewitz Eliezer A. , Hershko Chaim
Published: February 2007

We reported earlier an abnormal iron population in the serum of patients with transfusional hemosiderosis secondary to thalassemia. The iron is not bound to transferrin, ferritin, or hemoglobin and is referred to as nonspecific iron. This publication reports studies of the chemical reactivity and nature of the nonspecific iron and the development and validation of a method for its quantitative analysis. The quantitation depends on the mobilization of this iron from nonspecific macromolecular binding sites by ethylenediamine tetraacetic acid and subsequent separation from Fe3+‐transferrin‐CO⅔− and residual hemoglobin by ultrafiltration. Analyses of filtrate iron were carried out by atomic absorption and colorimetric methods. The accuracy of the test was established via an ultrafiltration titration of serum of known unsaturated iron‐binding capacity. The method proved to be accurate and highly reproducible. Sera containing artificial introduced nonspecific iron were prepared. The reactivity of artificial and thalassemic nonspecific iron was examined with regard to reduction and chelation, and chelation by apotransferrin. Artificial and thalassemic nonspecific iron were found to be virtually identical in reactivity and to exhibit multiphasic kinetics consistent with nonspecific binding to several serum protein sites. The reaction of apotransferrin with nonspecific iron was complete within one minute. The reduction‐chelation and apotransferrin reactivity studies offer independent analyses of nonspecific serum iron concentrations which compared closely with the chelation‐ultrafiltration technique.
Cold agglutinin autoimmune hemolytic anemia in nonhematologic malignancies
Authors: Wortman J. , Rosse W. , Logue G.
Published: February 2007

Four patients with nonhematologic malignancies had the simultaneous finding of hemolytic anemia due to high‐titer cold agglutinins. In each patient, the cold agglutinin had “anti‐I” specificity and was of the IgM kappa immunoglobulin class. Although patients with hematologic malignancies not uncommonly have cold agglutinins, the association between these antibodies and nonhematologic malignancies is unusual.
Zinc inhibition of calmodulin: A proposed molecular mechanism of zinc action on cellular functions
Authors: Brewer George J. , Aster Jon C. , Knutsen Conrad A. , Kruckeberg Walter C.
Published: February 2007

Calcium stimulates, and zinc inhibits, a wide variety of cell types. In the erythrocyte, we have found calcium and zinc to have antagonistic actions in a variety of systems. An important mechanism for calcium effects on cells is activation of calmodulin. Calmodulin is a small ubiquitous protein which, when activated by calcium, has a large array of cellular regulatory functions. We now report that calmodulin function is inhibited by low concentrations of zinc. Zinc inhibition of calmodulin provides a rational molecular mechanism for the diverse cellular inhibitory effects of zinc, as well as for zinc's antagonism of calcium effects.
Acute idiopathic thrombocytopenic purpura in children
Authors: McWilliams Nancy B. , Maurer Harold M.
Published: February 2007

Acute idiopathic thrombocytopenic purpura (ITP) characteristically follows a viral illness in preschool children. The exact role of viruses in the pathogenesis of this disorder remains uncertain, but the finding of markedly elevated levels of platelet‐associated IgG serves to distinguish it from the chronic form of the disease and permits speculation on the mechanisms of platelet destruction. Although the spleen is important in both antibody production and platelet destruction, bone marrow synthesis of IgG has also been shown to be increased.

The clinical course may be alarming, but mortality is low and prognosis excellent. Controversy has surrounded the role of steroids in the management of acute childhood ITP in retrospective studies. Controlled studies, however, indicate that thrombocytopenia is reversed sooner in treated patients.

New assays for platelet‐associated IgG offer new insights into this disorder and will allow delineation of acute and chronic disease at the time of diagnosis.
Characterization of platelets from normal mink and mink with the Chediak‐Higashi syndrome
Authors: Meyers K. M. , Holmsen H. , Seachord C. L. , Hopkins G. , Gorham J.
Published: February 2007

Bleeding times of mink with the Chediak‐Higashi (CH) syndrome was markedly prolonged. Platelet counts were normal but there was an impaired platelet aggregation response to collagen. The metabolic adenine nucleotide pool of platelets from normal and CH mink was labeled with 14C‐adenine and the platelets were gel‐filtered. Gel‐filtered platelets (GFP) from CH mink contained only 37.9% of the adenosine triphosphate (ATP) and 9.6% of the adenosine diphosphate (ADP) found in normal platelets and the ATP/ADP ratio was similar to the 14C‐ATP/14C‐ADP ratio. Platelet content of Ca2+, Mg2+, and in particular 5‐hydroxytryptamine was decreased. When GFP were incubated with thrombin to induce maximal secretion, only negligible amounts of ATP and ADP were released. The specific activity of the extracellular nucleotides approximated that within the platelet. These findings suggest that the stored nucleotide pool in CH platelets is virtually absent and that the abnormalities in platelet function may be due, in part, to the essential absence of secretable ADP and serotonin. The release of Ca2+ and Mg2+ by CH platelets was 56% and 27.8% of normal, respectively.
Autoimmune hemolytic anemia and the kell blood groups
Authors: Marsh W. Laurence , Øyen Ragnhild , Alicea Edith , Linter Meredith , Horton Susan
Published: February 2007

Approximately one in 250 people with autoimmunity involving their red cells have IgG autoantibodies with specificity in the Kell blood groups. Red cells of these individuals have an acquired temporary weakening of their Kell antigens. Some of the patients also have allo‐anti‐K in their serum. This report presents a case in which an IgG autoantibody may define a new high‐incidence red cell antigen related to the Kell blood groups. The patient's Kell blood group antigens are depressed, and his serum contains allo‐anti‐K. It is postulated that reduced red cell Kell antigenicity is caused by enzymatic degradation, possibly of bacterial origin, and that the acquired loss of Kell antigens, the Kell‐specific autoimmune state, and the serum allo‐anti‐K, are all related aspects of one phenomenon.
Fetal to adult hemoglobin switch in cultures of early erythroid precursors from human fetuses and neonates
Authors: Beuzard Yves , Vainchenker William , Testa Ugo , Dubart Anne , Monplaisir Nicole , Breton‐Gorius Janine , Rosa Jean , Bouguet Jacqueline , Cacheleux Janine , Rouyer‐Fessard Philippe
Published: February 2007

Erythroid burst colonies derived from the cord blood of nine neonates and from the blood and liver of three fetuses aborted after 20 weeks of gestation were grown in plasma clot culture. Their quantitative study revealed a higher proportion of burst‐forming units (BFU‐Es) in cord blood than in cord blood of normal adults. In addition, colony‐forming units (CFU‐Es) were present in cord blood but absent from adult blood. Study of haemoglobin synthesis in 14‐day cultures of cord blood BFU‐Es showed a significantly higher degree of Hb A synthesis than was found in reticulocytes from fresh cord blood; this proportion was, however, similar to that expected in vivo about three weeks after birth. These data suggest that the hemoglobin switch is already programmed in most of the early erythroid precursors present in cord blood of full‐term neonates and indicate that the differentiation time is probably of the same order of magnitude in vivo and in vitro. The proportion of Hb A and F synthesis in erythroid bursts was not influenced by the concentration of erythropoietin in the range studied – ie, from 0.5 to 12 international units. Low but identical proportions of Hb A synthesis were found both in erythroid cells from liver after two hours of incubation with [3H]‐leucine, and in 14‐day liver bursts from fetuses aborted at 20 weeks of gestation.
The diagnosis of pulmonary thromboembolism in sickle cell disease
Authors: Walker Brian K. , Ballas Samir K. , Burka Edward R.
Published: February 2007

The symptoms of thromboembolism in sickle cell anemia patients with acute chest syndromes are difficult to differentiate from the similar symptoms of painful thoracic crises and infectious pulmonary episodes. Furthermore, the chronic pulmonary abnormalities in sickle cell disease frequently contribute to the confusing results of noninvasive diagnostic procedures usually employed in evaluating pulmonary thromboembolism. In this study the chronic pulmonary status of asymptomatic sickle cell patients was defined, and this information was used in the evaluation of patients with acute chest syndromes suggestive of pulmonary thromembolism. Sixteen asymptomatic sickle cell patients were prospectively studied by chest roentgenography, spirometry, arterial gas analyses, and radioisotopic lung scans. There was an appreciable degree of preexisting chronic restrictive lung disease with mild to moderate arterial hypoxemia and abnormal lung scans in more than half of the patients. These prospective baseline data were incorporated into the diagnostic evaluation of four of these patients who later developed an acute chest syndrome suggestive of pulmonary thromboembolism. Determination of the cause of the chest pain was greatly facilitated by the existence of the baseline pulmonary data. In another patient persistence of abnormal studies following a presumed thromboembolic episode aided diagnostic evaluation when another episode of chest pain occurred. The findings indicate that comprehensive pulmonary studies in sickle cell patients while in an asymptomatic state will provide baseline data which aid the evaluation of possible pulmonary thromboembolism in acute chest syndromes without resorting to high‐risk invasive studies.
Oxygen dissociation curves in children with anemia and malignant disease
Authors: Festa Robert S. , Asakura Toshio
Published: February 2007

Two automatic apparatuses utilizing a dual wavelength spectrophotometer were used to perform oxygen dissociation curves on microsamples of blood. The method provides a complete print‐out of an oxygen dissociation curve in 15–20 min and the P50 values obtained in normal individuals agree closely with those obtained by classical methods. These apparatuses were used to measure oxygen affinity, ie P50, in anemic children with malignant disease prior to treatment and in children undergoing therapy. Red cell 2,3‐DPG levels were also measured. In patients with anemia at the time of diagnosis and prior to therapy, the P50 values and 2,3‐DPG levels were elevated as is usual in other types of anemia. However, when oxygen affinity and 2,3‐DPG levels were measured in anemic patients receiving treatment, three types of response to anemia were noted: 1) increased P50 and 2,3‐DPG; 2) normal or low P50 and 2,3‐DPG, and; 3) normal or low P50 with increased 2,3‐DPG. Patients who adapted poorly to anemia during treatment had usually received prior intensive chemotherapy and transfusion therapy, and their pattern of red cell glycolytic intermediates was consistent with a red cell population with an increased cell age. The failure of some patients to respond to anemia with a decrease in oxygen affinity has implications in regards to the hemoglobin level at which they should be transfused.
Mechanisms of thrombocytopenia in varicella
Authors: Feusner James H. , Slichter Sherrill J. , Harker Laurence A.
Published: February 2007

51Cr‐labeled platelet and 125I‐labeled fibrinogen kinetic studies in four thrombocytopenic children with varicella infection revealed marked platelet destruction (platelet survival times 0.1, 0.4, 1.0, and 2.4 days) and relatively normal fibrinogen disappearance. The platelet count was directly related to the platelet survival time. Marrow megakaryocyte mass was increased twofold to fourfold. IgG or IgM antiplatelet antibody was present on autologous platelets in the three patients tested. These data suggest that thrombocytopenia in some patients with varicella is the consequence of immune mediated platelet destruction.
(Ca2++Mg2+)‐ATPase activity of sickle cell membranes: Decreased activation by red blood cell cytoplasmic activator
Authors: Gopinath Rama M. , Vincenzi Frank F.
Published: February 2007

Human red blood cells (RBCs) contain a cytoplasmic protein that activates membrane‐bound (Ca2+ + Mg2+)‐ATPase and the transport of Ca2+. The (Ca2+ + Mg2+)‐ATPase of sickle cells showed a less than normal response to this activator. This was true whether the activator was obtained from normal or sickle cells. Activator present in sickle cell hemolysates fully activated the (Ca2+ + Mg2+)‐ATPase of normal RBC membranes. These results demonstrate that membranes of sickle cells are defective in their response to the activator. Neither the apparent affinity for calcium nor the apparent affinity for activator was different comparing the (Ca2+ + Mg2+)‐ATPase of sickle and normal membranes. Young, mature, and irreversibly sickled cells were separated by density gradient centrifugation, and membranes were prepared from each of these cell populations. No significant differences in ATPase activities were found based on cell age (density). The (Ca2+ + Mg2+)‐ATPase of all populations of sickle cells showed a decreased response to the activator. Thus, it appears unlikely that the decreased response of the (Ca2+ + Mg2+)‐ATPase of sickle cells is due to membrane damage caused by repeated sickling during the life‐span of the cell. Reduced activation of (Ca2+ + Mg2+)‐ATPase by the cytoplasmic activator may account for calcium accumulation in sickle cells.
Abnormal lymphocyte deoxyuridine suppression test: A reliable indicator of decreased lymphocyte folate levels
Authors: Colman Neville , Herbert Victor
Published: February 2007

The deoxyuridine (dU) suppression test measures the availability of folate and, indirectly, vitamin B12 in de novo thymidine synthesis and is of established value in defining biochemical megaloblastosis in bone marrow cells. Recent studies have suggested that the application of this test to DNA synthesis in transformed lymphocytes may be valuable in defining nutrient deficiency that is subtle, masked, or present in some cell lines but not in others. This use of the test has not been fully accepted because lymphocyte folate and B12 levels had not been simultaneously measured prior to the current study. In this study, vitamin availability for the dU suppression test was closely correlated with folate levels in radioassay and less well correlated with vitamin B12 levels in the cell. The folate levels varied widely when dU suppression was efficient but were uniformly low in subjects with ineffective dU suppression. These studies validate the use of the lymphocyte dU suppression test as a means of detecting folate deficiency in this cell line.
Quantitative assessment of bactericidal ability of leukemic cells in childhood acute leukemia
Authors: Komiyama Atsushi , Saitoh Hiroharu , Kawai Hiroshi , Tsukada Masashige , Akabane Taro
Published: February 2007

Bactericidal ability of leukemic cells was evaluated in four children with acute myeloblastic leukemia (AML) and in two with acute monocytic leukemia (AMoL) by means of quantitative assay of intracellular viable bacteria and by electron microscopy. The electron microscopy confirmed phagocytosis of Staphylococcus aureus by the leukemic cells. The leukemic cells killed a significantly smaller proportion of phagocytized bacteria than normal neutrophils. In some patients the leukemic cells virtually lacked bactericidal ability, despite presence of phagocytic ability. The defect of the cells in killing bacteria was more prominent in AML than in AMoL.

The clinical importance of the defective bactericidal ability of leukemic cells is discussed.
Mechanism of arsenic‐induced inhibition of erythropoiesis in mice
Authors: Morse Bernard S. , Conlan Maureen , Giuliani Dennis G. , Nussbaum Murray
Published: February 2007

Anemia accompanies arsenic intoxication in man. The present studies were undertaken to clarify further the effects of arsenic on erythropoiesis. A dose‐related inhibition of red cell 59Fe incorporation and reticulocyte response was observed in normal mice treated with a single injection of arsenic. Arsenite was approximately two times as inhibitory as arsenate. The effects of arsenic on erythropoietin‐induced erythroid differentiation revealed a significant inhibitory effect on young, proliferating marrow nucleated erythroid precursor cells. More mature, nonproliferating nucleated erythroid cells were resistant to the toxic action of arsenic. A dose‐related inhibitory effect of arsenic on DNA synthesis was observed in fetal liver nucleated erythroid cells incubated with 3H thymidine. Ineffective erythropoiesis as well as the megaloblastic morphology accompanying aberrant DNA synthesis – manifestations of arsenic toxicity in man – were not evident in the present studies.
Plasma beta‐thromboglobulin values in thrombocytopenic patients with acute leukemia
Authors: Kutti Jack , Zaroulis Charles G. , Kulpa Jolanta , Reich Lilian , Clarkson Bayard D. , Good Robert A.
Published: February 2007

Plasma beta‐thromboglobulin (β‐TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma β‐TG levels ranged 12–38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma β‐TG and venous platelet count was present.

During a thrombocytopenic period, the plasma β‐TG concentration was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was <38.5° C, and 18 when the highest temperature of the day was <38.5°C. The mean pretransfusion and post‐transfusion β‐TG values for the 14 platelet transfusions were 7 ± 2 and 20 ± 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 ± 2 ng/ml and 11 ± 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range.

We conclude that the plasma β‐TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma β‐TG over a wide range of venous platelet counts.
Acute promyelocytic leukemia—clinical management of 15 patients
Authors: Daly Peter A. , Schiffer Charles A. , Wiernik Peter H.
Published: February 2007

Fifteen patients with acute promyelocytic leukemia (APL) were treated with anthracycline agents alone or combined with arabinosylcytosine (Ara C). Disseminated intravascular coagulation (DIC) was managed individually based on the presence of clinical as well as laboratory evidence of DIC. Ten patients received heparin. Eleven patients (73%) achieved complete remission (CR) but there were two early deaths from infection. The median duration of CR was 232 days (range, 41–780 days). Six patients were studied during ten relapses. In all cases, a morphologic picture more typical of acute myelocytic leukemia was seen during relapse but the DIC was similar in severity to that seen initially. Fever, without obvious infection and possibly due to the leukemic process, was a common presenting feature. Regenerating bone marrow aspirates in many patients who subsequently achieved CR without further treatment showed an inordinate number of promyelocytes, and this finding should not be immediately interpreted as disease resistant to therapy.
Relationship of SV40 T‐antigen expression in vitro to disorders of bone marrow function
Authors: Lubiniecki A. S. , Blattner W. A. , Dosik H. , McIntosh S. , Wertelecki W.
Published: February 2007

Skin fibroblasts from patients with a variety of hematologic disorders were infected with SV40 virus in vitro in attempts to discover the reason for increased susceptibility of Fanconi anemia cells to this transforming virus. The proportion of skin fibroblasts expressing SV40 T‐antigen by immunofluorescent methods was elevated in 12 patients with Fanconi anemia and in seven of nine obligate heterozygous relatives. Elevated expression was also observed in three patients with other hematological disorders at high risk of acute nonlymphocytic leukemia, but was not apparent in seven sporadic aplastic anemia patients or four of their relatives. T‐antigen expression was elevated in about one‐half of patients with thrombocytopenia‐absent radius syndrome and related conditions, with familial aplastic anemia, and in their normal relatives. In the conditions under study, elevated T‐antigen expression seemed clearly correlated with predisposition to leukemia, which may be genetically determined, but it was not associated with cytogenetic or anemic manifestations.
Pseudo‐drumsticks in granulocytes of a male with a Yqh+ polymorphism
Authors: Moore Charleen M. , Weinger Ronald S.
Published: February 2007

An individual with normal male habitus, body proportions, and secondary sexual characteristics was admitted to the hospital with head trauma. A routine blood smear demonstrated that 36% of the granulocytes had “drumsticks.” Chromosomal analysis revealed a 46, XYqh+ karyotype. The extremely large Y chromosome was located by quinacrine fluorescence in the “drumstick” of the polymorphonuclear granulocytes. The presence of a large Y chromosome may thus produce pseudo‐drumsticks. Fluorescent staining can distinguish between true drumsticks bearing the inactive X of normal females and the pseudo‐drumsticks in a normal male produced by a large Y chromosome.
Acute unclassified leukemia. A clinicopathologic study with diagnostic implications of electron microscopy
Authors: Youness Ehsan , Trujillo Jose M. , Ahearn Michael J. , McCredie Kenneth B. , Cork Ann
Published: February 2007

By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate‐reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase‐positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocytic leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AMonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.