bluuebunny/crossref_metadata_2025 huggingface dataset:
A heparin‐like anticoagulant in an 8‐month‐old boy with acute monoblastic leukemia
Authors: Bussel James B. , Steinherz Peter G. , Miller Denis R. , Hilgartner Margaret W.
Published: February 2007

An 8‐month‐old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin‐antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
The multiple coagulopathies of biliary atresia
Authors: Yanofsky R. A. , Jackson V. G. , Lilly J. R. , Stellin G. , Klingensmith W. C. , Hathaway W. E.
Published: February 2007

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII‐X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K‐deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two‐stage (TGT) method than by the one‐stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K‐deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
An analysis of prognostic factors in preleukemia: Interest of bone marrow scintigraphy
Authors: Chomienne C. , Najean Y. , Vigneron N. , Dresch C. , Rain J. D.
Published: February 2007

Simultaneous bone marrow scintigraphy with 99m Technetium colloids and 111 Indium transferrin was performed on 34 cases of preleukemic anemias and was shown to be of good prognostic value. Groups of different outcome were defined: for a normal and parallel uptake of the two markers, 90% of the patients died of acute leukemia; for a low Indium and high Technetium uptake, only 1 patient out of 15 died of leukemia (P < 0.001). Standard clinical and hematological data were of no predictive value. Iron kinetic data and CFU/GM colony growth were correlated to the scintigraphic results. Taken together, these three kinetic parameters have a good sensitivity and specificity for the prognosis of preleukemic states.
Factor VIII: Structure and function in blood clotting
Authors: Chavin Stephen I.
Published: February 2007

Factor VIII (antihemophilic factor) is the protein that is deficient or defective in patients with classical hemophilia and Von Willebrand syndrome. Factor VIII in plasma is thought to be associated in a complex with the highest molecular weight multimers of another glycoprotein, Von Willebrand protein. Highly purified human factor VIII appears to have an Mr of between 200, 000 and 300,000 and to consist of several polypeptide chains. The concentration of factor VIII in plasma is around 100‐200 ng/ml, equivalent to around 1 nM. The purified proteins retain one or more of the known properties of factor VIII, including the acceleration of factor IXa‐mediated activation of factor X, ability to be activated by thrombin and factor Xa, inactivation by activated protein C, and by human antibodies to factor VIII.

Among the known clotting factors, factors VIII and V are exceptional in not possessing enzymatic activity. Factors IX3 and VIII and X appear to form a functional complex, all of which need to be present and active simultaneously for optimal activation of factor X. The mechanism by which factor VIII promotes activation of factor X by factor IXa is not known, but the major effect is to increase the rate of the reaction.

Following treatment of factor VIII with thrombin, a new and smaller polypeptide Mr around 70,000 ± 5,000 is produced. Factors IXa and Xa also have been reported to activate factor VIII. It is not known whether limited proteolytic cleavage is required absolutely for the expression of factor VIII activity or if it only increases an activity already expressed by the uncleaved protein. Factor VIII is inactivatd by thrombin and by activated protein C. Thus, factor VIII can be modulated by at least four of the serine proteases in the clotting system. A major goal for future research is to increase our understanding of the role in blood clotting played by factor VIII, and to apply this information to clinical problems which result from inherited abnormalities of factor VIII.
Effect of epinephrine on fibrinogen receptor exposure by aspirin‐treated platelets and platelets from concentrates in response to ADP and thrombin
Authors: Peerschke Ellinor I. B.
Published: February 2007

Synergistic effects between agonists on platelet aggregation have long been appreciated. Recently epinephrine was reported to induce maximal aggregation of aspirin‐treated platelets when combined with ADP or thrombin, and to increase fibrinogen binding of nonaspirin‐treated platelets stimulated with low doses of ADP. The present study extends these observations to correlate fibrinogen binding in response to various combinations of ADP, epinephrine, and thrombin with platelet aggregation and 14C‐serotonin release using aspirin‐treated platelets as well as platelets from stored concentrates. When fresh platelets were stimulated with epinephrine (5 μM) together with either ADP (10 μM) or thrombin (150 mU/ml), fibrinogen binding increased by 180% compared to binding observed in response to ADP or thrombin alone. This was accompanied by enhanced platelet aggregation, but no increase in 14C‐serotonin release. While both ADP and epinephrine potentiated the aggregation and fibrinogen binding of stored platelets in response to high doses of thrombin (150 mU/ml), maximal aggregation was achieved only with thrombin (150 mU/ml) and epinephrine (5μM) in combination. The data thus suggest that 1) epinephrine induces maximal aggregation of aspirin‐treated platelets stimulated with thrombin or ADP by significantly enhancing fibrinogen receptor exposure independently of the cyclooxygenase‐mediated release reaction; 2) epinephrine stimulates platelets by a mechanism different from that of thrombin or ADP; and 3) as demonstrated by others, the ability of platelets from stored concentrates to aggregate and to bind fibrinogen in response to ADP can be enhanced by epinephrine, and, in addition, these platelets can aggregate and bind fibrinogen maximally when stimulated with combinations of epinephrine and thrombin.
Monocyte transferrin‐iron uptake in hereditary hemochromatosis
Authors: Sizemore Delton J. , Bassett Mark L.
Published: February 2007

Transferrin‐iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe‐labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron‐loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin‐iron uptake by these cells.
A further characterization of the selective K movements observed in human red blood cells following acetylphenylhydrazine exposure
Authors: Orringer Eugene P.
Published: February 2007

Following brief exposure to acetylphenylhydrazine, the potassium permeability of the human erythrocyte membrane is selectively augmented. While a similar increase in potassium permeability results from the intracellular accumulation of calcium (the Gardos phenomenon), we have found a number of features that allow these two pathways to be distinguished from one another. The acetylphenylhydrazine pathway does not require calcium for its activation, and can be seen even in the presence of a molar excess of the calcium chelator EGTA. The transmembrane potassium movement via this channel has a specific requirement for the anion chloride, and it can be inhibited by furosemide. The potassium that moves through the Gardos pathway, on the other hand, can be accompanied by any permeant anion, and is inhibitable by quinidine or cetiedil. Thus, acetylphenylhydrazine exposure seems to promote K + Cl cotransport, whereas the Gardos pathway represents a potassium conductive channel.

While full demonstration of both these pathways requires harsh in vitro manipulation, the large electrochemical potassium gradient favoring the movement of this cation out from the erythrocyte suggests that even a partial activation of either pathway could cause intracellular dehydration and thus contribute importantly to the pathophysiology of in vivo red cell destruction.
Absence of platelet activating factor (PAF) mediated platelet aggregation: A new platelet defect
Authors: Pelczar‐Wissner Catherine J. , McDonald Elizabeth G. , Sussman Ira I.
Published: February 2007

The failure of normal human platelets to aggregate in response to platelet activating factor (PAF) has not been previously observed. We report here the first case of a patient whose platelets did not aggregate to PAF on multiple occasions.
Serum from outdated human platelet concentrates: An alternative supplement for tissue (fibroblast) culture media
Authors: Schwartz Kenneth A. , Lu Gina , Trosko James E. , Chang Chia‐Cheng
Published: February 2007

Fetal calf serum (FCS) is used as a component of the media for cells grown in culture. However, the high cost of FCS has stimulated a search for a possible alternative. Approximately 10% of human platelet concentrates prepared for clinical transfusions are outdated. Sera prepared from platelet concentrates were compared with FCS and calf serum (CS) as a media supplement. A similar number of fibroblast (NSF‐791) colonies grew in media supplemented with the three different sera. However, colonies grown in the presence of human platelet serum (HPS) were larger than those grown in media containing CS and FCS. Hence, serum prepared from outdated human platelet concentrates may be substituted for fetal calf serum as a cell culture nutrient, for fibroblasts.
Effects of thymocytes on marrow cells from normal and Busulfan‐treated mice
Authors: Adler Solomon S.
Published: February 2007

To study the effects of thymocytes on hemopoiesis, we 1) cocultured marrow cells with and without thymocytes in an erythroid burst (BFU‐E) culture system, 2) injected marrow cells with and without thymocytes into supralethally irradiated mice to assay CFU‐S, and 3) assessed the survival of supralethally irradiated mice transplanted with marrow cells with or without thymocytes. The marrow cells used were either from mice given six injections of busulfan and then permitted to rest for 2, 5, or 10 weeks or from mice treated similarly with the busulfan vehicle alone. Thymocytes did not alter spleen surface colony counts or survivorship in any of the test groups. Thymocytes did effect an increase in BFU‐E cultured from marrow obtained from the vehicle‐treated mice but not from marrow of busulfan‐treated mice. Thus, in addition to decreasing the population of hemopoietic precursors in the marrow, busulfan alters the nature of the remaining early erythroid precursor cell population rendering it unresponsive to thymocytes in vitro.
Enzymes of purine metabolism in B‐chronic lymphocytic leukemia
Authors: Vertongen F. , Cauchie C. , Courtois P. , Fondu P. , Mandelbaum I. M.
Published: February 2007

In order to study if enzymes of purine metabolism could be used as cell markers in B‐chronic lymphocytic leukemia (B‐CLL), the activities of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5′‐nucleotidase (5′N) were repeatedly measured in blood mononuclear cells from B‐CLL patients and were compared to those obtained in normal controls. Enzyme activities in patients were also compared to other biological parameters indicative of B‐CLL to activities of ADA and PNP in erythrocytes.

Results show that B‐leukemic cells display abnormal enzyme patterns: subnormal ADA activity is characteristic; 5′N activity is depressed in 60% of the cases but increased in 15%. An inverse relationship between PNP activity and corresponding lymphocytosis is observed in leukemic but not in normal cells. The enzymatic anomalies seem to be linked to the presence of an unusual peripheral lymphocytic population, induced by the leukemic process. Indeed, ADA and PNP are not abnormal in erythrocytes. In untreated nonevolutive patients, the enzyme profile tends to remain stable throughout the course of the illness; normalization of enzyme patterns in treated patients occurs only when therapy induces improvement in T and B cell distribution.
Comparison of continuous and intermittent factor VIII concentrate therapy in hemophilia A
Authors: Hathaway W. E. , Christian M. J. , Clarke S. L. , Hasiba U.
Published: February 2007

Comparison of continuous versus intermittent (every 12 h bolus) infusion of a highpurity Factor VIII concentrate in 12 severe hemophilia A patients undergoing surgical procedures indicated that a higher (50 u/dl versus 35 u/dl) minimal plasma level was seen with the same amount of product when given continuously. A continuous VIII concentrate infusion of 2 u/kg/h produces a mean VIIIc level of about 50 u/dl or, alternatively, about 0.04 u/kg/h raises the VIIIc level by 1 u/dl (1%). None of the patients showed any abnormal bleeding. Higher plasma levels of VIIIc were noted by the two‐stage VIIc assay than by the one‐stage VIIIc assay. Fibrinogen levels were normal or only slightly elevated, and the monomer test was consistently negative.
Confirming evidence for the clonal development and stem cell origin of philadelphia chromosome‐negative chronic myelogenous leukemia
Authors: Kaye Frederic J. , Najfeld Vesna , Singer Jack , Cuttner Janet , Fialkow Philip J.
Published: February 2007

A 74‐year old woman with Ph1‐negative chronic myelogenous leukemia (CML) and heterozygous for glucose‐6‐phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that Ph1‐negative CML has a stem cell origin and develops clonally.
Antioxidant metabolism during blood storage and its relationship to posttransfusion red cell survival
Authors: Lachant Neil A. , Noble Nancy A. , Myrhe Byron A. , Tanaka Kouichi R.
Published: February 2007

The status of the erythrocyte antioxidant defense system and its relationship to posttransfusion red cell survival were determined in erythrocytes stored for 35 or 42 days in CPD‐A1 anticoagulant with a saline‐adenine‐glucose additive. As storage progressed, there was a significant increase in incubated Heinz body formation (P < .001) and a significant decrease in reduced glutathione (GSH) stability (P < .001). Stimulated pentose phosphate shunt activity also declined during storage (P < .06), while unstimulated shunt activity remained unchanged. The increase in Heinz body formation was associated with decreased GSH stability (r = –.77, P < .001), which in turn was associated with the decline in stimulated pentose shunt activity (r = .67, P < .001). The changes in Heinz body formation (r = ‐.85), GSH stability (r = .83). and stimulated pentose shunt activity (r = .54) were all significantly (P < .001) related to the decline in adenosine triphosphate (ATP) content of the erythrocyte. Red cell survival 24 hours after transfusion was significantly related to the GSH stability (r = .80, P < .001) and to the ATP concentration (r = .76, P < .005) on the day of transfusion. Thus, dysfunction of the erythrocyte antioxidant defense system occurs during blood storage and appears to be related, in part, to ATP depletion. The ability to maintain a normal reduced glutathione concentration during oxidant stress appears to be an important determinant of red cell survival in the peritransfusion period.
In vitro elevation of red blood cell 2,3‐diphosphoglycerate with fructose, phosphate, and methylene blue
Authors: Farber Mark O. , Rubin Leslie R. , Manfredi Felice
Published: February 2007

2,3‐Diphosphoglycerate (2,3‐DPG) is an important regulator of hemoglobin oxygen affinity and thus can theoretically affect tissue oxygenation. Marked stimulation of DPG with substances that would likely be well tolerated by humans has not been reported previously. In order to achieve such stimulation, we investigated (n = 102) the effect of various combinations of fructose (2.8–11.1 mM) and sodium phosphate (1.0–130.0 mM) on 2,3‐DPG production by perfusing fresh human blood in dialysis tubing, 37°C, pH 7.15–7.70, with the appropriate solutions and with compressed air or 100% O2 for up to 6 hours. The DPG increased significantly with fructose/phosphate incubations for 6 hours. At pH > 7.35 the average increase was 25%; at pH < 7.35, 12%; PO4 > 6 mM + pH > 7.35 yielded the highest changes, 28%. Methylene blue 2.5–7.5 μM + PO4 > 2.5 mM + pH > 7.35 yielded similar results. Glucose + PO4 showed no effect on DPG. Results were comparable at all fructose levels either with compressed air or 100% O2. Significant elevations in 2,3‐DPG were also noted at 4 hours but were of lesser magnitude.

In conclusion, significant elevations in 2,3‐DPG can be achieved by incubating whole blood with fructose/phosphate solutions or with methylene blue and phosphate for 4–6 hours. It should be possible to adapt these solutions for human use to raise 2, 3‐DPG. The potential physiologic value of rightward shifts in hemoglobin oxygen affinity can then be tested under appropriate conditions.
Hemoglobin miyada: DNA analysis of the anti‐lepore βδ fusion gene
Authors: Driscoll M. Catherine , Ohta Yoshiro , Nakamura Frank , Bloom Arthur , Bank Arthur
Published: February 2007

Hemoglobin Miyada, an anti‐Lepore hemoglobin, represents the protein product of a nonhomologous crossover between β and δ genes. The mutant globin is β‐like from the N terminus to amino acid 12, and δ‐like from amino acid 22 through the C terminus, thus predicting a crossover site in the first coding region of the gene. DNA analysis, using multiple restriction endonucleases and hybridization to δ and β globin gene‐specific probes, confirms that the βδ hybrid gene 1) is located on a single chromosomal fragment between normal δ and β genes, and 2) has 5′ β promoter sequences, δ IVS 1 and 2, and 3′ coding and flanking sequences.
Chronic anemia progressing to auer rod‐positive and TdT‐positive acute leukemia with 5q– chromosomal anomaly
Authors: Xavier Anita M. , Kasimis Basil S.
Published: February 2007

The 5q– syndrome is a recently described entity characterized by partial deletion of the long arm of chromosome No. 5 and by hematologic findings of chronic anemia with reticulocytopenia, nonlobulated megakaryocytes, and megathrombocytes. We report on a patient with the hematologic features of the 5q– syndrome who progressed to acute leukemia and whose uniqueness consisted of 1) lack of additional cytogenetic abnormalities, 2) presence of blasts with Auer rods, and 3) bone marrow cells positive for terminal deoxynucleotidyl transferase. His leukemia was refractory to conventional chemotherapy.
5‐azacytidine and fetal hemoglobin
Authors: Heller Paul , Desimone Joseph
Published: February 2007

The evidence that 5‐azacytidine stimulates the production of Hb F and F cells in baboon and man is reviewed. The mechanism of this effect is not entirely clear, but 5‐azacytidine produces hypomethylation of the γ gene at certain sites, and gene expression and DNA hypomethylation are related phenomena in many other systems. Other mechanisms have been postulated by other investigators. The therapeutic significance of increased Hb F levels in homozygous β thalassemia and sickle cell anemia is exemplified. The potential risk of carcinogenicity has delayed more extensive clinical trials.
Monitoring of intensive phlebotomy therapy in iron overload by serum ferritin assay
Authors: Van Oost Bernard A. , Beld Bep Van Den , Van Asbeck B. Sweder , Marx Joannes J. M.
Published: February 2007

Four patients with idiopathic hemochromatosis were treated with intensive phlebotomy therapy. In 1 to 2 years, 8.8–16.7 g iron was removed. In three out of four patients hemoglobin levels fell at the end of therapy. Serum ferritin was continuously measured during therapy. The greatly elevated serum ferritin levels normalized or decreased to subnormal levels in all patients after therapy. Despite some fluctuations in the first phase of therapy, the fall in serum ferritin was regular with halving of the ferritin levels after about 50% of the excess iron was removed. The normalization of serum ferritin occurred in advance of the hemoglobin decrease at the end of therapy, indicating that in the later stages of therapy the normal iron stores are also depleted. It is emphasized that serum ferritin measurements are useful for monitoring of intensive phlebotomy therapy, and in particular to indicate the end of therapy before anemia develops.
A long‐term study of hemophilic arthropathy of the knee joint on a program of factor VIII replacement given at time of each hemarthrosis
Authors: Brettler Doreen B. , Forsberg Ann D. , O'Connell Francis D. , Cederbaum Andrew I. , Chaitman Andrea K. , Levine Peter H.
Published: February 2007

Because there is little available data to demonstrate whether demand therapy is adequate to prevent progression of hemophilic arthropathy, a cohort of 64 patients with severe Hemophilia A (Factor VIII level < 1%) and no inhibitor were studied with respect to the progression of knee arthropathy over a period of 6 years. Both degree of disease in flexion and extension and progression of disease were rated on an arbitrary scale. At the outset of the study, the majority of knees were either not restricted or mildy restricted as to motion. Of those knees that were not restricted at the outset, 96% remained not restricted. Of the knees that were mildy restricted, only 58% remained stable or improved over the 6 years, and of the knees that were moderately to severely restricted, 75% improved or remained stable. It thus appears that a demand therapy program can maintain normal range of motion in a knee joint. However, if the patient's joint has progressed to mild disease, the ability to maintain or improve the joint with demand therapy appears to be decreased.
Use of 75se‐labeled methionine to study the sequestration of senescent red blood cells
Authors: Smedsrød Bård , Aminoff David
Published: February 2007

Labeling red blood cells with Na251CrO4 enabled us to study certain aspects of red cell survival and sequestration from the circulation. As a random labeling procedure, however, the 51Cr method has certain limitations. Therefore, we developed a cohort labeling method using 75Se‐methionine as a two‐rat procedure. This gives us a clear pulse‐labeled population of rat red cells to study the dynamics of sequestration. With this labeling procedure, it was possible to demonstrate that 1) there is an increase in the density of red cells with age, 2) a significant sequestration of red cells from the circulation is apparent at the end of 48 days and essentially is complete at the end of 60 days, 3) there is a corresponding uptake of senescent red cells in the spleen, which peaks at 55 days, and 4) the 60‐day end point is sharper and is more definitive when the “specific activity” (cpm per red blood cell) of the labeled red cells in the spleen is compared to that of the red cells still in the circulation. Asialo red cells, obtained by removal of sialic acid with sialidase, frequently have been used as a model for the study of sequestration of senescent red cells. With the technique herein described, it was possible to show that while asialo red cells will inhibit the uptake of labeled asialo red cells, they have no effect on the sequestration of senescent red cells. Presumably, different sites and mechanisms of sequestration are involved.
Steroid‐induced hypersegmentation in neutrophiles
Authors: Eichacker Peter , Lawrence Christine
Published: February 2007

The effect of glucocorticoid administration on the nuclear segmentation of circulating granulocytes was studied in 13 patients with hematologic disorders and in two normal volunteers. In seventeen of eighteen courses, the granulocyte nuclear lobe count increased from 3.24 ± 0.12 (SD) to 3.41 ± 0.12 by the third day of treatment (P < .001). Nuclear segmentation increased even further with continued therapy during a week of observation. Thus, like deficiencies of folate and of vitamin B12, glucocorticoid therapy causes neutrophil hypersegmentation. The cause of this effect is not known.
Increased heinz body formation and impaired erythrocyte pentose phosphate shunt function during pregnancy
Authors: Lachant Neil A. , Gottlieb Arlan J. , Difino Santo M. , Landaw Stephen A. , Tanaka Kouichi R.
Published: February 2007

The erythrocytes of 90 pregnant women were evaluated for the presence of in vivo or in vitro oxidant damage. The reduced glutathione (P < 0.005) and the membrane reduced sulfhydryl (P < 0.001) concentrations were decreased in fresh erythrocytes. Following incubation with acetylphenylhydrazine, Heinz body formation was significantly increased (P < 0.001). Both the increase in Heinz body formation and the reduction in membrane reduced sulfhydryl content correlated strongly with duration of pregnancy. Glucose consumption was significantly decreased before, but not after, new methylene blue stimulation. Pentose phosphate shunt activity was impaired both before (P < 0.05) and after (P < 0.001) stimulation. No changes were observed in pentose phosphate recycling. The only alteration observed in the activity of the enzymes of the pentose shunt was an elevation of 6‐phosphogluconate dehydrogenase activity. Although the clinical significance of these findings remains to be determined, medications with an oxidant potential should be used judiciously during gestation.
Philadelphia‐chromosome‐negative chronic myelogenous leukemia with lymphoid stem cell blastic transformation
Authors: Kessler John F. , Grogan Thomas M. , Greenberg Bernard R.
Published: February 2007

A patient is described who had blastic transformation of Ph1 negative chronic myelogenous leukemia (Ph1 – CML). Characterization of the leukemic cells revealed a population with a lymphoid stem cell phenotype (cALL–, TdT +, Ia+, cIgM –). This particular phenotype may be responsible for the refractoriness to vincristine and prednisone and the rapid downhill course.
Platelet transfusion therapy in acute leukemia: Lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage
Authors: Witzig Thomas E. , Ducatman Barbara S. , Wick Mark R. , Letendre Louis , Moore S. Breanndan , Ilstrup Duane M. , Taswell Howard F.
Published: February 2007

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty‐nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.
Concentration‐dependent sedimentation properties of ferritin: Implications for estimation of iron contents of serum ferritins
Authors: Niitsu Yoshiro , Adachi Chikara , Takahashi Fumio , Goto Yoshiro , Kohgo Yutaka , Urushizaki Ichiro , Listowsky Irving
Published: February 2007

Serum ferritins from various sources sedimented at lower densities than tissue ferritins in sucrose gradient centrifugation systems. The sedimentation patterns of ferritins, however, were shown to be dependent on the concentration of the protein; as the concentration decreased the protein appeared to sediment at lower densities. Thus, at the low concentration levels usually used for analysis of serum ferritin, tissue ferritins also sedimented in the same lower density regions. Iron labeling experiments indicated that the sedimentation changes upon dilution were not due to release of iron or was there any indication that the protein dissociated into subunits. The anomalous sedimentation behavior of serum ferritin should therefore not be interpreted in terms of its iron content. The disclosure that serum ferritins may have full complements of iron is counter to the prevalent view that serum ferritins are low iron forms and has potential implications with regard to the sources and possible function of this protein in the circulation.
High‐dose intravenous igg in the management of pregnancy in women with idiopathic thrombocytopenic purpura
Authors: Besa Emmanuel C. , Macnab Malcolm W. , Solan Andrew J. , Lapes Melvin J. , Marfatia Usha
Published: February 2007

Idiopathic thrombocytopenic purpura (ITP) may develop during pregnancy or affect later pregnancies, causing serious risks of bleeding to the mother and fetus. High‐dose intravenous immunoglobulin (IGIV) has caused an immediate and predictable rise in platelet count during the infusion in both adults and children with chronic or acute ITP. The rapid rise in platelet counts may be important in preparing pregnant women with ITP for surgery or delivery. We report our experience in managing two women at weeks 29 and 37 week of gestation who required splenectomy and/or cesarean section. Both patients demonstrated an increase in platelet counts, underwent surgery without excess bleeding, and had normal infants with normal platelets, and with mild thrombocytopenia at delivery.
Platelet sensitivity to antiaggregatory prostaglandins (PGE1, D2, I2) in patients with peripheral vascular disease
Authors: Fitscha P. , Kaliman J. , Sinzinger H.
Published: February 2007

Platelet sensitivity to antiaggregatory prostaglandins (PGI2, PGE1, PGD2) was studied in 143 patients (122 male) with angiographically proven peripheral vascular disease and compared with age‐matched clinically normal controls. Patients had a significantly lower platelet sensitivity to PGI2, PGE1, and PGD2, than controls. Clinical stages had no significant influence on the platelet sensitivity to PGI2 and PGE1. Patients with stage IIa had a lower sensitivity to PGD2 than patients with stage IV, the difference not being significant. Analyzing the influence of risk factors like diabetes, hyperlipoproteinemia, or smoking, there seemed to be an inverse relation between risk factors and platelet sensitivity to PGI2 and PGE1. Smokers especially, together with smokers exhibiting an additional risk factor, exhibited the highest prostaglandin consumption (PGI2, PGE1) and therefore the lowest platelet sensitivity. However, it has to be emphasized that the differences were not significant.

There was a significant correlation between platelet sensitivity to PGI2 and PGE1, whereas this was not the case between the respective sensitivities to PGI2, and PGD2. This supports the hypothesis that both these prostaglandins (PGI2, PGE1) share the same receptor on the platelet surface, whercas PGD2 has its own receptor.
Hematologic genetic disorders among Southeast Asian refugees
Authors: Monzon Carlos M. , Fairbanks Virgil F. , Burgert E. Omer , Sutherland John E. , Elliot Stephen C.
Published: February 2007

Resettlement of Southeast Asian refugees has introduced into the Western Hemisphere many persons of all major ethnic groups from Indochina. They represent several distinctive cultural, genetic, and linguistic groups, and the prevalence of genetic traits among them varies accordingly. We studied 778 Southeast Asian persons resettled in the upper Midwest who belonged to 182 unrelated families from the five major Southeast Asian ethnic groups. High prevalences of hemoglobin E, α‐ and β‐thalassemia disorders, and glucose‐6‐phosphate dehydrogenase deficiency were found. The prevalences of these four conditions in the refugees are among the highest known in the world. For these groups, iron deficiency is an uncommon cause of microcytosis; instead, the most frequent causes are hemoglobin E and α‐thalassemia‐1. Very serious thalassemic disorders occur with unusually high frequency in the refugees, especially in the Tai‐Dam.
Adenosine deaminase (ADA) in leukemia: Clinical value of plasma ADA activity and characterization of leukemic cell ADA
Authors: Morisaki Takayuki , Fujii Hisaichi , Miwa Shiro
Published: February 2007

Adenosine deaminase (ADA) activity was measured in plasma, erythrocytes, and mononuclear cells from 18 patients with acute and chronic leukemia. High levels of ADA activities were found in plasma, erythrocytes, and mononuclear cells from patients with acute leukemia, especially acute lymphoblastic leukemia, and blastic crisis of chronic myeloid leukemia. Serial determination of plasma ADA activities was done in 9 patients with acute leukemia. All patients untreated or in relapse had an elevation of plasma ADA activity, which decreased to normal or subnormal levels during complete remission. On starch gel electrophoresis, plasma ADA in leukemic patients separated into two bands. The major band showed a mobility identical to that of normal red cells and mononuclear cells, and the minor band corresponded to that of normal plasma ADA. Enzymatic and immunological studies were performed on ADA from leukemic cells of acute myeloid and lymphoblastic leukemia. There were no differences in Michaelis constant for adenosine, thermostability, electrophoretic mobility, immunological reactivity, and specific activity between ADA of leukemic cells and normal mononuclear cells. These results strongly suggest that the increased ADA activity in leukemic cells is caused by an increased synthesis of a structurally normal enzyme and that increased plasma ADA activity in leukemic patients reflects an increment of leukemic cells in bone marrow. Therefore, serial determination of plasma ADA activities seems to provide a good indicator of the total mass of leukemic cells in bone marrow.
Defective complement activity in chronic lymphocytic leukemia
Authors: Heath Margo E. , Cheson Bruce D.
Published: February 2007

Patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infections with bacteria which require complement for osponization. We explored the possibility that patients with CLL have a defect in binding the potent opsonin C3b to bacteria. Bacteria selected for these experiments included Streptococcus pneumoniae type 3, which binds C3 by activating the classical complement pathway (CCP), type 25, which can bind normal amounts of C3b by the alternative complement pathway (ACP), type 14, which can activate both the CCP and ACP, and Staphylococcus aureus and Escherichia coli, both of which activate the CCP.

Bacteria were treated with normal serum or serum from 15 patients with CLL, and the bound C3b was quantified spectrophotofluorometrically. Despite normal serum concentrations of C3, C4, Factor B, C‐reactive protein, and total hemolytic complement activity, all 15 CLL sera bound reduced amounts of C3b to at least one bacterial species; 9 to S pneumoniae type 3, 8 to types 14 and 25, 11 to S aureus, and 13 to E coli. Mixing normal serum with CLL serum restored C3b binding to all bacteria, suggesting a deficiency rather than an inhibitor of activity. Serum from ten hypogammaglobulinemic CLL patients bound less C3b (62.7 ± 5% of normal) (X̄ ± SEM) than those with normal immunoglobulin levels (81.9 ± 5%) (p < 0.005). Nevertheless, the addition of specific antibacterial antibodies to CLL serum did not enhance C3b binding to any of the bacteria. Serum from patients with a history of a bacterial infection bound less C3b (62.3 ± 5%) than those without a history of infections (76.1 ± 6%) (p < 0.05). Thus, there is a defect in either the activation or activity of C3 in CLL serum which may contribute to the increased incidence of infections in these patients.
Immune hemolytic anemia following administration of antithymocyte globulin
Authors: Prchal Josef T. , Huang Shu T. , Court Wayne S. , Poon Man‐Chiu
Published: February 2007

Antithymocyte globulin is commonly used as a therapy for rejection of transplanted organs. Its use can be associated with many side effects. We report a significant hemolytic anemia following therapy with horse‐derived antithymocyte globulin. Several commercial Coombs' sera failed to yield a positive Coombs' test with the patient's erythrocytes; however, we were able to detect horse immunoglobulin on the patient's cells as well as on control red cells incubated with this particular preparation of antithymocyte globulin.
Identification of erythroid colony progenitors in a subset of human peripheral null lymphocytes devoid of Fc receptors
Authors: Rosenthal C. Julian , Hassan Mozaffar , Rieder Ronald F. , Brissette William , Parsa Ismail
Published: February 2007

This study was aimed at purifying the progenitors of erythroid burst units (BFU‐E) from human peripheral blood. Human mononuclear leukocytes from five normal donors were fractionated into several mononuclear cell subpopulations, including null lymphocytes with (null Fc+) and without (null Fc−) receptor for the Fc fragment of immunoglobulin G, through a succession of rosetting procedures and discontinuous Ficoll‐Hypaque gradient centrifugations. The fractionated cells were separately cultured for 14 days in plasma clots in the presence of erythropoietin. Among fractionated cell subpopulations large and numerous BFU‐E derived colonies grew only from the Fc− null lymphocyte subpopulation. This fraction, representing less than 4% of all mononuclear cells, also contains cells (42 + 11%) capable to differentiation towards the B‐cell and plasma‐cell lineages. The Fc+ null Imphocytes, representing less than 9% of all mononuclear cells, contained 15.2 + 3.3% cells capable of differentiation toward the T‐cell lineage. The whole null lymphocyte subpopulation generated half the number of BFU‐E colonies expected from its content in Fc− null lymphocytes. These data demonstrate that the progenitor of erythroid cells (BFU‐E) resides in a small heterogenous null Fc− subpopulation of circulating lymphocytes and suggest that its in vitro differentiation, though generally subjected to inhibitory and enhancing influences from other circulating cell subpopulations, does not necessarily require interaction with other peripheral blood cells.
Red cell superoxide dismutase and sickle cell anemia symptom severity
Authors: Schacter Lee P. , Delvillano Bert C. , Gordon Erlinda M. , Klein Bruce L.
Published: February 2007

Patients with sickle cell anemia vary in the severity of their symptoms but the basis of this variability is unknown. We have tested the hypothesis that this variability is related to differences in the activity of the antioxidant superoxide dismutase (SOD). The amount of superoxide dismutase I (SOD) enzyme activity in red cells of patients with different degrees of symptom severity and healthy black and white controls was measured and correlated with symptom severity in SCA patients. Blacks with normal (AA) hemoglobin had significantly (p < 0.001) more SOD activity (1.82 U/mg Hb) than white controls (1.44 U/mg Hb). Patients with moderate or severe symptoms had less SOD activity (1.16 and 0.95 U/mg Hb, respectively) than control blacks or SCA patients with mild symptoms (1.62 U/mg Hb). The correlation of SOD activity and symptom severity was not a function of age or sex and was unrelated to reticulocyte count or fetal hemoglobin level.
Complications of heparin administration in normal individuals
Authors: Schwartz Kenneth A. , Royer George , Kautman Donald B. , Penner John A.
Published: February 2007

The incidence, severity, and pathogenic mechanism of heparin‐associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty‐three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/μl. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased plateletassociated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C1q in seven. The heparin‐associated thrombo‐cytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on platelets.
Plasminogen‐dependent fibrinolytic activity in normal human lymphocytes: Diminished lymphocyte plasminogen activator in chronic lymphocytic leukemia
Authors: Zucker Stanley , Mehling Karen , Rai Kanti
Published: February 2007

Discrepancies in correlations between fibrinolytic activity and metastatic potential of malignant cells has resulted in speculation on the putative role of plasminogen activators (PA) in cancer. In this report we have compared lymphocyte PA from 40 patients with chronic lymphocytic leukemia (CLL) to normal human B‐ and T‐ lymphocytes. Lymphocytes were isolated from peripheral blood by Ficoll‐Hypaque centrifugation. The B‐ and T‐cells were further separated on nylon wool columns. Cell PA activity and cell membrane PA were determined using 3H‐fibrin‐coated plates with added human plasminogen. Lymphocytes did not lyse 3H‐fibrin in the absence of plasminogen. Plasminogen‐dependent fibrinolytic activities of normal B‐ and T‐ lymphocytes were comparable. The addition of protease inhibitors with trypsin or plasmin specificity to lymphocytes significantly inhibited normal PA, thus substantiating the serine protease spectrum of lymphocyte PA. Examination of lymphocytes from > 95% of patients with chronic lymphocytic leukemia revealed a marked decrease in lymphocyte and cell membrane PA as compared to normals. No correlation between Stage of CLL and lymphocyte PA was observed. Likewise, an inhibitor of PA in CLL lymphocytes was not detected. The function of PA in normal B‐ lymphocyte physiology and the potential pathogenetic role of diminished PA in CLL lymphocytes remain to be explored.
Anti‐Pr cold hemagglutination associated with livedo reticularis
Authors: Rose Virgil L. , Kwaan Hau C.
Published: February 2007

A report of anti‐Pr cold hemagglutination associated with livedo reticularis is presented. Livedo reticularis is descriptive of the superficial venous system appearing when blood flow is altered in this area. Cold antibody directed against the Pr antigen of the red cell membrane can cause hemagglutination, thereby altering blood flow in cooler areas of the body. This patient had livedo reticularis approximately 8 months prior to detection of the anti‐Pr cold agglutinin.
Salmonella infection in hairy cell leukemia: Report of a case
Authors: Tilly Hervé , Gardembas Martine , Berry Michel , Gray Christian , Monconduit Mathieu , Piguet Hubert
Published: February 2007

A patient with hairy cell leukemia who developed mediastinal mass and fever is described. A CT‐guided aspiration of the mass yielded Salmonella tiphymurium. Granulocyte response to infection was intact and could explain the favorable course of this unusual Salmonella infection. Although several reports deal with salmonellosis as a complication of immunodeficiency states, this type of infection is of rare occurence in hairy cell leukemia.
Irreversibly sickled erythrocytes in sickle cell anemia: A quantitative reappraisal
Authors: Rodgers Griffin P. , Noguchi Constance Tom , Schechter Alan N.
Published: February 2007

Irreversibly sickled cells (ISCs), considered by some to be of major pathophysiologic significance, have been reported to comprise between 5–50% of the total red cell population in patients with homozygous sickle cell anemia. Since the deformation of erythrocytes containing sickle hemoglobin is highly dependent on the concentration of hemoglobin in the deoxy conformation, any method established to enumerate the true ISC count requires the hemoglobin to be in the full oxy or liganded conformation. Because the oxygen dissociation curve for sickle erythrocytes is significantly shifted to the right, extremely high partial pressures of oxygen are required to approach full saturation. On the other hand, fully liganding the hemoglobin in the oxy conformation with carbon monoxide (CO) can be readily accomplished. We found that there is a significant reduction in the average number of sickled forms in the peripheral blood of sickle cell anemia patients after incubation in CO (to a value of 6.5 ± 3.5%) when compared to conventional methods for ISC preparations. These results suggest that fully liganded erythrocytes should be used in quantitating ISCs in studies of the pathophysiology of this disease, especially since ISCs are likely to affect rheology differently from reversibly sickling cells.