bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics and distribution of platelets in man
Authors: Tsan Min‐Fu
Published: February 2007

51Cr sodium‐chromate, though having been widely used in the last two decades for labeling platelets, suffers from several serious drawbacks, ie, low labeling efficiency, long physical half‐life, and low gamma photon yields. 111In‐oxine and 111In‐tropolone overcome these shortcomings and have the potential of precise determination of platelet kinetics as well as visualization and in vivo quantification of the temporal and spatial distribution of platelets in man. Computer analysis of platelet kinetics reveals that the multiple‐hit model fits the survival curve better than the linear or the exponential model. The multiple‐hit model provides not only the mean platelet survival time but also information on the initial recovery and the shape of the survival curve. The application of these techniques in normal and disease states should greatly enhance our understanding of the physiology and pathophysiology of platelets.
Familial hereditary thrombocytopenia and HLA
Authors: Naparstek Yaakov , Abrahamov Ayala , Cohen Tirza , Brautbar Chaim
Published: February 2007

Three generations of a Jewish family with hereditary thrombocytopenia (HT) are described. The disease was manifested clinically by mild bleeding tendency since infancy. Circumcision, however, did not result in excessive bleeding. HLA study in this family indicated that the HT locus is not linked to HLA.
Disappearance of microspherocytes in peripheral circulation and normalization of decreased lipids in plasma and in red cells of patients with hereditary spherocytosis after splenectomy
Authors: Sugihara Takashi , Miyashima Kosuke , Yawata Yoshihito
Published: February 2007

A possible mechanism of the formation of microspherocytosis in unsplenectomized patients with hereditary spherocytosis (HS) was investigated in relation to lipid metabolism in plasma and in red cells of these patients. Plasma lipids (total cholesterol, free cholesterol, high density lipoprotein cholesterol, free fatty acids, and phospholipids) were markedly reduced in unsplenectomized HS patients with microspherocytosis. Red cell membrane lipids (free cholesterol and phospholipids such as phosphatidyl ethanolamine, sphingomyelin, phosphatidyl choline, and lysophosphatidyl choline) were also decreased in these unsplenectomized HS patients. After splenectomy, microspherocytosis disappeared concomitant to substantial normalization of plasma and red cell membrane lipids. These observations suggest that plasma lipid decrement in the unsplenectomized HS patients is at least one of the causative factors in pathogenesis of the formation of microspherocytosis. So‐called “splenic conditioning” may not imply a physical “loss” of membrane by fragmentation or pitting of the once‐formed HS red cells in the peripheral circulation. Instead, the decreased plasma lipids in the presence of the spleen may affect the de novo synthesis of red cell membrane lipids, resulting in the formation of microspherocytosis.
Platelet‐activating factor is a weak platelet agonist: Evidence from normal human platelets and platelets with congenital secretion defects
Authors: Rao A. Koneti , Willis Janet , Hassell Barbara , Dangelmaier Carol , Holmsen Holm , Smith J. Bryan
Published: February 2007

We have examined the effects of a novel platelet agonist, platelet activating factor (PAF), on human platelets. Irreversible aggregation and14C‐serotonin secretion in response to PAF (10−5M) was found to be dependent on both thromboxane production and secreted adenosine diphosphate (ADP). Liberation of arachidonic acid (AA) from membrane‐bound phospholipids is a prerequisite step in platelet thromboxane production. Studies with3H‐AA‐labeled platelets revealed that PAF (10−5M) was a weak stimulus for the mobilization of AA. In addition, PAF (10−5M) was found to be a weak inducer of thromboxane synthesis (mean = 6 pmol/108platelets) as compared to thrombin 5 U/ml (mean = 177 pmol/108platelets), measured using a radioimmunoassay for thromboxane B2. Formation of phosphatidic acid is an early step in stimulus‐response coupling in platelets. Our studies indicate that PAF is a weak stimulus for phosphatidic acid formation as well. To obtain further insights into its action, we examined the effect of PAF on platelets from three groups of patients with congenital secretion defects: patients with the storage pool deficiency, those with impaired thromboxane synthesis due to impaired liberation of AA from phospholipids, and those with impaired secretion despite normal granule stores and thromboxane production. The response to PAF was impaired in all patients, providing further evidence that PAF‐induced platelet activation is dependent on secreted ADP and thromboxane A2synthesis, and occurs by mechanisms common to a number of agonists. Overall, these studies indicate that PAF is a weak platelet agonist.
Exaggeration of defective platelet function by methyldopa in hypothyroidism
Authors: Zeigler Zella , Hasiba Ute , Lewis Jessica , Vagnucci Anthony , West Valerie , Bezek Elizabeth
Published: February 2007

Platelet function was analyzed in two hypothyroid patients who were taking methyldopa. Results from these two patients are compared to those obtained in seven others with hypothyroidism on no medications. Bleeding times in the two drug patients were 33 and 26 minutes compared to normal values (4.0 to 8.0 minutes) in the other hypothyroid individuals. In addition, platelet aggregation responses to epinephrine, collagen, and ristocetin were abnormal in these two patients; these were normal in the others with hypothyroidism. Repeat studies were done in the first drug patient when she was euthyroid and still receiving methyldopa. Her bleeding time decreased to 11 minutes, platelet retention increased from 31% to 75%, and abnormal aggregation responses corrected to normal. Factor VIII coagulant activity, VIII antigenic activity, VIII ristocetin cofactor activity, and two‐dimensional immunoelectrophoresis of VIII antigen were normal. These findings suggest that methyldopa can potentiate the mild platelet function defect seen in patients with hypothyroidism.
Erythrocytic pyruvate kinase deficiency and hemolytic anemia inherited as a dominant trait
Authors: Etiemble Jeanne , Picat Christiane , Dhermy Didier , Buc Hélène A. , Morin M. , Boivin Pierre
Published: February 2007

A nonspherocytic hemolytic anemia, associated with a pyruvate kinase (PK) deficiency apparently inherited as a dominant trait has been identified in a family. In the affected members, the residual PK activities were 20% that of normal controls, an unusually low level for heterozygous subjects. The anemia was mild except in the proband, a 2‐year‐old boy who suffered from a severe anemia.

The PKs of the proband and of his both parents have been characterized as kinetically and electrophoretically normal enzymes. Immunoprecipitation tests indicated a large amount of L‐type inactive protein in the proband and his father. Moreover, an M2 type PK was present in the father's hemolysate, suggesting the existence of a compensatory process that derepressed the corresponding structural gene. We suggest that the presence of one or more mutated subunits in the tetrameric forms of L‐type PK leads to the inactivation of these tetramers. This hypothesis accounts for the low residual activity in affected heterozygous members of this family. The severity of the hematological symptoms in the proband, in comparison with the mild hemolysis observed in the other heterozygous members of the family points to the existence of a large spectrum of pathologic expression for an identical PK defect present in a family.
Kinin cleavage by human erythrocytes
Authors: Sidorowicz W. , Canizaro Peter C. , Běhal Francis J.
Published: February 2007

An aminopeptidase‐P has been purified 230‐fold from human erythrocytes. The purified enzyme cleaved arginine from des‐(Arg9)‐bradykinin (Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe) had a molecular weight in nondenaturing buffers of 155,000 ± 6,900 daltons, was not inactivated by chelating agents, had a pH optimum of 7.2, and was stimulated by manganous ions. The aminopeptidase‐P was stable in intact erythrocytes for at least 21 days. Extensively washed and intact human erythrocytes cleaved arginine from exogenously supplied des‐(Arg9)‐bradykinin; arginine was the earliest‐appearing reaction product. Purified aminopeptidase‐P also cleaved a group of X‐proline dipeptides including leucyl‐proline, methionyl‐proline, phenylalanyl‐proline, arginyl‐proline, and alanyl‐proline. The total intra‐erythrocytic aminopeptidase‐P activity of the “average 70‐kg man” was 2,600 units, approximately five times the amount of activity in the total lung mass. The human erythrocyte aminopeptidase‐P activity was not tightly bound to the erythrocyte membrane. Intact erythrocytes also exhibited some kinin‐converting enzyme activity.
Procainamide‐induced agranulocytosis with reversible myeloid sensitivity
Authors: Nelson John C. , Lutton John D. , Fass Arthur E.
Published: February 2007

A 56‐year‐old man developed procainamide‐induced agranulocytosis. Bone marrow aspiration showed the absence of myeloid elements beyond the promyelocyte stage. Procainamide at therapeutic concentrations in vitro depressed bone marrow granulocyte‐macrophage colonies (CFUc) while CFUc growth was normal in the absence of drug. Following the patient's recovery, CFUc growth was no longer suppressed by procainamide in vitro. The observations in this patient showing reversible sensitivity to drug contrast with those on other patients with drug‐induced agranulocytosis that show persistent marrow injury or drug sensitivity despite clinical recovery.
Lymphoma of host origin in a marrow transplant recipient in remission of acute myeloid leukemia and receiving cyclosporin A
Authors: Bloom Robert E. , Brennan James K. , Sullivan John L. , Chiganti R. S. K. , Dinsmore Robert , O'Reilly Richard
Published: February 2007

Lymphomas are an uncommon complication of solid organ transplantation and rarely occur after marrow transplantation. When post‐marrow transplant lymphomas have occurred, they have been of donor cell origin and when sought, Epstein‐Barr virus DNA has been found in the tumor. A 21‐year‐old woman developed a poorly differentiated lymphocytic lymphoma 6 months after bone marrow transplantation for acute myeloid leukemia in remission. Cyclosporin A had been used as an immunosuppressant. A chromosomal polymorphism demonstrated that the tumor was of host origin and contained a monoclonal tumor marker, 46, XX INV 4 (p16q12). The tumor did not contain the DNA of the Epstein‐Barr virus.
Relationship between patients' age, bone marrow karyotype, and outcome of induction therapy in acute myelogenous leukemia
Authors: Bernard Ph. , Lacombe F. , Reiffers J. , David B. , Marit G. , Bourdeau M. J. , Broustet A.
Published: February 2007

Bone marrow karyotypes were performed in 88 cases of adult acute myelogenous leukemia (AML) at diagnosis and classified NN (normal), AA (abnormal), and AN (mixture of normal and abnormal metaphases). A clear relationship was found between karyotype and complete remission (CR) rate: 58% CR in (NN + AN) cases; 14% CR in AA cases (P < .009). This relationship was even stronger when only patients under 60 years of age were studied. Considering failures of induction treatment, no relationship was found between the NN/AN/AA classification and a drug resistance. In patients over 60, the worse prognosis could be explained by an inferior ability to tolerate intensive treatment.
Rapid accurate absolute granulocyte count determination during severe leukopenia using the flow cytometer
Authors: Johnson Karen L. , Dougherty Carol , Vaughan William P.
Published: February 2007

The absolute granulocyte count (AGC) in 125 blood samples from patients with total white blood cell counts of less than 1,000/μl was estimated using three different methods, which were then compared for efficiency and accuracy. The three methods were 25 cell differential counts using Wright's‐stained blood smears, granulocyte percentage estimates from WBC counting chambers, and combined narrow‐ and wide‐angle light‐scatter characteristics determined on a flow cytometer. A survey of clinical laboratories at University Hospital Cancer Centers revealed that the smear differential was the most‐often‐used method in those laboratories even when less than 25 cells could be counted. Consequently the data obtained from the counting chamber and flow cytometer methods were compared to the smear differential “standard” using linear regression, and outliers were identified. There was good correlation between AGC determined by smear differential and WBC counting chamber (correlation coefficient .911) and excellent correlation between the AGC determined by smear differential and the flow cytometer method (correlation coefficient .970). The flow cytometer method used in this investigation required minimal specimen preparation, and test results were available at a rate of 60 seconds/sample. The ease of sample preparation, speed, and statistical reliability of test results makes the flow cytometer an attractive alternate method of determining granulocyte counts on leukopenic patients as compared to the stained blood smear differential.
Lack of relationship between in vitro cell measurements and response to busulfan in chronic myelocytic leukemia
Authors: Kirshner Jeffrey , Preisler Harvey D. , Raza Azra
Published: February 2007

Twenty‐three patients with chronic‐phase CML have been treated with intermittent courses of busulfan to determine if the duration of unmaintained remission becomes progressively shorter with successive courses of therapy and to determine whether there was a relationship between cluster and colony formation, suicide index of CFUc, labeling index, percentage of cells in S‐phase (as determined by cytofluoro‐graphic DNA histogram analysis), in vitro sensitivity of the CFUc to busulfan, and response to busulfan therapy. Serial studies in individual patients and the group as a whole revealed no relationship between changes in the cellular parameters described above and response to busulfan. The white blood cell (WBC) doubling time with serial courses of busulfan in individual patients did not always progressively decrease as has been previously reported. In vitro studies of CFUc in chronic‐phase CML appear to be of no value in predicting response to busulfan.
Extravascular hemolysis following the administration of cefamandole
Authors: Branch Donald R. , Berkowitz Lee R. , Becker Robert L. , Robinson Judy , Martin Marsha , Gallagher Michael T. , Petz Lawrence D.
Published: February 2007

Hemolytic anemia occurred in a 70‐year‐old female after a five‐day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole‐coated red cells sensitized with the patient's anticefamandole indicated that the anticefamandole could induce significant phagocytosis. The anticefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross‐reactivity, with the antigenic site primarily the 7‐amino‐cephalosporanic acid nucleus. Penicillins could inhibit the anticefamandole but only when using concentrations 3‐10× those of cephalosporins. Eleven examples of antipenicillin tested failed to react with cefamandole‐coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole‐coated red cells; three of these sera were also reactive with penicillin‐coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anticefamandole‐induced hemolytic anemia.
Hairy‐cell leukemia with hybrid B‐T features: A study with a panel of monoclonal antibodies
Authors: Armitage R. J. , Worman C. P. , Galvin M. C. , Cawley J. C.
Published: February 2007

The peripheral blood of three patients with otherwise typical hairy‐cell leukemia (HCL), but with a substantial number of circulating cells expressing both light chain restricted surface immunoglobulin (SIg) and sheep erythrocyte (E) receptor, was studied with a panel of monoclonal antibodies. The presence of hybrid B‐T surface features was confirmed and, although as in previous studies of E+SIg+ proliferations, the precise phenotypes varied at different times of study, E+ non‐T SIg+ and E+T+SIg+ populations were at times present in all three patients together with typical B hairy‐cell (HC) and phenotypically normal T‐cell populations. In one patient an E−OKT11+SIg+ population was also observed. Extensive precautions were taken to exclude spurious explanations for these hybrid phenotypes. These results are discussed in relation to the recent demonstration that both HCs and normal B cells can express T‐cell features after appropriate in vitro stimulation.
Simultaneous reticulocyte and platelet counting on a clinical flow cytometer
Authors: Vaughan William P. , Hall Janet , Johnson Karen , Dougherty Carol , Peebles Deborah
Published: February 2007

Laser flow cytometric analysis is well suited to many clinical immunofluorescent and hematologic applications. One of these is automated reticulocyte and platelet enumerations. We have performed a clinical evaluation of a fluorescence laser flow cytometer reticulocyte and platelet enumeration method using the fluorochrome acridine orange. One hundred and thirty‐two clinical specimens from inpatients in our comprehensive cancer center were analyzed for platelet counts and 101 samples from the same population were analyzed for reticulocyte counts by the flow cytometer and simultaneously by conventional techniques. Both the reticulocyte and platelet enumerations achieved a high degree of correlation with standard methods for the nonbone marrow‐transplant patients studied (R = .989 for reticulocytes and R = .995 for platelets). Marrow transplant patients had a slightly poorer correlation coefficient for the reticulocyte enumeration (R = .923), but analysis of serial determinations of these patients' samples for reticulocyte counts revealed that results were more consistent over time with the automated method than with the traditional manual method. The laser flow cytometer fluorescence reticulocyte and platelet enumeration methods described are efficient, rapid, and reliable for platelet and reticulocyte counting.
Mitral valve prolapse in sickle cell disease: Manifestation of a generalized connective tissue disorder
Authors: Lippman Scott M. , Abergel R. Patrick , Ginzton Leonard E. , Uitto Jouni , Tanaka Kouichi R. , Miyamoto Eric K. , Laks Michael M.
Published: February 2007

Previous studies have shown an association of sickle cell disease with generalized connective tissue disorders such as pscudoxanthoma elasticum. We recently documented an unexpectedly high prevalence of mitral valve prolapse, a connective tissue disorder, in sickle cell discase. To investigate this association, skin biopsies were analyzed from 32 sickle cell disease patients, 11 of whom had mitral prolapse. Total and type III collagen, collagen solubility, and uronic acid were not different between the patients with or without mitral prolapse (p > 0.05). Computerized morphometric quantitation of the volume fraction of elastic fibers was greater in sickle cell disease patients than in 10 normals (3.1 ± 0.1 mean ± SEM vs 2.0 ± 0.3%; p < 0.01) but less than in three patients with pseudoxanthoma elasticum (9.7 0.6%; p < 0.001). Desmosine radioimmunoassay (an index of elastic fibers) was greater in sickle cell disease patients with mitral prolapse than those without (239.3 ± 9.3 vs 171.7 ± 25.4 ng/mg wet weight; p < 0.02). Histopathologic grading showed a similar trend (p = 0.07). The combined probabilities of these three independent tests of elastic fiber quantity showed an increased elastic fiber concentration in mitral prolapse patients compared to those without mitral prolapse (p < 0.02). Thus, there is no evidence for a specific collagen defect; rather, sickle cell disease appears to be associated with a spectrum of elastic tissue disorders, a feature that could predispose to mitral valve prolapse.
β‐thromboglobulin in patents with breast cancer
Authors: Ferriere J. P. , Bernard D. , Legros M. , Chassagne J. , Chollet P. , Gaillard G. , Plagne R.
Published: February 2007

β‐thromboglobulin (βTG) plasma levels were determined in 52 female breast cancer patients at different stages and in 39 healthy controls (22 women and 17 men) of similar age distribution. βTG levels were high (mean ± SD: 61.6 ± 59.1 ng/ml) in patients before any treatment compared to controls (mean ± SD: 21.2 ± 7.4 ng/ml) and the difference was statistically significant (p < 0.001). No correlation with disease stage was observed. No other coagulation parameters were abnormal except fibrinogen, which increased. Fibrinogen degradation products (FDP) also increased but only in metastatic patients. Chemotherapy appeared to induce a considerable decrease in initial values at the end of the first cycle without modifying the platelet count. In addition, an attempt was made to correlate the βTG plasma level investigated serially for several months with disease evolution.
Pseudotumor of hemophilia in the orbit: The role of radiotherapy in management
Authors: Meyers Lee , Hakami Nasrollah
Published: February 2007

A case of pseudotumor of hemophilia is presented that occured in the right orbit of a boy with severe factor VIII deficiency and an inhibitor. After a period of observation and conservative management, low‐dose radiotherapy (750 rads) and Proples was used. Eighteen months after radiotherapy significant healing had occured. The role of radiotherapy in the treatment of hemophillic pseudotumor is reviewed.
Positive direct antiglobulin test associated with hyperglobulinemia in acquired immunodeficiency syndrome (AIDS)
Authors: Toy Pearl T. C. Y. , Reid Marion E. , Burns Maryann
Published: February 2007

This study determined the prevalence and clinical significance of a positive direct antiglobulin test (DAT) observed in pretransfusion tests on red cells from patients with acquired immunodeficiency syndrome (AIDS). Transfusion service records showed that prevalence of a positive DAT on red cells was 18% (10/55) in AIDS patients compared to 0.6% in general hospital patients during a 2‐year period (1981‐1983). A similar rate of 18% (8/45) was observed in other hyperglobulinemic patients. Of the 10 AIDS patients whose red cells were DAT positive, four had IgG and complement, four had IgG, and two had complement alone on their red cells. The eluates were not reactive with normal red cells nor with penicillin or cephalothincoated red cells. Clinically, no hemolysis was observed. In this series a positive DAT in AIDS patients appeared not to be associated with autoimmune hemolytic anemia. The positive DAT in AIDS patients may be due to the hyperglobulinemic state.
Protein kinases in human leukemic cells
Authors: Phan‐Dinh‐Tuy F. , Henry J. , Boucheix C. , Perrot J. Y. , Rosenfeld C. , Kahn A.
Published: February 2007

Protein kinase activities and cyclic AMP binding capacity were investigated in human peripheral blood cells from leukemic patients and normal controls. Using [γ32P] ATP as phosphoryldonor, the phosphorylating activities were not found to be significantly different in either normal or leukemic cells when measured on both artificial basic and acidic substrates. In contrast, the GTP‐dependent casein kinase activity, CK2, which is almost undetectable in normal granulocytes, was markedly increased in highly proliferating myeloblastic cells from patients with acute myelogenous leukemia (AML) or with chronic myelogenous leukemia in blastic crisis (BC‐CML).

Levels of endogenous phosphotyrosine were not higher in leukemic cells than in normal peripheral lymphocytes or granulocytes.

Finally, cAMP binding capacity was found to be increased in several types of proliferating leukemic cells, due to a higher amount of the R1‐type regulatory subunit of the cAMP‐dependent protein kinases. Specific patterns of cAMP binding proteins observed in the different types of normal blood cells were rather blurred in leukemic cells. In conclusion, modifications observed in human leukemic cells seem to be more related to proliferation or blockage in normal differentiation than to their cellular origin.
Adenosine deaminase and terminal deoxynucleotidyl transferase in human lymphomas: An aid to the diagnosis and subclassification of lymphoblastic lymphomas
Authors: Vezzoni Paolo , Giardini Roberto , Lucchini Roberto , Lombardi Luciano , Vezzoni Maria A. , Besana Carlo , Clerici Libero
Published: February 2007

Adenosine deaminase (ADA) and terminal deoxynucleotidyl transferase (TdT) activities were determined on 97 biopsic specimens obtained from patients with non‐neoplastic diseases (12 cases), Hodgkin (30 cases), and non‐Hodgkin lymphomas (55 cases). Thirty additional cases were tested only for TdT. TdT was positive in 10 out of 13 lymphoblastic lymphomas (LL) examined and negative in all the other specimens, including the ten cases of the immunoblastic type. Levels of ADA above 350 U/mg of protein were found in 10 out of 12 LL tested, but not in any other specimen. The 3 TdT−LL had high contents of ADA. Therefore, all LL can be detected using both ADA and TdT markers. The 3 TdT− LL had a heterogeneous phenotype and their possible origin is discussed in view of the possibility that they constitute a rare entity distinct from the more common TdT+ LL. Very low levels of ADA (below 100 U/mg of protein) were found in chronic lymphocytic leukemia and immunocytoma, and in Burkitt's lymphoma. In other B‐cell non‐Hodgkin lymphomas, intermediate values between 100 and 350 U were often found, and this finding could be relevant to the different cellular origin of the various B‐cell neoplasias. We conclude that ADA distribution in solid lymphoid tumors reflects the cellular origin of these neoplasias. Adenosine deaminase alone and in combination with TdT can be useful in the diagnosis and classification of childhood lymphomas in which the immature hystotypes predominate.
Histidine‐rich glycoprotein and changes in the components of the fibrinolytic system after streptokinase therapy in patients with pulmonary thromboembolism
Authors: Tim Goodnough Lawrence , Saito Hidehiko , Bell William R. , Heimburger N.
Published: February 2007

Although the biological function of histidine‐rich glycoprotein (HRG) is unknown, it may serve as an antifibrinolytic agent by interfering with the binding of plasminogen to fibrin. To define the role of HRG, plasma titers were measured by single radial immunodiffusion in eleven patients with thromboembolism before and after streptokinase (SK) therapy and were found unchanged (84.7 ± 6.2%, M ± SEM before, and 99.5 ± 6.3% after 12 hr of SK therapy). The HRG peaks on crossed immunoelectrophoresis before and after SK infusion were also unchanged. α2‐plasmin inhibitor fell during SK infusion as measured immunologically (102.0 ± 15.0% before and 28.0 ± 1.6% after 12 hr of therapy) and fibrinogen‐fibrin degradative products appeared (mean titer of 1:2, 048 after 12 hr of therapy), indicating that the infused SK was biologically active. Plasminogen levels before therapy were normal, as measured functionally and immunologically (105.4 ± 4.9% and 96.0 ± 5.6%, respectively), and both decreased after 12 hr of SK therapy (15.2 ± 5.6% and 50.8 ± 4.3%). No changes in functional antithrombin III titer, Hageman factor antigen level, or fibrinogen concentration, as measured turbidimetrically, were observed. Thus, although these data do not allow one to make any firm conclusions regarding the physiologic role of this protein in fibrinolysis, they do not exclude its increased catabolism, compensated by increased production, in patients undergoing fibrinolytic therapy.
Autoimmune hyperthyroidism and thrombocytopenia developing in a patient with chronic lymphocytic leukemia
Authors: Haubenstock Alexander , Zalusky Ralph
Published: February 2007

A 56‐year‐old white man is described whose course of chronic lymphocytic leukemia (CLL) was complicated by the Occurrence of the autoimmune hyperthyroidism/ thrombocytopenia syndrome. The implications of this syndrome on the treatment of CLL are discussed.
In vitro stimulation of monocyte tissue factor activity by autologous platelets
Authors: Pinder Patricia B. , Hunt Jane A. , Zacharski Leo R.
Published: February 2007

Washed human platelets were found to enhance phytohemagglutinin (PHA)‐stimulated tissue factor (TF) synthesis when incubated with autologous mononuclear cell cultures. Furthermore, platelets increased TF synthesis even when no other stimulator was present during the incubation. Experiments utilizing similar cultures derived from blood of patients with Glanzmann's disease, von Willebrand's disease, and platelet storage pool disease indicated that platelets with each of these genetic defects possessed the capacity to enhance the synthesis of this initiator of coagulation by unstimulated cells as did normal platelets.

The degree of platelet enhancement varied between individuals, but for any given donor, the extent of the effect depended on the concentration of platelets used. The effect was demonstrable at platelet/monocyte ratios ranging from a low of approximately 15 to the highest ratio used, about 300. For comparison the ratio of these two cellular elements in normal human blood is estimated to be approximately 1,000. These findings may reflect a relationship between these two cell types that can occur in vivo.
Interferon‐induced aplasia: Evidence for t‐cell‐mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin
Authors: Mangan K. F. , Zidar B. , Shadduck R. K. , Zeigler Z. , Winkelstein A.
Published: February 2007

A severe and persistent pancytopenia occurred in a 42‐year‐old woman with a non Hodgkin's lymphoma following a 10‐day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU‐E, BFU‐E, CFU‐GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E‐rosette +, Tγ+, OKT8 + (suppressor/cytotoxic) T‐and/or Leu 7 + natural killer (NK) lymphocytes and 50% were IgM Kappa, B1 +, B‐lymphocytes. In vitro erythroid culture studies were consistent with T‐cell‐mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10‐day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T‐ and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.
Low dose cytosine arabinoside in acute myeloid leukemia: Remission is not due to differentiation induction
Authors: Pinkerton Peter H. , London Betty , Cowan Donald H.
Published: February 2007

A patient with acute nonlymphoblastic leukemia (FAB M4), showing a near tetraploid chromosome complement on his marrow cells, was treated with low dose cytosine arabinoside and achieved remission. During remission the near tetraploid marrow chromosome complement disappeared and reappeared upon relapse of leukemia. These findings are interpreted as evidence against differentiation induction in the leukemic cell line as a mechanism for remission of the disease in this patient.
Haplotypes and levels of fetal hemoglobin and Gγ to Aγ ratios in mediterranean patients with thalassemia minor and major
Authors: Aksoy M. , Kutlar A. , Efremov G. D. , Nikolov N. , Petkov G. , Reese A. L. , Harano T. , Chen S. S. , Huisman T. H. J.
Published: February 2007

This study concerned the γ chain composition of Hb F and the haplotypes of 44 patients with β‐thalassemia major or intermedia and many of their relatives. Seventeen patients came from Northern (Turkish) Cyprus, 12 from the Istanbul area, and 15 from Macedonia and Bulgaria. Analysis of the AγT‐Gγ‐AγI ratio was made by HPLC, while haplotyping involved seven restriction sites.

Specific haplotypes were present in certain populations; haplotype I [1] is the dominant type among North Cypriot thalassemia patients. Numerous types were seen in the patients from the Balkan countries. A direct relationship between the Aγ to Gγ ratios and the haplotypes, which exists among black β‐thalassemia heterozygotes [3], was also observed among these Mediterranean patients, although such analyses were considerably complicated by extensive blood transfusion therapy. Haplotypes without the Hinc II restriction site within the Ψβ gene were associated with lower Gγ values than those that had this polymorphic site. The AγT chain was observed in a small number of β‐thalassemia homozygotes and heterozygotes. Three thalassemia chromosomes with slightly different haplotypes and one normal chromosome with a related haplotype were associated with the γ 75 Ile→Thr substitution. A few patients with a thalassemia intermedia were heterozygotes for β‐thalassemia with either haplotypes V or VII [1] while the “nonthalassemic” chromosome had a haplotype I, which is the most common “ β‐thalassemic” haplotype among the Mediterranean population(s). Detailed analyses of this chromosome have not been completed.
Liver involvement in multiple myeloma
Authors: Perez‐Soler R. , Esteban R. , Allende E. , Saloma C. Tornos , Julia A. , Guardia J.
Published: February 2007

One hundred twenty‐eight records of patients with multiple myeloma were reviewed to assess the incidence and manifestations of liver involvement. Histologic study of the liver was available in 21 patients. Diffuse infiltration of the liver by plasma cells was observed in 10 patients, myeloid metaplasia in four, amyloidosis in two, toxic hepatitis in two, and extrahepatic cholestasis secondary to infiltration of the peripancreatic tissue by plasma cells in one. The clinical signs of plasma cell infiltration of the liver consisted of hepatomegaly in seven patients, mild elevation of liver enzymes in five, and portal hypertension in two. Jaundice was only observed in patients with hepatitis or extrahepatic cholestasis. Liver infiltration by plasma cells did not appear to have a major prognostic significance.
Immunofluorescent plasma cell labeling indices (LI) using a monoclonal antibody (BU‐1)
Authors: Greipp Philip R. , Witzig Thomas E. , Gonchoroff Nick J.
Published: February 2007

Tritiated thymidine labeling indices (LI), although useful in diagnosis and prognosis of multiple myeloma, have not found wide‐spread application because autoradiographic analysis is diffucult and time consuming. Using a monoclonal antibody (BU‐1) reactive with 5‐bromo‐2‐deoxyuridine (BrdUrd), we have developed an immuno‐fluorescent procedure that allows DNA S‐phase measurements to be determined in 4 hr. Plasma cells are easily identified by reactivity with a fluorescein isothiocya‐nate‐conjugated antihuman immunoglobulin, and cells in DNA S phase are detected via BU‐1 and a rhodamine‐conjugated antimouse immunoglobulin. Results using this method on 12 patients with multiple myeloma compare favorably (correlation coefficient 0.84), with those obtained by tritiated thymidine. This immunofluorescent slide method will facilitate application of labeling indices as a clinical test to measure disease activity in patients with multiple myeloma and other hematologic neoplasms.
Abnormal erythrocyte fragmentation and membrane deformability in paroxysmal nocturnal hemoglobinuria
Authors: Smith Brian D.
Published: February 2007

Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is considered to be a result of an intrinsic membrane defect. This defect may result in abnormal material properties of PNH erythrocytes. To examine this hypothesis, fragmentation failure, and membrane deformability were assessed in the absence of complement by micropipette techniques. Membrane viscosity was determined by observing relaxation of deformed cells. Results show a bimodal distribution of force for membrane failure, membrane viscoelasticity, and elastic shear modulus. One population requires significantly less force for fragmentation, mean 0.56 × 10−6 dyne; has increased membrane viscosity, mean 0.205 × 10−2 dyne sec/cm; and has decreased elastic shear modulus, mean 0.56 × 10−2 dyne/cm. A second population resembles control with fragmentation force, mean 1.19 × 10−6 dyne, control 1.05 × 10−6 dyne; membrane viscosity, mean 0.112 × 10−2 dyne/cm, control 0.102 × 10−2 dyne sec/cm; elastic shear modulus, mean 0.70 × 10−2 dyne/cm, control 0.78 × 10−2 dyne/cm. The percent of cells with abnormal material properties corresponds to the percent of PNH III cells determined by complement lysis. Thus, the hemolysis attributed to an abnormal clone of erythrocytes in PNH is associated with an intrinsic membrane abnormality which predisposes to lysis.
Beta2 microglobulin in multiple myeloma
Authors: Alexanian Raymond , Barlogie Bart , Fritsche Herbert
Published: February 2007

Serum beta2 microglobulin levels (B2M) were evaluated before and during chemotherapy in 97 previously untreated patients with multiple myeloma. Pretreatment values were useful in confirming tumor mass grade, and marked reductions following chemotherapy correlated well with the onset of remission. No gain was evident from correcting the B2M for the level of serum creatinine. A pretreatment B2M value greater than 6 mg/L correlated with a low response rate and was the most important variable that predicted a short survival time.
Erythrophagocytosis in vivo in sickle cell anemia
Authors: Solanki Dilip L.
Published: February 2007

Recent observations that the sickle RBC are excessively susceptible to phagocytosis by macrophages in vitro prompted me to look for evidence of in vivo erythrophagocytosis (Ep) in patients with sickle cell anemia (SS). Freshly prepared smears of unmanipulated blood of 27 patients with SS in steady state were examined for Ep by a 500‐cell differential white blood cell (WBC) count performed in duplicate. Ten of 27 (37%) SS patients showed Ep (1–6/1,000 WBC or 1–10/100 monocytes). By contrast, no Ep was found in similarly prepared blood smears of 25 normal adult controls and nine splenectomized subjects. The mean hemotocrit value of the Ep(+) SS patients was significantly lower than that of the Ep(−) patients (21.0 ± 1.7% vs 24.0 ± 2.7% p < 0.01). Considering the rarity of spontaneous Ep in unmanipulated blood from normal subjects and the relative insensitivity of the method used, the finding of Ep in over one third of SS patients indicates a significant membrane injury of the sickle RBC and serves to validate the in vitro observations. The possible role of the “senescence” mechanism in the induction of Ep is discussed.
Fractionation of platelets according to size: Functional and biochemical characteristics
Authors: Carty D. J. , Gear A. R. L.
Published: February 2007

The functional and biochemical heterogeneity of platelets has been studied using graded differential centrifugation to fractionate human platelets according to size while maintaining their morphological and functional integrity as indicated by scanning electron microscopy and content of β‐thromboglobulin. Aggregation kinetics were studied by both optical and quenched‐flow methods involving single‐particle counting. Large platelets were significantly more sensitive to ADP, but aggregated less rapidly than small platelets. Thrombin exerted a similar influence. Large platelets were also enriched in surface sialic acid and sulfhydryl groups and in internal glycogen, ATP, ADP, calcium, cyclic AMP, malonaldehyde, and succinate cytochrome c reductase when compared to small platelets, even when normalized per unit volume. ADP caused a more rapid breakdown of cyclic AMP in small platelets.

Potential aging relationships were tested by isotope studies in rats. 75Se‐selenomethionine was incorporated in vivo at a similar rate into all fractions. Large platelets labeled with 51Cr disappeared from circulation linearly and had a longer mean lifespan than small platelets, which disappeared exponentially. This behavior supports independent aging of platelet populations of differing size.

The data suggest a distinct heterogeneity in platelet function and fate, which could derive from protection of large platelets against excessive activation by Ca2+‐regulated events.
Unbalanced 1;7 translocation and therapy induced hematologic disorders: A possible relationship
Authors: Morrison‐DeLap Sara J. , Kuffel Danlel G. , Dewald Gordon W. , Letendre Louis
Published: February 2007

An identical chromosome abnormality, which appears to be derived from a 1;7 translocation [ +der(1), t(1;7)(p11;p11)], was observed in the bone marrow of 12 patients with various hematologic disorders at the Mayo Clinic from 1980 to 1984. At the time of cytogenetic evaluation, nine of the patients had either a myeloproliferative disorder or a myelodysplastic syndrome, one had an acute leukemia, and two had treated multiple myeloma with no morphologic evidence of evolving myeloproliferative disease. Of the 11 patients for whom information about previous therapy was available, seven had a history of exposure to chemotherapy for a previous malignant disorder; we were unable to establish whether the remaining patient had had prior treatment. This study suggests a possible relationship between +der(1), t(1;7)(p11;p11) and some treatment‐induced hematologic disorders. Such chromosome abnormalities may be the result of a reciprocal chromatid translocation and adjacent I segregation of a quadriradial configuration in metaphase.
Acute myelocytic leukemia manifested by prominent generalized lymphadenopathy: Report of two cases with immunological, ultrastructural, and cytochemical studies
Authors: Davey Diane D. , Foucar Kathy , Burns C. Patrick , Goeken James A.
Published: February 2007

Although it is well recognized that granulocytic sarcoma can cause localized lymphadenopathy, widespread nodal involvement by acute myelocytic leukemia (AML), clinically mimicking non‐Hodgkin's lymphoma, has only been previously described twice. We report the clinicopathological, immunological, and cytochemical features of two patients who had widespread, prominent lymphadenopathy secondary to AML as well as concurrent marrow leukemia (M1 and M2). For one patient the lymphadenopathy was the predominant abnormality prompting him to seek medical attention, while the second patient had symptoms of infection following a 9‐month history of myelodysplasia. The disease in both patients was aggressive; one patient survived only 1 week and the other survived only 5 weeks after diagnosis. In both cases the granulocytic sarcoma was confirmed by cytochemistry studies (naphthol ASD‐chloroacetate esterase on tissue sections and myeloperoxidase on imprint smears), and electron microscopy, including morphology (both cases) or ultrastructural localization of myeloperoxidase (case 2). Non‐specific esterase activity was not detected in either patient's blasts, although serum lysozyme was elevated in both cases. Immunological studies revealed reactivity of both patients' cells with panleukocyte, MY4, MY7, OKM‐1, and Leu‐M1 monoclonal antibodies and with alpha‐1‐antitrypsin and muramidase antibodies. The cells of one of these patients also reacted wtih anti‐S‐100 protein. Although the cytochemical studies indicated that both cases exhibited only myeloid differentiation, the immunological markers suggested that the tumor cells possessed some features of monocytes, perhaps explaining their propensity for widespread tumor formation. Morphological, immunological, cytochemical, and ultrastructural methods of diagnosing granulocytic sarcoma are presented.
The effect of intravascular neutrophil chemotactic factors on blood neutrophil and platelet kinetics
Authors: Issekutz Andrew C. , Ripley Murray
Published: February 2007

Intravenous infusion of an analogue (f‐met‐leu‐phe [FMLP]) of a bacterial‐derived polymorphonuclear leukocyte (PMNL) chemotactic factor, or of the complementderived chemotactic stimulus, zymosan‐activated plasma (ZAP, containing C5ades Arg) into rabbits induces acute PMNL margination in the pulmonary vasculature. This process also occurs during hemodialysis and the adult respiratory distress syndrome. The pulmonary PMNL sequestration is accompanied by thrombocytopenia. Because of the role platelets and PMNLs play in hemostasis and defense against infection, we studied the fate of these blood elements following sequestration induced by chemotactic factors. By employing 111In‐labelled platelets and external radioisotope scanning, platelets were found to sequester in the pulmonary vasculature during FMLP infusion. Simultaneous 51Cr PMNL and 111 In‐platelet studies showed that following sequestration, PMNLs returned to the circulation and disappeared with a normal half‐life (T1/2) whereas the T1/2 of the platelets was markedly shortened (T1/2 of control = 49 ± 3.0 hr; FMLP or ZAP infused T1/2 = 27 ± 2.7 hr). Infusion of platelet‐activating factor (PAF) induced PMN and platelet sequestration with similar abnormalities in platelet kineties. Studies with 51Cr‐ and 14C‐serotonin‐labelled platelets showed that platelets did not release serotonin during FMLP, ZAP, or low dose PAF‐induced sequestration. In contrast to platelet survival, platelet size, platelet aggregation responses, and platelet glycoprotcins were not affected by transient sequestration. These results indicate that during PMNL margination induced by relatively „pure”︁ PMNL stimuli such as FMLP, platelets may reversibly marginate and subsequently be cleared at an accelerated rate. The reason for accelerated platelet clearance is not a result of circulating platelet aggregates or detectable proteolytic modification of membrane glycoproteins. Such altered platelet kinetics may contribute to thrombocytopenia during sepsis, the adult respiratory distress syndrome, and other states in which excess PMNL margination occurs.
T‐lymphocyte subpopulation changes during hemolysis in glucose‐6‐phosphate dehydrogenase (G6PD)‐deficient children
Authors: Schilirò G. , Minniti C. , Sciotto A. , Bellino A. , Russo A.
Published: February 2007

Lymphocyte subpopulations were studied by means of sheep red blood cell (SRC)‐rosetting technique and OKT11, OKT3, OKT4, and OKT8 monoclonal antibodies in ten Sicilian glucose‐6‐phosphate dehydrogenase‐deficient children during the hemolytic crisis due to fava bean ingestion. The number of SRC‐rosetting lymphocytes was significantly reduced, while the number of OKT3‐positive cells was normal. An inversion of the OKT4/OKT8 ratio was observed, due to a decrease of OKT4‐positive cells and an increase of OKT8‐positive cells. All these abnormalities reverted to normal in the four children studied after recovery.
Porcine factor VIII and plasmapheresis in the management of hemophiliac patients with inhibitors
Authors: Bona Robert D. , Pasquale Dominick N. , Kalish Robert I. , Witter Barbara A.
Published: February 2007

Management of hemophiliac patients with inhibitors can be a difficult problem. We report here a patient with severe hemophilia A, a high titer inhibitor, and an abdominal abscess requiring surgery. Despite significant cross reactivity of the inhibitor with porcine FVIII, he was successfully managed with plasmapheresis and porcine FVIII infusions. Other approaches to the management of such patients are briefly reviewed.