bluuebunny/crossref_metadata_2025 huggingface dataset:
A plasma inhibitor of ristocetin‐induced platelet aggregation in patients with sickle hemoglobinopathies
Authors: Leichtman David A. , Brewer George J.
Published: February 2007

Because of the high prevalence of thrombotic complications in patients with sickle cell anemia (SCA), we investigated platelet function in patients with sickle hemoglobinopathies. Platelet aggregation induced by epinephrine, ADP, and collagen, except for absent secondary wave in 3 of 10 patients with SCA, was qualitatively normal. However, ristocetin‐induced platelet aggregation (RIPA) with a final concentration of 1.12 mg/ml was markedly abnormal – absent or virtually absent in 9 of 10 patients with SCA, 3 of 3 patients with hemoglobin S‐C disease, and 2 of 3 patients with sickle trait. All 8 controls used in these experiments repeatedly demonstrated normal RIPA. Addition of normal plasma failed to correct abnormal RIPA in sickle hemoglobinopathy patients. All patients demonstrated normal RIPA with a ristocetin dose of 2.24 mg/ml and aggregated with bovine fibrinogen. Recombinant mixing experiments demonstrated that washed SCA platelets support RIPA (1.12 mg/ml) when resuspended in normal plasma or high dilutions of SCA plasma, but not in undiluted SCA plasma. Washed normal platelets do not support RIPA (1.12 mg/ml) when resuspended in SCA plasma. These findings suggest the presence of a plasma inhibitor of RIPA in patients with sickle hemoglobinopathies.
Development of chronic myelocytic leukemia during the course of acute lymphocytic leukemia in an adult
Authors: Fisher Barry L. , Lyons Roger M. , Sears David A.
Published: February 2007

A 59‐year‐old patient is described who presented with acute lymphocytic leukemia. Complete remission was induced rapidly with vincristine and prednisone. Nine months later he acquired the clinical and hematological picture of a myeloproliferative disease, and bone marrow cytogenetic studies demonstrated the presence of the Philadelphia chromosome. Within 4 months he again developed overt acute lymphocytic leukemia and died. Several lines of evidence have recently indicated a relationship between myeloproliferative and lymphoproliferative disorders, particularly chronic myelocytic and acute lymphocytic leukemia. This patient's course is another example of that association.
Alpha‐thalassemia
Authors: Adams Junius G. , Steinberg Martin H.
Published: February 2007

The current concepts of α‐thalassemia including incidence, genetics, clinical spectrum and diagnosis are reviewed. Speculation concerning clinical application of the molecular biology of α‐thalassemia is also presented.
The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse
Authors: Ganick D. J. , Segel G. B. , Chamberlain J. , Hirsch L. , Klemperer M. R.
Published: February 2007

We have studied the effects of splenectomy and glucocorticoids on the survival and sequestration of Heinz body‐containing red blood cells (RBC‐HZB). Mice were injected with phenylhydrazine damaged 51Cr labeled isologous red blood cells (RBCs). The spleen removed 36% and the liver 19% of the injected dose after 120 hrs. Red cell survival (T½) fell from 180 hrs for undamaged red cells to 16 hrs for RBC‐HZB. Splenectomy resulted in an increase in hepatic uptake of damaged RBCs (36% of the injected dose) and a modest improvement in red cell survival (T½ 54 hrs). Treatment of non‐splenectomized mice with glucocorticoids reduced the splenic uptake to 16% and the hepatic uptake to 14% of the injected dose. The reduction of splenic uptake was associated with a decrease in splenic mass rather than a decrease in uptake per unit weight of splenic tissue, while the reduction in hepatic uptake was associated with both a decrease in hepatic mass and uptake per unit weight. A marked decrease was observed in hepatic uptake and in phagocytosis by Kupffer cells in glucocorticoid‐treated splenectomized mice. These data suggest that increased hepatic uptake may decrease the effectiveness of splenectomy in RBC‐HZB hemolytic anemia and that glucocorticoids may decrease the hepatic uptake by reducing phagocytosis by Kupffer cells.
Continuous flow method for determination of erythrocyte osmotic fragility
Authors: Ito Yoichiro , Carmeci Peter , Steele Roderic
Published: February 2007

A simple and accurate micromethod for the determination of erythrocyte osmotic fragility is introduced. The method uses a laminar parabolic flow pattern, together with gravity, to retain cells in a long, small‐diameter tube while a solution with decreasing osmolarity is passed through the tube. As the cells hemolyze, hemoglobin released from the cells is quickly removed by the axial flow pattern and monitored with a 547 nm optical detector for recording the hemolysis curve. Consequently, a continuous curve is obtained, with a peak occurring at the salt concentration that produces the maximum hemolysis rate. The advantages of this method are simplicity, accuracy, and small sample size (2 microliters of whole blood). The small sample size is of particular importance for infants.

A comparison is made with the Parpart method using samples from 18 normal adults. Results are also given for a few abnormal adults and for a series of 26 normal newborns.
Increase in platelet aggregation following a rise in plasma free fatty acids
Authors: Burstein Yoav , Berns Lawrence , Heldenberg Dov , Kahn Yael , Werbin Ben Zion , Tamir Israel
Published: February 2007

Platelet aggregation was studied following intravenous injection of heparin to nine healthy adults. Heparin is known to produce an increase in the concentration of free fatty acids (FFA) within 10 minutes of intravenous injection. A significant correlation was found between the intensity of primary platelet aggregation and changes in plasma FFA levels. No correlation was found between plasma FFA levels and the intensity of secondary platelet aggregation.
Murine hemopoietic colonies in culture containing normoblasts, macrophages, and megakaryocytes
Authors: Hara Hiroshi , Ogawa Makio
Published: February 2007

Murine marrow cells, when incubated in methylcellulose culture in the presence of erythropoietin and conditioned medium for two weeks, produced large macroscopic bursts containing normoblasts, macrophages, and often megakaryocytes. The clonal nature of these mixed colonies was supported by linearity studies and analyses of the percentages of constituent cells in different plating conditions. Time course observations and studies of the effects of L‐cell‐conditioned medium revealed that colony‐forming cells for the mixed colonies (CFU‐mix) are at earlier stages of hemopoietic development than burst‐forming units (BFU‐E). The mean of the modal sedimentation velocities of CFU‐mix was 3.4 mm/hr and was in close agreement with that reported for the spleen colony‐forming units. Almost none of the CFU‐mix was in a DNA synthetic phase as measured by short‐term exposure to tritiated thymidine. These results strongly indicate that CFU‐mix represent a population of pluripotent hemopoietic stem cells in murine marrow.
The treatment of combination chemotherapy‐resistant Hodgkin disease with single‐agent vinblastine
Authors: Warren Robert D. , Bender Richard A. , Norton Larry , Young Robert C.
Published: February 2007

Vinblastine has been an effective single agent for initial induction therapy of advanced Hodgkin disease. To investigate the efficacy of this drug in combination chemotherapy‐resistant Hodgkin disease, 29 patients with Stage III or Stage IV disease who had previously received MOPP (nitrogen mustard, vincristine, prednisone, procarbazine) or C‐MOPP (cyclophosphamide, vincristine, prednisone, procarbazine) for initial remission induction were treated with vinblastine at the time of relapse, either as the first single agent at relapse (n = 17) or following unsuccessful attempts at reinduction with combination chemotherapy (n = 9) or other single agents (n = 3). Eighteen patients (62%) achieved an objective regression of disease. Two patients (7%) had a complete remission of nine and ten months duration and 16 patients (55%) had a partial remission with a median duration of four months. A response to combination chemotherapy did not predict for a vinblastine response, nor did nodal versus visceral involvement at time of relapse or initial stage of Hodgkin disease. There were no significant differences in age, sex, vinblastine dose, or disease duration between those patients who responded to vinblastine and those who did not. Patients with nodular sclerosis histology responded better to subsequent vinblastine therapy. Hematologic toxicity was moderate with 17 patients developing leukopenia (< 3,000 cells/mm3) and 12 patients developing thrombocytopenia (< 100,000 cells/mm3). The overall response rate of vinblastine in combination chemotherapy‐resistant Hodgkin disease is comparable to vinblastine single‐agent therapy for initial induction and appears not to be cross‐resistant with combinations containing vincristine.
Rosette‐formation with mouse erythrocytes: VI. T, B, and third population lymphoid cells in mycosis fungoides and effect of leukopheresis
Authors: Gupta Sudhir , Safai Bijan , Good Robert A.
Published: February 2007

Peripheral blood from 16 patients with mycosis fungoides and two patients with Sézary syndrome was examined for T, B, and third‐population (K) cells, using a battery of surface markers. T lymphocytes as determined by spontaneous rosette formation with sheep erythrocytes and third‐population cells as determined by the Ripley rosette test were present in normal proportions. Surprisingly, B lymphocytes, as determined by surface immunoglobulin and receptors for mouse erythrocytes, were either lacking or were present in low proportions in some patients. Normal proportions were present in others. Repeat studies of two of three patients lacking B lymphocytes, following treatment, revealed normal or low proportions of B cells. Two patients with mycosis fungoides had increased proportions of “null” cells. Study of lymphoid cell subpopulations before and after leukopheresis in a single patient demonstrated a decrease in T cell proportions associated with a concomitant increase in the proportions of “null” cells following this therapy.
Breast cancer and acute leukemia: Report of 24 cases and review of the literature
Authors: Rosner Fred , Carey Robert W. , Zarrabi Mohammad H.
Published: February 2007

Twenty‐four cases of breast cancer and acute leukemia and three cases of breast cancer and chronic myelocytic leukemia are reported. An additional 54 cases of acute leukemia and 13 cases of chronic myelocytic leukemia associated with breast cancer from the literature are reviewed.

The mean interval between the diagnosis of breast cancer and the occurrence of acute leukemia is 6.9 years. In eight patients, the two diseases occurred simultaneously or within one year of each other. Four patients had acute lymphoblastic leukemia; the remainder had acute myelocytic leukemia or one of its variants.

Seven patients received no postmastectomy radiotherapy or chemotherapy and the occurrence of acute leukemia between 1 and 23 years later cannot, therefore, be attributed to the therapy given for the breast cancer. Forty‐one patients received postoperative radiotherapy to the mastectomy site. Combination chemotherapy was administered to eight patients, five of whom were also treated with radiotherapy.

Acute leukemia is estimated to occur in patients treated for breast cancer with a sevenfold increased frequency over the expected number. This may be due to an increased risk of a second neoplasm in patients with a primary tumor; alternatively, the acute leukemia may be related to the radiotherapy and/or chemotherapy administered to treat the breast cancer. Late death from leukemia after chemotherapeutic or radiotherapeutic remission of metastatic breast cancer is preferable to morbidity and/or early death from inadequately treated breast cancer.
Hemorrhagic death associated with a high titer factor V inhibitor
Authors: Coots Macie C. , Muhleman Albert F. , Glueck Helen I.
Published: February 2007

An acquired bleeding diathesis was first noted in a 51‐year‐old patient 11 days following an exploratory laparotomy. Laboratory studies indicated the cause of bleeding to be the development of a circulating anticoagulant which inhibited factor V activity. The inhibitor, an immunoglobulin of the IgG class, was separated by use of Sephadex G‐200 filtration, disc electrophoresis, and isoelectric focusing. Despite vigorous immunosuppressive, antifibrinolytic, and replacement therapy, including the use of a “prothrombin complex” and plasmaphoresis, the bleeding diathesis could not be reversed and the patient died of hemorrhage.

Although inhibitors to factor V are not usually associated with major life‐threatening hemorrhage, this case demonstrates that the development of such an inhibitor can be an ominous finding. The use of an aminoglycoside antibiotic in this and other patients so reported may be one of the contributing causes to the development of such an inhibitor.
Hodgkin disease: An analysis of 128 cases
Authors: Dawar Ramesh , Mangalik Aroop
Published: February 2007

An analysis of 128 cases of Hodgkin disease seen at the Department of Pathology, All India Institute of Medical Sciences, New Delhi, during the period 1968–1974 is presented with reference to histopathological and clinical findings. A male preponderance is noted in all age groups, and this is most noticeable in children under 15 years of age. There is a predominance of cases with the histologic subtypes associated with a poor prognosis (mixed cellularity and lymphocyte depleted). Only nine cases of nodular sclerosis type were seen.
In vitro functional capabilities of canine polymorphonuclear neutrophils collected simultaneously by continuous‐flow centrifugation and continuous‐flow filtration leukopheresis
Authors: Cook Lloyd O. , Boxer Laurence A. , Allen John M. , Griep John A. , Baehner Robert L.
Published: February 2007

Polymorphonuclear neutrophils were simultaneously collected from dogs by continuous‐flow centrifugation and continuous‐flow filtration leukapheresis. In vitro studies were performed on cells obtained by the two methods as well as on control cells. Studies consisted of assessment of phagocytic capacity, degranulation, chemotaxis, hexose monophosphate (HMP) shunt activity, and bacterial killing. The cells obtained from the filter were metabolically more active than those harvested by centrifugation, as evidenced by increase in resting HMP shunt activity and dimunition in total available lysozyme‐secreting activity compared to centrifuged cells. Despite their impaired phagocytic capacities, the filtered cells were able to kill Staphylococcus aureus as efficiently as the centrifuged cells. Both cell populations responded to chemotactic gradients equally.
Studies on red‐cell aplasia: IX. Ferrokinetics during remission of the disease
Authors: Wibulyachainunt Saengsuree , Price Ronald , Brill A. Bertrand , Krantz Sanford B.
Published: February 2007

Ferrokinetic studies and external organ measurements of radioiron were performed on five patients with pure red‐cell aplasia (PRCA) in remission. One patient with PRCA in relapse was also studied. Of those in remission, one patient had erythroid hyperplasia and ineffective erythropoiesis after the remission occurred. This was indicated by a very short 59Fe clearance rate and reduced red‐cell 59Fe incorporation, a marked increase of the erythron iron turnover over the fixed red‐cell iron turnover, and a prolonged marrow transit time. These indices were normal three years later. Four patients had normal effective erythropoiesis while in remission. Two patients had an extended marrow distribution. These studies indicate that some cases of PRCA evolve into a state of ineffective erythropoiesis with erythroid hyperplasia. It is possible that in some patients, primary refractory anemia with ineffective erythropoiesis may be related to PRCA because of the evolution from one state into the other. Alternatively, a second pathologic process may have been acquired between the PRCA and normal hematopoiesis.
Radioimmunoassay of human prothrombin—The quantitation of plasma factor II antigen
Authors: Lox Charles D. , Strohm G. Henry , Corrigan James J.
Published: February 2007

Human factor II (prothrombin) was isolated by chromatographic techniques and showed a single band on electrophoresis. 125I‐tagged factor II was prepared by standard chloramine‐T oxidation and sodium metabisulfite reduction. The radioimmunoassay (RIA) method used was a specific double‐antibody radioimmunoassay similar to that described for the pituitary trophic hormones. The method showed high precision and sensitivity. A dose‐response curve was generated by adding known amounts of normal human plasma to human barium sulfate‐absorbed oxalated plasma. A straight‐line relationship existed between 15 to 140% coagulant activity and 7 to 50 μg/ml antigen content. Plasma factor II antigen in 20 normals was 86.1 ± 8.4 μg/ml. Eight patients with induced vitamin K deficiency revealed normal antigen levels and reduced coagulant activity, whereas three patients with severe hepatocellular disease were found to have both antigen and coagulant activity reduced. Although coagulant activity decreased with prolonged storage, it was found that antigen content did not change with up to three months' storage at − 20°C. The use of the RIA for measuring prothrombin protein in conjunction with coagulation factor assays may have clinical application in studying the mechanism of action of vitamin K, the developmental aspects of factor II production and activation, and the understanding of acquired coagulopathies.
Association of 5q− and refractory anemia
Authors: Kaffe Sara , Hsu Lillian Y. F. , Hoffman Ronald , Hirschhorn Kurt
Published: February 2007

The association of refractory anemia with partial deletion of the long arm of one No. 5 chromosome (5q−) has been reported in six patients within the last two years. We wish to report an additional patient with refractory anemia and an acquired chromosomal deletion, del(5)(q15), in a direct bone‐marrow preparation. The specificity of this deletion for refractory anemia is discussed. It remains to be seen whether patients with refractory anemia and 5q− tend to develop acute leukemia, as has been recently suggested.
A case of acute myelogenous leukemia with an 8–21 translocation, missing Y, and additional karyotypic abnormalities
Authors: Kaneko Yasuhiko , Sakurai Masaharu , Hattori Masao
Published: February 2007

A patient with acute myelogenous leukemia (AML) whose bone marrow cells had complicated chromosomal abnormalities, in addition to an 8–21 translocation and a missing Y chromosome, is reported. The complex additional abnormalities did not appear to have much influence on the clinical aspects of the disease, eg, cytology of the leukemic cells and the patient's response to chemotherapy, even though the patient did have a rectal tumor due to leukemic cell infiltration.
Hemopoietic support capacity of the adult mouse liver: II. Studies in acetylphenylhydrazine‐treated mice
Authors: Adler Solomon S. , Trobaugh Frank E.
Published: February 2007

We investigated the hemopoietic support capacity of the liver in intact and splenectomized adult mice treated with three daily injections of acetylphenylhydrazine (APH). Packed red cell volumes, liver and spleen weights, numbers of pluripotent hemopoietic stem cells (CFU‐S) in blood and liver, and liver histology were evaluated 4, 8, 12, 16, and 20 days after the first injection.

We found that 1) splenectomized, APH‐treated mice had a greater and more sustained increase in the weights of their livers than the increase found in livers of intact APH‐treated mice; 2) APH treatment elicited a much greater increase in the blood and liver CFU‐S of splenectomized mice (47 and 42 times normal, respectively) than it elicited in the blood and liver CFU‐S of intact mice (4–5 and 4 times normal, respectively); and 3) APH treatment induced numerous foci of hemopoietic tissue in the livers of splenectomized mice. The results of the CFU‐S studies can be explained by, and to some extent support, the thesis that the adult mouse liver does not support proliferation of normal CFU‐S, but can trap large numbers of circulating CFU‐S. In addition, these studies suggest that the livers of adult mice are able to support only limited proliferation of differentiated hemopoietic elements.
Prognostic value of nucleoli and cell size in chronic lymphocytic leukemia
Authors: Dubner Howard N. , Crowley John J. , Schilling Robert F.
Published: February 2007

In an effort to improve prediction of duration of survival in chronic lymphocytic leukemia, correlations between blood‐cell morphology and survival were investigated. Blood films made on 108 patients at the time of diagnosis of chronic lymphocytic leukemia were reviewed by a single hematologist. Lymphocyte diameter and the fraction of lymphocytes containing nucleoli were both found to have an inverse correlation with survival.

Bone‐marrow aspirate films were available for 64 patients. Differential leukocyte counts showed that the median for marrow lymphocytes was 64%. Those patients with a greater than median proportion of lymphocytes on marrow aspirate had a shorter survival time than those with less than median.
Combined effect of dextrose and sodium chloride on red cell osmotic fragility
Authors: Minn Sang K. , Harnchonboth Kwanruen , Mandel Emanuel E.
Published: February 2007

Observations indicating an enhancing effect of sodium on hemolysis of red cells suspended in dextrose solution prompted study of the mechanism of this effect. Osmotic fragility of red cells from normal subjects and from patients was measured in 5% dextrose solution (5D/W), 5% dextrose combined with various concentrations of sodium chloride (5D/NaCl), lithium chloride, and potassium chloride. The influence of ouabain on osmotic hemolysis in 5D/ NaCl was also studied, and the glucose content of ghost red cells was determined when incubated in 5% dextrose with 0.05% NaCl (5D/O.05NaCl), as compared with 5D/W.

In the presence of minimal amounts of NaCl (0.05%) at pH 4.8, average hemolysis was greater than in the absence of NaCl, ie, 39% vs 24% in normal subjects (P < 0.02) and 40% vs 31% in a group of unselected patients (P < 0.05). When the pH was adjusted to 7.4 in the patient group, the results were 34% vs 21% (P < 0.05). The sodium‐induced enhancement of hemolysis in dextrose solution was virtually duplicated when LiCl and KCl were substituted for NaCl (P < 0.01 and < 0.05, respectively). On the other hand, in the presence of ouabain, the sodium‐induced enhancement of hemolysis was abolished. The overall glucose content of ghost red cells incubated in 5D/0.05NaCl was 53% greater than in 5D/W (P < 0.005), whereas with ghost red cells depleted of adenosine triphosphate (ATP), it was only 32% greater (P < 0.01).

These results suggest that glucose transport across the red cell membrane is enhanced by the sodium ion, presumably by triggering the membrane sodium‐potassium ATPase system.
Coulter S hematocrit and microhematocrit in polycythemic patients
Authors: Dosik H. , Prasad B.
Published: February 2007

Falsely high microhematocrits are found when compared to Coulter S hematocrit levels. This increase is exaggerated when hematocrit levels are increased and the cells are hypochromic and microcytic. Polycythemic patients monitored with microhematocrits may be phlebotomized incorrectly because of this abnormality. We suggest the use of Coulter S hematocrits or spectrophotometric hemoglobin levels to monitor polycythemic patients.
Myelofibrosis with complex chromosome abnormality in a patient with erythrocytosis due to hemoglobin rainier and treated with 32P
Authors: Najfeld Vesna , Price Thomas H. , Adamson John W. , Fialkow Philip J.
Published: February 2007

A patient with familial erythrocytosis associated with Hemoglobin Rainier, and previously treated with 32P, developed myelofibrosis with a hyperdiploid chromosome clone in the myeloid cells (51, XX, +1, 2q‐(q33), +6, +9, +11, ‐19, +20q +,+ mar 1). This transformation from a benign disorder of differentiated erythrocytes to a malignant disorder may have been secondary to radiophosphorus therapy.
Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant
Authors: Firkin B. G. , Booth P. , Hendrix L. , Howard M. A.
Published: February 2007

A lupus‐type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl‐cellulose‐immunoglobulin (DEAE‐cellulose‐IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet‐poor plasma (PPP) with a rabbit anti‐IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.
A case of red‐cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan
Authors: Miwa Shiro , Fujii Hisaichi , Matsumoto Noboru , Nakatsuji Tadako , Oda Susumu , Miura Yukari , Asano Hiroyuki , Asano Seiichi
Published: February 2007

A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38‐year‐old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51 Cr‐labeled red cell half‐life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40‐fold increase while that of the mother showed 4‐fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010‐1,550); adenine nucleotide pool, 46% of the normal mean; 2,3‐diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170‐5,300); increased oxygen affinity of hemoglobin, P50 of intact crythrocytes being 21.8 mmHg (normal, 24.1‐26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2‐deoxyadenosine. The ADA activity of lymphocytes was nearly normal.
Some observations on propranolol on platelet aggregation and release
Authors: Leon Rafael , Tiarks Cheryl Y. , Pechet Liberto
Published: February 2007

Platelet function was investigated in four normal volunteers, one patient with a mild form of von Willebrand disease, and one with a thrombocytopathy, all taking propranolol. No effect on platelet function attributable to this drug could be demonstrated in any of these subjects. It is suggested that propranolol administered in conventional doses does not impair platelet hemostatic function.
B‐Cell leukemia‐lymphoma with striking resemblance to burkitt lymphoma in a 70‐year‐old woman
Authors: Shaw Michael T. , Palmer Charles , Yuhas John M. , Rembe Armin , Robertson Gerald , Bankhurst Arthur D.
Published: February 2007

A 70‐year‐old woman developed acute leukemia and a serum IgM spike. She entered complete remission with an adriamycin, vincristine, cytosine arabinoside, and prednisone combination. Bone marrow remission was maintained with intermittent cytosine arabinoside; however, she developed large skin nodules which partly remitted following adriamycin, vincristine, cyclophosphamide, and prednisone combination. They very rapidly recurred, and she died soon after. Autopsy revealed extensive tumor in the abdomen, pelvis, and thoracic cavity, but no bone marrow involvement. Histology revealed a “starry sky” appearance. Cytology showed undifferentiated cells with vacuolated cytoplasm resembling Burkitt lymphoma cells. Peroxidase and esterase stains were negative. There was strong pyroninophilia and the periodic acid‐Schiff reaction showed granular activity in the cytoplasm. Electron microscopic appearances also resembled Burkitt lymphoma. Cytogenetic studies were normal, with no Ph1 chromosome. Immunofluorescence demonstrated surface IgM and a little IgA. 3H‐thymidine incorporation was high, indicating rapid growth. Dibutyral cyclic adenosine monophosphate (cAMP) stimulated growth, which was further evidence of the lymphoid origin of the tumor. The close resemblance of this tumor to Burkitt lymphoma emphasizes the difficulties in systematically classifying the lymphomas.
New leukemia in the course of therapy of acute lymphoblastic leukemia
Authors: Ravindranath Yaddanapudi , Inoue Susumu , Considine Basil , Lusher Jeanne , Zuelzer Wolf W.
Published: February 2007

We have recently observed the development of second leukemia of a morphologically different type in three patients with acute lymphoblastic leukemia (ALL) while on therapy. The “second” leukemia occurred while on therapy at 23, 27, and 32 months of initial remission. All three were receiving systemic chemotherapy (CT) and prophylactic fractional irradiation to the central nervous system (CNS). The second leukemias in these three cases were one case of juvenile chronic myelogenous leukemia (JCML) and two cases of acute leukemia of the myeloblastic type by the usual morphologic criteria including the presence of Auer rods in one. In two cases a cytogenetically new clone was detected in the remission marrow 10 and 12 months preceding the overt change in clinical status.

These three cases demonstrate that second leukemia occurs in patients with ALL and that some late “relapses” fall into this category. The possible etiologic role of modern intensive treatment regimens in the development of second leukemia is discussed.
A new chromosome abnormality in idiopathic sideroblastic anemia: 46, XY, del11q23
Authors: Hyder Dan M. , Bottomley Sylvia S. , Bottomley Richard H.
Published: February 2007

A new marker chromosome, deletion 11q23, was observed with the Giemsa banding technique in the bone marrow of a patient with idiopathic sideroblastic anemia. The abnormality was not detectable in the peripheral blood or with nonbanded chromosome studies. Nineteen of 40 cases of this disorder studied and reported to date had chromosomal aberrations, although the majority had only nonbanded karyotypes performed. This apparently high incidence of chromosomal defects and the finding in the present case indicate that more banded‐karyotype analyses are needed to assess the presence of possible nonrandom cytogenetic changes in idiopathic sideroblastic anemia.
Antibody‐induced von willebrand syndrome: Inhibition of VIII VWF and VIII AGN with sparing of VIII AHF by the autoanti body
Authors: Gazengel C. , Jacques C. , Nedellec J. , Josso F. , Buriot D. , Prieur A. M.
Published: February 2007

Acquired von Willebrand syndrome is reported in a 16‐year‐old girl with systemic lupus erythematosus. Routine coagulation studies showed a normal platelet count, prolonged bleeding time, and abnormal glass bead retention. Factor VIII molecular complex respective activities were 8% for VIII AHF and undetectable for VIII VWF (ristocetin aggregation of washed platelets) and VIII AGN (electro‐immunodiffusion).

In vitro, the patient's plasma exhibited an inhibitory activity against exogenous VIII AGN and VIII VWF but did not neutralize VIII AHF activity of control plasma, even after a two‐hour incubation at 37°C. This inhibitory activity was supported by the purified plasma IgG fraction. In vivo, following cryoprecipitate administration (20 units VIII AHF/kg), only 50% of the infused VIII AHF activity was recovered after 15 mn, and the original level was reached four hours later. Only a transient peak of VIII VWF activity was observed, and VIII AGN level did not increase at all after the infusion.

After the start of prednisone therapy the three factor VIII related activities returned to normal levels in the following order: VIII AHF and VIII VWF (9‐12 days); VIII AGN (3 weeks).

These findings could be explained by the formation of a short‐lived circulating immune complex between the antibody and the factor VIII molecular complex. In such an hypothesis the autoantibody would respect the site of VIII AHF activity and would mask the site reacting with anti VIII AGN heteroantibodies.
Control factors of granulopoiesis in human serum
Authors: Bolin Rex W. , Robinson William A.
Published: February 2007

The role of serum factors in the modulation of production of colony‐stimulating activity (CSA) has been investigated. A factor has been described, and partially characterized, in human serum that has the capacity to stimulate increased synthesis and release of CSA by human mononuclear cells (MNC). MNC RNA and protein synthesis are required to demonstrate this effect of serum, but DNA synthesis and mitotic division are not required. The factor in serum resulting in this effect is a heat‐labile protein with a molecular weight slightly greater than that of CSA.
Studies on hematopoietic stem cells: XI. Lack of erythroid burst‐forming units (BFU‐E) in patients with aplastic anemia
Authors: Moriyama Yoshiaki , Sato Masatsugu , Kinoshita Yasutami
Published: February 2007

The marrow concentration of erythropoietic precursors was examined in normal donors and patients with idiopathic aplastic anemia using a plasma clot culture system. On time course observations the heterogeneity of human erythroid precursors assayable in culture was demonstrated. To evaluate human erythropoiesis in vitro, the benzidine‐positive colonies were divided into three groups: small colony, containing 8–50 cells; medium‐sized colony, containing 50–500 cells; and large colony, containing more than 500 cells. The majority of the large colonies assumed the morphology of erythropoietic bursts (BFU‐E) consisted of several subcolonies. The small colonies were counted as CFU‐E1, the medium‐sized as CFU‐E2, and the large as BFU‐E to evaluate the erythroid precursor cell compartment in aplastic anemia.

The marrow concentration of CFU‐E1 and CFU‐E2 was shown to be quantitatively diminished in aplastic anemia. In addition, there was no ability of the marrow cells from aplastic patients to grow BFU‐E in vitro even in the presence of a large dose of erythropoietin. This lack of BFU‐E colony growth may play an important role in the mechanism of the erythropoietic deficiency in aplastic anemia.
The periodic acid‐schiff reaction and prognosis in children with acute lymphoblastic leukemia
Authors: Raney R. Beverly , Festa Robert S. , Waldman Maria T. G. , Manson David , Hann Hie‐Won L.
Published: February 2007

We evaluated the intensity of the periodic acid‐Schiff (PAS) stain reaction by examining 200 lymphoblasts from the initial marrow aspirate specimen of 38 children with acute lymphoblastic leukemia (ALL). The patients were separated into low, intermediate, and high groups according to mean PAS score. The groups were then compared in terms of age, sex, initial hematologic values, T‐ and B‐lymphocyte markers, percentage of patients in remission six months after diagnosis, and percentage surviving. Significant differences were found between the low group and the other two groups with respect to sex, height of initial white blood cell (WBC) count, outlook for continued remission at six months, and overall survival (P < 0.05). The low‐score patients were predominantly males, whereas the other PAS‐score groups contained approximately equal numbers of males and females. The low‐score patients had a higher median initial WBC than the others, but all three groups had a similar proportion of patients with initial WBC under 20,000/cu mm. Low‐score patients were less likely to be in remission six months from diagnosis, and they had shorter survival than the intermediate‐ and high‐score patients (P < 0.05). The results suggest that children with ALL whose lymphoblasts stain weakly with PAS have a worse prognosis than those with intermediate or high PAS reactivity. PAS reactivity may vary independently of the WBC at diagnosis in children with ALL, because children with a low PAS score have a poor outlook even with initial WBC under 20,000/cu mm.
Acute leukemia and preleukemia in eight males in a family: An X‐linked disorder?
Authors: Li Frederick P. , Marchetto David J. , Vawter Gordon F.
Published: February 2007

Eight males in a family died of acute leukemia or a potentially preleukemic blood disease. Three patients were descendants of a man through his first wife, and the other five through his second wife. The pattern of disease in the family suggests X‐linked inheritance through the two wives, although other mechanisms cannot be excluded. No detectable action of environmental leukemogens was observed in this family disorder.
Reduced ferrochelatase activity in fibroblasts from patients with porphyria variegata
Authors: Viljoen D. J. , Cayanis E. , Becker D. M. , Kramer S. , Dawson B. , Bernstein R.
Published: February 2007

Ferrochelatase deficiency has been shown in both porphyria variegata (PV) and erythropoietic protoporphyria (EPP). It has been suggested that in PV there is a decrease in the enzyme, whereas in EPP the enzyme is unstable. In the present study ferrochelatase activity was measured in skin fibroblasts from three patients with PV and three normal subjects. The enzymatic activity in the patients with PV (17.5 ± 4.5 pmoles heme formed per 107 fibroblasts per hour) was 50% of that of the control group (31.0 ± 3.2 pmoles heme formed per 107 fibroblasts per hour). This supports the contention that the enzyme is deficient in PV and that an inactive ferrochelatase is the primary deficiency in this type of porphyria.
Chromosomes and causation of human cancer and leukemia. XXXIII. 5q– in a case of acute lymphoblastic leukemia (ALL)
Authors: Abe S. , Kohno S. , Kubonishi I. , Minowada J. , Sandberg A. A.
Published: February 2007

The case of a 4‐year‐old boy with ALL, possibly developing subsequent to a lymphoma involving the throacic cavity, which was shown to be of the T‐cell type, is presented. The leukemic cells had a 5q– anomaly, which had previously been described only in cases of refractory anemia and/or AML. The 5q– abnormality was invariably accompanied by a 9p– chromosome in the leukemic cells. The interstitial deletion leading to the 5q– chromosome was shown with banding techniques to be similar to that described previously in myeloproliferative disorders. Some aspects of the 5q– anomaly in ALL and its relation to previous experience with this karyotypic change are discussed.
Antisickling agents: Effects of carbamyl phosphate or cyanate on survival, erythrocytes, and leucocytes in the mouse
Authors: Kraus Lorraine M. , Jernigan Howard M. , Schrank Gordon D. , Kraus Alfred P.
Published: February 2007

Equal mole doses of the anions of disodium carbamyl phosphate (carbamyl P) or sodium cyanate, antisickling agents, have been compared in C57B1 mice. Using 15 mice per group, two groups were given the equivalent ip dose of carbamyl P or cyanate anion (7 mmoles/kg/day) in a divided dose, in the morning and six hours later, for 17–18 days. The control group received sodium chloride (13.8 mmoles of Na+ or C1−/kg/day). Surviving mice per group were sodium chloride, 15/15; disodium carbamyl P, 14/15; and sodium cyanate, 0/15, all mice died by day 2. Surviving mice appeared normal throughout the study, and no abnormalities were seen at necropsy. The hematologic measurements were the same for sodium chloride or disodium carbamyl P, including hemoglobin, packed cell volume, erythrocyte counts, leucocyte counts, and differential counts. The mean hemoglobin carbamylation was 1.24 (±0.06 SE) moles of valine hydantoin/mole of hemoglobin tetramer in mice receiving disodium carbamyl P for 18 days, sufficient for antisickling activity. The enzymatic degradation of carbamyl P to NH3, CO2, and Pi was measured in serial blood samples in additional C57B1 and DBA/2J mice following ip injections of carbamyl P or cyanate. Both NH3 and Pi increased immediately after giving carbamyl P, but no increase occurred after cyanate administration. Thus enzymatic degradation of carbamyl P occurs in vivo and appears to be an important detoxification mechanism. When equivalent mole doses of anion are administered, disodium carbamyl P is less toxic than sodium cyanate in mice.
The kinetics of immunoglobulin synthesis by pokeweed mitogen stimulated peripheral blood lymphocytes in multiple myeloma
Authors: George Edward R. , Cohen Harvey J.
Published: February 2007

As a means of investigating the immunoglobulin (Ig) deficiency in multiple myeloma, the effects of pokeweed mitogen (PWM) on morphologic transformation and concomitant immunoglobulin synthesis and secretion kinetics were studied in peripheral blood lymphocytes (PBL) of normals and patients with myeloma. Lymphocyte Ig production kinetics, both in the unstimulated state and after five days of culture with PWM, were evaluated by 3H‐leucine incorporation. B‐lymphocytes were found to be decreased by EC3 rosetting in the myeloma patients studied. In addition their lymphocytes had a mean of 30% transformation compared to 53% for normals (P < 0.005). After five days of mitogen stimulation in culture, myeloma PBL failed to show the rise in intracellular Ig production seen in normal PBL under similar conditions. Thus, myeloma patients were found to have decreased numbers of EC3 rosetting B‐cells, decreased morphologic transformation rate in response to mitogenic stimulation, and failure to increase intracellular Ig after mitogenic stimulation. Possible etiologic mechanisms for the decreased Ig production are discussed.
Ferritin synthesis and Iron uptake in developing erythroid cells
Authors: Konijn A. M. , Hershko C. , Izak G.
Published: February 2007

The effect of maturation on ferritin synthesis and iron uptake by erythroid precursor cells was studied in vitro in rabbit bone marrow cells synchronized by actinomycin D. Early mononuclear precursors were compared with basophilic normoblasts and reticulocytes. Apoferritin synthesis was measured by following the incorporation of 3H‐amino acids into purified ferritin, and this was correlated with total protein synthesis and with radioactive iron uptake by whole cells and radioactive iron incorporation into heme and ferritin. With increasing cellular maturation, a progressive reduction in both apoferritin and total protein synthesis has been observed, undifferentiated cells synthesizing 12 times more protein and 20 times more ferritin than reticulocytes. The rate of ferritin synthesis was inversely related to the rate of radioactive iron uptake by whole cells and radioactive iron incorporation into heme; lowest rates of radioactive uptake and heme synthesis were found in undifferentiated cells, and highest rates in reticulocytes. Radioactive iron incorporation into ferritin was higher in basophilic normoblasts than in undifferentiated cells but was very low in reticulocytes. This sequence of events indicates that in developing erythroid cells the phase of maximal ferritin synthesis precedes the phase of maximal iron uptake. The accumulation of newly formed apoferritin is followed by an increase in cellular iron uptake and an increased retention of iron in ferritin. Finally, with continuing cellular maturation, ferritin iron and iron derived directly from transferrin are utilized for hemoglobin synthesis.
Marrow culture in diffusion chambers in rabbits: III. Effect of endotoxin and leukocyte products on cell production
Authors: Willemze Roel , Walker Richard I. , Herion John C. , Palmer Jeffress G.
Published: February 2007

Soluble leukocyte products harvested from incubated peritoneal exudate leukocytes, injected intravenously or intramuscularly, increased production of granulocytes and macrophages in marrow in diffusion chambers implanted into the peritoneal cavity of rabbits. Red cell production in the chambers was not consistently affected. Endotoxin increased production of all cell types. Endotoxin tolerance induced by daily injection of endotoxin to host rabbits abolished granulopoietic stimulation by endotoxin given during the culture period but did not diminish the granulopoietic stimulation produced by injected leukocyte products. Attempts to induce tolerance to leukocyte products by daily injections did not reduce the granulopoietic stimulation produced by either endotoxin or leukocyte products injected during the culture period. Intraperitoneally administered leukocytes products markedly inhibited production of all cell types.

Endotoxin or leukocyte products given to normal rabbits increased plasma colony stimulating activity (CSA); the increase occurred sooner after leukocyte products than after endotoxin. Endotoxin‐tolerant animals showed no rise in CSA after endotoxin, but their response to leukocyte products was normal. Leukocyte products added to agar cultures neither supported nor inhibited colony growth but augmented CSA‐stimulated colony production. Endotoxin, leukocyte products, and CSA are different and may interact in regulating granulopoiesis.
The aplastic anemia‐paroxysmal nocturnal hemoglobinuria syndrome
Authors: Conrad Marcel E. , Barton James C.
Published: February 2007

Occasionally it is difficult to differentiate paroxysmal nocturnal hemoglobinuria (PNH) from idiopathic aplastic anemia in patients who present with pancytopenia and an aplastic bone marrow. Patients with PNH may not have an abnormal acid hemolysis test, and patients with aplastic anemia may present with evidence of abnormal sucrose lysis, acid hemolysis, and antibody‐mediated complement hemolysis. Demonstration of a population of red blood cells which are highly susceptible to antibody‐mediated complement lysis makes a diagnosis of PNH probable. Donor red blood cell survival studies, which distinguish intracorpuscular from extracorpuscular hemolytic disorders, permit differentiation of the two disorders.
Iron chelation therapy in sickle cell anemia
Authors: Cohen Alan , Schwartz Elias
Published: February 2007

Iron stores, ascorbic acid levels, and urinary excretion of iron in response to deferoxamine (DFO) were studied in nine patients with sickle cell anemia who had received 8–55 liters of red blood cells. Ferritin levels ranged from 2, 168 to 6,300 ng/ml and were elevated even in patients who had normal serum iron concentrations. Leukocyte ascorbic acid levels were low in three patients. Urinary iron excretion in response to 2.0 gm DFO administered as a 12‐hour subcutaneous infusion after ascorbic acid supplementation was 13–39 mg/24 hours. With this method of DFO therapy daily, urinary iron excretion would exceed transfusional iron accumulation in eight of nine patients. Following the intramuscular injection of 0.75 gm DFO, urinary iron excretion was 5–16 mg/24 hours. Iron excretion would exceed iron accumulation in only one of nine patients with this method of DFO therapy. Urinary iron excretion in response to 1.5 gm DFO infused intravenously in 18 hours after ascorbic acid supplementation was 11–38 mg/24 hours. In six regularly transfused but nonchelated patients iron excretion in response to intravenous DFO had increased 46–107%, in comparison with previous studies 15–22 months before. These data indicate that negative iron balance can be obtained in regularly transfused patients with sickle cell anemia by the use of overnight subcutaneous infusions of DFO. Urinary iron excretion in response to DFO should be evaluated periodically in appropriate patients with sickle cell anemia to determine the proper time for the institution of chelation therapy.