bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution of a receptor for IgM (μFcR) on haemic cells
Authors: Burns G. F. , Cawley J. C. , Worman C. P. , Barker C. R. , Hayhoe F. G. J.
Published: February 2007

A range of normal and malignant haemic cells is examined for expression of receptors of the Fc of IgM (μFcR) in order to establish the distribution and possible nosological significance of this receptor. It is shown that μFcR expression by freshly isolated cells is restricted to a small population of normal lymphocytes and to the pathological B cells of most of 45 cases of chronic lymphocytic leukaemia (CLL) and all 23 cases of hairy‐cell leukaemia (HCL) examined. The pathological cells of acute lymphoblastic leukaemia (eight cases), prolymphocytic leukaemia (two cases), a variety of non‐Hodgkin lymphomata (eight cases) and immunoproliferative disorders (25 cases), Hodgkin disease (three cases), and a range of myeloid and histiocytic proliferations (22 cases) were all negative for the μFcR. The pathological cells of the Sezary syndrome were also shown to possess a μFcR, but this required a period of in vitro incubation in RPMI medium containing foetal calf serum for its demonstration. This and other differences between μFcR expression by T‐ and B‐cells are discussed. The possible immunological, nosological, and diagnostic significance of the observed restriction of μFcR expression is considered.
A comparison of methods for the rapid quantitation of unsaturated transcobalamin II and the r‐binding proteins
Authors: Fernandes‐Costa Francisco , Metz Jack
Published: February 2007

Methods for the rapid quantitation of unsaturated transcobalamin II (TC II) and R‐binders in serum following separation of these binders using (a) adsorption by uncoated charcoal, (b) adsorption by Quso G32, (c) precipitation with ammonium sulphate, and (d) acidification of serum, have been compared with the standard gel filtration technique. In serum from healthy subjects and patients with elevated R‐binders, the serum acidification and Quso methods yielded results in closest agreement with those obtained by gel filtration. When TC II was markedly elevated, the recommended concentration of Quso failed to remove all TC II from serum. Both the serum acidification and Quso methods are suitable for routine use, providing that with the latter method the concentration of Quso is increased when elevated levels of TC II are anticipated, as, eg, in severe jaundice. All the rapid methods tested yielded clinically significant results in patients with myeloproliferative disorders.
Myelomatous pleural effusion: Clinical course and immunologic characterization of the pleural fluid cells
Authors: Scullin Daniel C. , Cohen Harvey Jay
Published: February 2007

Multiple myeloma is a disease that infrequently involves nonreticuloendothelial tissues and rarely causes pleural effusion. A 59‐year‐old woman had pleural effusion as the major manifestation of multiple myeloma. Light microscopy of her pleural fluid with Wright stained preparations showed all cells to be bizarre and often multinucleated plasmacytes. Electron microscopy confirmed these results. Intracellular immunofluorescence revealed IgG‐kappa immunoglobulin (Ig) in greater than 90% of these cells. Surface immunofluorescence using anti‐Ig sera was seen on less than 5% of the pleural fluid cells. 3H leucine incorporation into Ig in vitro was measured for these cells, and secretory curves were obtained that have the typical secretory kinetics of bone marrow plasmacytes. This demonstrates that such cells are viable and are able to synthesize and release immunoglobulin. Treatment of our patient with prednisone, melphalan, and cyclophosphamide resulted in symptomatic improvement and complete resolution of her pleural effusion. Pleural effusion is an unusual but important complication of multiple myeloma and does not necessarily carry the grave prognosis implied in previous reports.
Abnormal erythrocyte metabolism in hepatic disease: Effects of NADP repletion
Authors: Smith J. Robert , Kay Neil E. , Gottlieb Arlan J. , Oski Frank A.
Published: February 2007

Erythrocytes from ten patients with severe liver disease displayed low methylene blue‐stimulated hexose monophosphate (HMP) shunt activity and glucose recycling despite elevated total glucose consumption when compared to controls. Heinz body formation was increased and reduced glutathione concentration significantly decreased. After hemolysis, no differences in methylene‐blue stimulated HMP shunt activity or glucose recycling could be demonstrated between patients and controls. The addition of 2‐ and 4‐mM NADP to the hemolysates produced significantly greater HMP shunt activity and glucose recycling in the patients' hemolysates. The addition of NADPH to the incubation mixture produced no significant stimulation of either HMP shunt activity or glucose recycling, unless methylene blue was also added. Omission of NAD or phosphate from the incubation mixture produced no change in shunt metabolism. The absence of supplemental ATP resulted in extremely low shunt metabolism and refractoriness to NADP stimulation in both patients and controls. In the absence of additional magnesium, a reduction of shunt metabolism was noted.

These data suggest that the defect in stimulated shunt metabolism in the intact erythrocytes of patients with hepatic disease does not result from an absolute enzyme deficiency, but rather from an unavailability of NADP or other cofactor.
Leukemia in patients with acquired idiopathic sideroblastic anemia: An evaluation of prognostic indicators
Authors: Lewy Robert Ira , Kansu Emin , Gabuzda Thomas
Published: February 2007

The initial clinical and laboratory data of 25 patients with acquired idiopathic sideroblastic anemia (AISA) were anlayzed. Criteria for accepting the diagnosis were hyperferremia, ringed marrow sideroblasts, ineffective erythropoiesis, and exclusion of associated hematologic disorders. The findings of a mean age at onset of 70 years, increased mean corpuscular volume, relative neutropenia, and occasional splenomegaly at diagnosis corresponded with previous reports.

During the followup for a median period of 32 months, 6 patients (25%) transformed to acute myelogenous or myelomonocytic leukemia after widely variable intervals. The initial data base of these patients was compared to that of the remaining 19 patients in order to isolate predictive features. Only a lesser degree of hyperferremia (P < 0.001) made the group going on to leukemia distinctive. The median survival of these patients was 20 months. The median survival of 19 patients not developing leukemia was 72 months for males and 42 months for females
.

Hemochromatosis was diagnosed in four patients and was a primary or associated cause of death in three. Analysis of the transfusion history suggested that intrinsic iron leading was a major factor in these patients.

We conclude that leukemic transformation in AISA is a common, poorly predictable event which required lengthy followup for detection. Hemochromatosis in AISA occurs frequently and shortens the median survival.
Myelogenous leukemia evolving during the course of lymphoid malignancy in children
Authors: Hutter J. J. , Hays T. , Rosen R. C. , Shende A. , Lanzkowsky P. , Corrigan J. J.
Published: February 2007

Two children who presented initially with a lymphoid malignancy were noted to develop recurrences with myeloid features late in the course of their disease. In both cases, evidence of lymphoid differentiation was present in the myelogenous cells that were Ph1 chromosome negative. The first patient had acute myelogenous leukemia and developed a recurrence with morphologic features of acute myelogenous leukemia. Terminal transferase was present in the myelogenous blasts. The second patient initially had a diffuse lymphoblastic non‐Hodgkin lymphoma. During the course of her illness she developed a myeloproliferative disorder characterized by basophilic meningitis, splenomegaly, and hypereosinophilia. Lymphocyte T‐cell (E‐rosette) markers were present on the eosinophils. These observations lend further support to the hypothesis of varying lymphoid and myeloid differentiation in certain cases of leukemia.
Acid phosphatase in leukemic blasts: Characterization by isoelectric focusing in polyacrylamide gel
Authors: Kass Lawrence , Munster Donald
Published: February 2007

Using the high resolution technique of isoelectric focusing in polyacrylamide gel, isoenzymatic components of acid phosphatase were detected in cell‐free extracts prepared from different cytologic types of leukemic blasts in adults. Results indicate that for different cytologic types, different characteristic patterns of acid phosphatase isoenzyme could be detected. These studies extend conventional cytochemistry and indicate that characteristic patterns of acid phosphatase isoenzyme can be detected for various cytologic types of acute leukemia.
Prognostic signs in chronic myelocytic leukemia
Authors: Schilling Robert F. , Crowley John J.
Published: February 2007

In a retrospective search for prognostic factors in 127 patients with chronic myelocytic leukemia we found that thrombocytopenic patients had a significantly shortened life‐span. Patients with the Philadelphia chromosome lived longer and were significantly younger than those lacking it. Females lived longer than males. Numerous other single features failed to correlate significantly with survival, but several combinations of two did. Patients having a low hematocrit with a low white blood count had an impressively short life‐span compared to all others. Those having a high cholesterol and a low uric acid survived significantly longer than all others.
Acute lymphoblastic leukemia–hand mirror variant. An analysis of a large group of patients
Authors: Schumacher Harold R. , Champion John E. , Thomas William J. , Pitts Loring L. , Stass Sanford A.
Published: February 2007

One hundred and thirty‐four initial bone marrows and 102 peripheral blood smears were evaluated for hand mirror cells (HMC) on pediatric patients with acute lymphoblastic leukemia (ALL). Twenty (15%) of the 134 patients were found to have greater than 5% HMC in their bone marrows. Only rarely were a few HMC noted in the peripheral blood. Survival did not appear to be related to the number of HMC in the bone marrow. Also, the median survival was not significantly greater in those HMC patients with greater than 40% HMC in their bone marrows when compared to the non‐HMC group.

From the available data in this study, it would appear that the number of HMC does not affect prognosis in the bone marrows of children with ALL. However, the prognostic significance of the HMC has not been clearly established in adults.
Circulation and migration of small blood lymphocytes in the rat: II. Study of the lymphocyte selective migration by light and electron microscopic autoradiography
Authors: Schnuda N. D.
Published: February 2007

Fourteen male Wistar rats were the recipients of labeled small lymphocytes (1.5 × 107 each) collected from the peripheral blood of syngeneic donors. The migrating labeled lymphocytes were traced in the various organs from one to 60 minutes following their transfusion. Sections from the lymph nodes, bone marrow, spleen, thymus, ileum, liver, lung, and kidney were analyzed morphologically by autoradiographic studies. The results showed that some of the labeled small blood lymphocytes migrate to the lymph node and bone marrow as early as one minute following transfusion; their exodus from these two organs occurs within three minutes. In the case of the spleen, the lymphocytes did not migrate selectively to the marginal zone of the lymphoid follicles until ten minutes following transfusion. The electron microscopic study of the spleen and lymph node showed that the labeled lymphocytes selectively migrate to certain areas which consist of reticulum cells, macrophages, unlabeled lymphocytes, and plasma cells. The term “immunocompetent zones” is proposed for these areas because of the biological significance of this selective migration with reference to immunity.
Chemical modification of nuclear proteins by erythropoietin
Authors: Spivak Jerry L. , Peck Lorna
Published: February 2007

The spleen of the exhypoxic polycythemic mouse was employed as a model system to study the effect of erythropoietin on enzymes that chemically modify nuclear proteins. At selected time intervals after in vivo administration of erythropoietin, acetyltransferase and methyltransferase activity were measured in nuclei isolated from the spleens of treated mice. In addition, the incorporation of labeled methyl and acetate groups into individual histone proteins was also examined. A 36% increase in nuclear acetyltransferase activity was observed eight hours after administration of erythropoietin, whereas nuclear methyltransferase activity increased by 42% 24 hours after administration of the hormone. Selective acetylation or methylation of individual histone proteins was not observed, and it is concluded that activation of transcription by erythropoietin is not the result of acetylation or methylation of nuclear proteins.
The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes
Authors: Sagone Arthur L. , Burton G. Mark
Published: February 2007

In cell free systems Adriamycin induces oxygen radicals. We have shown previously that Adriamycin generates peroxide in human erythrocytes. BCNU, by inhibiting glutathione reductase, interferes with the major erythrocyte pathway to degrade peroxide. In this investigation we looked at interactions of these drugs with normal and abnormal erythrocytes.

In G6PD‐deficient erythrocytes Adriamycin posed a significant oxidant stress as demonstrated by hexose monophosphate shunt (HMPS) activity, hydrogen peroxide (H2O2) production, and glutathione depletion. At similar molar concentrations Adriamycin was a stronger oxidant than acetylphenylhydrazine.

BCNU‐treated normal erythrocytes showed an enhanced susceptibility to oxidant stress as demonstrated by a lack of HMPS response to H2O2 and glutathione depletion during incubations with Adriamycin. The HMPS shunt of BCNU treated RBC was intact as shown by their nearly normal response to methylene blue stimulation. These BCNU studies also demonstrated the inability of H2O2 to react directly with NADPH.

In conclusion Adriamycin poses a potent oxident stress to G6PD‐deficient erythrocytes. BCNU promotes enhanced susceptibility of normal RBC to oxidant stress and BCNU can act as a probe to define drug interactions with the HMPS. These studies add to a growing body of evidence postulating the importance of oxygen radicals in the therapeutic and/or effects of Adriamycin.
A new treatment strategy for hemophilia B: Incorporation of factor IX into red cell ghosts
Authors: Goldsmith Jonathan C. , Roer Marjorie E. S. , Orringer Eugene P.
Published: February 2007

Although patients with severe hemophilia B have lifelong spontaneous hemorrhage and crippling hemarthroses, patients with 0.01–0.03 U/ml Factor IX activity have a milder disease state. The clinical condition of severely affected individuals could potentially be improved by prolonging the half‐life of transfused Factor IX. The feasibility of incorporating Factor IX into red cell ghosts was suggested by resealing experiments with similar sized molecules such as albumin. We have prepared resealed red cell ghosts containing human Factor IX and X. Human red cells were subjected to hypotonic lysis at 0°C, pH 6.0. Commercial prothrombin complex concentrate was dissolved in the lysing medium immediately prior to the addition of the red cells. After being returned to isotonicity, the red cell ghosts were annealed at 37°C for 30 minutes and then washed extensively. When intact red cell ghosts were tested, no Factor IX or X activity could be demonstrated. After disruption of the red cell ghost membranes with 3M urea or 2% Triton X–100, the procoagulants could be quantitatively recovered. Similar recovery of the clotting factors could be demonstrated from the lysate and the early wash samples. Red cells from Factor IX and X deficient patients served equally well as those from normal subjects. Red cell ghosts prepared in similar fashion but not exposed to the procoagulants had negligible clotting activity. We have demonstrated that human clotting factors can be incorporated into red cell ghosts. The ability of this system to prolong the biological half‐life of Factor IX is under investigation.
Hemopoietic precursor cells in human peripheral blood
Authors: Niskanen Eero , Olofsson Tor , Cline Martin J.
Published: February 2007

Human peripheral blood contains two types of stem cells that differentiate along the granulocytic pathway. They are separable by their ability to form colonies in agar in vitro (CFU‐C) and in plasma clots in diffusion chambers in vivo (CFU‐DG). Kinetic studies suggest that CFU‐DG represents an intermediate between the still hypothetical human pluripotent stem cell and CFU‐C.
Inhibitors of fibrinolysis in diabetic children, mothers, and their newborn
Authors: Ambrus Clara M. , Ambrus Julian L. , Courey Norman , Mosovich Luis , Bruck Erika , Allen James , Jung Okhee , Mirand Edwin , Niswander Kenneth
Published: February 2007

Late diabetic complications are often related to vascular changes and formation of thrombi in the altered vasculature. Contributing factors to thrombosis susceptibility of diabetic patients include changes in clotting factors, platelets, and inhibition of fibrinolysis. We have measured various fibrinolytic inhibitors in the blood of diabetic children, diabetic pregnant women and their offspring, and healthy controls. Inhibitors studied included 1) fast (immediate) antiplasmin, 2) slow (progressive) antiplasmin, 3) alpha‐2‐macroglobulin, and 4) alpha‐1‐antitrypsin.

It appears from our study that high fast‐antiplasmin levels, and low or missing slow‐antiplasmin levels are characteristic of diabetic patients and of newborn of diabetic mothers. The reason for high fast‐antiplasmin levels is not clear: Levels are not connected with the age of the patient or duration of diabetes, and are not elevated in response to a fibrinolytic process (fibrin decomposition products could not be shown to be present in the serum of diabetic children).

Alpha‐2‐macroglobulin was significantly higher and alpha‐1‐antitrypsin significantly lower in diabetic women than in controls. In the other groups of patients studied differences in these inhibitors from the appropriate control groups were not statistically significant.
Positive direct antiglobulin test on thawed deglycerolized units of erythrocytes: Prediction and prevention
Authors: Reid M. E. , Ellisor S. S. , Avoy D. R.
Published: February 2007

Occasional units of red blood cells develop a positive direct antiglobulin test (DAT) when frozen and deglycerolyzed by the Meryman method. The presence of cold autoagglutinins with a high titer at 4°C or autoreactivity at room temperature were generally predictive of which units would develop a positive DAT, but neither was reliable in all cases. An indicator system is presented in which a DAT is performed on a segment that has been glycerolized and deglycerolized in a manner similar to the Meryman method for freezing a donor unit. This system is extremely reliable in predicting which units will convert from DAT‐negative to DAT‐positive during processing.

The positive DAT of deglycerolized red blood cells was due to C4 and weak C3d binding. This complement binding can be prevented by addition of ethylenediaminetetraacetic acid (EDTA) or removal of plasma before the addition of glycerol.
Hereditary deficiency of erythrocyte acetylcholinesterase
Authors: Shinohara Kenji , Tanaka Kouichi R.
Published: February 2007

A 36‐year‐old white man was found to have low erythrocyte acetylcholinesterase activity. Plasma cholinesterase activity was normal. The propositus had mild anemia and moderate elliptocytosis, but was asymptomatic. A sister, brother, father, and nephew were hematologically normal, but had slightly subnormal red cell acetylcholinesterase activities. There was no exposure to organophosphates, and paroxysmal nocturnal hemoglobinuria was excluded. Mixing experiments failed to demonstrate the absence of an activator or the presence of an inhibitor. The propositus enzyme showed normal kinetics for the substrate and various inhibitors, normal thermostability, and electrophoretic migration. Major protein bands of the red cell membrane were normal by electrophoresis. Membrane cholesterol and phospholipid content were also normal. The mild anemia is presumably secondary to the presence of moderate elliptocytosis. The pattern of inheritance of the variant gene is unclear, but the propositus may be homozygous for the abnormal allele, and other family members may be heterozygous.
The plasma kinetics of hydroxyethyl starch 350/0.60: A potential new adjunct for centrifugal leucapheresis
Authors: Mishler John Milton
Published: February 2007

A modified species of hydroxyethyl starch (HES 350/0.60) possessing a Mw̄ of 350,000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0.60 (60 hydroxyethyl groups · 100 glucose residues) was clinically assessed in seven normal subjects to determine the influence of these chemical modifications on intravascular clearance kinetics concomitantly with effects on the suspension stability (ESR) of blood. Following a standardised intravenous dose (30 gm · m2 BSA), the concentration of HES 350/0.60 in serum fell to half its peak value in 11.8 ± 1.3 (SD) hours, while the ESR remained elevated for up to 12 hours post‐injection. By adopting a Mw̄ of 350,000 daltons, the critical molecular weight (Cmw) of this colloid was surpassed, while the critical concentration (Cc), below which the suspension stability of blood is not affected, was shown to range between 0.3 and 0.5 gm · dl−1. In comparison to the present species of HES (Mw̄ 450,000 daltons, MS: 0.70) utilised as a sedimenting agent during centrifugal leucapheresis, HES 350,000/0.60 appears to affect the ESR in a similar manner, but is removed from the intravascular space approximately twice as rapidly. This more rapid clearance should be useful in avoiding cumulative build‐up of HES in blood concomitant with reducing the total amount of intravascular H2O bound to this colloid, in normal and CML donors undergoing multiple cell collection procedures.
Disparity between circulating and marginated neutrophils: Evidence from studies on the granulocyte alkaline phosphatase, a marker of cell maturity
Authors: Fehr Jorg , Grossmann Hans‐Caspar
Published: February 2007

Since circulating and marginated human granulocytes are in rapid kinetic equilibrium, cells of these two compartments have been considered to be a homogeneous population. Our studies on the relationship between neutrophil maturity and the granulocyte alkaline phosphatase (GAP) activity cast doubt on this assumption. After iv administration of hydrocortisone, 12 male volunteers showed an augmentation in circulating granulocytes of 5730 cells/mm3, accompanied by an increase of band neutrophils from 18% to 33% (p < 0.001). During this influx phase, the GAP activity decreased by 73% when measured cytochemically and by 28% when assayed biochemically (p < 0.001 and < 0.01, respectively). When granulocytes were demarginated by epinephrine, the mean count increased by 38%, accompanied by a rise in the portion of segmented forms from 74% to 79% (p < 0.005) and by an increase of the cytochemical GAP activity by 24% (p < 0.01). Exact complementary results were obtained during an excessive transient margination, the hemodialysis neutropenia: bands increased from 24% to 54% (p < 0.02), while the cytochemical GAP dropped by 40% (p < 0.005). Thus, our analysis of three situations with an acute transient shift of granulocytes indicates that functionally or chronologially “older” cells have a higher GAP activity, and that the transfer of granulocyte from the circulating to the marginal pool is selective.
Idiopathic thrombocytopenic purpura occurring in Hodgkin disease after splenectomy: Report of two cases and review of the literature
Authors: Waddell Caroline C. , Cimo Philip L.
Published: February 2007

The occurrence of idiopathic thrombocytopenic purpura (ITP) in Hodgkin disease is uncommon. Even more unusual is the development of ITP in Hodgkin disease following splenectomy. This report describes two patients with Hodgkin disease who developed severe ITP with negative platelet antibody studies very soon after splenectomy (20 days in one and three months in the other). A review of the literature of 21 other patients with well‐documented ITP and Hodgkin diesease indicated that ITP occurring in Hodgkin disease may be more severe and refractory to therapy than ITP unassociated with Hodgkin. Nodular sclerosis or mixed cellularity histologic types of Hodgkin disease were present in all but one of the patients with ITP and Hodgkin disease, and males constituted 65% of cases. There appeared to be no correlation between the onset of ITP and activity of Hodgkin disease. Of five splenectomized patients with Hodgkin disease who developed ITP and were treated with immunosuppressive drugs for thrombocytopenia, three had an excellent response and two had a good response, suggesting that the combination of corticosteroids and immunosuppressive drugs may be indicated at the outset in patients with Hodgkin disease who develop ITP following splenectomy.
Deformability and spectrin properties in three types of elongated red cells
Authors: Smith Joseph E. , Mohandas Narla , Clark Margaret R. , Greenquist Alfred C. , Shohet Stephen B.
Published: February 2007

Three types of unusual, elongated erythrocytes have been studied in our effort to understand factors that regulate the shape and deformability of red blood cells. Measurements of deformability, morphologic response to membrane‐shape‐altering drugs, spectrin phosphorylation, spectrin extractability, and casein kinase activity were measured in llama cells, irreversibly sickled cells, and nonhemolytic human elliptocytes. The results of these studies support the concept that the physical properties of spectrin are important in maintaining the shape and deformability of the erythrocyte. Furthermore, changes in spectrin extractability and phosphorylation appear to be associated with changes in the viscoelastic properties of the membrane. However, it seems that spectrin's regulatory role is permissive rather than direct and active.
Erythroid colony studies on sickle cell anemia in hypoproliferative crisis
Authors: Lutton J. D. , Schmalzer E. A. , Rao A. N. , Rao S. P. , Levere R. D.
Published: February 2007

Bone marrow cells, peripheral blood lymphocytes, and sera from patients with sickle‐cell anemia in hypoproliferative crisis were studied in the plasma clot culture system in the presence or absence of erythropoietin (Epo). Bone marrow cells from five patients demonstrated a marked ability to form erythroid colonies in the presence of Epo. These studies also suggested that bone marrow cells from some patients may have an increased sensitivity to Epo. The most outstanding observation in the present study was the marked erythroid colony inhibition by serum taken from one patient during crisis. Serum taken from the same patient two months after hypoproliferative crisis had no suppressive effect on erythroid colony formation. Lymphocytes taken from three patients in crisis had a stimulatory effect on erythroid colony formation when included in culture. The conclusion is that the defect of erythropoiesis in sickle‐cell anemia during hypoproliferative crisis is not due to the absence of erythroid precursor cells or to the presence of suppressor lymphocytes, but may in some cases be associated with a circulating inhibitor of erythroid maturation.
Studies on hemolytic anemia in pregnancy with evidence for autoimmunization in a patient with a negative direct antiglobulin (coombs') test
Authors: Yam Priscilla , Wilkinson Lee , Petz L. D. , Garratty George
Published: February 2007

Three patients were studied who had acquired hemolytic anemia during pregnancy. One patient had a relapsing hemolytic anemia of pregnancy with a negative direct antiglobulin test. Previously reported cases have been presumed to be antibody‐mediated because of rapid destruction of transfused blood, transient hemolysis in the newborn, and a favorable response to corticosteroid therapy. Our findings with the complement‐fixation antibody consumption (CFAC) test offer support for an immune pathogenesis, since we documented abnormal concentrations of IgG on the patient's red cells during pregnancy and also on a sample of cord blood. The hemolytic anemia responded partially to prednisone during pregnancy and resolved postpartum. A repeat CFAC test postpartum revealed a marked reduction in the number of IgG molecules per red cell on the mother's cells, and IgG was no longer detectable on the infant's red cells.

The other patients had serologic abnormalities characteristic of an autoimmune hemolytic anemia with an IgG warm autoantibody. The patients were followed closely during pregnancy because of previous reports of life‐threatening morbidity in mothers, as well as stillbirths, neonatal death, and seriously affected infants. An amniocentesis was performed in one patient because of persistent hemolysis in spite of prednisone therapy. The mothers and their infants did well, but serologic abnormalities and mild hemolytic anemia persisted in both mothers. Therefore, an elective splenectomy was performed with significant improvement in both instances.
Functional characteristics of red cells of sickle cell anemia patients with and without α‐thalassemia‐2
Authors: Abraham E. C. , Huisman T. H. J.
Published: February 2007

Oxygen equilibrium curves, red cell indices, 2,3‐DPG levels, and the percentages of ISC and Hb F were determined for red cell fractions isolated by Dextran 40 density gradient centrifugation from blood of a sickle cell anemia (SS) patient, an SS patient with an additional homozygosity for α‐thalassemia‐2, and a normal control. In the SS patient, the MCHC and P50 values increased and 2,3‐DPG levels decreased with an increase in red cell density; the P50 values were directly related to the MCHC values and inversely related to the 2,3‐DPG levels. The bottom fraction contained about 80% ISC, and had the highest MCHC and P50 values and the lowest 2,3‐DPG level. In the SS α‐thalassemia‐2 patient, a decrease in the P50 value corresponded with a decrease in 2,3‐DPG levels because no change in MCHC value was observed. The bottom fraction contained about 10% ISC and had the lowest P50 value. These data confirm that both MCHC and 2,3‐DPG levels influence the oxygen affinity of SS red cells; an increase in MCHC decreases the oxygen affinity to a great extent while a concomitant decrease in 2,3‐DPG level partially abolishes this effect.
Imbalance of T cell subpopulations in peripheral blood of children with non‐Hodgkin malignant lymphoma
Authors: Beck J. D. , Wollner N. , Miller D. R. , Good R. A. , Gupta S.
Published: February 2007

Peripheral blood lymphocytes from 13 children with newly diagnosed untreated non‐Hodgkin malignant lymphoma were investigated for the proportion of Tμ and Tγ cells. Tumor involvement was classified as stage II in two patients, stage III in five patients, and stage IV in six patients. Diffuse poorly differentiated lymphoblastic histological‐type lymphomas, as defined by the Rappaport classification, were found in eight patients. The proportion of Tγ cells was found to be increased and that of Tμ cells decreased in the patient group as compared to levels in healthy controls. A marked imbalance of the Tμ/Tγ ratio was observed in ten of 13 patients. There was no correlation between Tμ/Tγ ratios and stage of the disease. Imbalances of Tμ and Tγ cell proportions are discussed in relation to humoral and cellular immunodeficiencies observed in patients with non‐Hodgkin malignant lymphoma.
Preselection of donors to improve the quality of cryoprecipitate
Authors: Tomasulo Peter A. , Richards William , Bailey Marilyn , Gajewski Mieczyslaw , Aster Richard H. , Lazerson Jack
Published: February 2007

In theory, the potency of cryoprecipitated antihemophilic factor (cryo) can be increased by utilizing plasma only from donors with high levels of factor VIII procoagulant activity (fVIIIc). Previous reports have suggested that plasma of group O individuals has, on the average, less fVIIIc than plasma from individuals of blood groups A, B, and AB. We have investigated the feasibility of increasing the potency of cryo by preselecting plasma for cryo production on the basis of the blood group of the donor. FVIIIc levels of fresh plasma, fresh frozen plasma (FFP), and cryo (prepared both by air‐thaw and water‐thaw methods) were assayed. The plasma, FFP, and cryo from group O donors contained only 75% of the fVIIIc present in plasma from group A, group B, and group AB donors. Following infusion to patients with hemophilia, in vivo recovery and survival of fVIIIc activity from groups A, B, and AB cryo reflected the higher in vitro levels. The mean potency of bags of cryo can be increased, and the cost of hemophilia treatment with cryo can be reduced by excluding group O plasma from the production of cryoprecipitate.
Concomitant presentation of two chronic leukemias: Evidence for independent clonal evolution
Authors: Vilpo J. A. , Klemi P. , Lassila O. , De La Chapelle A.
Published: February 2007

A case of chronic lymphocytic leukemia (CLL) occurring simultaneously with Philadelphia chromosome‐positive chronic granulocytic leukemia (CGL) in a 58‐year‐old man is described. The patient presented with typical CGL (all bone marrow mitoses having a Philadelphia chromosome), but during the course of busulfan therapy, CLL became more prominent, less than half of the bone marrow mitoses having a Philadelphia chromosome. The patient is in good clinical condition after a follow‐up of 3.5 years, and the clinical picture resembles that of typical CLL.

The coexistence of CGL and CLL here may be explained by chance alone. Evidently the histogenesis of two chronic leukemias in our patient took place as an independent evolution of two malignant hematopoietic clones. In spite of the frequent association of chronic leukemias with secondary cancer, no well‐documented cases of two chronic leukemias with a simultaneous presentation have been described previously.
Factor II antigen in liver disease and warfarin‐induced vitamin K deficiency: Correlation with coagulant activity using echis venom
Authors: Corrigan James J. , Earnest David L.
Published: February 2007

Four coagulation factors (II, VII, IX, X) are synthesized in the liver as precursor forms. Vitamin K is necessary for their conversion to functional factors. Factor II precursor is antigenically similar to factor II and can be activated to form thrombin by Echis carinatus venom. Forty‐one patients with liver disease and 30 patients with vitamin K deficiency (Warfarin treated), were compared with 51 normal patients. Rats with CCl4‐induced hepatic necrosis and animals given Warfarin were also studied. The following measurements were made: standard prothrombin time; Echis clotting time; factor II coagulant assay with thromboplastin; factor II assay with Echis venom; and factor II antigen (human) by electroimmunoassay. In animals and humans with liver disease, factor II was reduced, as measured by all techniques. With vitamin K deficiency functional factor II was reduced, but factor II antigen and Echis factor II activity were normal. The data suggest that the prothrombin time and Echis coagulation methods can be used to differentiate whether the coagulopathy in liver disease is due to reduced precursor levels of factor II, vitamin K deficiency (ie, impaired formation of functional from precursor factor II), or both.
Von willebrand disease with an increased ristocetin‐induced platelet aggregation and a qualitative abnormality of the factor VIII protein
Authors: Takahashi Hoyu , Sakuragawa Nobuo , Shibata Akira
Published: February 2007

Two cases of von Willebrand disease (VWD) that revealed an increased ristocetin‐induced platelet aggregation (RIPA) and a qualitative abnormality of the factor VIII protein are reported. The threshold concentration of ristocetin giving a 30% increase in light transmission was 0.5 mg/ml in the proband and 0.4 mg/ml in her father (normal: 1.16 ± SD 0.18 mg/ml) although both patients showed reduced plasma von Willebrand factor activity (VIIIR:WF). In both patients, the amount of factor VIII related antigen (VIIIR:AG) in their platelets were normal, but an increased binding affinity of platelets to plasma factor VIII was demonstrated. The qualitative abnormality of the factor VIII protein was characterized by an increased anodal migration of VIIIR:AG in crossed immunoelectrophoresis (CIE), a delayed elution pattern as demonstrated by gel filtration on Sepharose 2B, and a decreased precipitation with concanavalin A (Con A). The response to DDAVP was also investigated.
Diarrhea in streptococcus pneumoniae bacteremia
Authors: Seeler Ruth Andrea , Jacobs Norman M.
Published: February 2007

Diarrhea with fever was a significant complaint in 26 of 280 (9.3%) of non‐SS children with S. pneumoniae bacteremia and four of 30 (13%) children with sickle syndromes and S. pneumoniae bacteremia. Two additional children with sickle‐cell disease and S. pneumoniae bacteremia developed diarrhea within hours of hospital admission; four of the six died. The mortality rate among 24 additional SS patients with S. pneumoniae bacteremia without diarrhea was 12.5% (3/24). Only one of 26 non‐SS patients with diarrhea and S. penumoniae bacteremia died; she was surgically asplenic and had fulminant 9‐hour course. The seasonality of the diarrhea cases was similar to our overall experience, and the serotypes associated with the diarrhea cases were also representative of our overall experience. Although predominantly seen in infants, the oldest non‐SS patient was 12 years, and the oldest SS patient was nine years.
Sickle red cell calcium metabolism: Studies on Ca2+‐Mg2+ATPase and ca‐binding properties of sickle red cell membranes
Authors: Litosch Irene , Lee Kwang Soo
Published: February 2007

Sickle (Hb SS) red cells, preloaded with 45Ca by reversal of hemolysis, exhibit an incomplete 45Ca extrusion, retaining approximately four times more 45Ca than normal cells. Studies indicated that neither the reduction in Hb SS cell Ca2+‐Mg2+ ATPase activity (84% of normal) nor the activation of Ca2+‐Mg2+ ATPase by calmodulin was sufficiently different from normal cells to attribute a major role to the calcium pump in 45Ca retention. These results suggested that 45Ca retention may reflect an alteration in the calcium‐binding properties of Hb SS cell membranes. Low‐affinity calcium‐ binding (freely dissociable) was similar in normal and Hb SS cell membranes. However, the total calcium bound with high‐affinity (tightly bound) was four‐to‐five times greater in Hb SS cell membranes than in normal membranes. These results are compatible with the hypothesis that Hb SS cell 45 Ca retention reflects an exchange of a fraction of the total 45Ca with a tightly bound calcium pool, larger in Hb SS cell membranes than in normal membranes.

A comparable degree of red cell 45Ca retention, which did not correlate with the reticulocyte population, was observed in other chronic anemic states. These findings suggest that the increased high‐affinity calcium binding by the membrane may be a consequence of cellular changes induced by the anemic condition.
An unusual factor‐X inhibitor in leprosy
Authors: Ness P. M. , Hymas P. G. , Gesme D. , Perkins H. A.
Published: February 2007

Two cases of Hansen disease demonstrating a lupus‐like inhibitor directed against the activation of coagulation factor X are described. Each case showed factor‐X activity markedly depressed by an inhibitor when measured in one assay system; yet normal levels were measured by three alternate factor‐X assay systems.
Intrinsic neutrophil defects in a child with impaired neutrophil chemotaxis and immunodeficiency
Authors: Morosawa Hironori , Yamazaki Munehiro , Sugita Kenichi , Saitoh Hiroharu , Komiyama Atsushi , Akabane Taro
Published: February 2007

A boy with recurrent pyogenic infection was found to have occasional neutropenia, defective neutrophil chemotaxis, hypogammaglobulinemia with increased IgM, and impaired cellular immunity. The T and B lymphocytes were defective in IgG production in vitro. Ultrastructure of the neutrophils was normal. The marrow cells formed normal numbers of granulocytic colonies in culture, but the colonies were apparently small in size. The levels of colony‐stimulating activity were normal. The lymphocytes did not impair granulopoiesis of control marrow cells. These data indicate that the neutropenia and defective neutrophil chemotaxis are due to the intrinsic neutrophil defects and are not secondary to T and/or B lymphocyte dysfunctions in the patient.
Cutis verticis gyrata: Unusual chloromatous disease in acute myelogenous leukemia
Authors: Cheson Bruce D. , Christiansen Robert M.
Published: February 2007

Chloromas are an unusual finding in patients with acute or chronic granulocytic leukemia. The present report describes a man with acute myelogenous leukemia (AML) whose course was complicated by cutis verticis gyrata (CVG), a mediastinal mass, neuropathies, and hepatosplenomegaly as a result of visceral involvement. Leukemic tumors and organ infiltration developed independent of his hematologic status and resulted in significant morbidity and, eventually, mortality from gastrointestinal hemorrhage. Nevertheless, at least temporary control over these complications was achieved when they were managed as leukemic “sanctuaries” and treated with local irradiation.
Fibrinogen chapel hill: Hypodysfibrinogenemia with a tertiary polymerization defect
Authors: McDonagh R. P. , Carrell N. A. , Roberts H. R. , Blatt P. M. , McDonagh Jan
Published: February 2007

A patient with a functionally defective fibrinogen (fibrinogen Chapel Hill) has been investigated. Fibrinogen Chapel Hill is characterized by hypofibrinogenemia, with a plasma concentration about one third of normal, as measured both functionally and immunochemically. Fibronogen survival is normal; so also is fibrinopeptide release. A polymerization defect in this fibrinogen results in the delay of fibrin fibrils in solution to form a normal three‐dimensional gel. This defect is not associated with end‐to‐end aggregation or with lateral associations in solution. Delayed gelation results from an abnormality in a tertiary contact site involved in network branching, which is associated with the hydrophilic, carboxy‐terminal segment of the α chain. Fibrinogen Chapel Hill exhibits two additional abnormal responses, which are also associated with the same region. The early plasmin cleavages of fibrinogen and fragment X are delayed, and there is a concomitant delay in the appearance of fragments Y, D, and E. This fibrinogen also has an unusual sensitivity to Ancrod proteolysis, whereby Ancrod cleaves a large carboxy‐terminal segment of the α chain more rapidly than in normal fibrinogen. The abnormalities in fibrinogen Chapel Hill can be explained by a structural abnormality which is functionally related to an α chain associated polymerization domain.
Von willebrand factor (VIIIVWF) in lyophilized factor VIII concentrates
Authors: McCue Miles J. , Brossoit Arthur D. , Marmer Daniel J. , Head David R.
Published: February 2007

Several (14) commercially prepared, lyophilized Factor VIII concentrates were assayed for VIIIAHF, VIIIAg, and VIIIVWF. Significant levels of VIIIAg (immunologic) and VIIIVWF (von Willebrand Factor) were present in addition to VIIIAHF (Functional VIII, Antihemophilic Factor, Factor VIII coagulant activity). An average of 0.95 units of VIIIVWF (range 0.47–1.7) were present for every 1.0 unit of VIIIAHF (as stated on the manufacturer's label). We suggest that the various lyophilized preparations of Factor VIII concentrate available could be assayed for VIIIVWF and should be tested therapeutically in patients with von Willebrand disease.
Acute lymphoblastic leukemia in idiopathic refractory sideroblastic anemia: Evidence for a common lymphoid and myeloid progenitor cell
Authors: Barton James C. , Conrad Marcel E. , Parmley Richard T.
Published: February 2007

Acute leukemia of myeloblastic or erythroblastic morphology occasionally occurs as a complication of idiopathic refractory sideroblastic anemia, but the development of acute lymphoblastic leukemia has not been previously reported in these cases. A patient with idiopathic refractory sideroblastic anemia is described in whom acute lymphoblastic leukemia occurred. The leukemic cells were characterized by typical lymphoblastic morphology on Wright's stain, periodic acid‐Schiff‐positive cytoplasmic clumps, elevated levels of deoxynucleotidyl transferase (143 units/108 cells), high numbers of specific glucocorticoid binding sites (16,845 sites/cell, Kd = 5.40 × 10−9 M), non‐B, non‐T cell immunologic characteristics and clinical responsiveness to therapy with vincristine, prednisone, and methotrexate. Ultrastructural studies of the lymphoblasts identified ferruginous material in lysosomes and occasional mitochondria similar to but less abundant than that seen in abnormal sideroblasts. The concurrence of these two disorders supports the theory that in humans both lymphoid and myeloid cell lines arise from a common pluripotent stem cell.
Provoked priapism in sickle cell anemia
Authors: Conrad Marcel E. , Perrine George M. , Barton James C. , Durant John R.
Published: February 2007

Two patients with sickle cell anemia are reported who developed relative impotence after repeated episodes of priapism. They learned that excessive ethanol ingestion produced an erection and utilized this mechanism to satisfy sexual partners. Hospitalization and transfusion therapy were required for repeated episodes of priapism. Extensive interviews were required in order to learn the sequence of events. This synergistic relationship between ethanol and priapism should be sought in patients with repeated hospitalizations for this complication of sickle cell anemia because it is preventable with appropriate counseling.
The synthesis of the Gγ and Aγ chains of human fetal hemoglobin in erythroid colonies cultured from peripheral blood BFUe's of normal adults and newborn and of subjects with an Aγ or a Gγ chain abnormal fetal hemoglobin
Authors: Huisman T. H. J. , Reese A. L. , Gravely M. E. , Harris H. , Wilson J. B.
Published: February 2007

Peripheral blood mononuclear cells from normal adults, normal newborn infants, and from newborn and adult subjects with one of three γ chain variants (GγF‐Malta I, GγF‐Port Royal, AγF‐Hull) were cultured in vitro with erythropoietin. The 35S‐methionine‐labelled hemoglobin from 13‐ to 15‐day‐old BFUe‐derived colonies was studied by chromatography on columns of DEAE‐cellulose and the quantities of Hbs A2, Fx, and F0 determined. The percentages of Gγ and Aγ chains in isolated Hb Fx and Hb F0 were determined using high‐performance liquid chromatography (HPLC) of the tryptic peptides of these proteins. Calculation of these percentages was based on the total activities of the GγT‐15 and AγT‐15 peptides which contain one (35S‐labelled) methionyl residue each and can be separated by the HPLC procedure.

The data show an increased synthesis of Hb F in the „adult”︁ colonies and a decreased synthesis in the „newborn”︁ colonies. The Gγ to Aγ ratio of the Hb F from adult colonies varied greatly. The percentages of Gγ and Aγ chains in the Hb F from adult colonies correlated with the percentages in the Hb F isolated from the Hb F of circulating red blood cells. The Gγ to Aγ ratio in the Hb F from newborn colonies was high as in the Hb F from cord blood samples.

Gγ and Aγ chain abnormal Hb F variants were readily detectable in colonies from both adults and newborn. The Gγ to Aγ ratio in the Hb F of colonies of adult Hb F‐Malta I and Hb F‐Hull heterozygotes approached 1, but that of adult Hb F‐Port Royal heterozygotes remained about as high as in colonies from newborn heterozygotes. The percent Hb F‐Port Royal in the Hb F of adult colonies was twice that in the Hb F of newborn colonies.

These results are discussed in the light of information from recent detailed studies of genomic DNA assuming controlling functions for the segments of DNA that are interspersed between the various structural genes.