bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochemical “normal” and “abnormal” eosinophils in acute leukemias
Authors: Liso Vincenzo , Troccoli Giuseppe , Specchia Giorgina , Magno Maddalena
Published: February 2007

Eosinophilic leukocytes may accompany a great variety of disorders and different types of acute leukemias. The most striking morphologic feature of eosinophils is their specific granules, but morphology alone often is insufficient to differentiate normal from abnormal eosinophils. Cytochemically, the eosinophils were considered “normal” when they did not contain alkaline phosphatase, chloroacetate esterase, toluidine blue metachromasia, Astra blue positivity, and specific PAS‐positive granules, but did have peroxidase and cyanide‐resistant peroxidase activities, Sudan black positivity and moderate naphthol‐AS esterase or α‐naphthyl esterase and acid phosphatase positivities. In seven cases of acute leukemias (two acute myeloblastic and five myelomonocytic), in contrast with their normal behaviour, the eosinophils show “abnormal” cytochemical positivities consisting of chloroesterase activity, PAS and Astra blue positivities of the specific granules, toluidine blue metachromasia, and cyanide‐resistant peroxidase of a few specific granules. Cytochemical investigations may provide additional criteria for evaluating the abnormality of the eosinophilic cell in leukemias.
Borate and glycerol inhibition of the aggregation of guinea pig platelets by bovine factor VIII and ristocetin
Authors: Kuwahara Steven S.
Published: February 2007

To demonstrate the importance of the carbohydrate portions of bovine factor VIII and ristocetin for the induction of platelet aggregation, guinea pig platelets were treated with either borate or glycerol before and after addition of ristocetin or bovine factor VIII. Both borate and glycerol were capable of inhibiting the aggregation of blood platelets induced by adding bovine factor VIII or ristocetin to platelet‐rich plasma. Furthermore, aggregates formed after treatment with either agent could be dispersed by high concentrations of either borate or glycerol. These effects did not appear to be solely the result of high ionic strength or of irreversible damage to the platelets. The results obtained support the hypothesis that the binding of the carbohydrate groups of factor VIII plays an important role in the induction of platelet aggregation and in the maintenance of aggregates formed in response to the treatment of platelet‐rich plasma with bovine factor VIII or ristocetin.
Overwhelming postsplenectomy infection
Authors: Krivit William
Published: February 2007

One of the more intriguing aspects of the spleen is the protection against certain bacterial infections afforded by its unique vascular and immune function. There have been extensive clinical surveys which indicate an incidence of overwhelming postsplenectomy infection (OPSI) above that of the disease for which the splenectomy was done. In the absence of the spleen, either congenital or subsequent to surgical removal, this overwhelming sepsis has a 50% case fatality rate. The most common infective organism has been Diplococcus (Streptococcus) pneumoniae (D. pneumoniae). Intensive investigations indicated loss of phagocytic function of the spleen, depression of serum IgM levels, a possible suppression of the lymphocyte responsiveness, and changes in opsonin‐alternative complement system as potential causes of OPSI. Preventive measures against OPSI include trials of prophylactic Phenoxymethyl Penicillin (penicillin) and pneumococcal vaccine.
Comparative ultrastructure of late rabbit‐embryo erythroid cells in liver and peripheral blood
Authors: Brunner A. , Mitsutani C. Y. , De Peres C. Araújo
Published: February 2007

A morphological study of hemoglobin biosynthesis activity in rabbit‐embryo liver and peripheral blood was comparatively developed. Orthochromatic erythroblasts and reticulocytes of the same maturing degree were analysed through thin sections, as to their organellar constitution and behaviour regarding iron incorporation. It was found that peripheral blood erythroid cells contain mainly hemosomes, organelles taken as sites of final hemoglobin molecule biosynthesis. The ratio between the mean number of hemosomes in blood erythroid cell sections and that in liver erythroid cell sections reaches a little more than 6:1. Inversely, late liver erythroid cells are predominantly constituted by mitochondria that directly or indirectly participate in hemosome formation. The ratio between the mean number of mitochondria in blood erythroid cell sections and that in liver erythroid cell sections reaches 1:11. Besides this, the iron incorporation activity is higher in peripheral blood erythroid cells than in liver erythroblasts and reticulocytes. It is apparent that erythroid cells in the liver accumulate heme, given the ratio of the means of iron incorporation activity per cell to hemosome per cell (3.67), while blood erythroid cells, with a 1.08 ratio, synthesize heme, which is immediately afterwards integrated into the globin chains. The sudden increase in the formation of hemosomes when liver orthochromatic erythroblasts and reticulocytes enter the peripheral blood, reflecting an enhancement of hemoglobin synthesis, agrees with biochemical findings of other authors.
Lack of prognostic value of the periodic acid‐schiff reaction and blast cell size in childhood acute lymphocytic leukemia
Authors: Shaw Michael T. , Bennett Humphrey G. , Lawrence Roberta , Fischer Diana B.
Published: February 2007

Conflicting evidence has been published as to the prognostic significance of the periodic acid‐Schiff (PAS) reaction and cell size in acute lymphocytic leukemia (ALL). Therefore, a large collaborative study was undertaken to evaluate the prognostic significance of the PAS reaction and cell size of bone marrow lymphoblasts obtained at the time of diagnosis in children with ALL. Known prognostic factors (age and white blood cell [WBC] counts) were also evaluated. Data from 80 newly diagnosed cases of ALL were analyzed. These patients were treated with similar therapy by members of the Pediatric Division of the Southwest Oncology Group. The PAS reaction was scored. Microlymphoblasts were defined as having a diameter of ≤ 12 μm; macrolymphoblasts, > 12 μm. Patients 10 years and older at the time of diagnosis had a significantly shorter duration of first remission and survival than those younger than 10 years. Those with pretreatment peripheral WBCs of ≤ 25,000/μl had significantly longer duration of first remission and survival than those with a peripheral WBC > 25,000/μl. There was no significant difference in duration of first remission or survival in patients having predominantly macrolymphoblastic or microlymphoblastic marrows. PAS reaction was of no value in predicting the duration of first remission or survival.
Production of paroxysmal nocturnal hemoglobinuria‐like red blood cells by tea
Authors: Benjamin Lennette J. , Goldstein Bernard D. , Distenfeld Ariel , Troll Walter
Published: February 2007

Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria‐like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement‐dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement‐dependent hemolysis in tea‐incubated red cells was inhibited by antisera to C3 and to C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement‐dependent hemolysis of red cells incubated with tea.

Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.
Hemolysis by complement and cold‐reacting antibodies: Time and temperature requirements
Authors: Rosse Wendell F. , Adams Judith , Logue Gerald
Published: February 2007

The time and temperature requirements of certain steps involved in hemolysis of normal human red cells by cold‐reacting antibodies and normal human serum were examined by means of techniques that measure the amount of antibody and the fourth (C4), third (C3), and fifth (C5) component of complement bound to red cell membranes. For all cold‐reacting antibodies, the greatest degree of lysis was obtained in bithermic reactions with the first phase at temperatures 15° or below, and the second phase at 37°. For anti‐I antibodies, only antibody and C1 are fixed at temperatures below 15°, and the fixation of C4 and C3 to the membrane occurs during warming. C4 but not C3 is fixed at temperatures below 15° when the reaction is initiated by the Donath‐Landsteiner antibody. During warming, antibody and C1 elute. No C4 and C3 are fixed after the temperature reaches 37° and the amount of “active” C3 diminishes rapidly with continued incubation at 37°. C5 is rapidly fixed during warming from 15° to 37° and for a short time at 37°, but the hemolytic activity of C5 is unstable. Thus these cold‐reactive antibody‐mediated complement reactions occurring on human red cells in human serum must occur during and very shortly after the warming phase. If the rate of change of temperature is prolonged during the warming phase, greater C3 fixation and hence more lysis occurs.
Characterization of tumour cells in concomitant chronic lymphocytic leukaemia and acute monocytic leukaemia
Authors: Adams P. B. , Ding J. C. , Cooper I. A. , Cornell F. N.
Published: February 2007

A 68‐year‐old woman presented with haematological changes of chronic lymphocytic leukaemia and acute monocytic leukaemia. This diagnosis was confirmed by identification of cell surface markers for T and B lymphocytes and the identification of abnormal immunoglobulins and lysozyme in serum and urine.
Exceptionally high serum erythropoietin activity in an anephric patient with severe anemia
Authors: Ortega Jorge A. , Malekzadeh Mohammed H. , Dukes Peter P. , Ma Andrew , Pennisi Alfred V. , Fine Richard N. , Shore Nomie A.
Published: February 2007

An exceptionally high serum erythropoietin (EPO) activity was documented in an anephric patient with severe anemia who required transfusions every 4 weeks. The patient's serum EPO was comparable to normal human urinary EPO in the polycythemic mouse assay and was neutralized by an antiserum against EPO. The patient's serum inhibited EPO stimulated‐heme synthesis by normal human marrow cells in vitro. This finding suggests that an inhibitor played an important role in causing the anemia of this uremic patient.
Identification of hemoglobins in single erythrocytes by electrophoresis
Authors: Anyaibe Stephen I. O. , Headings Verle E.
Published: February 2007

We present here a method for electrophoretic identification of hemoglobin variants in many individual erythrocytes simultaneously, which is made possible by instruments developed in our laboratory. The system spaces and aligns the erythrocytes along a common origin and prevents “doubling up” of cells. Unambiguous separation of different hemoglobins (Hbs) occurred from single erythrocytes, such as Hbs A, C, F. Staged micrographs showed that hemoglobins of differing mobility from a single cell arise from a single point source of hemoglobin. In principle this capability is applicable to other proteins and could facilitate investigation at a cellular level into a variety of questions pertaining to gene action.
Hb leiden‐β° thalassemia in a chinese with severe hemolytic anemia
Authors: Lie‐Injo Luan Eng , Randhawa Z. I. , Ganesan J. , Peterson D. , Kane J. P.
Published: February 2007

The first case of Hb Leiden (α2β2 6 or 7 Glu→0)‐β° thalassemia in a young patient with chronic severe hemolytic anemia, which improved after splenectomy, is described. His parents were Chinese. The patient's blood showed no Hb A or normal β chains when no blood transfusion was given. His mother was heterozygous for β° thalassemia, and his father and brother had the trait for the unstable Hb Leiden. The Hb Leiden level of the father was 22.6% and that of the brother was 19.3%. It is probable that the abnormal hemoglobin in this Chinese family resulted from an independent gene mutation, unrelated to the one found in 2 Caucasian families reported earlier.
The oxygen affinity of concentrated human hemoglobin solutions and human blood
Authors: Horvath Steven M. , Malenfant Arthur , Rossi Francesco , Rossi‐Bernardi Luigi
Published: February 2007

The log P50 of normal human blood at 37°, PCO2 = 0, 21, 42, and 57 mm Hg, in the absence and in the presence of 2,3‐DPG and ATP, has been determined in the pH range 7.0 to 7.6. Similar data have been obtained for human hemoglobin isotonic solutions at different protein concentrations in the presence of various amounts of each of the cofactors which are known to affect hemoglobin oxygen affinity in blood. It has been found that the addition of KCl, organic phosphates, magnesium ions, and CO2 confers to a 32% human hemoglobin solution the same oxygen affinity (over the entire physiological pH range) of whole blood. Thus there is no room for significant effects caused by some other unidentified molecules or ions.
Kaposi's sarcoma presenting as autoimmune hemolytic anemia
Authors: Hammond Denis B. , Ellman Leonard , Sirota Ronald L.
Published: February 2007

A case of Kaposi's sarcoma which presented as a warm type of immune hemolytic anemia is described. The malignancy was discovered at the time of splenectomy, which was required for control of the hemolytic anemia. Three other cases of immune hemolytic anemia in patients with Kaposi's sarcoma have been reported. An association between Kaposi's sarcoma and immune hemolytic anemia is suggested. Careful examination of the skin for Kaposi's sarcoma seems appropriate in cases of immune hemolytic anemia.
Two dimensional view of combination chemotherapy in vitro
Authors: Grünwald Hans W. , Rosner Fred , Hirshaut Yashar
Published: February 2007

A newly developed micromethod to evaluate the cytotoxic effects of drugs on rapidly growing lymphoid cell lines is described, which permits evaluation of more than one variable. This technique allows a checkerboard titration of two drugs to determine the optimum concentration of each needed for the augmentation of the other's cell‐killing activity. Such studies have shown that the minimum concentration of vincristine capable of killing a human lymphoid cell population is 5.6 ng/ml. The addition of prednisolone at a concentration of 460 ng/ml reduces the minimum lethal concentration of vincristine to 1.6 ng/ml. When prednisolone is added to vincristine at concentrations of 2.8 μ/ml (a level readily achieved in the serum in vivo) concentrations of vincristine as low as 200 pg/ml are clearly cytotoxic. Similar potentiation of cytotoxicity following the addition of prednisolone has been demonstrated for cytosine arabinoside, but not for daunorubicin and only slightly for methotrexate. The micromethod for the study of optimal doses to be used in drug combinations is simple and gives highly reproducible results. It should be of considerable utility to anyone interested in screening a wide variety of drug concentrations for augmentation or synergistic effects.
The distinctive features of acute monocytic leukemia
Authors: Shaw Michael T.
Published: February 2007

Acute monocytic leukemia is an uncommon form of acute leukemia. Distinctive clinical features include gingival hypertrophy, lymphoadenopathy, coagulation disorders, and lysozymuria. Blast cell morphology and cytochemistry are diagnostic. Receptors for the Fc fragment of IgG have been demonstrated on the basis of a few cases. The drug VP 16–213 has been shown to be very effective in treatment of untreated and previously treated patients.
NADPH‐oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears
Authors: Auclair Christian , Torres Martine , Hakim Jacques , Troube Huguette
Published: February 2007

Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide‐resistant NADPH‐oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activities responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low‐density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH‐oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis.
Increased granulocytic, erythrocytic, and megakaryocytic progenitors in myelofibrosis with myeloid metaplasia
Authors: Chikkappa G. , Carsten A. L. , Chanana A. D. , Chandra P. , Cronkite E. P.
Published: February 2007

Nucleated cells obtained from blood and/or bone marrow of patients with myelofibrosis with myeloid metaplasia (MMM) were cultured in diffusion chambers (DC) implanted into the peritoneal cavities of irradiated mice. A total of five blood studies and two bone marrow studies were performed using cells obtained from five patients. The DC were harvested at intervals from the host mice and the total and differential cellularity of DC contents were evaluated. The results obtained from MMM cultures were compared with those from similar cultures of blood cells and marrow cells of four and six normal individuals respectively. The proliferation and maturation of the granulocytic, erythrocytic, and megakaryocytic lines in MMM cultures occurred in an orderly fashion as they occur in vivo. The patterns of proliferation and maturation of the three cell lines in cultures after day 7 suggest that they primarily originate from progenitor cells. The numbers of granulocytes in the multiplicative pool, recognizable red cell precursors, and megakaryocytes recovered were significantly greater from the MMM cultures than those from the normal blood or marrow cultures. These results suggest that the blood and marrow cells of MMM patients have increased numbers of progenitors for granulocytes, erythrocytes, and megakaryocytes.
Glutathione reductase deficiency in a kindred with hereditary spherocytosis
Authors: Nakashima Koji , Yamauchi Katsuyo , Miwa Shiro , Fujimura Kingo , Mizutani Akiko , Kuramoto Atsushi
Published: February 2007

A kindred with hereditary spherocytosis was found to have erythrocyte glutathione reductase deficiency. The glutathione reductase was evaluated enzymatically and immunologically. The enzyme activity could not be restored either by flavin adenine dinucleotide (FAD) in vitro, or by oral administration of FAD. Kinetic and electrophoretic studies, heat stability tests, and pH curves revealed no evidence of a variant enzyme. The results of electroimmunodiffusion and neutralization tests using an antiserum indicated that the deficiency is caused by a diminished production of enzyme protein. Hereditary spherocytosis and glutathione reductase deficiency traits segregated independently. The amount of reduced glutathione in the erythrocyte was normal, and the deficiency state without hereditary spherocytosis was asymptomatic. All deficient members in this kindred were heterozygous and the residual enzyme activity in the heterozygote might be sufficient to maintain the reduced glutathione level to prevent oxidative stress.
Combination chemotherapy for haematological relapse in adult acute lymphoblastic leukaemia (ALL)
Authors: Woodruff R. K. , Lister T. A. , Paxton A. M. , Whitehouse J. M. A. , Malpas J. S.
Published: February 2007

Twenty‐three adult patients (median age 22 years) with haematological relapse of acute lymphoblastic leukaemia were given reinduction therapy with vincristine, adriamycin, prednisolone, and L‐asparaginase. Complete remission (CR) was achieved in 16 patients (69%), and only one patient was completely unresponsive to therapy. The duration of second remission was short except in three patients who had experienced long first remissions (> 2.5 years). The median duration of survival from first relapse was seven months.
β‐thalassemia arising as a new mutation in an American child
Authors: Noronha Peter A. , Honig George R.
Published: February 2007

A 6‐year‐old child of northern European ancestry was found to have microcytic, hypochromic anemia with an elevated level of hemoglobin A2 and an unbalanced pattern of globin chain synthesis characteristic of β‐thalassemia trait. Hematologic and globin synthesis studies of both parents yielded entirely normal results. Identification of the mother and father as the biological parents was established with a high order of reliability by determination of erythrocyte, serum, and HLA genetic markers. These findings suggest that the picture of β‐thalassemia observed in this child represents a new mutation.
Non‐leukemic dividing cells in the blood of leukemic patients
Authors: Humbert James R. , Morse Helvise G. , Hutter John J. , Rose Barbara , Robinson Arthur
Published: February 2007

Spontaneous mitoses in the blood of 67 patients with acute leukemia were enumerated and their identity determined by cytogenetic methods. Most patients were children with acute lymphoblastic leukemia. Simultaneous 16‐to 20‐hour cultures of blood leukocytes (Bu) and of bone marrow (BM) cells were performed without phytohemagglutinin (PHA). Blood leukocytes were also cultured with PHA for 72 hours (BPHA). Mitoses in Bu cultures were counted, and karyotypic analysis performed on cells from the three culture types. In 21 control subjects, Bu cultures usually yielded no mitoses. Relapse and remission patients both displayed significantly more Bu mitoses than the controls. The karyotypes of Bu, BPHA, and BM mitoses in remission patients were normal. Fifty percent of relapse patients displayed cytogenetically abnormal leukemia cell lines; the percentage of their abnormal karyotypes was significantly higher in BM cells than in Bu or BPHA cells. The majority of the mitotic cells in Bu cultures from both relapse and remission patients appear to be of a nonleukemic origin. The number of mitoses could not be correlated with type of leukemia, hematologic parameters, or prognosis.
Accumulation modes of alkylating agents on normal peripheral blood lymphocytes
Authors: Brody Jerome I.
Published: February 2007

The in vitro uptake by normal peripheral blood lymphocytes of 14C‐labeled cyclophosphamide and nitrogen mustard has been measured in a manner which parallels cell exposure to drugs used in the nitrogen mustard‐oncovin‐procabazine‐prednisone (MOPP) and cyclophosphamide‐oncovin‐procarbazine‐prednisone (COPP) clinical protocols. Accumulation of these alkylating agents occurs in two recognizable patterns. The first exhibits a saturation phenomenon, since radioactivity can be partially blocked by an equal concentration of unlabelled drug, reflects stereospecificity, and represents a minor fraction of total deposition. The second form, proportionately larger than the first, is dependent on drug concentration in the suspending medium, with radioactivity increasing in an apparently limitless linear fashion, uninfluenced by competitive inhibition. This part also is less tenaciously held by the lymphocyte. While the mere presence of drug on the lymphocytes does not necessarily imply injury or lethality, the fact that these peripheral lymphocytes are able to accumulate cytotoxic agents and are partially interchangeable with an analogous fixed lymphoid cell mass suggests that clinical immunosuppression and lymphocytopenia may be related, in part, to cell drug deposition.
Parasinusoidal location of megakaryocytes in marrow: A determinant of platelet release
Authors: Lichtman Marshall A. , Chamberlain Jack K. , Simon William , Santillo Patricia A.
Published: February 2007

Megakaryocytopoiesis occurs in the hematopoietic (extravascular) compartment of marrow. Thus, platelets must traverse the wall of the vascular sinuses of marrow to enter the circulation. We have examined mouse and rat marrow, fixed by rapid immersion so as to maintain anatomical relationships as close to the natural state as possible. Quantitative transmission electron microscopy (TEM) of random transections of femurs established that megakaryocytes reside less than 1 μ from a marrow sinus wall with a probability unlikely to be the result of chance (P < 0.001). An intimate relationship exists between the megakaryocyte periphery and the abluminal surface of the endothelial lining cell. At the time of platelet release megakaryocyte cytoplasm invaginates and penetrates the endothelial lining cell. The penetrating cytoplasm is detached and enters the marrow circulation. From their dimensions in comparison to circulating platelets, the released cytoplasm represents a packet of platelets that undergoes further fragmentation in the circulation. The parasinusoidal location of megakaryocytes and the process of sinus‐wall penetration and platelet delivery was observed by TEM and scanning electron microscopy. These studies provided quantitative support for a specific anatomical arrangement of megakaryocytes in marrow. Moreover, the process of platelet release appears to be a physiological form of metastasis with invasion of vascular walls and vascular spread of cells, that are in this case amitotic.
Guidelines for protocol studies in chronic lymphocytic leukemia
Authors: Silver Richard T. , Sawitsky Arthur , Rai Kanti , Holland James F. , Glidewell Oliver
Published: February 2007

The treatment of any malignant disease requires appropriate criteria for diagnosis of the disease, appropriate methods for study, and techniques for evaluating response to treatment. In the past five years, there have been a number of proposed guidelines for studies in chronic lymphocytic leukemia (CLL).

These submitted guidelines represent a further re‐evaluation of concepts in CLL, and are currently in use by Cancer and Leukemia Group B for protocol studies. It is clear that revisions will continue to be made as new knowledge accumulates. In the meantime, these are submitted for publication for use by other investigators.
A new mutant erythrocyte glucosephosphate isomerase (GPI) associated with GSH abnormality
Authors: Zanella Alberto , Rebulla Paolo , Izzo Crescenzio , Zanuso Francesco , Sirchia Girolamo , Kahane Itzhak , Molinari Ermete
Published: February 2007

A case of congenital nonspherocytic haemolytic anaemia associated with a new abnormal glucosephosphate isomerase (GPI), GSH (reduced glutathione) deficiency, and instability and altered carbohydrate membrane composition is reported. The only functional abnormality of the mutant enzyme seems to be a marked instability to heat, urea, and guanidine‐HCl. Family studies suggest that the propositus is doubly heterozygous for a maternal gene producing an inactive enzyme and a paternal gene responsible for a structural alteration causing marked lability of the coded enzyme. Experiments of incubation of normal GPI and the propositus's GPI with oxidizing and reducing agents seem to indicate that the abnormality resides in the SH groups of the mutant GPI.
Deoxyuridine suppression studies in bone marrow in primary refractory sideroblastic anemia
Authors: Goodman Anita , Bacon Bruce , Hines John D.
Published: February 2007

Because unexplained megaloblastic erythroid maturation occurs in patients with primary refractory sideroblastic anemia (PRSA), deoxyuridine (dU) suppression tests using125 I‐UdR were performed on bone marrow from five patients with PRSA. All patients had megaloblastic alterations in the marrow erythroid precursors (with normal serum folate and B12 levels) and numerous ringed sideroblasts, and most had marrow iron overload. Results of the dU suppression tests were normal in all five, both with and without incubation with pharmacologic amounts of folate, B12, and pyridoxal phosphate with or without 1‐serine.

Despite occasional hematologic improvement subsequent to folate, pyridoxine, or pyridoxal phosphate (PLP) administration in some patients with PRSA, normal dU suppression implies that in our group the availability of B12 and folate (and possibly PLP) was not limiting in the utilization of folate for DNA‐thymine synthesis. The marrow erythroid maturation defect remains unexplained.
Adult severe combined immunodeficiency and sarcoid‐like granulomas with hypersplenism
Authors: Edelstein Alan D. , Neiman Richard S. , Miller Aaron , Zimelman Abraham P. , Rocklin Ross E.
Published: February 2007

A patient presented with lymphopenia, anergy, hypogammaglobulinemia and hypersplenism. Histologic examination of the spleen and lymph node revealed noncaseating sarcoid‐like granulomas. Despite a significant rise in circulating lymphocytes after splenectomy there was in vivo and in vitro evidence of B‐ and T‐lymphocyte dysfunction. A histologic picture mimicking sarcoidosis may occur in patients with immune deficiency. The granulomatous proliferation may represent an altered host response to antigen.
Cytosine arabinoside modulation of the mitotic index in treatment of adult acute leukemia
Authors: Mackinney Archie A. , Flynn Bridgett
Published: February 2007

Twenty‐three unselected adult acute leukemic patients were treated with an initial intravenous pulse of cytosine arabinoside (Ara‐C) 5 mg/kg. The mean mitotic index dropped from 7.7/1,000 to 2.8/1,000 at 4 hours after Ara‐C pulse and rebounded to 6.7/1,000 at 18 hours. Infusions of Ara‐C 7‐10 mg/kg were given for 9 or 12 hours, depending on changes in the mitotic index. The group of responders (M1 or M2 marrows) could be predicted by the initial blast count in the marrow and the change in the mitotic index 18 hours after the Ara‐C pulse. There were 9 (39%) complete and partial remissions. Six patients remained in remission more than 200 days. Since the changes in the mitotic indices induced by Ara‐C were indistinguishable from those of another more successful trial, we infer that factors other than modulation of the cell cycle are critical to the success of this mode of therapy.
Proliferative function of cadaveric bone marrow cells
Authors: Liu Paul L. , Ogawa Makio , Crook Lynn , Ochia Roland , Upshur Jane K.
Published: February 2007

The proliferative function of human and murine cadaveric bone marrow was studied using methylcellulose clonal cell culture assays and the murine spleen colony technique. The study revealed persistence of hemopoietic functions for as long as 19 postmortem hours in cadaveric marrows of some patients. Studies of murine cadaveric marrows corresponded with those of human marrows. These results strongly suggest that human pluripotent hemopoietic stem cells survive in cadaveric marrows.
Permanent preparations of granulocyte macrophage cultures in agar gel
Authors: Mendelow B. , Grobicki D. , De La Hunt M. , Katz J.
Published: February 2007

A simple method for the permanent preservation of agar cultures is described. The technique involves fixation of agar cultures after incubation, drying, and subsequent remounting and staining on glass slides. The technique permits differential counting of colony type, approximate quantitation of cell numbers within individual colonies or clusters, and permanent preservation of cultures for purposes of interlaboratory standardization, and for routine reference in patient records.
Control of Hemoglobin Synthesis in Fetal Erythroid Cells by L‐Thyroxine
Authors: Fuhr J. E. , Dunn C. D. R.
Published: February 2007

Fetal mouse liver cells were incubated in the presence of L‐thyroxine. Globin synthesis by cells from the 13th to 15th days of gestation was stimulated by the presence of the hormone. Although protein synthesis by cells from the 17th day of gestation was stimulated, the protein was not identified as globin. A tentative conclusion was drawn that fetal erythroid tissue may be preferentially stimulated by thyroid hormone.
Elevated plasma levels of fibrinopeptide a during sickle cell anemia pain crisis–evidence for intravascular coagulation
Authors: Leichtman David A. , Brewer George J.
Published: February 2007

A role for coagulation in the pathogenesis of sickle cell anemia (SCA) pain crisis has long been suspected. We have observed evidence for in vivo coagulation in patients with SCA during pain crisis utilizing a radioimmunoassay for fibrinopeptide A (FPA). Since the proteolytic activity of thrombin results in the release of FPA from fibrinogen, plasma levels of FPA may be used as an index of in vivo thrombin activity. In 20 normal controls FPA plasma levels had a range of 0.6–1.4 ng/ml and a mean of 0.7 ± 0.2 ng/ml. We observed elevations of FPA, values greater than the mean plus 4 standard deviations of the control group, in 21 consecutive plasma samples obtained from 8 SCA patients during pain crisis. FPA determinations on 7 of 10 plasma specimens obtained from 10 SCA patients during pain‐free periods were within the normal range. Elevations of FPA in 2 of 3 of these pain‐free patients could be explained by recent extensive oral surgery and faulty venopuncture, conditions known to cause elevated levels of the peptide. Plasma specimens were obtained from 2 SCA patients patients with subjective complaints of pain, but who were suspected of malingering prior to FPA determination. In both instances, FPA was within the normal range.

In summary, plasma levels of FPA appear to be elevated in SCA patients during crisis as contrasted to pain‐free periods and normal controls. This study provides new evidence for the occurrence of intravascular coagulation during SCA pain crisis. Further studies are needed to assess whether this activation of the coagulation system is a cause or an effect of pain crisis.
Erythroleukemia: In vitro studies of erythropoiesis
Authors: Newcomb M. M. , Balducci L. , Coleman M. B. , Steinberg M. H.
Published: February 2007

We studied the growth of erythroid burst‐forming units (BFU‐E) and erythroid colony forming units (CFU‐E) from bone marrow and blood in six patients with erythroleukemia. Five patients grew CFU‐E, while BFU‐E were found in the marrow of two and in the peripheral blood of only one patient. In all cases with colony growth, the numbers of colonies were markedly decreased with respect to normal controls. Patient BFU‐E were composed of fewer clusters than those of controls. BFU‐E and CFU‐E growth was dependent on the addition of erythropoietin to the medium, and no growth was observed in absence of erythropoietin. At present it is not known if the growth obtained is derived from residual normal erythropoietic stem cells or from abnormal erythroid precursors of the leukemic cells.
The lipids of the erythrocyte in paroxysmal nocturnal hemoglobinuria
Authors: Gockerman Jon P.
Published: February 2007

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder characterized by the production of abnormal erythrocytes (PNH‐E). The PNH‐E undergoes early intravascular destruction which appears to be related to an intrinsic membrane defect that results in extreme sensitivity to lysis by complement. The lipids of the PNH‐E have been evaluated because of the variable results reported in the past. This study shows a normal content of cholesterol and lipid phosphorus with a normal distribution of the phosopholipids except for a slight increase in lysophosphatidyl choline (LPC) when measured using the complete lipid extract of the PNH‐E. Fractionation of the lipid extract over a silicic acid column produced an alteration in the distribution of the phospholipids, with LPC and sphingomyelin increasing, and the other phospholipds decreasing. These alterations were seen only when the phospholipids were fractioned over a silicic acid column and were clearly an in vitro phenomenon. The levels of plasmalogen and malonaldehyde were normal, unlike those seen with oxidant stress. Fatty acid analysis of the phospholipids showed small but consistent changes: increased 16:0 and decreased 18:2. The total glycosphingolipids were slightly decreased in the patients with severe PNH. The results support and extend previous lipid data indicating abnormalities in the phospholipids of the PNH‐E. The alterations of the phospholipids with fractionation correlate with previous whole cell data that suggest lipid instability in the PNH‐E.
Unbalanced globin chain synthesis by Hb lincoln park (anti‐lepore) reticulocytes
Authors: Honig George R. , Mason R. George , Tremaine Larry M. , Vida Loyda N.
Published: February 2007

Hemoglobin synthesis was studied in vitro in reticulocytes from a patient with the anti‐Lepore variant Hb Lincoln Park. Incorporation of L‐leucine‐3H into the α and βδ chains of Hb Lincoln Park was substantially less than the incorporation into the corresponding globin chains of Hb A, with the rate of synthesis of the βδ chain being similar to that of the δ chain of Hb A2. Synthcis of the a and total non‐α globin components was unbalanced, with a substantial excess of α chain synthesis. These findings help to explain the mild hemolytic disease present in individuals with this hemoglobin variant.
Quantitation of globin chains using cellulose acetate electrophoresis: Analysis of fetal globin chain production
Authors: Barton Jennifer , Smith Merran B. , Cauchi M. N.
Published: February 2007

A technique involving the quantitative estimation of globin chains using cellulose acetate electrophoresis is described, and applied to the analysis of fetal globin chain production. When cord blood was analyzed, there was poor correlation between the globin chain ratios namely β/α, γ/α and β/γ ratios with either age or weight of newborn babies between 36–40 weeks gestation: best correlations were obtained for the β/γ ratio against weight (P < 0.05). However, there was highly significant correlation between the various globin chain ratios and either age or weight of the newborn infant up to 12 weeks of age (P < 0.001). This technique allows visual demonstration and quantitation of abnormal haemoglobins in a single procedure.
An acquired cell‐directed inhibitor of neutrophil chemotaxis and hypogammaglobulinemia
Authors: Casciato Dennis A. , Ford Larry C. , Busch David F.
Published: February 2007

An unusual combination of host defense abnormalities was demonstrated in an adult male with recurrent pulmonary infections due to a variety of microorganisms. Polymorphonuclear neutrophil chemotaxis was defective. Other neutrophil and T‐lymphocyte function tests were normal. The patient's serum also showed a severe deficiency of IgG, no detectable IgA, IgM, or IgD, and increased IgE. The chemotactic defect was shown to be due to a cell‐directed inhibitor in the patient's serum. The effect of the inhibitor on chemotaxis could be antagonized by factors in normal serum. The chemotaxis defect persisted for several months, but eventually returned to normal.
Heterogeneity of hemoglobin gamma chains in normal newborns and in cases of alpha and beta thalassemia
Authors: Lie‐Injo Luan Eng , Randhawa Z. I. , Kane J. P. , Ganesan J. , George R.
Published: February 2007

The ratio of Gγ to Aγ chains was studied in 13 normal healthy newborns and in eight neonates with hydrops fetalis due to homozygous α‐thalassemia. The findings in the normal healthy newborns agreed with those of earlier reports. In homozygous α‐thalassemia the Gγ and Aγ ratio appeared generally lower than in healthy control newborns, but one of the hydrops fetalis cases had a very high Gγ value.

In all 13 normal healthy newborns, in 8 patients with homozygous α‐thalassemia, and in 4 patients with homozygous β‐thalassemia, Tγ chains with threonine at position 75 were detected in addition to Iγ chains with isoleucine at position 75. In homozygous α‐thalassemia, the Tγ‐to‐Iγ ratio seemed lower and in homozygous β‐thalassemia higher than in normal newborns.
A method for cloning T‐lymphocytic precursors in agar
Authors: Löwenberg B. , de Zeeuw H. M. C.
Published: February 2007

A new technique for the culture of T‐lymphocytic colonies is reported. The method may be regarded as a human lymphocyte precursor cell assay, as is the myeloid colony culture for granulocyte‐macrophage progenitors. The colonies arise under the simultaneous stimulation of phytohemagglutin and a leukocyte feeder. A linear relationship is found between colony numbers and cell numbers plated. The colonies represent aggregates of lymphoblast‐like cells, the majority of which are capable of E‐rosette formation, are responsive in mixed lymphocyte cultures, and do not exhibit surface immunoglobulins. Their density distribution profile is very similar to that of myeloid colony‐forming cells. The finding that most of these colony‐forming cells are recovered in the so‐called lymphocyte‐free stem cell fraction following density fractionation suggests that they originate from a lymphocytic precursor.
A simplified [3H] serotonin release assay for the detection of platelet antibodies
Authors: Marmer Daniel J. , Bowman Robert P. , Kennedy Peter S.
Published: February 2007

The [3H] platelet serotonin release assay is a sensitive means for detecting antiplatelet antibodies. We have found that by using prelabeled frozen platelets which have been treated with the cryoprotective agent dimethyl sulfoxide (DMSO) the performance of this assay can be facilitated without interfering with its sensitivity. There was 100% correlation between the standard [3H] platelet serotonin release assay using fresh platelets and the modified assay using prelabeled, frozen, cryopreserved platelets when sera from 12 patients with known antiplatelet antibodies were tested. When normal serum samples (n = 111) were tested against ten platelet donors, a false‐positive rate of 3.9% was observed. This modification provides a simple means for quickly screening large numbers of potential platelet donors at one time.
The association of sickle cell anemia with heterozygous and homozygous α‐thalassemia‐2: In vitro HB chain synthesis
Authors: Felice A. E. , Webber B. , Miller A. , Mayson S. M. , Harris H. F. , Henson J. B. , Gravely M. E. , Huisman T. H. J.
Published: February 2007

The in vitro synthesis of hemoglobin chains was investigated in 34 scikle cell anemia (SS) patients and five patients with Hb S‐βo‐thalassemia. Incubations were made for 30 minutes and for 120 minutes. Hematological and family data were also obtained. Although the 30‐minute α/non‐α total activity ratios were more widely distributed than the ratios at 120 minutes, a distinct classification of SS patients into groups without an α‐thalassemia, with a heterozygous α‐thal‐2, or with a homozygous α‐thal‐2 could not be made. Family studies indicated that four patients who had 30‐minute α/non‐α ratios below 0.82 and mean corpuscular volume (MCV) values below 70 fl had a homozygosity for both α‐thal‐2 and Hb S. They had mild hematological features of SS disease. Many SS patients with 30‐minute α/non‐α ratios between 0.8 and 1.0 and MCV values above 70 fl had an associated α‐thal‐2 heterozygosity. Their hematological features were similar to those of SS patients with four active α chain genes. It appears that an α‐thal‐2 heterozygosity (−α/αα; βS/βS) does not alter the hematological expression of SS disease. An α‐thal‐2 homozygosity −α/−α;βS/βS results in a microcytosis similar to that seen in Hb S‐βo‐thalassemia patients. The diagnosis of these α chain deficiencies in association with SS disease (by in vitro chain synthesis analyses) leaves several uncertainties.
Acquired aplastic anemia: Antibody‐mediated hematopoietic failure
Authors: Freedman Melvin H. , Gelfand Erwin W. , Saunders E. Fred
Published: February 2007

The hematopoietic failure in aplastic anemia was studied in six patients by assessing marrow erythroid stem cell (CFU‐E) and granulocytic stem cell (CFU‐C) colony growth in vitro. CFU‐E and CFU‐C were absent or reduced in five patients, and their serum did not inhibit CFU‐E or CFU‐C growth from control marrows. In contrast, marrow from one patient yielded 80 CFU‐E/105 and 16 CFU‐C/105 (control CFU‐E: 197/105 cells plated, range 110–387; control CFU‐C: 48/105, range 15–106). His serum decreased CFU‐E (122 to 9/105) and CFU‐C (71 to 32/105) from control marrow, and CFU‐E from his own marrow (80 to 37/105). His peripheral blood lymphocytes cocultured with autologous or control marrow similarly decreased CFU‐C. The inhibition was more marked in cocultures using a B‐cell enriched lymphocyte fraction obtained by albumin density gradient centrifugation. IgG separated from the patient's serum demonstrated a dose‐responsive suppression of CFU‐E (102 to 8/105), and of CFU‐C (58 to 28/105) from control marrow. We conclude that of the six patients, one demonstrated an antibody‐mediated hematopoietic failure. It is recommended that all patients with acquired aplastic anemia be studied for this, since in vitro testing can detect those in whom immunosuppression and plasmapheresis may be more appropriate therapy than marrow transplantation.
Marked hypodiploidy in a case of acute undifferentiated leukemia
Authors: Como Ronald , Sarna Gregory , Sparkes Robert S.
Published: February 2007

A 29‐year‐old white man with acute undifferentiated leukemia had bone marrow cells with predominantly 42 chromosomes including several rearrangements. Following a brief induced “complete” remission, during which normal chromosomes were observed, bone marrow cells with 42 chromosomes but a different karyotype than before remission were found. Evaluation of that karyotype indicates not only a reduced chromosome count but also a reduced quantity of chromosome material.
Immune thrombocytopenic purpura in Hodgkin disease
Authors: Hassidim Kamran , McMillan Robert , Conjalka Michael S. , Morrison John
Published: February 2007

Immune thrombocytopenic purpura is rarely seen in Hodgkin disease and the presence of platelet‐associated antibody has not been previously reported in these patients. A patient with Hodgkin disease is described who developed a destructive thrombocytopenia demonstrated by shortened platelet survival. In conjunction with his thrombocytopenia, he had marked elevation of platelet‐associated immunoglobulin G levels (nanograms IgG per 109 platelets: 15,187 prior to splenectomy and 71,130 and 81,900 after surgery). Mean values (± SD) of control subjects averaged 1,975 ± 381 and four patients with Hodgkin disease and normal platelet counts had levels ranging from 1,581 to 4,011.

We suggest that this patient had immune‐mediated thrombocytopenia; whether the increase in platelet‐associated immunoglobulin G was due to antiplatelet antibody or to adsorbed or phagocytosed immune complexes cannot be demonstrated by these studies. The platelet‐associated immunoglobulin G test may be useful in evaluating these patients.
Chromosome changes in a patient achieving complete remission in the acute phase of chronic myelogenous leukemia
Authors: Stern Ronald , Sorenson Julie , Wurster‐Hill Doris H. , Cornwell Gibbons G. , McIntyre O. Ross
Published: February 2007

A patient with chronic myelogenous leukemia (CML) had a Philadelphia chromosome (Ph′) [t(9q+;22q–)] in all cells and trisomy C in 13% of cells (later determined to be trisomy 8) at the time of diagnosis. After 21 months of intermittent treatment with busulfan, the acute phase developed with the appearance of an additional abnormality (trisomy ?19). During a complete remission and reconversion to the chronic phase, trisomies 8 and ?19 disappeared, although the Ph′ remained. Following a period of marked thrombocytosis, a second relapse occurred with the reappearance of both marker chromosomes.