bluuebunny/crossref_metadata_2025 huggingface dataset:
Bleeding time in Uremia: A useful test to assess clinical bleeding
Authors: Steiner R. W. , Coggins Cecil , Carvalho Angelina C. A.
Published: February 2007

Modified Ivy bleeding time (template) and platelet aggregation to ADP, epinephrine, and collagen were studied in 26 uremic patients who had not recently ingested anti‐platelet drugs. Regardless of the aggregating agent used, the abnormalities in platelet aggregation were often mild, even with advanced uremia, and frequently less severe than the effects of common anti‐platelet drugs. The inhibition of collagen‐induced aggregation was significantly correlated with both increased bleeding time and blood urea nitrogen. Platelet aggregation was not discriminative between clinically bleeding and non‐bleeding groups of patients, but the bleeding time was helpful in this regard. In certain cases, the aggregometric patterns differed between drug‐induced and uremic thrombocytopathies. Platelet aggregometry appears to be of little help clinically in assessing the severity of the uremic bleeding diathesis.
Subpopulations of human peripheral blood cells: Analysis of granulocytic progenitor cells by flow cytometry and immunologic surface markers
Authors: Drapkin R. L. , Adreeff M. , Koziner B. , Strife A. , Wisniewski D. , Darzynkiewicz Z. , Melamed M. R. , Clarkson B.
Published: February 2007

Normal human peripheral blood cells were separated into different populations based upon isopycnic sedimentation, E rosetting, and EAC rosetting. Each population was characterized according to morphology, surface markers, granulocytic colony formation in semi‐solid media, and stainable RNA content by acridine orange (AO) flow cytometry. These techniques enrich for a population of cells that is characterized by a lymphoid morphology, a high granulocytic‐macrophage progenitor cell cloning efficiency, a lack of surface markers, and a high stainable RNA content not found in the other two populations of peripheral blood lymphocytes (T cells and B cells). The stainable RNA content serves as a new metabolic marker for the population of cells in which the preponderance of granulocytic progenitor cells reside.
A factor V inhibitor: In vitro interference by calcium
Authors: Coots Macie C. , Muhleman Albert F. , Glueck Helen I.
Published: February 2007

A patient with a factor V inhibitor resistant to all standard methods of therapy was recently reported. Because of this resistance, further investigation of the inhibitor was carried out employing the inhibitory plasma, serum, and isofocused fraction. It has subsequently been shown in vitro by use of the prothrombin time, partial thromboplastin time, and Russell's viper venom time that the activity of the inhibitor is diminished by the addition of calcium chloride or calcium gluconate to the inhibitory plasma, serum, or isofocused fraction before the addition of normal pooled plasma. This inhibitor, an IgG4 (λ) immunoglobulin appears to have a high calcium binding affinity and is markedly potentiated in acid pH.

These findings suggest that there may be a role in vivo for calcium infusion as part of the clinical management of such an inhibitor and that the metabolic acidosis associated with hemorrhagic shock may potentiate this type of inhibitor.
Bone marrow necrosis
Authors: Conrad Marcel E. , Carpenter John T.
Published: February 2007

Bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with poor prognosis. In contrast, we believe that it is a commonplace finding in bone marrow specimens which is frequently overlooked and which occurs in patients with multiple acute and chronic disorders. It is postulated that bone marrow necrosis eventuates from vascular occlusion of small blood vessels as a result of a number of causes. When bone marrow necrosis is prolonged, it may be associated with the development of bone marrow fibrosis and serve as a predisposing lesion for idiopathic myelofibrosis. Additional investigation of this phenomenon is required to determine its usefulness in the diagnosis of disease states and its role in the pathophysiology of a number of disorders.
Quinine protects pyruvate‐kinase deficient red cells from dehydration
Authors: Koller Charles A. , Orringer Eugene P. , Parker John C.
Published: February 2007

Pyruvate kinase deficient red blood cells have an abnormal tendency to lose ATP when exposed to low pO2 or cyanide, whereas normal red cells do not. Once energy is depleted, all red cells take up calcium and subsequently lose intracellular potassium and water. It has been shown previously that quinine will inhibit the potassium and water flux seen in energy depleted normal cells. The present study indicates that quinine protects cyanide treated pyruvate kinase deficient erythrocytes from water and potassium loss. Quinine does not prevent ATP depletion or calcium uptake. By six hours, cyanide treated pyruvate kinase deficient cells have lost an average of 486 gm of water per kilogram cell solids and 140 mmoles of potassium per kilogram of cell solids, while cells treated with both quinine and cyanide have lost only 106 gm of water per kilogram of cell solids and 77 mmoles of potassium per kilogram of cell solids.

These data support the concept that the membrane lesion in pyruvate kinase deficiency is secondary to ATP depletion and is a manifestation of the Gardos effect. Quinine may have therapeutic potential in the treatment of pyruvate kinase deficiency hemolytic anemia.
Microcapillary agglutination assay for detection of specific antileukocyte reactivity in neutropenic patients
Authors: Smith Wade K. , Mold James W. , Tseng Susan L. , Burton Nadine N.
Published: February 2007

Serum leukoagglutinating activity against the leukocytes of four patients with neutropenia was demonstrated using a modified microcapillary agglutination test. Cells from a panel of donors proved useful in attempting to define the identity of the antigens involved. In one instance anti‐HLA‐A9 activity could be demonstrated in a patient possessing HLA‐A9. In the other three individuals no definite antigen assessment to HLA Series A and B antigens or the Lalezari series of neutrophil antigens could be made. Two of the patients' sera showed cross‐reactivity and may be reactive with the same antigen or antigenic group. The microcapillary agglutination test appears to be useful in the evaluation of possible cases of autoimmune neutropenia.
The Chediak‐Higashi syndrome: Microtubules in lmonocytes and lymphocytes
Authors: White James G. , Clawson C. C.
Published: February 2007

Recent investigations of Chediak‐Higashi syndrome (CHS) leukocytes have suggested that defective cell function and formation of giant granules may be due to an inability of the cells to assemble microtubules because of an abnormality in synthesis of cyclic 3′, 5′‐guanosine monophosphate (cGMP). In the present study we have examined normal and CHS lymphocytes and monocytes for the presence and frequency of centriole‐associated microtubules. No statistically significant differences between the mean numbers of centriole associated microtubules in normal and CHS monouclear cells could be detected. Results of the study fail to support the hypothesis that microtubule assembly is a fundamental defect in all CHS leukocytes.
Acute myeloblastic leukemia following treatment for non‐hematopoietic cancers: Report of 19 cases and review of the literature
Authors: Zarrabi M. Hosein , Rosner Fred
Published: February 2007

Nineteen patients are reported who developed acute myeloblastic leukemia following treatment for a variety of solid tumors, including seminoma (four cases), melanoma (one case), and cancer of the ovary (six cases), colon or rectum (three cases), bladder (two cases), cervix, endometrium, and larynx (one case each). There were nine men and ten women, with a median age of 49.8 years (range 29 to 75). The mean interval between the diagnosis of solid tumors and acute leukemia is 5.8 years. In two patients the two diseases occurred simultaneously or within six months of each other.

One patient was treated only surgically. Eight patients were treated with radiotherapy, five with chemotherapy, and five received both chemotherapy and radiotherapy. Pancytopenia was commonly noted prior to the onset of leukemia with chromosomal abnormalities observed in four cases in which a karyotype was performed. Three patients achieved complete hematological remission following antileukemic therapy.

One hundred and six additional patients with non‐hematopoietic neoplasms and acute leukemia are reviewed. Although acute leukemia may occur in a higher than expected frequency in patients with solid tumors because of a possible increased risk of a second neoplasm, it seems more likely that the acute leukemia is related to the radiotherapy and/or chemotherapy administered to treat the first neoplasm.
Ocular complications following blast transformation in chronic myelogenous leukemia
Authors: Hendrick Alex M. , Rogers John S. , Guliner Robert J.
Published: February 2007

A number of ocular problems compromising vision occurred in a patient with chronic myeloid leukemia following blastic transformation. Hemorrhagic retinopathy developed with systemic relapse and resolved with control of systemic disease. Optic nerve involvement occurred with meningeal leukemia and was controlled with intrathecal cytosine arabinoside and methotrexate. Leukemic retinal infiltrates developed despite control of systemic and meningeal disease and were successfully treated with radiation therapy. Finally, bilateral vitreous hemorrhages occurred, severely impairing vision.

Leukemic infiltration of the eye may occur with increasing frequency in CML as the survival following blastic transformation improves. Infiltration should be recognized and treated promptly if serious loss of vision is to be avoided. Central nervous system prophylaxis should be considered in patients achieving a complete response following therapy for transformation.
Acute promyelocytic leukemia
Authors: Groopman Jerome , Ellman Leonard
Published: February 2007

Acute promyelocytic leukemia (APL) is characterized by proliferation of morphologically abnormal promyelocytes and a severe bleeding diathesis. The abnormal promyelocyte is characterized by abundant, large granules, many of which are spindle‐shaped. Electron microscopic appearance of the granules closely resembles that of Auer rods. The granules appear to possess tissue thromboplastin activity by both immunologic and clotting assays. Coagulation studies in APL are generally consistent with disseminated intravascular coagulation. Prolongation of the prothrombin time and elevation of fibrinogen degradation products are the tests that are most commonly abnormal. Although occasional reports indicate a favorable response of the coagulopathy to drugs that inhibit fibrinolysis, the use of prophylactic heparin appears to be the treatment of choice. The response rate of APL to chemotherapy regimens that contain an anthracycline is comparable to that of acute myelogenous leukemia. The recent description of the 15;17 chromosomal translocation which may be pathognomonic for APL is only the second example of a chromosomal marker of human neoplasia. Marked elevation of serum vitamin B12 and B12 binding proteins appears to be another characteristic feature of APL. An in vitro cell line of APL cells has been demonstrated to have the capacity to differentiate to functional polymorphonuclear leukocytes, but the cause for the maturation arrest is unknown.
Studies of marmoset megakaryocytopoiesis in vitro
Authors: Burstein Samuel A. , Breton‐Gorius Janine , Harker Laurence A.
Published: February 2007

Liquid culture of the mononuclear fraction of the blood of marmosets without any added stimulator resulted in the appearance of megakaryocytes. These cells could not be identified by light microscopy or by indirect immunofluorescence using antiplatelet antiserum. Ultrastructural idetification was made using platelet peroxidase. Some megakaryocytes demonstrated sparse but detectable demarcation membranes, early granule formation, and platelet formation.

The results indicate that marmoset megakaryocytic progenitor cells circulate and can begin to differentiate in vitro, although unstimulated liquid culture conditions do not promote the development of the usual light‐microscopic features of differentiation.
Homozygous hemoglobin E mimics β‐thalassemia minor without anemia or hemolysis: Hematologic, functional, and biosynthetic studies of first north American cases
Authors: Fairbanks Virgil F. , Oliveros Rhaiza , Brandabur Joseph H. , Willis Richard R. , Fiester Richard F.
Published: February 2007

A young American woman of Thai ancestry living in Ohio and a man of Vietnamese origin living in Iowa are believed to be the first recognized hemoglobin E homozygotes residing in the western hemisphere. Both were clinically well and exhibited neither pallor nor icterus nor splenomegaly. Their blood exhibited marked microcytosis and mild erythrocytosis. Hemoglobin was 99% E and 1% F, 97% E and 3% F, respectively. These features were similar to those previously reported from Southeast Asia and Madagascar in the few well‐documented reports of homozygous hemoglobin E. A 51Cr erythrocyte survival study indicated a normal t1/2 of 28 days. Also demonstrated were minimal decrease in whole blood O2 affinity and increased ratio of α/non‐α globin chain synthesis. Mild hemolytic anemia is not, as usually stated, a feature of this condition, which closely mimics a very mild thalassemia minor. Anemia, when found with high proportions of hemoglobin E, should not be attributed to the homozygous hemoglobinopathy. Persons with homozygous hemoglobin E should be reassured as to its benign implications.
Interaction of the β chain variant hemoglobin leslie and the α chain variant hemoglobin montgomery in a black female
Authors: Huisman T. H. J. , Gravely M. E. , Wilson J. B. , Webber B. , Felice A. E. , Miller A.
Published: February 2007

A black family is described in which the β chain variant hemoglobin Leslie, the α chain variant hemoglobin Montgomery, and α‐thalassemia‐2 occurred in different combinations. All members studied had normal hematological values and no chronic ill health. The propositus had 11% hemoglobin Montgomery, 24% hemoglobin Leslie, and only about 0.5% of the Hb Montgomery–Leslie hybrid. The mother of the propositus was a Hb Leslie heterozygote with 31% Hb Leslie. Her father had 26% and her son had 17% Hb Montgomery, suggesting that the father is heterozygous for α‐thalassemia‐2; this designation was supported by data from in vitro biosynthetic studies. The β‐Leslie chain generally shows reduced ability to pair with the normal α chain. However, in the propositus, who is heterozygous for both variants, the assembly of β‐Leslie and α‐Montgomery chains might be reduced even more, and the instability of the Hb Montgomery‐Leslie hybrid appears much greater than was expected.
Acceleration of F‐cell production in response to experimentally induced anemia in adult baboons (Papio cynocephalus)
Authors: Nute Peter E. , Papayannopoulou Th. , Chen P. , Stamatoyannopoulos G.
Published: February 2007

Changes in levels of fetal hemoglobin and Hb F‐containing erythrocytes (F‐cells) were monitored in adult baboons (Papio cynocephalus) rendered acutely anemic by phenylhydrazine or phlebotomy, or chronically anemic by a combination of both forms of treatment. The highest levels of Hb F were observed in acutely anemic animals from 21 to 29 days after initiation of treatment and represented 2.2‐ to 5.6‐fold increases over levels measured prior to induction of anemia. Changes in F‐cell levels correlated well with changes in proportions of Hb F (r = 0.89), and peak F‐cell levels exceeded initial levels by factors ranging from 6 to 11.7. These data confirm previous findings and indicate that adult baboons respond to severe anemic stress by producing increased numbers of Hb F‐containing cells. Thus, P cynocephalus appears to be a suitable model for the study, in vivo, of Hb F regulation in man, since it is likely that changes in Hb F production are mediated by similar mechanisms in both species.
Combination chemotherapy for acute lymphocytic leukemia in adults: Results of a retrospective study in 82 patients
Authors: Amadori Sergio , Montuoro Aldo , Meloni Giovanna , Spiriti Maria Antonietta Aloe , Pacilli Leonardo , Mandelli Franco
Published: February 2007

Since 1970, 82 previously untreated adult patients with acute lymphocytic leukemia (ALL) were treated for induction of remission with combination chemotherapy either including vincristine and prednisone (18 patients), vincristine, prednisone and daunomycin (27 patients), or vincristine, prednisone, and asparaginase (37 patients). Upon achievement of complete remission patients were started on continuous maintenance with daily mercaptopurine, weekly methotrexate, and periodic vincristine and prednisone reinforcement pulses. Central nervous system prophylaxis consisted of six weekly intrathecal injections of methotrexate and prednisone given during induction, followed by monthly doses during maintenance. Overall, 55 of the 82 patients (67%) achieved complete remission; the addition of daunomycin or asparaginase to vincristine and prednisone did not significantly improve the response rate. Severe myelosuppression was common, being responsible for the death of 23 patients during induction. The predicted median duration of remission was 25 months, with 24 patients continuing in remission after 3.5–60 months. Duration of remission was significantly shorter in those patients who initially had a peripheral blood count greater than 50 × 109/liter. The predicted median survival was 39.5 months in those who achieved remission, less than one month in those who did not, and 12 months overall.
Diamond‐blackfan anemia: The role of immunoglobulin blocking factor in remission
Authors: Steinberg Martin H. , Coleman Mary B. , Pennebaker James B.
Published: February 2007

Some patients with Diamond‐Blackfan syndrome may have suppressor T‐cells responsible for the failure of normal erythropoiesis. The capacity of Diamond‐Blackfan syndrome mononuclear cells to react in mixed leukocyte culture to the stimulus of nucleated red cells was tested using bone marrow as the cell source. In all but one instance, Diamond‐Blackfan mononuclear cells and cells from normal or a multiply‐transfused control showed similar degrees of stimulation. Patient mononuclear cells reacted normally to phytohemagglutinin (PHA). The presence of a cytotoxic effect of Diamond‐Blackfan mononuclear cells on normal nucleated red cells was examined using a 59Fe‐release assay. There was no evidence for lymphocyte‐mediated erythroid cytotoxicity. Immunoglobulins (Ig) were removed from Diamond‐Blackfan serum by affinity chromatography. Erythroid burst‐forming units (BFU‐E) failed to grow normally in Ig‐depleted patient autologous serum, but growth failure was reversed when Ig eluted from the affinity column was added back to the culture. Diamond‐Blackfan Ig added to autologous mononuclear cells in the absence of autologous serum normalized colony growth. T‐cells of some Diamond‐Blackfan syndrome patients may suppress BFU‐E growth, but they do not react abnormally in mixed leukocyte culture to nucleated erythroid cells and are not cytotoxic for erythroblasts under our conditions of study. The serum‐blocking factor in our patients appears to be an Ig that promotes BFU‐E generation despite the presence of suppressor T‐cells. Although it cannot be proved, this may be related to the remission of disease in our patients.
Calmodulin, zinc, and calcium in cellular and membrane regulation: An interpretive review
Authors: Brewer George J.
Published: February 2007

A considerable amount of work in recent years has indicated that the intracellular effects of calcium are mediated primarily by calcium‐binding proteins. One of the most important of these proteins is a 17,000‐molecular weight protein–calmodulin. Calmodulin, when activated by calcium, has the potential to activate many enzymes and to stimulate many intracellular events. While calcium is required for many types of cellular activations, zinc tends to be a cellular inhibitor. It appears that zinc is antagonistic to calcium, tending to inhibit the same cellular reactions triggered by an influx of intra‐cellular calcium. Recent investigations have led us to hypothesize that the zinc‐calcium antagonism mentioned above may be the result of inhibitory effects of zinc on calmodulin‐stimulated functions. This inhibition may operate through binding of zinc to the target proteins of calmodulin or through binding of zinc to calmodulin after the calmodulin is complexed to protein. This area will be reviewed in the first part of this paper.

In the erythrocyte, excessive intracellular calcium causes hemoglobin retention by erythrocyte membranes and causes erythrocyte shrinkage. Both of these events may occur in sickle erythrocytes because of sickling‐induced calcium accumulation. Recent studies suggest that excessive calcium‐activated calmodulin may be responsible for both hemoglobin retention by the membrane and for erythrocyte shrinkage. On the other hand, trifluoperazine — a phenothiazine drug that inhibits the action of calmodulin — causes erythrocyte swelling (membrane expansion). These observations have led us to hypothesize that calmodulin is intimately involved with regulation of the erythrocyte membrane expansion/shrinkage state. The possible role of excessive calcium‐activated calmodulin in inducing abnormalities in the sickle membrane may lead to a more rational therapy aimed at the membrane lesion in this disease. This therapy might involve a combination of inhibitory agents such as zinc and a phenothiazine.

In the last part of the review, we present a model for the regulation of membrane shrinkage by calmodulin in equilibrium with membrane expansion by spectrin‐actin phosphorylation. Whether or not this model is right in its basic elements, we hope it will provoke some additional thinking and experimental work. In fact, this entire review should be viewed as interpretive. That is, observations from diverse sources have been put together in an attempt to make sense out of them and, in particular, to provoke thinking and stimulate experimental work in these areas.
Inhibition of platelet aggregation with histamine
Authors: Mazza Joseph J. , Gatlin Patience F. , Marx James J.
Published: February 2007

A sensitive in vitro technique was used to demonstrate the inhibitory effects of histamine on human blood platelets. Platelet aggregation by epinephrine was completely inhibited at 10−3 M concentrations of histamine. Persistent elevations of cyclic AMP levels were shown to occur in the platelets when histamine was added and corresponded to the inhibitory effects on platelet aggregation. In contradistinction to the analogous inhibitory effects by histamine on other cellular elements of the hematopoietic system, this inhibitory effect on platelets could not be blocked by equimolar concentrations of either of the classes of histamine antagonists presently available. It is suggested that there may be other additional histamine receptors on the surface of membranes of platelets or that histamine mediated its inhibitory effect on platelets through a mechanism other than surface receptors.
Red cell indices in normal adults residing at altitudes from sea level to 2670 meters
Authors: Ruíz‐Argüelles G. J. , Sánchez‐Medal L. , Loría A. , Piedras J. , Córdova M. S.
Published: February 2007

Hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBCs), mean cell volume (MCV), and mean cell hemoglobin concentration (MCHC) were measured by a single operator in a single laboratory by means of an electronic particle counter in 942 healthy adults (491 females and 451 males) residing at five altitudes: 0, 1000, 1860, 2220, and 2670 meters above sea level. The subjects were carefully screened clinically, and subjects with low transferrin saturation ( < 15%) were excluded.

In both sexes there was a differential behavior as a function of altitude, of Hb and PCV on the one hand, and number of RBCs on the other. The findings suggest the presence of two sequential mechanisms of adaptation to progressively lower atmosphere oxygen pressure: One operating from sea level to 1860 meters, which leads to a progressively increasing number of relatively microcytic RBC; and a second one – from 1860 to 2670 meters – in which there is an increased but constant number of progressively more normocytic RBC, so that a simplistic model of equal magnitude increases in the three parameters and is seen at 2670 meters, but not at the intermediate altitudes. The middle group's comparativity, essential to these interpretations, apparently was achieved with regard to time elapsed between sampling and testing and with regard to the people integrating the groups.
A new density gradient system for the separation of human red blood cells
Authors: Vettore Luciano , De Matteis Maria Concetta , Zampini Patrizia
Published: February 2007

A new density system for the separation of human red blood cells by density‐gradient centrifugation is described.

The gradient medium is made with colloidal silica particles coated with polyvinylpyrrolidone suspended in aqueous solution of meglamine diatrizoate.

By this method, more than 10 red‐cell fractions can be separated. These show different ages (by creatine content and 59Fe in vivo labelling) and different characteristics (ie, potassium content). A 40‐fold enrichment in reticulocytes can be obtained in the top layers, with a great improvement of specific activity in labelling procedures of newly synthesized globin chains.

The method is simple, rapid, inexpensive, reliable, nontoxic for erythrocytes, and is suitable for globin synthesis and other studies of erythrocyte metabolism.
Congenital neutropenia: Studies of pathogenesis
Authors: Chusid Michael J. , Pisciotta Anthony V. , Duquesnoy Rene J. , Camitta Bruce M. , Tomasulo Peter A.
Published: February 2007

Congenital neutropenia (CN) was diagnosed in a five‐month‐old boy. A variety of studies was performed to define the pathogenesis of his disease. Opsonic antineutrophil antibodies were present in his serum. Transfused normal granulocytes circulated poorly. Incubation of the patient's serum with normal granulocytes failed to alter their metabolic or functional activity. The patient's marrow demonstrated increased numbers of colony‐forming units (CFUs) in vitro compared with control marrow. The patient's parents had low marrow CFU activity. The patient's serum and peripheral lymphocytes failed to inhibit normal marrow CFU activity. The patient's marrow did inhibit CFU growth of an HLA‐identical‐sibling's marrow in coculture. Histocompatibility studies demonstrated the HLA‐B12 antigen in this patient, a histocompatibility marker previously associated with CN. These studies suggest some cases of CN are associated with a genetically transmitted marrow factor capable of suppressing myelopoiesis in normal marrow.
Heterogeneity of hypogammaglobulinemia
Authors: Miller Michael E.
Published: February 2007

In 1952, Ogden Bruton described the first patient with recurrent infections and hypogammaglobulinemia [1]. For many years thereafter, hypogammaglobulinemia (or agammaglobulinemia) was believed to result from a deficiency (or absence) of the antibody‐producing cells, or “B” cell line of the lymphoid system. With increased recognition of functional subpopulations of the lymphoid system, however, it has become apparent that a variety of mechanisms may result in the phenotype of hypogammaglobulinemia. Since these entities may be clinically indistinguishable, it is important to understand the various categories of disease which may be involved. In this concise review, these areas are briefly summarized, More complete reviews of the subject (including acquired forms of immunodeficiency) are available [2, 3].
Bone marrow lipids in normal and anemic mice
Authors: Potter Jane E. R. , Wright Eric G.
Published: February 2007

The lipids in the bone marrow of six strains of normal mice, and mice with genetically determined anemias (W/Wv and S1/S1d) and experimentally induced anemia were analyzed. Cholesterol and phospholipid accounted for 60–75% of total lipid; the remainder was triglyceride and neutral glyceryl ether lipids. In mice with phenylhydrazine (PHZ)‐induced hemolytic anemia there was a threefold increase in neutral glyceryl ether lipids immediately preceding a twofold increase in recognizable erythroid precursors.

Comparisons were made between the femoral bone marrow and the cells maintained in the adherent populations of long‐term bone marrow cultures. In cultures of B6D2F1 bone marrow (which support long‐term proliferation and differentiation of hemopoietic stem cells) the adherent layers contained the same lipids as freshly aspirated bone marrow. In W/Wv and S1/S1d cultures (which duplicate, respectively, the stem cell and environmental defect found in vivo) the lipid content of the adherent layers differed from bone marrow, particularly in the absence of ether‐containing lipids.

The results are consistent with the hypothesis that marrow lipids have an active (as opposed to passive) role in murine hemopoiesis and indicate that long‐term bone marrow culture may prove useful in further biochemical studies of the hemopoietic inductive microenvironment.
Lymphopenic response of patients presenting with chronic lymphocytic leukemia associated with carcinoma of the prostate to diethylstilbestrol: Correlation of response to the in vitro synthesis of rna by patient lymphocytes and its relationship to transcortin
Authors: Narasimhan Parthasarathy , Amaral Leonard
Published: February 2007

Three patients with chronic lymphocytic leukemia (CLL) and carcinoma of the prostate were treated for the latter condition with diethylstilbestrol (DES). All three patients responded with rapid reductions in their peripheral white counts. The previously observed lymphocytic infiltration of the bone marrow of one patient was not evident after three months of DES treatment. The response of this patient to DES correlates well with the enhanced level of plasma transcortin subsequent to treatment. Treatment of this patient with DES alters the ability of peripheral lymphocytes to incorporate radioactive uridine into RNA as well as the in vitro response to either cortisol or β‐estradiol.
The first stable variant of erythrocyte glucose‐phosphate isomerase associated with severe hemolytic anemia
Authors: Zanella A. , Izzo C. , Rebulla P. , Perroni L. , Mariani M. , Canestri G. , Sansone G. , Sirchia G.
Published: February 2007

A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described. The defective enzyme showed increased affinity for fructose‐6‐phosphate (F‐6‐P), decreased affinity for glucose‐6‐phosphate (G‐6‐P), altered electrophoretic and isoelectrofocusing patterns, and shift to the left of the precipitin curve. The enzyme was stable under all the conditions tested (heat, urea, guanidine‐HCl, and storage). Optimum pH, Ki for 6‐phosphogluconic acid (6‐PGA) and for erythrose‐4‐phosphate (E‐4‐P), molecular weight, GPI‐related antigen concentration, immunodiffusion pattern, and immunoinactivation were in the normal range. This is the first example of the association of a stable mutant GPI with severe hemolytic anemia. Enzyme instability has been present in all previously reported cases.
Platelet interaction with bacteria. VI. Contrasting the role of fibrinogen and fibronectin
Authors: Clawson C. C. , White James G. , Herzberg Mark C.
Published: February 2007

The roles of fibrinogen and fibronectin were contasted in the responses of human platelets to Staphylococcus aureus and collagen. Congenital afibrinogenemic (CA) platelets and washed normal platelets had delayed aggregation due to a prolonged latent phase in response to contact with the bacteria when fibrinogen was absent from the suspending media. When a physiologic level of human fibrinogen was added to the CA platelets in autologous plasma or to the washed platelets in balanced saline, the times to aggregation were significantly shortened (P < 0.05) and restored to rates comparable to those of normal platelets in whole plasma. In contrast, the presence or absence of fibrinogen in the media had no significant effect on the initial adherence and shape‐change response of CA or washed platelets to collagen. Platelets with a demonstrated aberration of fibronectin responded normally to all ratios of S aureus, but they responded only to doses of collagen that were several times the threshold levels for normal platelets. These results demonstrate an important role for fibrinogen as a cofactor in platelet interactions with S aureus and indicate that fibronectin is not a major factor in the responses of human platelets to this microorganism.
31P NMR spectroscopy of erythrocytes in congenital hemolytic anemias: Detection of heterogeneous erythrocyte populations and quantification of intracellular 2,3‐diphosphoglycerate
Authors: Labotka Richard J. , Honig George R.
Published: February 2007

Phosphorus‐31 nuclear magnetic resonance (NMR) spectra were determined from intact erythrocytes of a patient with homozygous β‐thalassemia and from three patients with pyruvate kinase (PK) deficiency.

The intracellular 2,3‐diphosphoglycerate‐(2,3‐DPG) were mildly elevated in the thalassemia patient and in PK heterozygotes, and were markedly elevated in the PK‐deficient homozygotes. The 2,3‐DPG chemical shifts in the patients' NMR spectra were consistently positioned at a higher magnetic field than normal. When the patients with thalassemia or PK deficiency were transfused with blood from a normal donor, or when a patient's erythrocytes were mixed with normal erythrocytes, two distinct sets of 2,3‐DPG resonances appeared in the resulting spectra, allowing the simultaneous quantification of the 2,3‐DPG levels in each erythrocyte population. The ability of NMR to detect heterogeneous cell populations may be useful for the diagnosis of congenital hemolytic anemias in patients who have been transfused.
Infectious mononucleosis and acute lymphoblastic leukemia—hand mirror cells: A qualitative and quantitative ultrastructural study
Authors: Schumacher H. R. , Thomas W. J. , Creegan W. J. , Pitts L. L.
Published: February 2007

The hand mirror cell (HMC) in infectious mononucleosis (IM) is a T cell which appears at the time of improvement and apparently has an important role in immune surveillance. Fifty electron micrographs of HMC from an unusual untreated patient with ALL‐HMC variant were compared to 50 electron micrographs of HMC from five patients beginning to recover from IM. Quantitative differences between the IM‐HMC and ALL‐HMC were observed in multivariate analysis of variance (p < 0.001), nuclear perimeter (p < 0.0001), nuclear length (p < 0.0001), cytoplasmic length (p < 0.0001), total cell area (p < 0.0001), cytoplasmic area (p < 0.0001) and nuclear cytoplasmic ratio (p < 0.004), and numbers of mitochondria (p < 0.001). The qualitative differences included greater nuclear irregularity in the IM‐HMC, and prominent nucleolonema in some of the ALL‐HMC. In addition, the IM‐HMC showed more polyribosomes, parallel tubular arrays and microtubules, but much less glycogen. Since the IM‐HMC apparently enter effectively into immune surveillance, and some cases of ALL have HMC, the ultrastructural similarities and differences above contribute to a better understanding of the importance of this unique cell configuration in benign and malignant disorders.
Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency
Authors: Crist William M. , Parmley Richard T. , Holbrook C. Tate , Castleberry Robert P. , Denys Francis R. , Malluh Ahmad
Published: February 2007

Neutropenia and/or leukopenia (associated with elevated serum lysozyme levels) in three children with vitamin B12 deficiency were evaluated using soft agar culture and ultrastructural and cytochemical techniques. In two patients a marked increase in peripheral blood myeloid colony forming cells (CFC) was observed; whereas a marginal increase in CFC was present in the third, less symptomatic, patient. Marrow CFC was normal or slightly increased. Serum colony stimulating activity (CSA) was normal but elaboration of CSA by white blood cells was low. Normal maturation of the progenitors was present in vitro and serum inhibitors of myelopoiesis were absent.

Megaloblastic neutrophils and monocytes with nuclear‐cytoplasmic asynchrony were observed ultrastructurally in directly sampled marrow specimens. These cells contained autophagic and/or heterophagic vacuoles and an increase in cytoplasmic granules. Both monocytes and neutrophils also contained enlarged‐disrupted centrioles. Many marrow macrophages contained phagocytic vacuoles, which enclosed disrupted neutrophils and cellular debris.

We conclude that although a large number of dysmorphic myeloid cells degenerate in the marrow, sufficient marrow CFC are present and peripheral blood CFC are elevated, suggesting abnormal release and/or maturation failure. All of these abnormalities are corrected by administration of vitamin B12.
A patient with apparent idiopathic A‐megakaryocytic thrombocytopenia
Authors: Kim Hyoung D. , Boggs Dane R.
Published: February 2007

A 71‐year‐old woman developed life‐threatening thrombocytopenia which resolved (probably spontaneously), recurred, and then again resolved. The thrombocytopenia was characterized by selective aplasia of megakaryocytes, near‐normal platelet survival, and very slow recovery. No underlying disorder nor any drug could be incriminated, so we must assume this patient suffered from an idiopathic and very rare form of thrombocytopenia.
Diurnal changes in circulating myeloid progenitor cells in man
Authors: Verma Dharmvir S. , Fisher Richard , Spitzer Gary , Zander Axel R. , McCredie Kenneth B. , Dicke Karel A.
Published: February 2007

To examine the diurnal changes in circulating myeloid progenitor cells (CFU‐Cs), 15 normal human volunteers were studied. Total and differential peripheral blood leukocyte counts and CFU‐C levels, using the in vitro agar culture method, were obtained at 8 AM, 11 AM, 3 PM, and 8 AM the following morning (in nine subjects) or only at 8 AM and 3 PM (in six subjects). On the average, an approximate twofold rise in circulating CFU‐C levels (per ml of blood) was found at 3 PM as compared to the 8 AM levels (P 0.002), and a smaller rise at 11 AM was found than at 8 AM levels (P 0.03). The ratios of CFU‐C per ml of blood to mononuclear cells per ml of blood and neutrophils per ml of blood, respectively, were significantly higher at 3 PM than at 8 AM (P 0.002 and 0.004, respectively). The rise in CFU‐C levels is usually significantly higher when compared to that in peripheral leukocyte counts.
Chronic idiopathic neutropenia: Granulopoietic assessment by both marrow culture and granulocyte kinetics
Authors: Rickard K. A. , Brown R. D. , Yuen E. , Kronenberg H.
Published: February 2007

Granulopoietic assessment was made in 14 patients with chronic idiopathic neutropenia (CIN) whose neutrophils were consistently less than 1.5 × 109/ liter and in whom there was absence of splenomegaly and recent drug ingestion. Granulopoiesis was studied using a combination of bone marrow culture in nutrient agar and granulocyte kinetics. Agar colony growth assessed bone marrow concentration of granulocyte progenitor cells (GPC) and the proportion of GPC in DNA synthesis by in vitro 3HTdR suicide. Granulocyte kinetics with in vitro DF32P labelling of patient granulocytes measured granulocyte half‐life (T1/2), turnover rate (GTR), and the circulating, marginated, and total blood granulocyte pools. The results indicated that either GPC concentration or the proportion of GPC in DNA synthesis was outside the normal range in all but one patient and decreased in ten out of 14 patients. CIN was also characterized by reduced total, circulating, and marginated blood granulocyte pools, reduced GTR, and normal granulocyte half‐life. The neutropenia appeared to be due to a variety of intra‐marrow causes, including either a reduction in the GPC compartment, a reduction in GPC proliferation, a maturation arrest, or a reduced amplication during granulopoiesis. Increased granulocyte utilization, intra‐vascular destruction or excessive margination could be excluded as possible causes of CIN in this series. Although GPC parameters tended to be reduced, suggesting a production defect, there were signs in nine patients that the bone marrow was attempting to compensate for the peripheral neutropenia. It is suggested that for a complete assessment of granulopoiesis in man, granulocyte kinetic studies need to be combined with quantitative studies of the bone marrow granulocyte progenitor compartment using the agar colony system.
Successful doxorubicin therapy of primary macroglobulinemia resistant to alkylating agents
Authors: Clamon Gerald H. , Corder Michael P. , Burns C. Patrick
Published: February 2007

Two patients with macroglobulinemia refractory to alkylating agent therapy did have an objective response to therapy with doxorubicin. For patients refractory to alkylating agents, doxorubicin is an alternative to other alkylating agents or procarbazine.
Recent advances in the quantitation of human fetal hemoglobins with different gamma chains
Authors: Huisman T. H. J. , Wilson J. B.
Published: February 2007

Three types of γ chain of human hemoglobin (Hb) F have been discovered. The γ and Aγ chains differ at position 136 (glycine in Gγ; alanine in Aγ) and are the products of nonallelic genes. The Tγ chain is found in rather high frequency in certain world populations, and is characterized by a threonyl residue at position 75 replacing the commonly occurring isoleucyl residue. Convincing evidence is present that the Tγ chain is the product of an allele of the Aγ chain gene, and should be renamed AγT chain. Thus, the three γ chains are GγI, AγI, and AγT.

Until recently, the presence and the quantity of these chains were determined by chemical analyses of the tryptic peptides of the isolated Hb F. These procedures involve chromatographic separations or fingerprinting methods. The introduction of high pressure liquid chromatography (HPLC) has greatly facilitated the separation of these peptides. Since minute quantities are required, the latter method is ideally suited for the identification of the Hb F produced in in vitro cell colonies.

Electrophoretic and chromatographic (HPLC) methods have been developed which make it possible to separate the Gγ and Aγ chains in small amounts of Hb F (less than 0.5 mg). These procedures allow accurate quantitation of the Gγ/Aγ ratio in the Hb F and may also be suitable for in vitro biosynthetic analyses. One of the HPLC procedures has been modified so that the three types of γ chain can be quantitated in one single chromatographic experiment. Examples of separations are provided, details of some of the methods are discussed, and their applicability illustrated.
Fibrinogen houston: A dysfibrinogen exhibiting defective fibrin monomer aggregation and α‐chain cross‐linkages
Authors: Weinger Ronald S. , Rudy Christine , Moake Joel L. , Conlon Charles L. , Cimo Philip L.
Published: February 2007

A 38‐year‐old male patient with a life‐long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin‐induced platelet aggregation of gel‐separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of Aα, Bβ and γ‐polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin‐induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded α‐α polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the addition of streptokinase).
The pennsylvania hemophilia program 1973–1978
Authors: Eyster M. Elaine , Lewis Jessica H. , Shapiro Sandor S. , Gill Frances , Kajani Mehdi , Prager David , Djerassi Isaac , Rice Samuel , Lusch Charles , Keller Anne
Published: February 2007

In Pennsylvania, the prevalence of hemophilia is one per 10,000 males. Factor VIII deficiency is five times more frequent than Factor IX deficiency, and 34% of the patients have no relatives affected with the disease. The mean age is 23 years old, and 50% of the patients are less than 20 years old. Approximately one‐third of the patients with Factor VIII deficiency and one fourth of the patients with Factor IX deficiency have levels of < 0.01 μ/ml. By clinical criteria, 55% of those with Factor VIII deficiency are severe compared to 45% of those with Factor IX deficiency. Factor VIII‐deficient patients are treated an average of 18 times per year compared to ten times per year for patients with Factor IX deficiency. Hemarthroses account for 70% of the hemorrhages treated and for 40% of the concentrate usage. Home therapy patients use an average of 45,950 Factor VIII units per year at a cost of $4,170 per patient and their use accounts for 60% of the total Factor VIII usage of 1.7 million units. Less than five days per patient per year are lost from school or work because of bleeding, and patients are hospitalized for bleeding an average of only two to three days per patient per year. Adverse immediate reactions to therapy are infrequent. Five percent of patients have persistence of the hepatitis B virus, and 7.5% have inhibitors. The mortality rate is 0.04% per year, with half of the deaths being hemophilia‐related.
Terminal deoxynucleotidyl transferase in the blastic phase of chronic myelogenous leukemia: An indicator of response to vincristine and prednisone therapy
Authors: Tanaka Masao , Kaneda Tsuguhiro , Hirota Yutaka , Yoshida Shonen , Kitajima Koichi
Published: February 2007

Terminal deoxynucleotidyl transferase (TdT) activity was assayed in leukemic cells of 34 patients in blastic phase of Philadelphia‐positive chronic myelogenous leukemia (CML). The TdT levels were correlated with the response to vincristine and prednisone therapy. None of 20 TdT‐negative patients, but 10 of 14 TdT‐positive patients responded to vincristine and prednisone. There was poor correlation between blast cell morphology and response to this therapy. This study confirms that TdT levels in the majority of patients predict effectiveness of vincristine and prednisone therapy in blastic phase of CML.