bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal hemoglobins in a quarter million people
Authors: Schneider RG , Hightower B , Hosty TS , Ryder H , Tomlin G , Atkins R , Brimhall B , Jones RT
Published: October 2019

Hemolysates of erythrocytes from more than a quarter million people in Alabama were electrophoresed on cellulose acetate, pH 8.4, and those samples exhibiting an abnormality were also electrophoresed in citrate agar, pH 6.0. The globin chains of mutants other than Hb S and C were electrophoresed in urea-mercaptoethanol buffers at both pH 8.9 and pH 6.0, and 60 of them were also analyzed structurally. Of about 6000 samples from whites, only three contained abnormal hemoglobins--Hb D Los Angeles, Hb J Baltimore, and one unidentified. Of 249,000 samples from blacks, about 29,000 contained electrophoretically detectable abnormalities, most of them associated with Hb S or C, present in a frequency of about 9% and 3%, respectively. About 1000 samples resolved into patterns of potential clinical significance. Twenty other mutant hemoglobins were detected, in various genetic combinations in 164 kindreds; four of these-Hb Alabama, Montgomery, Titusville, and Mobile-- were previously unknown. The methods used are rapid, economical, and well suited for large scale surveys. They provide highly specific characterizations of many mutant hemoglobins, and no discrepancies were found between the presumptive identifications based on these characterizations and the definitive identifications obtained from structural analyses.
A new alkali-resistant hemoglobin alpha2J Oxford gammaF2 in a Sicilian baby girl with homozygous beta0 thalassemia
Authors: Schiliro G , Musumeci S , Pizzarelli G , Russo A , Marinucci M , Bruni E , Russo G
Published: October 2019

A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia.
Hemoglobin M equon beta 41 (C7) phenylalanine leads to tyrosine
Authors: Burkert LB , Sharma VS , Pisciotta AV , Ranney HM , Bruckheimer S
Published: October 2019

A severe hemolytic crisis was observed in a 34-yr-old female of English- Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide beta Tp-5, and automated sequencing of I 125-labeled beta chains indicated a replacement of phenylalanine (C7) beta 41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) beta 42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of beta41 and beta 42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.
Causal mechanisms of multiple acquired red cell enzyme defects in a patient with acquired dyserythropoiesis
Authors: Kahn A , Cottreau D , Boyer C , Marie J , Galand C , Boivin P
Published: October 2019

A patient with an unclassified form of acquired dyserythropoiesis was found to have multiple defects in erythrocyte enzyme activity, involving especially pyruvate kinase (PK), glucose phosphate isomerase (GPI), and phosphofructokinase (PFK). The PK activity defect was associated with a normal concentration of PK-related antigen, and the enzyme could be reactivated during the procedure of partial purification of the enzyme. The concentration of GPI-related antigen was as reduced as the GPI enzymatic activity, and the defect was not improved by any treatment (cross-incubation of red cells or treatment of the hemolysate by SH reagents); the residual enzyme had a normal stability to heat, and a normal electrophoretic and electrofocusing pattern. The PFK activity defect was not improved either by cross- incubation of red cells or by treatment with SH reagents. Immunologic data with antimuscle and antileukocyte antisera seemed to indicate that the defect involved especially the muscle-type subunit of erythrocyte PFK. In agreement with this assumption was the fact that deficient PFK was markedly more inhibited by ATP than normal enzyme. Changes similar to those of deficient PFK herein studied were noted for PFK of unfractionated erythrocytes from premature newborns or of “old” erythrocytes from full-term infants. It appeared that each of the three enzyme defects detected in the patient could be due to a different mechanism, involving post-translational changes, decreased synthesis, and possible reversion of the genetic regulation mechanisms of the abnormal erythroid precursors toward a fetal type. The possible relationships between these various phenomena and the nature of a hypothetical common underlying cause are discussed.
Reticulocyte size in nutritional anemias
Authors: Clarkson DR , Moore EM
Published: October 2019

Alterations in reticulocyte size occur 2–3 days after the onset of iron deficient or megaloblastic erythropoiesis and precede, by several weeks, changes in mean corpuscular volume (MCV). Iron-deficiency anemia induced in a normal subject by repeated phlebotomies was characterized by the initial development of larger than normal reticulocytes followed by an abrupt decrease in reticulocyte size. Microreticulocytes appeared 3 days after the fall in per cent iron saturation and antedated the decrease in MCV to below normal by 6 wk. Mean reticulocyte size was disproportionately smaller than normal in patients presenting with iron deficiency. In contrast, reticulocyte size increased abruptly in a patient (and rats) 2–3 days after administration of methotrexate. Mean reticulocyte size was disproportionately larger than normal in patients presenting with folate or vitamin B12 deficiency. Specific replacement therapy with iron, folate, or vitamin B12 was quickly followed by normalization of reticulocyte size.
Specific chromosomal aberrations in polycythemia vera
Authors: Zech L , Gahrton C , Killander D , Franzen S , Haglund U
Published: October 2019

The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received no treatment with cytotoxic drugs, while three had received 32P only and the other three, in addition, had received busulfan or busulfan and procarbazine. One 73- yr-old male patient treated with venesection only for 4 yr lacked the Y chromosome and had a deletion of the long arm of chromosome 20 (20q-) in all cells investigated. One of the other three patients who had received no drugs had a chromosome abnormality, but only in 1 of 19 identifiable metaphases. However, the abnormality was the same (+9) as the most common one in treated patients. In the group of treated patients, an extra chromosome 9 (+9) was found in three patients, an extra chromosome 8 (+8) in one, and a deletion of the long arm of one chromosome 20 (20q-) in one patient. Multiple aberrations in addition to the extra chromosome 9 were found in one patient in whom the disease had transformed into acute myeloblastic leukemia. The finding of identical chromosomal aberrations (20q- and +9, respectively) in two patients who had received no drugs and in four patients who had received 32P and busulfan or procarbazine favors the view that these aberrations are specifically associated with the disease and not induced by the drugs. With the exception of the patient with acute myeloblastic leukemia, all other patients are alive 1–11 mo after chromosome analyses and 1–229 mo after diagnosis.
Human lymphocyte motility: normal characteristics and anomalous behavior of chronic lymphocytic leukemia cells
Authors: Jarvis SC , Snyderman R , Cohen HJ
Published: October 2019

The characteristics of human lymphocyte motility and its relationship to the redistribution of surface membrane antigens (capping) are poorly defined. Since chronic lymphocytic leukemia (CLL) cells cap poorly when compared with normal human lymphocytes, this study was undertaken to compare the motility of these two cell types. A modification of the Boyden chamber system was employed to quantify lymphocyte motility by placing lymphocyte suspensions on 8-mum convoluted-pore nitrocellulose filters and measuring the depth of migration of the cells into the filter at 37 degrees C. After 3 hr of incubation, CLL cells migrated significantly less into the filter than normal cells. Incubation in the presence of sodium azide or at 4 degrees C abolished all motility, indicating the active nature of the process. The relative motility of individual CLL patients' cells correlated best with the proportion of abnormal cells present as determined by surface receptor assays. The possibility that decreased cell motility in CLL was a reflection of enrichment by a “bone marrow-derived” (B cell) population was eliminated by the finding that normal B cells purified by gradient separation of rosetted cells migrated faster than normal T cells and considerably faster than CLL cells. Motility of normal and CLL lymphocytes was decreased by cytochalasin B and increased by colchicine, vincristine, and vinblastine. Thus, human lymphocyte motility appears to be dependent on microfilament integrity but not to require the colchicine-sensitive cytoskeleton. The decreased motility of CLL cells is the result of an intrinsic cell abnormality, but this finding cannot fully explain the decreased capping, since in human lymphocytes the latter is not prevented by an inhibitor of motility.
Stimulation of megakaryocytopoiesis by acute thrombocytopenia in rats
Authors: Odell TT , Murphy JR , Jackson CW
Published: October 2019

Rats were made acutely thrombocytopenic by injection of antiplatelet serum. Marrow sections and squash preparations were made at intervals during 120 hr. Determinations were made of mitotic index, stage of maturation, ploidy level, and cell size of megakaryocytes; number and size of platelets were measured. Increased endomitosis among megakaryocytes was followed by an increase in the proportion of immature megakaryocytes, a greater average ploidy level of recognized megakaryocytes, and larger megakaryocytes. Maximum changes in these several parameters occurred between 32 and 72 hr after induction of thrombocytopenia. By 120 hr all megakarocyte parameters were near normal. For about 3 days, beginning at about 36 hr, platelet numbers increased rapidly. Average platelet size rose and returned to normal within about 60 hr. Changes in ploidy and size of megakaryocytes were measured in the immature and mature maturation stages. The results suggest that the initial stimulus in response to acute thrombocytopenia acts primarily on diploid precursors, programming them to mature into a population of megakaryocytes with an average ploidy approximately one level greater than in normal rats and a proportionate increase in cell size. The larger megakaryocytes presumably produce more platelets, accounting for a major part of the increased rate of platelet production. Since the changes in megakaryocytes begin to reverse before circulating platelet numbers have reached the normal level, reversal of the stimulus appears to be initiated by some change other than platelet mass.
Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas
Authors: Saito H , Goldsmith G , Waldmann R
Published: October 2019

Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface- mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas.
Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation
Authors: Bowers TK , Craddock PR , Jacob HS
Published: October 2019

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.
Cytofluorometric analysis of the kinetics of lymphocyte transformation after phytohemagglutinin stimulation: comparison with the kinetics of thymidine incorporation
Authors: Utsinger PD , Yount WJ , Fallon JG , Logue MJ , Fuller CR , Elliott D
Published: October 2019

The technique of flow cytofluorometry has been employed to assess the response of unfractionated and highly purified human lymphocyte subpopulations to phytohemagglutinin (PHA) and pokeweed mitogen. Normal values for cytofluorometric responses were established and compared to the uptake of tritiated thymidine in simultaneous experiments. Cytofluorometric analysis offered the advantages of increased sensitivity and direct measurement of DNA content per cell, and provided percentages and absolute numbers of responding cells. B-cell responses to pokeweed mitogen were absent, but brisk T-cell responses were noted. Between 4% and 8% of highly purified human B cells were found to respond to PHA by increasing their DNA content; modest but significant uptake of tritiated thymidine by B cells following PHA stimulation was also observed.
Enhancement of colony-stimulating activity production by lithium
Authors: Harker WG , Rothstein G , Clarkson D , Athens JW , Macfarlane JL
Published: October 2019

Since lithium causes granulocytosis in some patients, its effect upon granulocyte production was investigated using mouse marrow in the agar culture system. When lithium was added to semisolid cultures of mouse marrow, there was no stimulation of colony formation in the absence of colony-stimulating activity (CSA). In addition, lithium did not potentiate the action of already formed CSA. However, lithium did stimulate the production of CSA by lung tissue. Lithium enhancement of CSA production was blocked by puromycin, indicating that lithium action required active new protein synthesis. It was concluded that lithium promoted enhanced granulocyte production in vitro by stimulating the synthesis of CSA.
T and B lymphocyte antigen-positive null cell leukemias
Authors: Kaplan J , Ravindranath Y , Peterson WD Jr
Published: October 2019

To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T cell leukemia and from 2 of 10 patients with null cell leukemia expressed T cell but not B cell antigens. Blasts from 8 of 10 patients with null cell leukemia, one patient with B cell leukemia, and 3 of 3 patients with acute myelogenous leukemia expressed B cell but not T cell antigens. T lymphocyte antigen-positive null cell ALL appear to be a form of T cell ALL. B antigen-positive null cell leukemia could arise from either immature B cell precursors or from multipotential stem cells.
Semicontinuous flow centrifugation for the pheresis of immunocompetent cells and stem cells
Authors: Weiner RS , Richman CM , Yankee RA
Published: October 2019

Mononuclear cells from human peripheral blood were purified by semicontinuous flow centrifugation (SCFC) using the Haemonetics model 30 blood cell separator; 64% +/- 7% of the mononuclear cells in 600 ml of peripheral blood were collected in a 30-ml volume. Analysis of sequential 5-ml aliquots of the mononuclear cell concentrate revealed that both immunocompetent cells and granulocytic progenitor cells (CFU- C) were proportional to the cell count throughout the buffy coat. In vitro pheresis of large volumes of human bone marrow resulted in recovery of 63% of the cells, 12% of the hemoglobin, and 84% of the CFU- C in 20% of the original volume. Further centrifugation eliminated 80% of the platelets without loss of cells or CFU-C. SCFC of peripheral blood or bone marrow selectively concentrated mononuclear cells and reduced the contamination by granulocytes and erythrocytes. Large numbers of mononuclear cells can thus be collected for studies in vitro or for cryopreservation and the autologous reconstitution of immunosuppressed or myelosuppressed patients undergoing intensive antitumor therapy.
In vitro stimulation of primate hemoglobin synthesis by L-thyroxine
Authors: Fuhr JE , Gengozian N , Overton M
Published: October 2019

Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H- leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.
Congenital neutropenia: an intrinsic cell defect demonstrated by electron microscopy of soft agar colonies
Authors: Zucker-Franklin D , L'Esperance P , Good RA
Published: October 2019

Congenital neutropenia (CN), a disease characterized by recurrent infections leading to death in infancy, shows a maturation arrest of the myeloid series at the promyelocyte-myelocyte level. The potential value of marrow transplantation in this disease would be determined by the nature of the underlying defect. However, studies to date have failed to define whether the defect is intrinsic in the cells or attributable to “environmental” factors. Therefore, marrow of four patients with CN was cultured on soft agar, and the colonies were analyzed by a newly developed ultrastructural method. In parallel, patients' cells were used in feeder layers for normal marrow. Although the patients' colonies appeared grossly normal in size and number, electron microscopy showed only rare neutrophil colonies. These colonies contained markedly aberrant cells exhibiting asynchronous nucleocytoplasmic maturation, convoluted nuclei, excessive cytoplasm, and dearth of granules. Monocyte and eosinophil colonies differentiated normally. Patients' cells and sera supported growth of normal colonies. The studies have demonstrated unequivocally that the neutrophil cell line of patients with CN is intrinsically defective and suggest that attempts at marrow grafting are warranted.
Effect of cyanide on NADPH oxidation by granules from human polymorphonuclear leukocytes
Authors: DeChatelet LR , McPhail LC , Shirley PS
Published: October 2019

Cyanide has been shown to stimulate both oxygen uptake and hexose monophosphate shunt activity in phagocytizing human polymorphonuclear leukocytes. It also stimulates the oxidation of NADPH by a particulate fraction derived from phagocytizing cells. This stimulation of NADPH oxidase is not observed in the presence of exogenous Mn2+. Studies with purified enzymes have shown that CN- also stimulates NADPH oxidation by horseradish peroxidase or lactoperoxidase, suggesting that the respiratory burst might be initiated by activation of a peroxidase-like enzyme in the human polymorphonuclear leukocyte. Based on studies of others, however, it does not appear as though the enzyme is identical to myeloperoxidase. The mechanism of the CN- stimulation appears to involve an oxidatic chain reaction, since it stimulates markedly NADPH oxidation in the presence of an artificial superoxide-generating system.
Gamma heavy chain disease: clinical aspects and characterization of a deleted, noncovalently linked gamma1 heavy chain dimer (BAZ)
Authors: Faguet GB , Barton BP , Smith LL , Garver FA
Published: October 2019

This report describes the clinical and immunoglobulin features of a patient with gamma heavy chain disease (HCD), who presented with a clinical picture suggestive of an underlying malignancy rather than the usual picture of lymphoma or granulomatous disease. A unique clinical feature was the nearly total replacement of the submaxillary glands by plasma cells. The patient's serum and urine contained a paraprotein, gammaHCD protein BAZ, which belongs to the gamma1 subclass and forms noncovalently linked dimers with a molecular weight of approximately 60,000 daltons. This mutant protein exhibited a deletion which encompassed most of the variable (V) region, the first constant domain (CH 1), and the hinge region. In addition, preliminary structural analyses demonstrated the replacement of alanine by glycine in position 431 of the carboxyterminal octadecapeptide. This substitution may possibly represent another allotypic marker on IgG1 proteins.
Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells
Authors: Burgess AW , Wilson EM , Metcalf D
Published: October 2019

Medium conditioned by human placental tissue was found to stimulate granulocytic and monocytic colony formation by human marrow cells in semisolid agar cultures. The colony-stimulating activity of unfractionated conditioned medium was equivalent to the activity of standard peripheral blood underlayers. Placentas were a reliable source of active material, and one placenta provided enough material to stimulate 5,000–10,000 cultures of normal or leukemic cells. The colony- stimulating factor in human placental conditioned medium (CSFHPCM) was concentrated and purified 1800-fold using ammonium sulfate precipitation, calcium phosphate gel absorption, DEAE-cellulose batch absorption, gel filtration on Sephadex G-150, and polyarcylamide gel gel electrophoresis. The active factor behaved on gel filtration as a macromolecule with an apparent molecular weight of 30,000 daltons. The active factor in placental conditioned medium was not dependent on the presence of adherent marrow cells with endogenous colony-stimulating activity.
cGMP stimulation of stem cell proliferation
Authors: Oshita AK , Rothstein G , Lonngi G
Published: October 2019

The process by which resting hemopoietic stem cells become activated is poorly understood, but it has been suggested that cyclic nucleotide levels in the cell may play an important role. In the present study, the effect of various, nucleotides and stimulators of nucleotide synthesis upon the formation of in vitro granulocyte colonies has been examined. It was found that physiologic concentrations of 3′, 5′-cyclic guanosine monophosphate enhanced the formation of granulocyte- macrophage colonies in the presence of colony-stimulating activity. The cells sensitive to cGMP activation were resistant to thymidine suicide and could not be activated by colony-stimulating activity alone. Therefore it was suggested that the cGMP sensitive stem cell was an ordinarily resting stem cell which was triggered into a proliferative state by cGMP.
Carriers with excessively low factor VIII procoagulant activity (VIII AHF): a study of two unrelated families with mild hemophilia A
Authors: Eyster ME , Ladda RL , Bowman HS
Published: October 2019

Two unrelated families are described with mild hemophilia A in whom six obligate carriers had unusually low VIII AHF levels. In each family, successive generations of males were affected with hemophilia A as determined by low VIII AHF in the presence of normal VIII AGN and VIII VWF levels. In the first family, two of five obligate carriers had low VIII AHF levels associated with clinical bleeding and one other had a history of bleeding. While receiving oral contraceptives, one of these two carriers was found to have a normal VIII AHF level. In the second family, four cousins below age 10 who were obligate carriers had significantly low VIII AHF levels, while a paternal aunt and paternal grandmother who were also obligate carriers had VIII AHF levels within the normal range. Hemorrhagic diathesis in multiple obligate carriers in these families is not readily explained by the Lyon hypothesis, and suggests that these families may be exmaples of an unusual allelic form of hemophilia A or that they may be transmitting several independent genes affecting VIII AHF levels. Our experience suggests that VIII AHF levels should be determined on all obligate or possible carriers prior to surgery to identify those individuals at risk for postoperative bleeding. Furthermore, it is suggested that hormonal therapy might be effective in the management of carriers with low levels of VIII AHF and clinical bleeding.
Demonstration and mode of action of an inhibitor for activated Hageman factor (factor XIIa) of the intrinsic blood coagulation pathway from Schistosoma mansoni
Authors: Tsang VC , Damian RT
Published: October 2019

An anticoagulant activity from adult Schistosoma mansoni whole worm homogenate is described. The inhibitor appears to be specific for the contact activation step of the intrinsic pathway. Experiments with both human and mouse plasmas have defined the specificity of the inhibitor as follows: (1) It lengthens the partial thromboplastin time of normal plasma. (2) It has no effect on the prothombin time and Russell's viper venom time of normal plasma. (3) Preactivation of normal plasma by a contact activator such as Celite eliminates essentially all inhibitory activity. (4) The inhibitor appears to be heat stable and can be precipitated by centrifugation above 27,000 g. (5) The inhibitor has no effect on the activation of factor XII by Celite. (6) The activation of factor XI by factor XIIa, however, is inhibited by the schistosomal inhibitor. The above data are consistent with the view that S. mansoni adults possess an anticoagulant that is capable of specifically inhibiting the conversion of factor XI to factor XIa by factor XIIa.
Variations in lymphocyte counts four hours after administration of hydrocortisone in patients with chronic lymphocytic leukemia
Authors: Dighiero G , Vaugier G , Charron D , d'Athis P , Binet JL
Published: October 2019

The peripheral lymphocyte count and the number of large unstained cells (LUC) were investigated prior to and 4 hr after a single intravenous injection of 400 mg of hydrocortisone in 23 controls and 51 patients with lymphoid disorders (43 chronic lymphocytic leukemia, 3 cases of Waldenstrom macroglobulinemia, 2 hairy cell leukemias, 1 Sezary syndrome, and 2 cases of infectious mononucleosis). A reduction in both the peripheral lymphocyte counts and the number of LUC was observed in all normal controls, the mean decrease being 54% and greater than 60%, respectively, with differences according to age. In chronic lymphocytic leukemia (CLL), the peripheral lymphocyte count showed a variable response: decrease, no change, or increase. A correlation was shown to exist between a decrease in peripheral lymphocyte counts and anatomical- clinical staging: patients with involvement restricted to blood and bone marrow very often exhibited a drop in their peripheral lymphocyte count (p less than 0.01). In addition, the percentage of circulating T lymphocytes was higher (54%) in CLL patients whose peripheral lymphocyte count dropped than in other CLL patients (p less than 0.001).
Chronic myeloid leukemia: physical and functional similarities to acute leukemia
Authors: Senn JS , Price GB
Published: October 2019

Blast crisis, closely resembling acute leukemia, is the usual terminal event in chronic myeloid leukemia. Using physical (“fingerprint”) and cultural (colony-forming) methods, we have demonstrated distinctive patterns in the stable phase of chronic myeloid leukemia and in blast crisis. An unusual fingerprint alteration preceding the onset of the terminal phase is noted, and cell culture perturbation is evident at different stages of the disease. Our findings indicate that the application of these methods to the study of hemopoietic disorders is valid, and suggest that the use of such techniques may allow a better understanding of the complex cellular events occurring in the course of chronic myeloid leukemia.
Induction of serum stimulation and plasma cell proliferation during chemotherapy of multiple myeloma
Authors: Karp JE , Burke PJ , Humphrey RL
Published: October 2019

Sequential sera from 45 patients with multiple myeloma (MM) and from 6 patients with solid tumors but normal bone marrows who received cyclophosphamide, 15 mg/kg/day for 4 days, were assayed for their effects on tritiated thymidine (3H-TdR) incorporation by normal bone marrow cells and malignant plasma cells. Pretreatment sera from 23 of the 45 patients with MM inhibited normal marrow cell proliferation relative to the effects of normal sera. Of these 45 sera, 30 inhibited plasma cell proliferation. This humoral inhibition was overcome by the induction of humoral stimulation at a predictable time during chemotherapy. The sera obtained sequentially from patients with MM and patients with normal bone marrows increased 3H-TdR uptake by both cell types by days 12–15 of therapy. Sequential changes in malignant marrow plasma cell 3H-TdR labeling indices paralleled the changes in serum activity, with an increased tumor cell growth fraction occurring at the time of peak serum stimulatory activity. The relationship between serum stimulation and malignant plasma cell proliferation was confirmed in vitro.
Chronic granulocytic leukemia: cytogenetic conversion of the bone marrow with cycle-specific chemotherapy
Authors: Smalley RV , Vogel J , Huguley CM Jr , Miller D
Published: October 2019

Sixteen patients with Ph1-positive chronic granulocytic leukemic (CGL) were entered on a pulsing chemotherapy program consisting of cytosine arabinoside 100 mg/sq m/day X 5 and thioguanine 100 mq/sq m/day X 5 every 21 days in an attempt to convert the Ph1-positive marrow to a Ph1- negative state and thereby achieve a complete remission. Twelve patients had an adequate trail of drug treatment, and ten of these had adequate chromosome examinations. There were two “conversions,” one of which was maintained for 5+ mo, while the other was transient. The program was unacceptable, however, to most patients due to intolerable nausea and vomiting. Thus a prospective chemotherapeutic attempt to convert a Ph1-positive marrow without splenectomy has induced a conversion in two of ten patients. Other regimens which might induce less nausea and vomiting and a higher rate of conversions should be sought in future attempts to alter the invariably fatal outcome of CGL.
Intracellular enzymes of collagen biosynthesis in human platelets
Authors: Anttinen H , Tuderman L , Oikarinen A , Kivirikko KI
Published: October 2019

Activities of four intracellular enzymes of collagen biosynthesis-- prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase--were demonstrated in human platelets, and the presence of prolyl hydroxylase protein was further demonstrated by direct radioimmunoassay. The ratio of the specific activities of the four enzymes in the four enzymes in the human platelet extract to those in human adult skin extract varied from about 0.1 to 1, the lowest relative activity being found with prolyl hydroxylase and the highest with collagen glucosyltransferase. Only a very small amount of prolyl hydroxylase protein, probably 1%, was in the form of the active enzyme tetramer. The collagen glucosyltransferase from human platelets readily glucosylated galactosylhydroxylysine in denatured collagen, but did not glucosylate native collagen. Also, native collagen did not act as an inhibitor of the glucosylation reaction. Therefore, platelet collagen glucosyltransferase cannot form either an enzyme--substrate complex or an enzyme--inhibitor complex with native collagen. The results thus argue against the theory which maintains that platelet collagen glucosyltransferase is involved in collagen--platelet adhesion.
Myeloperoxidase--H2O2--halide system: cytotoxic effect on human blood leukocytes
Authors: Clark RA , Klebanoff SJ
Published: October 2019

Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human blood leukocytes is demonstrated, employing 51Cr release and dye exclusion assays. Cytotoxicity is dependent on enzymatically active myeloperoxidase, H2O2, or a peroxide-generating enzyme system and either chloride or iodide. Cell damage is rapid, with maximal levels of 51Cr release occurring within 30--60 min. Approximately equal sensitivity to the peroxidase system is observed for polymorphonuclear leukocytes and mononuclear leukocytes. Since myeloperoxidase and H2O2 are released from polymorphonuclear leukocytes under certain conditions, such as during particle ingestion, it is suggested that peroxidase-mediated leukocyte injury may be an important feature of the inflammatory response.
ABO blood group system and bone marrow transplantation
Authors: Gale RP , Feig S , Ho W , Falk P , Rippee C , Sparkes R
Published: October 2019

The role of the ABO blood group system in determining the outcome of bone marrow transplantation was investigated in 53 patients with aplastic anemia and acute leukemia grafted from HLA-identical siblings. There was no correlation between ABO compatibility and marrow engraftment, graft rejection, or graft-versus-host disease. In 5 recipients with antibodies prior to transplantation to antigens of the ABH system present on the cells of their donors, plasma exchange and antibody absorption in vivo were effective in permitting engraftment of ABO-incompatible bone marrow. These findings indicate that the ABO system is not a clinically significant barrier to successful bone marrow transplantation in otherwise histocompatible individuals.
An unusual case of leukemia with high fetal hemoglobin: demonstration of abnormal hemoglobin synthesis localized in a red cell clone
Authors: Pagnier J , Lopez M , Mathiot C , Habibi B , Zamet P , Varet B , Labie D
Published: October 2019

A high level of fetal hemoglobin was found in an 8-yr-old boy without any hematologic disorders except for a moderate anemia. The absence of hemoglobin abnormalities in the parents led us to suspect a latent malignant disease that, on follow-up, was confirmed to be myelomonocytic leukemia. Hemoglobin biosynthetic studies provided evidence of unbalanced synthesis of globin subunits by reticulocytes, while the production of non-alpha chains was equal to that of alpha chains in bone marrow cells. The expression of red cell antigen i was increased, while those of I, A, and A1 antigens were found to decrease progressively. Two populations of erythrocytes, A-positive and A- negative, were distinguished and could be separated by differential agglutination. Unbalanced globin chain synthesis, increased fetal hemoglobin, and antigenic changes of the membrane were shown to be restricted to the A-negative population. The biologic data were not entirely consistent with a genuine reversion to fetal erythropoiesis. The question remains of a polychromosomal lesion of either quiescent F cells or adult stem cells.
X-linked syndrome of platelet dysfunction, thrombocytopenia, and imbalanced globin chain synthesis with hemolysis
Authors: Thompson AR , Wood WG , Stamatoyannopoulos G
Published: October 2019

An unusual family is described with a congenital bleeding disorder present in four males belonging to three generations. Of the three surviving affected males, all had splenomegaly and petechiae. The three had moderate thrombocytopenia (55–90 X 10(9)/liter) and markedly prolonged Ivy-template bleeding times (greater than 30 min). They were also noted to have reticulocytosis and, upon further investigation, imbalanced globin chain synthesis resembling that of beta-thalassemia minor. Studies on nine additional family members in four generations were normal except for slight elevations of reticulocyte counts in female members, one of whom had the abnormal globin chain synthesis ratio. In male members, the bleeding tendency and clinical signs always occurred in the presence of the globin chain synthesis defect and reticulocytosis. This previously undescribed condition was apparently transmitted as an X-linked disorder.
Influence of HLA-A2 on the effectiveness of platelet transfusions in alloimmunized thrombocytopenic patients
Authors: Duquesnoy RJ , Filip DJ , Aster RH
Published: October 2019

Platelet transfusions from donors selectively mismatched for cross- reactive and certain non-cross-reactive HLA antigens were found to be more effective in HLA-A2 negative than in HLA-A2 positive, alloimmunized thrombocytopenic patients. The two groups of patients responded equally well to platelets matched for antigens of the HLA-A and B loci. Certain alloimmunized patients negative for HLA-A2 continued to respond satisfactorily to platelets selectively mismatched for non-cross-reactive HLA antigens as long as platelets containing HLA- A2 were avoided. The data indicate that platelet transfusion support can be provided within a broader range of donor-recipient HLA antigenic disparity to HLA-A2 negative alloimmunized patients than to those who are positive for this antigen.
beta-O-thalassemia from Algeria: genetic and molecular characterization
Authors: Godet J , Verdier G , Nigon V , Belhani M , Richard F , Colonna P , Mitchell J , Williamson R , Tolstoshev P
Published: October 2019

beta-Thalassemia is a major public health problem in Algeria. During a survey, a family including two cases of betaO-thalassemia was studied. The family study indicated that two of the affected siblings had homozygous beta-thalassemia; there were also both normal and heterozygous siblings, and both parents had beta-thalassemia trait. In the two cases of betaO-thalassemia there was no hemoglobin A in the peripheral blood, and no beta-globin chain synthesis in whole cell incubations. Hybridization of purified complementary DNA specific for alpha- and beta-globin messenger RNAs demonstrated less than 1% mRNAbeta relative to mRNAalpha in circulating reticulocytes, and for one case in total RNA from bone marrow. There is no apparent beta- globin gene deletion as determined by hybridization in globin cDNAbeta sequence excess. Therefore the Algerian cases studied are similar in molecular pathology to some Southern Italian and Asian cases described previously, and differ from other Italian and Chinese betaO- thalassemias, in which hybridizable mRNAbeta has been demonstrated, and from deltabetaO-thalassemia, which is caused by a gene deletion.
Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation
Authors: Storb R , Graham TC , Epstein RB , Sale GE , Thomas ED
Published: October 2019

Baboons were given 1200 R total body irradiation from two opposing 60Co sources. Three animals were given supportive therapy only and died, as expected, within 8 days of irradiation with profound marrow hypoplasia. Five baboons were cross-circulated with unirradiated partners and died within 14 days with evidence suggestive of graft-versus-host disease. Their marrows were repopulated with hemopoietic precursor cells, and three of the five had rises in peripheral white blood cell counts to more than 1500/cu mm before death. These results are compatible with the presence of hemopoietic stem cells in the peripheral blood of a nonhuman primate, the baboon.
Molecular defect in platelets from patients with bernard-soulier syndrome
Authors: Degos L , Tobelem G , Lethielleux P , Levy-Toledano S , Caen J , Colombani J
Published: October 2019

An IgG antibody isolated from the serum of a patient with the Bernard- Soulier syndrome induced platelet agglutination in the platelet-rich plasma of 50 normal subjects regardless of their ABO, KOa, KOb, HLA, or PlA1 types. This antibody was nonreactive with platelets from three other Bernard-Saulier syndrome patients. Indirect immunoprecipitation tests using this serum (or purified IgG) and soluble membrane antigens labeled with 125I that had been extracted from normal platelets by the nonionic detergent Nonidet P-40 gave a single radioactive peak at 150,000 MW in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These findings strongly suggest that the antigenic determinant reacting with this antibody is absent from platelets of Bernard-Soulier syndrome patients and that the deficient molecule is of 150,000 MW. The role of this molecule in subendothelial adhesion and macromolecular-mediated aggregations is discussed.
Megakaryocyte maturation indicated by methanol inhibition of an acid phosphatase shared by magakaryocytes and platelets
Authors: Markovic OS , Shulman NR
Published: October 2019

Optimal conditions necessary for the cytochemical demonstration of megakaryocyte (Mk) and platelet acid phosphatase (AP) were determined. Methanol, a constituent of fixatives commonly used in AP cytochemistry, was found to inhibit MkAP, and the degree of inhibition varied with Mk maturity. Immature Mk contained predominantly methanol-resistant AP, and mature Mk, predominantly methanol-sensitive AP. Platelets contained methanol-sensitive AP similar to mature Mk, suggesting that this enzyme provides an index of platelet formation by Mk. Soluble platelet AP showed three bands on polyacrylamide gel electrophoresis, visualized by the same reactions applied cytochemically. Two bands, accounting for 98% of the platelet AP activity, were slow moving and methanol sensitive; and one fast moving band accounting for 2% of activity was methanol resistant. Measurement of Mk and platelet AP isoenzymes may prove to have applications in evaluating Mk function.
Plateletpheresis in the management of thrombocytosis
Authors: Taft EG , Babcock RB , Scharfman WB , Tartaglia AP
Published: October 2019

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2–9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.
Stimulation of the hexose monophosphate shunt independent of hydrogen peroxide and superoxide production in rabbit alveolar macrophages during phagocytosis
Authors: Tsan MF
Published: October 2019

Phagocytosis and oxidative metabolism of human polymorphonuclear leukocytes (PMN) and rabbit alveolar macrophages (AM) were studied. Human PMN ingested a mean of 12 polyvinyl toluene latex particles (2 micrometer in diameter) per cell. There was stimulation of O2- and H2O2 production, light emission, and activation of the hexose monophosphate shunt during phagocytosis by human PMN. Rabbit AM ingested 51 latex particles (2 micrometer in diameter) per cell. There was no stimulation of the production of O2- and H2O2 or light emission associated with phagocytosis by rabbit AM, while the hexose monophosphate shunt was activated. Similar metabolic changes were obtained in both cell types when opsonized zymosan was used as phagocytic particles. 1-14C- glucoseoxidation was stimulated by H2O2 and methylene blue in both resting human PMN and rabbit AM. It is concluded that activation of the hexose monophosphate shunt in rabbit AM during phagocytosis is independent of O2- and H2O2 production.
Effect of protein deprivation on erythropoiesis
Authors: Anagnostou A , Schade S , Ashkinaz M , Barone J , Fried W
Published: October 2019

The effects of protein deprivation on erythropoietin (Ep) production were studied. The posthypoxia plasma Ep levels of rats fed a protein- free diet for only 1 day prior to being exposed to 0.5 atmosphere for 7 hr were significantly lower than those of comparably hypoxic rats maintained on a normal diet. The postthypoxia plasma Ep levels were even lower in rats kept on protein-depleted diets for longer periods of time. Rats fed diets with 0.5%, 5% or 12% protein content for 6 days had lower posthypoxia plasma Ep levels than those fed a normal diet (20% protein content). When a single protein meal was force-fed to protein-deprived rats 0–4 hr after initiating the exposure to hypoxia, the posthypoxia plasma Ep levels were significantly higher than in protein-deprived rats that were fed water or dextrose. The posthypoxia plasma Ep titers of protein-deprived rats fed protein 4–8 hr prior to exposure to hypoxia did not differ significantly from those of protein- deprived rats. Although the posthypoxia plasma Ep levels of protein- deprived rats fed a hemolysate containing 0.8 g of hemoglobin 4 hr after beginning hypoxia were greater than those of protein-deprived rats fed only water, the rate of oxygen consumption in these two groups did not differ. We conclude that, in addition to its response to the availability of oxygen, Ep production is infl,enced by the availability of amino acids.