bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymic Studies on Phosphatidic Acid Synthesis in Human Platelets
Authors: Okuma Minoru , Yamashita Satoshi , Numa Shosaku 
Published: October 2019

Abstract
Particulate preparations of human platelets were capable of catalyzing acylation of sn-glycerol 3-phosphate by long-chain fatty acyl-CoA thioesters. The principal lipid product formed was identified as phosphatidic acid. The highest specific activity was found in the particulate fraction that sedimented between 12,000 g and 105,000 g. The reaction exhibited a broad pH optimum around 7.4-8.5. The apparent Michaelis constant for sn-glycerol 3-phosphate was 0.48 mM when 28.5 µM palmityl-CoA was used as acyl donor. Palmityl- and oleyl-CoA were better substrates than stearyl-, linoleyl-, and arachidonyl-CoA, as far as the maximal velocity was concerned. Particulate preparations of platelets from normal subjects catalyzed the incorporation of 0.271 ± 0.048 nmole of sn-glycerol 3-phosphate/min per mg of protein. The capacity of human platelets to acylate sn-glycerol 3-phosphate was approximately 40% that of human liver, as compared on the basis of the specific activity of the microsomal fraction. These results suggest that the glycerophosphate pathway makes an essential contribution to the de novo synthesis of phospholipids in human platelets.
Hemodialysis Coil-induced Transient Neutropenia and Overshoot Neutrophilia in Normal Man
Authors: Jensen Douglas P. , Brubaker Leonard H. , Nolph Karl D. , Johnson Charles A. , Nothum Richard J. 
Published: October 2019

Abstract
Profound transient neutropenia, followed by an overshoot of the neutrophil (N) count to an average of 2.5 ± 1.0 (mean ± 1 SD) times higher than average control N count, has been induced in seven normal subjects by reinfusion of heparinized blood that had been stagnated in a hemodialysis coil for 15 min. This was similar to the neutropenia-neutrophilia cycle occurring shortly after the initiation of hemodialysis in uremic patients. At the time of neutropenia, profound monocytopenia was also observed, but only a slight drop in lymphocyte count occurred. Neither monocytes nor lymphocytes subsequently recovered to higher than control values. A DF32P standard N survival procedure, performed in one subject with Hodgkin’s disease in complete unmaintained remission, showed that a large number of unlabeled N appeared during the overshoot, suggesting their marrow origin. Although in two of three attempts neutropenia was produced by reinfusion of blood through the coil without stagnation, no significant overshoot of N count following neutropenia occurred without the stagnation step. Simple phlebotomy and reinfusion of blood without the coil had no effect on the N count. This model may prove useful in studying the possible immediate regulation of the N count by marrow release of N and marrow N reserves in various patients.
Observations on the Settling and Recoverability of Transplanted Hemopoietic Colony-forming Units in the Mouse spleen
Authors: Lord B. I. , Hendry J. H. 
Published: October 2019

Abstract
A series of experiments was designed to study the effect of spleen size on the seeding and retention of spleen colony-forming units (CFU) after injection into irradiated mice. The cellularity of the spleens of recipient mice was varied using a variety of experimental procedures, and the resulting spleen colony production was analyzed with respect to CFU seeding. It was found that the major factor determining the seeding and ultimate retention of CFU in the spleen of a recipient mouse is the size of the spleen. It is concluded that the most reasonable value of the fraction of injected CFU that produces spleen colonies should be determined from the number of CFU recoverable from the fully shrunken spleen. In these mice, the fraction was 9.5%.
Acute Promyelocytic Leukemia: Results of Treatment by Daunorubicin
Authors: Bernard Jean , Weil Marise , Boiron Michel , Jacquillat Claude , Flandrin Georges , Gemon Marie-François 
Published: October 2019

Abstract
Daunorubicin induces complete remissions in about 50% of patients with acute promyelocytic leukemia. The median duration of these remission is 26 mo. Failures are mainly due to hemorrhages as a result of disseminated intravascular coagulation during the first 5 days (25%) or due to sepsis during the second and third week (25%). Long-term survivals are more frequent than in the other acute granulocytic leukemias.
Lymphocyte Lysosomes and Lysosomal Enzymes in Chronic Lymphocytic Leukemia
Authors: Douglas Steven D. , Cohnen Georg , KÖnig Erika , Brittinger GÜnter 
Published: October 2019

Abstract
Electron microscopic cytochemical and biochemical studies of lysosomal markers have been performed in unstimulated normal and chronic lymphotic leukemia (CLL) lymphocytes. Decreased activities of the lysosomal enzymes acid phosphatase and β-glucuronidase but not of the nonlysosomal enzyme malate dehydrogenase were observed in CLL lymphocytes as compared to normal cells. At the electron microscopic level, the number of membrane-bounded acid phosphatase-positive organelles was diminished in CLL cells. (Average 1.07 per cell profile in normal cells and 0.17 in CLL lymphocytes). The findings indicate that the diminution of acid hydrolase activities in CLL lymphocytes is most likely due to a reduced number of lysosomes, rather than to a diminished enzyme content of these organelles.
Disturbed Bone Marrow Cell Proliferation in Primary Shunt Hyperbilirubinemia
Authors: Hamer Jack W. , Fitzgerald Peter H. 
Published: October 2019

Abstract
Cell proliferation studies, utilizing 3H-thymidine radioautography combined with quantitative DNA microdensitometry, demonstrated a gross disturbance of bone marrow cell proliferation in a 17-yr-old youth with primary shunt hyperbilirubinemia. Early erythroid and myeloid cells were arrested at the S, G2 and mitotic phases of the cell cycle, but late normoblasts were not affected. Intramedullary death of the abnormal early erythrmoid cells probably results and is compensated by increased hemopoiesis with a hyperplastic marrow, which 59Fe studies suggest leads to the production and early release of "stress" reticulocytes. The increased early bilirubin production that characterizes this disorder is considered to be derived primarily from intramedullary death of early normoblasts and secondarily from hemolysis in the marrow and spleen of stress reticulocytes.
Recessive Familial Erythrocytosis: Aspects of Marrow Regulation in Two Families
Authors: Adamson John W. , Stamatoyannopoulos George , Kontras Stella , Lascari Andre , Detter James 
Published: October 2019

Abstract
Studies of marrow regulation were carried out in two families with recessively expressed erythrocytosis. The erythrocytosis in the affected individuals was associated with increased erythropoietin (ESF) production. However, hormone production was uninfluenced by alterations in the O2 carrying capacity of the blood when the hematocrit was lowered acutely by phlebotomy. Hemoglobin and red cell function (p50; 2, 3-diphosphoglycerate) in the affected, as well as the unaffected, family members were normal. Renal arteriography revealed no mass lesions and no anatomic abnormalities of the renal macro- or microvasculature. Antisera capable of neutralizing the biological activity of normal human ESF completely inhibited the erythropoietic activity in the serum and urine of those studied. Since increased production of ESF occurred in the absence of recognizable physiologic requirements and since the normal reciprocal relationship between O2 delivery and hormone production was absent, the most likely explanation for this clinical constellation is a cellular defect in the regulation of production of ESF or of its precursor substances.
Immunologic Identification of Tissue Factor (Thromboplastin) Synthesized by Cultured Fibroblasts
Authors: Zacharski Leo R. , Hoyer Leon W. , McIntyre O. Ross 
Published: October 2019

Abstract
Immunologic methods were employed in an attempt to identify a potent procoagulant present in homogenates of human skin fibroblasts cultured in vitro. The activity of this procoagulant was restricted to the early stages of coagulation and was heretofore considered to be due to tissue factor (tissue thromboplastin, factor III) either alone or in combination with one or more of the first-stage coagulation factors (VIII, IX, XI, XII). The present studies demonstrated that procoagulant activity was not diminished by incubation with anti-VIII or anti-IX antibodies of human origin or with anti-VIII antibody of rabbit origin. Furthermore, cell culture homogenates failed to bind antifactor VIII antibody and did not contain an inhibitor of the reaction between factor VIII and its antibody. By contrast, procoagulant activity was obliterated by an antibody to tissue factor protein regardless of whether plasmas deficient in factor VIII, IX, XI, or XII were used in the assay system. The antitissue factor antibody failed to block the procoagulant effect after tissue factor had complexed factor VII. The procoagulant, therefore, consisted entirely of tissue factor.
Cyclic Leukocytosis in Chronic Myelogenous Leukemia: New Perspectives on Pathogenesis and Therapy
Authors: Gatti Richard A. , Robinson William A. , Deinard Amos S. , Nesbit Mark , McCullough Jeffrey J. , Ballow Mark , Good Robert A. 
Published: October 2019

Abstract
Studies were performed on a teen-age female identical twin with cyclic leukocytosis and Ph1-positive chronic myelogenous leukemia (CML), in an attempt to analyze the relationship of these cycles to her disease and to utilize the cycles as reference points for kinetic studies and as landmarks in the progression of her disease. She remained untreated for 2½ yr. Colony-stimulating factor levels showed an inverse relationship to the peripheral leukocyte count. Two distinct phases in cyclic patterns of peripheral leukocyte counts prior to treatment could be appreciated in retrospect: phase 1, a stable 15-mo period during which leukocyte counts peaked every 10 wk and then returned to baseline levels, and phase 2, an 18-mo period of insidious deterioration during which the low points of successive cycles became progressively higher and leukocytes were accumulating in the peripheral blood at a rate of 400 x 106/day. We propose that the increased marrow production of myeloid cells in this disease does not represent a life-threatening situation until cell accumulation begins. We attempted, therefore, to halt or to reverse this accumulation by cell separator leukapheresis.
Effects of Vitamin A on the Erythrocyte Membrane Surface
Authors: Murphy Martin J. 
Published: October 2019

Abstract
The scanning electron microscope was used to examine the effects vitamin A has on the surface of human erythrocytes. The hemolytic properties of vitamin A, both time- and dose-dependent, are confirmed, and the observations are extended to the establishment of a sequence of cellular events that leads to the destruction of the red cell. The biochemical means whereby vitamin A induces these changes are discussed. In addition, the present study indicates that only selective areas of the erythrocyte membranes are responsive to the action of vitamin A, thereby supporting the proposal that the erythrocytic membrane may not be a homogeneous mass.
Radioautographic Observations on Iron Absorption by the Duodenum of Mice With Iron Overload, Iron Deficiency, and X-linked Anemia
Authors: Bédard Yvan C. , Pinkerton Peter H. , Simon Géerard T. 
Published: October 2019

Abstract
The uptake of iron by the absorptive cells of the duodenum, and its subsequent transfer to the lamina propria, has been studied using 55Fe and high-resolution radioautography in mice rendered iron deficient by diet, in mice with dietary iron overload, and in mice with hereditary malabsorption of iron (s/a). In all, as in normally iron replete mice, two phases of iron absorption can be distinguished. There is an early active phase of uptake and transfer, followed by a second "storage" phase. The pathway of iron absorption is qualitatively similar to the normal with rapid uptake by the brush border, passage through the terminal web to the rough endoplasmic reticulum, and areas rich in free ribosomes. Iron passes through the lateral cell membrane, intercellular spaces and epithelial basement membrane to the vessels of the lamina propria. The rough endoplasmic reiculum and areas rich in free ribosomes form the major localization of iron at all stages of absorption. Only a relatively small amount of radioactive iron is found over ferritin in iron-loaded mice and mice with s/a; morphologically recognizable ferritin was not observed at any stage in iron-deficient animals. Significant numbers of grains have not been seen over mitochondria in any group of animals studied. In iron-deficient mice, the rate of uptake and of transfer of iron is increased. With the 10 µg dose of iron used, all iron taken up by the absorptive cell is transferred to the lamina propria within 3 hr, with none remaining in the cell during the second, storage phase. In mice with iron overload, transfer of iron is decreased, resulting in considerable storage of iron in the cell. In s/a mice, uptake does not appear to be unduly reduced, but transfer is reduced, thereby resulting in increased storage of iron in the absorptive cell. The rough endoplasmic reticulum and areas rich in free ribosomes appear to play an important role in the uptake, transfer, and storage of iron by the absorptive cell regardless of the state of the body iron stores. Ferritin would seem to have a less important part in iron absorption, possibly acting as a storage or detoxifying mechanism.
Sickle Cell Safari
Authors: Bemis Edwin L. 
Published: October 2019

Abstract
A narrative concerning mass screening of a large population at risk for sickle hemolobin, glucose-6-phosphate dehydrogenase deficiency, anemia, and lead poisoning is presented. At the time of writing, more than one-tenth of a black community totaling over 104,000 individuals have been tested. The manner of community education and organization, laboratory methodology, results obtained, means of reporting, and follow-up procedures are detailed.
Treatment of Thrombotic Thrombocytopenic Purpura With Antiplatelet Drugs
Authors: Amir Jacob , Krauss Stephen 
Published: October 2019

Abstract
Thrombotic thrombocytopenic purpura (TTP) is a disease with an extremely high mortality rate. Many modalities of therapy have been tried with very limited success. Lately, antiplatelet drugs have been proposed in the treatment of TTP. We report a well-documented case of TTP that presented with severe hemolytic anemia, thrombocytopenia, neurologic manifestations, kidney involvement, and fever. The patient did not respond to splenectomy, corticosteroids, and heparin sodium, but she made a full recovery after antiplatelet drugs (aspirin and dipyridamole) were added to the therapeutic regimen. The coagulation studies showed thrombocytopenia, hypofibrinogenemia, and a positive protamine sulfate test, indicative of disseminated intravascular clotting. The spleen showed numerous arterioles occluded with subendothelial hyaline material. The platelet investigations during antiplatelet therapy revealed impaired platelet aggregation and clot retraction that became normal after discontinuance of the drugs. The patient has now been in full remission more than 12 mo.
Hematopoietic Stem Cell Regulation. II. Chronic Effects of Hypoxic-Hypoxia on CFU Kinetics
Authors: Lord Brian I. , Murphy Martin J. 
Published: October 2019

Abstract
Hypobaric-hypoxia, an established stimulator of erythropoiesis, was used to perturb normal steady-state hematopoiesis and thereby to facilitate an analysis of stem cell kinetics. BDF1 male mice were exposed to a simulated altitude of 22,000 ft for 1-15 days. The following parameters were assessed at daily intervals: packed red cell volumes (PCV), femoral and splenic nucleated cellularity, the relative concentration and total number of colony-forming units (CFU, i.e., stem cells) in the femoral shaft and whole spleen, as well as the turnover of this population of cells using the "3H-thymidine-killing" technique. By 10 days of hypoxia the PCV had risen to 65% and by a fortnight was elevated to, and stabilized at, 70%-75%. After an evanescent increase, the femoral cellularity became slightly hypocellular but returned to normal by 3 days, thence becoming hypercellular from days 5 to 15. The spleen was markedly depleted of cells for 48 hr and recovered to hypercellular levels between 4 and 6 days. It then oscillated from hypercellular to normal levels with a period interval of 5 days. Both femoral and splenic CFU demonstrated oscillations, as did the estimations made on the state of CFU turnover. The femoral and splenic CFU did not decrease in number during the 15 days of hypoxia, indeed, they both revealed cyclic increases. These results are discussed in terms of CFU kinetics and humoral mediation.
In Vivo Aging of Transfused Erythrocytes and 2,3-Diphosphoglycerate Levels
Authors: Dickerman Joseph D. , Ostrea Enrique M. , Zinkham William H. 
Published: October 2019

Abstract
Levels of 2,3-diphosphoglycerate (2,3-DPG) and oxygen affinity were measured in a patient with refractory congenital hypoplastic anemia in order to determine the response of aging transfused erythrocytes to a decrease in tissue oxygen tension. Ferrokinetic studies revealed that the rate of erythropoiesis after transfusion was approximately 10% of normal. In the interval between transfusions, the level of 2,3-DPG and P50 rose to values considerably above the normal range as the level of the hematocrit decreased. On five separate occasions, the 2,3-DPG concentration was elevated (average 25.5 µmoles/g of hemoglobin) and the P50 level increased (average 33.2 mm of mercury) 24 hr prior to transfusion. It is concluded that in vivo aging of transfused erythrocytes does not prevent these cells from responding to an increasingly hypoxic environment by elevating 2,3-DPG levels and by decreasing oxygen affinity.
Identification of Cells in Primate Bone Marrow Resembling the Hemopoietic Stem Cell in the Mouse
Authors: Dicke K. A. , van Noord M. J. , Maat B. , Schaefer U. W. , van Bekkum D. W. 
Published: October 2019

Abstract
The colony-forming unit culture (CFU-C) in the thin-layer agar colony technique is considered to be representative for hemopoietic stem cells (HSC), according to our studies in mouse and monkey bone marrow. Using this in vitro assay as a guide, stem cell concentrates were prepared from monkey and human bone marrow by repeated density gradient centrifugation. The number of CFU-C could be enriched up to 70-100-fold. In such concentrated CFU-C suspensions, a cell, morphologically identical with the hemopoietic stem cell in the mouse (MSCLC, mouse stem cell-like cell) was frequently observed, using a May-Grünwald-Giemsa (MGG) staining method and electron microscope techniques. In MGG-stained preparations, the MSCLC superficially resembles the small lymphocyte; therefore, a staining method has been described, the polychrome procedure, by which both cell populations could be clearly distinguished. Since a fair correlation exists between the number of MSCLC and the number of CFU-C in a variety of primate hemopoietic suspensions, we concluded that the MSCLC might be a good candidate for being the HSC in monkeys and man.
Correlation Between Cytokinetically Resting Lymphocytes and Bone Marrow Restoration: Experiments Using a Discontinuous Albumin Gradient
Authors: Haas Rainer J. , Flad Hans-Dieter , Fliedner Theodore M. , Fache Ingeborg 
Published: October 2019

Abstract
Rats were labeled with 3H-thymidine (3H-TdR) in utero and for 6 wk after birth in order to obtain 100% labeling of all bone marrow cells. Six weeks after the last 3H-TdR injection only cytokinetically resting cells were still labeled. At this time, the regenerative capacity of fractions obtained after centrifugation on a discontinuous albumin gradient was tested in 1200-R x-irradiated recipients, and the results were compared with the effect observed after transplantation of the same number of unfractionated bone marrow cells. One of the fractions obtained had a regeneratory capacity tenfold that of unfractionated cells. In contrast, when the response to a PHA stimulation test was evaluated, this fraction showed a decreased incorporation of 14C-TdR as compared to other fractions. In a second test system, fractions of bone marrow from 3H-TdR-labeled donors made hypoplastic by repeated injections of hydroxyurea were transfused into 1200-R x-irradiated recipients. Regenerative capacity was similar to that seen in the first experiment. The findings indicate a correlation between cytokinetically resting, small mononuclear cells and the regeneratory process in lethally x-irradiated recipients.
Survival in Chronic Lymphocytic Leukemia
Authors: Zippin Calvin , Cutler Sidney J. , Reeves William J. , Lum Diana 
Published: October 2019

Abstract
Survival of 839 chronic lymphocytic leukemia patients has been reviewed in relation to a number of patient and disease characteristics. Over-all, the relative 5-yr survival rate was 44%. Studying survival by age and sex led to the following observations: Dividing age into intervals < 50, 50-59, 60-69, 70-79, and 80 yr and over, relative survival declined with increasing age; relative 5-yr survival for females was higher than that for males-50% versus 41%. This pattern of superior survival of females over males was noted in all but one of the age intervals. Survival was negatively associated with the presence of recorded clinical signs and symptoms, hematological abnormalities, and pathological bone marrow findings. Differences in survival were also found by treatment category and interval from diagnosis to initiation of treatment. Adjustment for differences in distribution of each of these variables did not materially diminish the survival differences noted by age and sex. An unexpected pattern of survival in relation to white blood count level was noted. Survival increased with increasing white blood count at diagnosis, peaking in the interval at 25,000-49,000, and decreasing after that. When survival by white blood count was adjusted for some variables which were found to be associated with survival, the gradient was still noted, though somewhat reduced.
Antibodies to Factor VIII. I. Variations in Stability of Antigen-Antibody Complexes in Hemophilia A
Authors: Allain J.-P. , Frommel D. 
Published: October 2019

Abstract
Human factor VIII-anti-factor VIII complexes were formed in vitro in slight antigen excess, using plasma of hemophiliacs who were found to have antibodies neutralizing AHF activity. These complexes, stable at +37°C and pH 7.4, were submitted to classical procedures known to favor dissociation of antibody from antigen. The methods used to obtain dissociation, incubations at +56°C and at pH 4.2, inactivated both unbound factor VIII and that released as a consequence of dissociation. The extent of dissociation was measured by the recovery of anti-factor VIII activity. Increasing resistance of complexes towards dissociation was observed in the plasma of the patients whose titer of inhibitor was increasing after recent transfusions. These observations suggested the emergence, as a direct consequence of renewed antigenic stimulation, of a population of different antibodies characterized by higher combining strength.