bluuebunny/crossref_metadata_2025 huggingface dataset:
RECENT STUDIES OF MULTIPLE MYELOMA: STERNAL AND RIB PUNCTURE AND THE RESULTS OF TREATMENT WITH STILBAMIDINE
Authors: PROPP SIMON , GORHAM L. WHITTINGTON , KANTOR SAMUEL
Published: October 2019

1. The value of bone marrow aspiration in the diagnosis of multiple myeloma was confirmed and discussed. This procedure should be utilized in all patients suspected of having this disease.

2. The importance of a reliable technic of studying bone marrow obtained by aspiration was stressed, and a method emphasizing certain important features described in detail.

3. The theory that multiple myeloma is derived from a dysplastic line of plasma cells originating in the bone marrow was supported by this study.

4. The original observation of Snapper has been confirmed, that after treatment of multiple myeloma patients with stilbamidine, large basophilic inclusion bodies can be demonstrated in the cytoplasm of a majority of myeloma cells obtained from bone marrow aspiration and stained by Wright’s stain. This was produced on a nonrestricted as well as on a low animal protein diet.

5. Relief of pain was produced in two out of five patients with multiple myeloma treated with stilbamidine. One patient who was relieved of pain was on a low animal protein diet while the diet of the second was unrestricted. In both caess basophilic inclusion bodies appeared in the myeloma cells following treatment. Stilbamidine therapy failed to allevaite pain or to produce basophilic granulation in the myeloma cells in three patients who exhibited hyperglobulinemia.

6. Relief of pain and vertigo occurred in one patient treated with stilbamidine while osteolytic lesions were observed to enlarge by roentgenological examination.

7. Trigeminal neuropathy with severe discomfort still continued six months following treatment in one patient.

8. An arrest or remission in the course of the disease was not obtained in five cases of multiple myeloma treated with stilbamidine.
THE OCCURRENCE OF THE PERIODIC ACID-SCHIFF REACTION IN VARIOUS NORMAL CELLS OF BLOOD AND CONNECTIVE TISSUE
Authors: WISLOCKI GEORGE B. , RHEINGOLD JACK J. , DEMPSEY EDWARD W.
Published: October 2019

An account is given of the periodic acid-Schiff reaction in the cytoplasm of various normal cells of blood and connective tissue of man, rhesus monkey and rabbit. Saliva treated control sections were used to distinguish glycogen from other reactive substances. The effects of malt diastase were compared briefly with those of saliva. The results of the present study may be summarized as follows (table 1):

See PDF for Table
EOSINOPHILIC LEUKEMIA
Authors: EVANS THEODORE S. , NESBIT ROBERT R.
Published: October 2019

1. The data in a case of fatal leukemia with predominant eosinophilia in the peripheral blood and bone marrow are presented; we believe that this case was one of eosinophilic leukemia.

2. During the period of observation, these eosinophils showed progesssive immaturity as the symptoms became more severe. Eventually this "left shift" became so marked that a large proportion of the cells were terminally myeloblasts in both the blood and the bone marrow.

3. Autopsy revealed invasion of many of the tissues and organs with these mature and immature eosinophil granulocytes and with myeloblasts.
PLATELET THROMBOSIS IN HUMAN HEMOSTASIS
Authors: ZUCKER HOWARD D.
Published: October 2019

The histologic appearance of human skin puncture wounds obtained at biopsy, after measurement of the local bleeding times, has been studied in serial section in 3 patients with normal hemostasis and in 4 patients with idiopathic thrombocytopenic purpura. It is found that agglutinated platelets arrest hemorrhage in normal skin by rapidly sealing the mouths of all cut vessels larger than capillaries. Such platelet thrombi can resist the effective blood pressure in a cut arteriole of 55 micra. The puncture tract is normally filled with red cell-fibrin clot into which the platelet thrombi protrude. The red clot seals the mouth of the few opened capillaries which can be identified. Other capillaries may be sealed by endothelial agglutination. Fibrin does not enter or form within the injured vessels.

Platelet thrombosis does not occur in idiopathic thrombocytopenic purpura. When larger arterioles and venules are cut the bleeding time is greatly prolonged and fibrin fails to form within the wound because of the speed of blood flow. When smaller vessels are cut in purpura the bleeding time is moderately prolonged, but the cut vessels are eventually sealed by fibrin alone. In thrombocytopenic purpura the bleeding time is normal if only capillaries are cut, since these are normally sealed by fibrin.

The similarity of the histologic appearance of human puncture wounds to that described after experimental vascular injury in other mammals, suggests considerable similarity in mammalian hemostatic mechanisms.

Clinical bleeding time tests vary greatly in depth of puncture and in the caliber and number of the vessels cut. Sufficient volume of hemorrhage during the first minute is thought to be the best guide to an adequate test of the entire hemostatic mechanism.
THE CLINICAL ASSOCIATION OF MACROCYTIC ANEMIA WITH INTESTINAL STRICTURE AND ANASTOMOSIS
Authors: CAMERON D. G. , WATSON G. M. , WITTS L. J.
Published: October 2019

1. The case is reported of a woman in whom a macrocytic anemia developed after a short-circuit operation for regional ileitis. At a second operation, multiple constrictions and distentions were present in the bypassed loop.

2. The literature of macrocytic anemia associated with intestinal stenosis and anastomosis is reviewed. The anemia differs from Addisonian pernicious anemia in that the gastric secretion of hydrochloric acid and intrinsic factor may be normal. There need be no steatorrhea. It is concluded that the anemia is probably due to stagnation of intestinal contents and the absorption of toxic substances.

3. The production of blind loops in the small intestine of experimental animals offers a promising approach to the study of the macrocytic anemias.
THE EFFECT OF STASIS OF BLOOD IN VARICOSE VEINS ON ERYTHROCYTE FRAGILITY, WITH ACCOMPANYING STUDIES COMPARING RED CELLS AND OTHER BLOOD ELEMENTS WITH CUBITAL VEIN BLOOD
Authors: METTIER STACY R. , WEAVER JOHN C. , MCBRIDE ALICE F.
Published: October 2019

1. Blood from varicose veins was compared with cubital vein blood in 20 patients in order to determine whether or not the degree of stasis present in varicose veins would increase red cell fragility. Corollary studies consisted of comparative determinations of red cells, hemoglobin, packed cell volume, white blood cells, platelets and serum proteins.

2. There was no increase in red cell fragility in the varicose vein specimen, indicating that the theory that minor degrees of intravascular erythrostasis contribute substantially to some of the hemolytic anemias is untenable.

3. There was a small but statistically significant elevation in red cells per cu. mm. in varicose vein blood as compared with blood from cubital veins. There was a suggestive, but not significant, increase in packed cell volume and serum protein in the varicose vein samples. The evidence indicates a mild degree of hemoconcentration.

4. White cells, platelets and hemoglobin determinations were found to have the same values in varicose vein blood as in blood from the cubital vein.
Immunochemical Characterization of a Monoclonal γG4, λ Human Antibody to Factor IX
Authors: Pike Isadore M. , Yount William J. , Puritz Elliot M. , Roberts Harold R.
Published: October 2019

A circulating inhibitor specific for factor IX in a patient with hemophilia B was characterized with antisera to human immunoglobulins. Inhibitor-rich plasma was mixed with an excess of specific antiserum and then assayed for residual inhibitor activity. Inhibitor activity was completely removed by antisera specific for γG4 heavy chains and lambda light chains. Antisera specific for γA, γM, γD, γE, γG1, γG2, and γG3 heavy chains and kappa light chains had no effect on the inhibitor. On preparative zone electrophoresis, inhibitor activity was localized in a sharp band in the anodal portion of the γG peak, an electrophoretic distribution paralleling that of γG4. Precise localization of the inhibitor activity on calibrated gel filtration columns revealed a relatively narrow zone of fractions containing the inhibitor, wherein the proteins have an estimated molecular weight of 145,000. The relative homogeneity of the antibody may reflect specificity for a uniform, discrete portion of the human factor IX molecule.
Globin Chain Synthesis in the Marrow and Reticulocytes of Beta Thalassemia, Hemoglobin H Disease, and Beta Delta Thalassemia
Authors: Shchory Mordechai , Ramot Bracha
Published: October 2019

α, β, and γ globin chain synthesis in bone marrow and peripheral blood reticulocytes were studied in two patients with thalassemia major, two with thalassemia intermedia, one with thalassemia minor, one with Hb H disease, and one with homozygous βδ-thalassemia. Nine nonthalassemic patients served as controls. In thalassemia major, a marked imbalance of α- to β-chain synthesis was found in the bone marrow as well as in reticulocytes. The imbalance, however, was slightly more evident in the latter. In the patients with thalassemia intermedia and minor the α- to β-globin chain ratios in the reticulocytes were of the same order of magnitude, despite the marked clinical differences between thalassemia intermedia and minor. A balanced synthesis was found in the bone marrow of the patient with thalassemia minor. The bone marrow globin synthesis in thalassemia intermedia was not studied. Contrary to that in Hb H disease and βδ-thalassemia, the imbalance was more apparent in the bone marrow. In the latter, no evidence for imbalance was detected in the reticulocytes. These results point out the need for further studies on globin chain synthesis in the bone marrow and reticulocytes of patients With the various thalassemia syndromes and the effect of the free globin chain pool on those results.
Methods for Obtaining Purified Lymphocytes, Glass-adherent Mononuclear Cells, and a Population Containing Both Cell Types From Human Peripheral Blood
Authors: Levis William R. , Robbins Jay H.
Published: October 2019

Methods are presented for obtaining simultaneously or separately two populations of cells from human peripheral blood, lymphocytes and monocytes, both of which are required to obtain blastogenesis and DNA synthesis in human leukocyte cultures. A simple 5-min centrifugation of heparinized blood yields a mononuclear leukocyte culture fluid containing 70-90% lymphocytes with few granulocytes but with sufficient numbers of monocytes so that the latter cell is not a limiting factor in the blastogenic reaction. A method is also presented for removing both granulocytes and monocytes from lymphocyte populations in a manner that permits monitoring and choice of the degree of lymphocyte purification. A method is also presented for obtaining glass-adherent mononuclear cells that do not undergo blastogenesis but will enable suitably stimulated "purified" lymphocytes to undergo blastogenesis. Studies of the function and morphology of these different cell populations are presented.
Kinetics of Cell Proliferation of Murine Bone Marrow Cells Cultured in Diffusion Chambers: Effect of Hypoxia, Bleeding, Erythropoietin Injections, Polycythemia, and Irradiation of the Host
Authors: Boyum Arne , Carsten Arland L. , Laerum Ole Didrik , Cronkite Eugene P.
Published: October 2019

Mouse bone marrow cells were cultured in diffusion chambers implanted in the abdominal cavity of host mice that were subjected to different kinds of treatment. Preirradiation of the chamber host enhanced the cell growth in the chambers as follows: the number of cells capable of proliferation and differentiation in the chambers (diffusion chamber progenitor cells, DCPC) as determined by a limiting dilution method increased significantly. Similarly, the spleen colony-forming units (CFU’s) in the chambers proliferated more rapidly in irradiated than in normal hosts. The total number of cells in the granulocytic series harvested after culture periods of 3-7 days was also significantly increased. The number of cells in the granulocytic series harvested per DCPC in irradiated animals was twice normal. These findings indicate that the progenitor cells probably proceed through multiplicative mitoses before differentiation in the irradiated animals. A higher cloning efficiency or a shortened generation time of stem cells are other possibilities. The increased number of differentiating granulocytes may simply be a consequence of the events taking place in the stem cell compartment, but a stimulating effect of the irradiation environment on proliferating cells in the granulocytic series cannot be excluded. Preirradiation also stimulated the growth of macrophages but less consistently. When normal mice carrying chambers with normal marrow were subjected to intermittent hypoxia during the culture period, the number of DCPC’s and of cells in the granulocytic series and macrophages were reduced approximately to the same extent. Hypoxic treatment of donor animals for 3-5 days resulted in a similar reduction in number of DCPC’s and CFU’s at both intervals. These findings may suggest competition for a common pool of stem cells for erythrocytes, granulocytes, and macrophages. However, a toxic effect cannot be excluded. Erythropoiesis, which is usually absent, was significantly increased when hypoxia and irradiation of the chamber hosts were combined. Bleeding and erythropoietin injections also enhanced erythropoiesis to some extent.
Binding of Concanavalin A to Rat, Normal Human, and Chronic Lymphatic Leukemia Lymphocytes
Authors: Novogrodsky Abraham , Biniaminov Miriam , Ramot Bracha , Katchalski Ephraim
Published: October 2019

This study was aimed to find a correlation between the extent of concanavalin A (Con A) binding to lymphocytes and the blastogenic effect of the lectin on these cells. 63Ni-labeled Con A was used in the lectin-binding experiments. Binding of Con A to a small fraction (approximately 3%) of Con A binding sites in rat lymphocytes is required for the maximal stimulation of RNA synthesis. Binding of Con A to additional sites resulted in a less stimulatory effect. Lymphocytes from patients with chronic lymphatic leukemia (CLL) are impaired in their blastogenic response to Con A. Maximal stimulation of DNA synthesis induced by Con A in CLL lymphocytes is attained by treatment of the cells with the lectin at concentrations that are smaller than those required for the induction of maximal DNA synthesis in normal lymphocytes. The number of Con A binding sites in CLL lymphocyte is smaller than in normal lymphocyte.
Present Status of Spiculed Red Cells and Their Relationship to the Discocyte-Echinocyte Transformation: A Critical Review
Authors: Brecher G. , Bessis M.
Published: October 2019

The literature on spiculed red cells, contains a redundant nomenclature and contradictory claims on the pathogenesis of the abnormal red cells. A resolution of these difficulties requires knowledge of the many conditions that induce crenation in normal and abnormal red cells because these artifacts have frequently been confused with spiculed cells in the patient’s circulation.

The biconcave red cells (disocytes) can be transformed into crenated red cells (echinocytes) (1) by extrinsic factors (plasma incubated at 37°C for 24 hr, lysolecithin, high levels of fatty acid or physiologic levels of fatty acid in the presence of lysolecithin and many others); (2) by intrinsic factors, such as aging of red cells, which are probably related to depressed ATP; and (3) by washing in saline and the "glass effect" of observing cells between slide and cover slip. The extrinsically induced discocyte-echinocyte transformation is generally reversible by washing in fresh plasma, the intrinsically induced transformation is not. The discocyte-echinocyte transformation due to glass contact is prevented by observation between plastic cover slips. Echinocytes probably occur in various diseases, but such claims must be reevaluated because examination of fresh cells between plastic cover slips is necessary to exclude artifactual crenation during preparation of smears.

Sphero-echinocytes and spherocytes may develop with higher concentration of echinocytogenic agents. The relationship of these cells to echinocytes, on one hand, and prelytic spheres, on the other, needs further clarification.

The spiculed cells in the circulation of certain patients with liver disease are indistinguishable from the acanthocytes of abetalipoproteinemia. Acanthocytes can develop crenation superimposed on their own spicules and become acanthoechinocytes. It is suggested that the term burr cell for echinocyte and spur cells for the acanthocytes of liver disease be abandoned because they are redundant and do not allow for designation of the mixed forms of acantho-echinocytes which are of diagnostic importance.

Speculations are presented on the pathogenesis of echinocyte formation and their importance for an understanding of the structure of the red cell membrane.
Oxymetholone Treatment for the Anemia of Bone Marrow Failure
Authors: Alexanian Raymond , Nadell Judith , Alfrey Clarence
Published: October 2019

Oxymetholone was given to 28 adults with chronic anemia from bone marrow disease. Changes in hematocrit and red cell mass were correlated with serial assessments of erythropoietin and erythropoiesis. Erythropoietin excretion was enhanced more than five-fold over the level expected for the hematocrit in 70% of the patients. Only 23% of the patients with an evaluable treatment trial increased their red cell mass by at least 20%. In all responders, the T½ of 59Fe disappearance ranged from 86-136 min and erythron iron turnover exceeded 0.25 mg/100 ml blood/day. A decline in serum iron concentration to the 50-100 µg/100 ml range after 1 mo of oxymetholone was frequently associated with a subsequent response to therapy. Patients with severe bone marrow failure, for whom frequent red cell transfusions were required, did not improve. The failure of other patients to respond was attributed to complicating factors that either impaired maximal erythropoietin production or restricted iron supply to the bone marrow. Hepatic toxicity was detected in less than 10% of treated patients. Results support the use of oxymetholone in the treatment of patients with moderate degrees of bone marrow failure and symptomatic anemia.
The Activated Phagocyte of Polycythemia Vera
Authors: Cooper M. R. , DeChatelet L. R. , McCall C. E. , Spurr C. L.
Published: October 2019

Leukocytes isolated from patients with polycythemia vera (PCV), a panmyelopathy, have increased metabolic activity during the resting and phagocytizing states. Phagocytes from patients with PCV were studied by counting particle ingestion, measuring hexose monophosphate shunt (HMP) activity by the conversion of glucose-1-14C to 14CO2, and determining O2 consumption and nitroblue tetrazolium (NBT) reduction. Phagocytosis of polystyrene particles was increased. Resting glucose-1-14C activity was 6.9 ± 2.7 nmoles of glucose oxidized per hour per 5 x 106 phagocytes in normal and 16.4 ± 7.6 nmoles in polycythemia vera phagocytes. Hexose monophosphate shunt following phagocytosis increased to 50.6 ± 10.4 nmoles in normal and 91.7 ± 17.0 in polycythemia vera phagocytes (p < 0.005). Oxygen consumption was 3.6 ± 0.2 µl/hr/5 x 106 phagocytes in resting and 11.4 µl/hr/5 x 106 phagocytes in stimulated controls as compared to 4.8 ± 0.2 µl in resting and 18.4 µl in phagocytizing PCV cells (p <0.001). The reduction of NBT by leukocytes was increased in all resting polycythemia vera phagocytes as compared to control phagocytes. The cells from some patients had increases in the amount of NBT reduced during phagocytosis. Phagocytes from four severly infected patients had increases in HMP activity in both resting and phagocytizing cells similar to those found in noninfected PCV phagocytes. Although the increased metabolic activity associated with phagocytosis can be explained by increased particle ingestion, the increased activity of resting PCV cells suggests other metabolic abnormalities perhaps related to the age of the phagocyte.
Thrombotic Thrombocy openic Purpura: Report of a Case With Possible Immune Etiology
Authors: Mant Michael J. , Cauchi Maurice N. , Medley Gabriele
Published: October 2019

Thrombotic thrombocytopenic purpura (TTP) is a disorder of unknown etiology. An immunologic basis has been suggested, although proof is lacking. The immunologic, hematologic, and autopsy findings in a case of TTP occurring 6 wk postpartum are described. Immunofluorescent studies revealed the presence of IgM and complement, as well as fibrin in the vicinity of the endothelium and in thrombi in small blood vessels in multiple organs. These findings suggest an active immunologic process in this case. While TTP is probably of diverse etiology, confirmation of these findings in further cases would provide a rational basis for the use of immunosuppressive therapy.
Identification of Circulating Micromegakaryocytes in a Case of Refractory Anemia: An Electron Microscopic-Cytochemical Study
Authors: Gorius J. Breton , Dreyfus B. , Sultan C. , Basch A. , d’Oliveira J. G.
Published: October 2019

In a case of refractory anemia with an excess of myeloblasts in the bone marrow and with thrombocytopenia, examinations of the blood cells under the electron microscope have revealed nucleated cells similar in size to small lymphocytes. Some of these lymphocytelike cells have scanty cytoplasm identical to that of giant platelets present in the blood, which are pathologic in view of their highly developed system of membranes. In the perinuclear space and in short segments of the smooth endoplasmic reticulum, these blood micromegakaryocytes exhibit a peroxidase activity that is identical to that of mature megakaryocytes of normal bone marrow. They also spread over glass like giant platelets. In the past these nucleated cells could well have been confused with atypical lymphocytes, because on stained slides their atypical appearance makes identification difficult.
The IgG Subclasses of Red Cell Antibodies and Relationship to Monocyte Binding
Authors: Abramson Neil , Schur Peter H.
Published: October 2019

Purified IgG1, IgG2, IgG3, and IgG4 myeloma proteins were coupled to red blood cells with chromic chloride either individually or in various combinations. Only red blood cells coated with IgG1 or IgG3 formed rosettes; red cells coated with IgG3 appeared to predominate in this reaction. IgG2, IgG4, and IgA myeloma proteins coupled to red blood cells did not appear to inhibit the IgG1 and/or IgG3 also on the red cells from forming rosettes. The IgG subclass specificity of a number of red cell isoantibodies was determined. The majority were IgG1 and IgG3, as previously noted. IgG2 was observed among some of these antibodies, namely in anti-D, anti-CD, anti-CDE, anti-s, and anti-Jka. Although rosette formation was strongly associated with the relative amounts of IgG1 and IgG3, particularly the latter, on red cells, a number of exceptions were noted.
Improved Viability of Previously Frozen Platelets
Authors: Handin R. I. , Valeri C. R.
Published: October 2019

The main feature of this new approach to platelet freezing is a controlled rate of addition and postthaw removal of 5% dimethylsulfoxide (DMSO). When DMSO was removed from fresh nonfrozen platelet concentrates before transfusion, no adverse effect on posttransfusion survival was observed. The 51Cr recovery of autologous fresh platelet concentrates in vivo was 65% ± 5%, while that of autologous platelets previously frozen with DMSO and washed prior to transfusion was 47% ± 3%. The lifespan values were similar for fresh platelets and previously frozen washed platelet concentrates. When approximately 95% of the DMSO was removed from previously frozen washed platelets before transfusion, the 51Cr recovery was about 70% of the value for fresh platelet concentrates, and the lifespan value was similar to that of fresh platelet concentrates. No adverse side effects were observed. The hemostatic effectiveness of these platelets has yet to be studied.
Postnatal Fetal and Adult Hemoglobin Synthesis in D1 Trisomy Syndrome
Authors: Bard Harry
Published: October 2019

Studies were carried out during the neonatal period in three infants with D1 trisomy syndrome to measure the proportion of fetal and adult hemoglobin being synthesized. These values were compared on the one hand to those previously reported from samples obtained from cord blood of normal newborn infants ranging from 25 to 43 wk gestation, and on the other hand to those values determined in critically ill infants of the same postconceptional age. Blood samples were incubated in an amino acid mixture containing 14C-leucine followed by column chromatography on DEAE Sephadex for separation of fetal and adult hemoglobin fractions. Liquid scintillation counting was carried out on the hemoglobin fractions. In infants with the D1 trisomy, the delay in transition to adult hemoglobin synthesis was 7-8 wk behind that expected for their postconceptional ages, and there was no accelerated transition to adult hemoglobin synthesis in the one case studied beyond the early neonatal period. Unlike the D1 trisomy infants, the critically ill controls showed no retardation in their transition toward adult hemoglobin synthesis. The duplication of the genes in one of the 13-15 chromosome groups is a factor that delays the developmental synchrony of hemoglobin synthesis.
The Zeta Sedimentation Ratio
Authors: Bull Brian S. , Brailsford J. Douglas
Published: October 2019

The zeta sedimentation ratio (ZSR) is a measurement similar to the determination of the erythrocyte sedimentation rate (ESR) but possesses sevaral advantages. It is unaffected by anemia and responds in a linear manner to increase in fibrinogen and/or gamma globulin. The normal range is identical for males and females. A blood sample, contained within a vertically oriented capillary tube, is subjected to four cycles of dispersion and compaction. At the conclusion of this process, the hematocrit of the blood in the red cell-containing portion of the capillary tube is measured. This hematocrit, a measure of the closeness with which red cells will approach each other under a standardized stress, is the ZSR.
The In Vivo Seeding of Hemopoietic Colony-forming Cells in Irradiated Mice
Authors: Testa N. G. , Lord B. I. , Shore N. A.
Published: October 2019

The seeding of transplanted CFUc and CFUs in the spleen and femur of irradiated mice has been investigated in order to compare their kinetic behavior following transplantation. The conditions in which the seeding of transplanted CFUc into lethally irradiated recipient mice can be studied were determined. Irradiated femoral or splenic cells produce potentiation of colony growth when added in relatively low numbers and result in serious inhibition at higher concentrations. By using a preirradiated recipient in which the postirradiation cell loss has been completed, rather than one that has only just been irradiated, changes in plating efficiency during the course of the experiment are prevented in the spleen and are maintained constant in the femur. It is shown that significant numbers of CFUc and CFUs quickly appear in both the spleen and bone marrow after transplantation. A fall in CFUc numbers occurs after 2-3 hr both in femur and spleen, while CFUs numbers remain stable. The possible mechanisms involved are considered, and differentiation is suggested as the cause of the fall.
Evidence for the De Novo Synthesis of Erythropoietin in Hypoxic Rats
Authors: Schooley J. C. , Mahlmann L. J.
Published: October 2019

Significant increases in the serum erythropoietin of male rats occur after the end of a brief hypoxic exposure. These increases in the hormone are almost completely abolished when the kidneys are removed after the hypoxic exposure. Injection of puromycin or cycloheximide after the hypoxic exposure significantly decreases the subsequent increases in serum erythropoietin titers, whereas injections of actinomycin D at this time have no significant effect on erythropoietin levels. Injections of actinomycin D before the hypoxic exposure prevent the increase in serum erythropoietin that normally occurs. These findings suggest that a brief period of hypoxia initiates a DNA-dependent RNA synthesis that regulates the de novo ribosomal synthesis of protein(s) involved in the biogenesis of erythropoietin and that the kidney is essential for these reactions to occur.
Cellular Immunity to Platelets in Idiopathic Thrombocytopenic Purpura
Authors: Wybran Joseph , Fudenberg H. Hugh
Published: October 2019

The possibility of cell-mediated immune mechanisms against platelets in idiopathic thrombocytopenic purpura (ITP) was suggested in a previous observation. Therefore, the uptake of labeled thymidine by the lymphocytes of 14 patients with ITP and of 16 controls was studied in vitro in the presence of autologous platelets. The control group (normal subjects and patients with nonimmune thrombocytopenia) never demonstrated any sigficant uptake of thymidine in this autologous system. Positive stimulation, as judged by thymidine uptake, occurred in seven of eight patients with severe ITP, whereas only three of six patients with mild ITP showed significant stimulation. Two patients with severe ITP, studied 4 and 6 days after splenectomy, showed a conversion to negativity in the test. These results indicate that cellular immune mechanisms against autologous platelets are present in ITP and suggest that they may play a role in the pathogenesis of the disease. It is suggested that ITP may represent more than one disease.
Successful Management of a Subdural Hematoma in a Hemophiliac With an Anti-Factor VIII Antibody
Authors: Edson J. Roger , McArthur James R. , Branda Richard F. , McCullough J. Jeffrey , Chou Shelley N.
Published: October 2019

A 20-yr-old hemophiliac with an anti-Factor VIII antibody level of 8 units/ml of plasma was hospitalized with a subdural hematoma and progressive neurologic deterioration. He underwent craniotomy and evacuation of the hematoma, and was discharged with minimal neurologic deficit. His successful management required two exchange transfusions utilizing an Aminco continuous flow Celltrifuge, immunosuppression with cyclophosphamide and corticosteroids, ε-aminocaproic acid (EACA), and large doses of AHG concentrates. Complications included hemolysis and platelet dysfunction due to hyperfibrinogenemia, leukopenia, and Gram negative sepsis. The cost of the patient’s 6½ wk hospitalization was $58,751, of which $38,039 was for AHG concentrates.
Cell Kinetics in Human Acute Lymphoblastic Leukemia: Computer Simulation With Discrete Modeling Techniques
Authors: Mauer Alvin M. , Evert Carl F. , Lampkin Beatrice C. , McWilliams Nancy B.
Published: October 2019

A model for cell kinetics of human acute lymphoblastic leukemia has been constructed with discrete modeling techniques for computer use with the GPSS/360 computer language. The model has produced results corresponding to observed biological data. It has been possible to explore mechanisms for control of the growth of the leukemic cell population. In addition to the flow of cells from the resting to the proliferative phase, two other important parts of the cell life cycle, cell death and the intracellular events after mitosis, were identified as potentially important regulatory mechanisms. Chemotherapeutic drug effects could be simulated, and in the case of vincristine an unsuspected effect was suggested. This effect of vincristine on transformation of the resting cell to an active proliferative phase has been supported by studies of vincristine effect on blast transformation of phytohemagglutinin-stimulated lymphocytes. A single cell was found to take 3½ yr to grow to a population of 1012 cells, a clinically recognizable number. Although this observation cannot be confirmed from biological studies, this time has an interesting correspondence to the peak incidence of acute lymphoblastic leukemia in childhood. It indicates that a mutational event in a single cell could account for the leukemic process in childhood acute leukemia.
Humoral Stimulators of Granulocyte Production
Authors: Rothstein G. , Hügl E. H. , Chervenick P. A. , Athens J. W. , Macfarlane J.
Published: October 2019

These studies were designed to determine whether colony stimulating factor (CSF) and diffusible granulocytopoietic stimulator (DGS) represented a single substance which stimulates the production of granulocytes in vitro and in vivo. The effect of endogenous CSF upon DGS activity was studied after injection of 40 µg endotoxin. This resuited in both DGS activity and high serum CSF levels, but the time of appearance and duration of the two activities followed different patterns. In particular, CSF peaked and was declining 24 hr following endotoxin at which time DGS was not yet detectable. Then, as serum CSF fell, the DGS activity rose. These data support the concept that the DGS activity detectable with short term Millipore chamber cultures is not due to CSF and suggests the effects of CSF in vitro and DGS in vivo are due to different factors.
Prognosis of Acute Myeloblastic Leukemia: Chromosomal Correlation
Authors: Sakurai Masaharu , Sandberg Avery A.
Published: October 2019

A correlation was made between chromosomal findings in the marrow of AML patients obtained during the course of the disease, some of the clinical and cytologic features, and the survival span of these patients. The median survival time for each patient was obtained by the use of log-probability paper. Of the 69 patients with AML studied, 29 showed abnormal metaphases in the marrow at least once during the course of the disease (A-patients) and 40 did not (N-patients). In the former group, ten cases were never shown to have a normal metaphase (AA-patients), even upon repeated examinations, whereas the remaining 19 cases had at least one normal metaphase during the course of the AML (AN-patients). The median life-span for the A-patients was 8.0 mo and 11.5 mo for the N-patients. Among the former group, the AN-patients had a median life span of 10.3 mo and the AA-patients only 3.2 mo. A dissociation between the proportion of cells with chromosomal abnormalities and the cellular differential in the marrow suggested the appearance of the karyotypic changes in the later stages of the disease in some patients and the presence of such changes in both erythroid and myeloid cells in erythroleukemia. The results indicate the importance of the presence in the marrow of even one normal metaphase in the prognosis of AML and a possible correlation of AA-patients with acute erythroleukemia.
The Monocytopenia of Aplastic Anemia
Authors: Twomey J. J. , Douglass C. C. , Sharkey O.
Published: October 2019

Eight out of 22 patients with aplastic anemia died from infections. All five patients with fewer than 100 granulocytes and 20 monocytes per cu mm of blood succumbed to overwhelming sepsis. The relationship that existed between absolute granulocyte and monocyte counts made it impossible to determine whether neutropenia or monocytopenia carried the greater risk. Monocytopenia correlated with reduced numbers of phagocytic cells in WBC cultures. This lack of phagocytes was associated with impairment of macrophage-dependent reactions, e.g., the mixed WBC reaction. The data suggest that aplastic anemia reduces the delivery of macrophage precursors into the circulation; this could ultimately deplete tissues of macrophages. Thus, monocytopenia, as well as neutropenia, may contribute to the risk from infection in patients with bone marrow failure.
Relationship of Glucose Oxidation to Aggregation of Human Platelets
Authors: Chaudhry Asif A. , Sagone Arthur L. , Metz Earl N. , Balcerzak Stanley P.
Published: October 2019

The effect of aggregating agents on the hexose monophosphate shunt (HMPS) and the relationship of 14CO2 production to platelet aggregation were studied in normal volunteers. Platelets collected in ACD were suspended in modified Ringer’s bicarbonate buffer without washing and were studied before and after the addition of collagen, adenosine diphosphate (ADP), epinephrine, or thrombin. HMPS and Kreks cycle activities were estimated by the yields of 14CO2 from glucose-1-14C (C1) and glucose-6-14C (C6). 14CO2 production from each substrate was measured continuously during experiments using paired, vibrating reed electrometers and incubation flasks. Both flasks contained aliquots of the same platelet suspension. Baseline 14CO2 production averaged 22 ± 4.5 mµmoles/hr/109 platelets from C6 as compared to 33 ± 6 mµmoles/hr/ 109 platelets from C1. Each aggregating agent gave a prompt and striking increase in 14CO2 production from C1. In contrast, the increase in 14CO2 production from C6 was not detectable for 10 min and then production increased slowly. Inhibition of 14CO2 nate (25 mM) did not interfere with platelet aggregation. Stimulation of 14CO2 production from C1 by aggregating agents was unaffected by malonate. These data indicate that platelet aggregation coincides with stimulation of the HMPS, but the increase in Krebs cycle activity occurs later and is not essential for platelet aggregation.
Iron Fortification of Food: Its Measurement by the Extrinsic Tag Method
Authors: Layrisse M. , Martãnez-Torres C. , Cook J. D. , Walker R. , Finch C. A.
Published: October 2019

The assimilation of fortification iron has been studied in 228 subjects by the extrinsic tag method. The first study was made comparing the absorption from ferric and ferrous iron salts given with a complete meal. Labeled wheat enriched with 2 mg of iron as ferric chloride was given with a complete meal, and the same study was repeated in the same subjects with wheat enriched with ferrous sulfate. The same protocol was followed in the second study, but the meal contained no meat. Ferric chloride was absorbed, as well as ferrous sulfate in both studies. Multiple absorptions were performed from test meals containing foods of either animal or vegetal origin tagged biosynthetically with 55Fe (intrinsic tag) to which was mixed iron as 59FeCl3 (extrinsic tag) in doses from 0.5 to 60 mg of iron. With test meals of labeled maize given along or with unlabeled meat, the ratio of extrinsic to intrinsic tag absorption was close to unity along a wide range of absorption percentage and was independent of the dose of iron fortification administered. It is concluded that fortification iron added as a soluble iron salt mixed with the nonheme iron pool of the diet and its absorption reflects the absorption of the nonheme iron. Similar studies in which increasing doses of 59FeCl3 were added to a test meal of tagged animal meat showed a progressive fall in the ratio of extrinsic to intrinsic tag absorption, indicating that assimilation of dietary iron occurs from two independent pools—heme and nonheme iron. Absolute absorption of fortificaiton iron added to maize increased from 0.07 to 0.34 mg iron with an increase in the dose of nonheme iron from 2.5 to 62 mg. Over a similar dose range of fortification iron added to animal muscle, absorption increased from 0.17 to 3.3 mg iron. These studies indicate that food iron fortification is likely to be effective only in individuals who take animal protein as part of their diet.
Rabbit Heart Valve Basement Membrane: Low Platelet Reactivity
Authors: Suresh Arcot D. , Stemerman Michael B. , Spaet Theodore H.
Published: October 2019

Electron microscopic studies were performed on rabbit heart valves, and all four valves were found to be lined with a continuous basement membrane (BM). The valvular BM was liable to digestion by either trypsin or collagenase, but brief exposure to trypsin was suitable for desquamating endothelial cells, while leaving BM exposed and intact. Such preparations were used to determine their platelet reactivity with heparinized and citrated whole blood or with platelet-rich plasma. Although various conditions of exposure were used, including shaking and centrifugation, little or no platelet adhesion to the BM was observed. With similar conditions of exposure, preparations of collagen showed massive platelet adhesion accompanied by aggregation. This vascular BM was similarly nonreactive to platelets when endothelial cell removal was accomplished by mechanical methods. Rabbit valvular BM appears to be a poorly thrombogenic surface.
Kinetics of Lymphocytes in Chronic Lymphocytic Leukemia. I. Equilibrium Between Blood and a "Readily Accessible Pool"
Authors: Manaster J. , FrÜhling J. , Stryckmans P.
Published: October 2019

Seven patients with chronic lymphocytic leukemia were investigated by isotopic and electron microscopic techniques to study dynamic and morphologic aspects of the kinetics of their lymphocytes. Autotransfusion studies of labeled leukemic lymphocytes showed rapid equilibration of blood lymphocytes between the vascular space and a "readily accessible pool." With increasing absolute blood lymphocytosis (900/cu mm-670,000/ cu mm), the relative importance of the readily accessible pool to the vascular space gradually decreases from eleven to one. Electron microscopic studies of the postcapillary venules in lymph nodes suggest a passage of lymphocytes from the vessel lumen, through the endothelial cells and into extravascular sites. About 20% of lymphocytes counted within the perivascular sheet were found in the wall, irrespective of the blood lymphocytosis and akin to the situation found in hematologically normal persons. These studies indicate that the readily accessible pool is complex and consists of at least two spaces, one of which is the classical recirculation space. The vascular pool of leukemic lymphocytes, as do the blood lymphocytes in hematologically normal persons, participates in this recirculation. There is a second space that has yet to be defined anatomically.
Intravascular Hemolysis Associated With Intravenous Urea Infusions in Normal Individuals
Authors: Bensinger Thomas A. , Glader Bertil E. , Conrad Marcel E.
Published: October 2019

The infusion of normal volunteers with 6 M urea in 10% invert sugar solution caused intravascular hemolysis similar to that reported in patients with sickle cell anemia. In vitro studies demonstrated that hypertonic solutions of urea and invert sugar caused little hemolysis, but these solutions preconditioned erythrocytes for lysis when the cells were resuspended in isotonic solutions. The primary mechanism for hemolysis appeared related to osomotic lysis of cells, but direct membrane injury could not be excluded as a contributing factor.
Biochemical Abnormality of DNA Synthesis of Erythroblasts in Acute and Chronic Myeloid Leukemia
Authors: Ernst Peter , Baccarani Michele , Killmann Sven-Aage
Published: October 2019

Six patients with acute and chronic myeloid leukemia (AML and CML) showed a low incorporation of labeled DNA precursors into basophilic erythroblasts. Based on mitotic indices and the use of vincristine as a stathmokinetic tool, it was evident that brisk proliferation in this cell compartment took place. Microspectrophotometric determination of single-cell DNA content showed that a considerable fraction of the erythroid cells were in DNA synthesis without incorporating an exogeneously supplied DNA precursor. Following inhibition of the de novo synthesis of nucleoside triphosphates, the cells showed capacity for precursor incorporation. It is suggested that a biochemical abnormality, which leads to a high intranuclear nucleoside triphosphate pool, may inhibit nucleoside kinases and hence the utilization of labeled nucleosides, as well as diluting the labeled precursors. The defect should probably be considered to be a biochemical expression of "leukemicness" of the erythroid cells. The frequency of the phenomenon described here cannot be determined from the present study. The patients are part of a series of 44 patients who were studied with the purpose to investigate the effect of cytostatic treatment on the cell cycle of the leukemic cells. Many of the patients had so little erythropoiesis left that studies as those described here could not be carried out. Therefore, the reported frequency of 6/44 of the observed phenomenon is almost certainly an underestimate. Consequently, cytokinetic studies of erythropoiesis in CML and AML, using tracer techniques alone, must be evaluated with caution.
Increase in Circulating Stem Cells in Patients With Myelofibrosis
Authors: Chervenick Paul A.
Published: October 2019

In the article "Increase in Circulating Stem Cells in Patients With Myeloflbrosis" By Paul A. Chervenick (Blood, Vol. 41, No. 1, January 1973, pages 67-71) in Table 3 on page 70, the word "myeloblasts" should head column 3 and the word "myelocytes" should be included in column 4.
Granulopoiesis in Neutropenic Disorders
Authors: Greenberg Peter L. , Schrier Stanley L.
Published: October 2019

Evaluation of proliferative activity of granulocytic progenitor cells from marrows of neutropenic patients was performed by utilizing in vitro culture methods measuring granulocytic colony-forming capacity (CFC) and the proportion of granulocytic progenitor cells in the DNA synthetic (S) phase of the cell cycle. Except for low CFC values found in five patients with myeloid hypoplasia, the remaining 20 patients had values comparable to or above those of 22 control subjects. In five control subjects 31%-39% of the progenitors were in S phase. The proportion of such cells from marrow of a patient with cyclic neutropenia markedly increased as his peripheral neutrophils decreased from peak to lowest levels. In patients with splenomegaly or megaloblastic anemia, where rapid granulocyte turnover was expected, the proportion of progenitors in S phase was increased. In contrast, in patients with idiopathic neutropenia and Felty’s syndrome this proportion was normal or decreased, suggesting that suboptimal granulopoietic compensation contributed to the neutropenia present in these disorders.
Isoantibody Specificity in Post-transfusion Purpura
Authors: Gockerman Jon P. , Shulman N. Raphael
Published: October 2019

Antiplatelet antibody in the serum of a fatal case of post-transfusion purpura showed specificity for the PlA1 platelet isoantigen in that the antibody was adsorbed by all PlA1-positive platelets tested but not by PlA1-negative platelets. However, some PlA1-positive platelets that fixed complement with the reference anti-PlA1 did not fix complement with this patient’s antibody. When used with these platelets, the patient’s antibody competitively blocked the complement-fixing activity of reference anti-PlA1. There was no evidence for lack of antigenic sites on the noncomplement-fixing platelets or for antibodies with more than one specificity in the patient’s serum. These studies, therefore, indicated that the complement-fixing activity of different examples of anti-PlA1 is variable, and that this variation is probably due to distribution of PlA1 antigenic sites on cell surfaces rather than to differences in antigenic structure that affect antibody affinity.
The Biconcavity of the Red Cell: An Analysis of Several Hypotheses
Authors: Bull Brian S. , Brailsford J. Douglas
Published: October 2019

New evidence is presented to show that the dimple and the annulus of the red cell are not restricted to specific locations on the membrane. This eliminates all but one of the current theories of biconcavity and supports the view that the membrane has unusual mechanical properties such that, although it cannot support surface shear, it can resist both bending and increase in total surface area. The feasibility of such a material is demonstrated by means of a macromodel. The model represents a class of structure that until recently has received little attention but that strongly suggests long-range protein interaction in the membrane surface.
The Effect of Iron Deficiency on the Expression of Hemoglobin H
Authors: O’Brien Richard T.
Published: October 2019

Two brothers with hemoglobin H disease are described. In one boy, a concomitant iron deficiency was associated with a complete suppression of hemoglobin H in the peripheral blood. The effects of iron on globin synthesis are discussed.