bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Amyloidosis Associated with Cyclic Neutropenia in the Dog
Authors: CHEVILLE N. F.
Published: October 2019

Amyloid occurred in the spleen, liver, and kidney after recurrent episodes of fever and infection in dogs affected with cyclic neutropenia (gray collie syndrome). In areas of splenic amyloid formation, large reticular cells contained polyribosomal material and amyloid fibrils, but endothelial cells did not. Early in the disease, the dogs were slightly hypergammaglobulinemic, whereas those examined terminally with amyloidosis had lowered gamma-globulin levels Neutrophilic leukocytes appeared normal when examined by electron microscopy.
Metabolic Interrelationship between Vitamin B12 and Ascorbic Acid in Pernicious Anemia
Authors: KAHN SIGMUND BENHAM , BRODSKY ISADORE , Fein Sandra A.
Published: October 2019

An interrelationship between vitamin C and vitamin B12 was studied in three patients with vitamin B12 deficiency associated with pernicious anemia. Subnormal plasma ascorbate concentrations were found prior to therapy confirming previous observations. Following vitamin B12 administration and utilizing methylmalonate (MMA) excretion as a biochemical index of vitamin B12 deficiency, low plasma ascorbate concentrations persisted until MMA excretion was abolished. In two patients, RBC vitamin B12 activity was also serially measured in order to evaluate its sensitivity as an index of vitamin B12 stores when compared to MMA excretion. The data demonstrate that in these two vitamin B12-deficient patients undergoing slow repletion therapy, RBC vitamin B12 activity returns to normal before MMA excretion is abolished.

Whether continued MMA excretion in these patients indicates a greater sensitivity of MMA excretion as an index of deficiency of vitamin B12 stores than does RBC vitamin B12 activity remains to be answered by future work.
Blood Formation in the Pregnant Mouse
Authors: FRUHMAN GEORGE J.
Published: October 2019

Pregnancy in mice was accompanied by increased erythropoiesis which was most marked in the spleen and was reflected peripherally by increased percentages of circulating erythrocytes. During the last four or five days of pregnancy, there was an equally significant drop in erythropoiesis to normal or below normal values and this occurred despite a falling hematocrit. It is suggested that the changing oxygen requirement of the fetuses may be the primary determinant of these erythropoietic changes.
Proliferation of Megaloblasts in Pernicious Anemia as Observed from Nucleic Acid Metabolism
Authors: YOSHIDA YATARO , TODO AKIO , SHIRAKAWA SHIGERU , WAKISAKA GYOICHI , UCHINO HARUTO
Published: October 2019

In order to elucidate the nature of the megaloblastic lesion at the cellular level, DNA, RNA, and protein synthesis was studied in megaloblasts of pernicious anemia. While microphotometric estimation of DNA content showed an increase in cells with DNA values ranging around the 4c value, autoradiographic studies with H3-thymidine indicated, rather, a decreased ability to synthesize DNA. Combined microphotometric and autoradiographic studies suggested the impaired DNA synthesis with occasional arrests of synthesis, as well as the prolongation of the S period with or without the prolongation of the G2 period. On the other hand, active incorporation of H3-uridine and H3-leucine indicated active or unaffected RNA and protein synthesis. Vitamin B12 treatment rapidly corrected these aberrant patterns of synthesis. The significance of these findings has been discussed in relation to the mechanism of megaloblastic hemopoiesis.
Immunofluorescent Studies of Human Leukemic Cells with Antiserum to a Murine Leukemic Virus (Rauscher Strain)
Authors: IOANNIDES ANGELIKI KATRAHOURA , ROSNER FRED , BRENNER MARTIN , LEE STANLEY L.
Published: October 2019

Cells from bone marrow aspirates and liver, kidney and spleen imprints from patients with leukemia and other nonleukemic hematological and non-hematological disorders were tested for reactivity with murine leukemia (Rauscher) virus antibody using the technique of immunofluorescence. The cells of all eleven patients with acute lymphoblastic leukemia and four out of five patients with chronic lymphatic leukemia reacted strongly. In only six of the 15 patients with myelogenous leukemia and approximately one-third of the 47 patients with miscellaneous disorders (Table 1) was strong immunofluorescence demonstrated.
Brief Report: The Development of Lymphomas in Mice with Autoimmune Disorders Treated with Azathioprine
Authors: CASEY T. P.
Published: October 2019

Administration of azathioprine causes suppression of lupus nephritis in NZB x NZW F1 hybrids. Malignant lymphoid neoplasms, particularly affecting the thymus, occurred in 7 out of the 12 mice treated. Similar neoplasms developed in 6 out of 8 young NZB mice treated with azathioprine. No such tumors occurred in the control animals.
Regeneration of Locally Irradiated Bone Marrow. II. Induction of Regeneration in Permanently Aplastic Medullary Cavities
Authors: KNOSPE WILLIAM H. , BLOM JOHANNES , CROSBY WILLIAM H.
Published: October 2019

Marrow cavities permanently aplastic after irradiation were mechanically disrupted and locally injected with bone marrow obtained from an opposite leg. Hemopoietic bone marrow regenerated with restoration of normal parenchymal and sinusoidal architecture. Mechanical disruption alone or intravenous transfusions of isogeneic bone marrow alone failed to induce any evidence of regeneration of the aplastic marrow.
Treatment of Chronic Lymphocytic Leukemia by Extracorporeal Irradiation
Authors: STORB R. , EPSTEIN R. B. , BUCKNER C. D. , THOMAS E. D.
Published: October 2019

Six patients with advanced chronic lymphocytic leukemia were treated with extracorporeal irradiation and followed for one to three years. There was a marked reduction in the circulating white cells in all patients, but in four cases the white cell counts returned to high levels in 3-7 months. Two patients are in good partial remission 37 and 22 months after the initial course of ECI. Clinical and hematological events in these cases are detailed.

It was concluded that ECI is effective in lowering leukocyte levels without systemic toxicity and is beneficial in some cases of chronic lymphocytic leukemia.
Brief Note: A Screening Test for the Presence of Urinary Lysozyme (Muramidase)
Authors: SNAPPER I. , SELD D.
Published: October 2019

A screening test for increased concentrations of lysozyme (muramidase) in the urine is described.
Hypothesis: A Case of Multiple Autoimmune Disease, Lymphoid Proliferation and Hypogammaglobulinaemia
Authors: SAGE R. E. , FORBES I. J.
Published: October 2019

A 75 year old woman who had had rheumatoid arthritis for 21 years and Sjögren’s syndrome for 12 years developed autoimmune hemolytic anemia. Antibodies to tissue extracts, erythrocytes, cell nuclei, and altered γ-globulin were detected in the serum, although the serum γ-globulin level was low.

The bone marrow was densely infiltrated by lymphocytes having similar abnormalities to the circulating lymphocytes.

Analysis of the proteins synthesized by the peripheral lymphocytes showed a relatively low output of immunoglobulins.

The hemolytic process was controlled by azathioprine after unsuccessful treatment with prednisolone.

A hypothesis is put forward to explain the not infrequent association of multiple autoimmune disorders, lymphoproliferative disease and disorders of immunoglobulin synthesis such as hypogammaglobulinemia and paraproteinemia. It is suggested that the disturbance of immunological function in such cases occurs at the site of recruitment for immunological activity in the peripheral lymphoid organs, constituting a disturbance of terminal immunological differentiation. The basic abnormality may, therefore, be found in the supporting cells of the lymphoid organs.
Fine Structural Alterations Induced in Platelets by Adenosine Diphosphate
Authors: WHITE JAMES G.
Published: October 2019

Blood platelets exposed to the nucleotide adenosine diphosphate (ADP) lose their discoid appearance and adhere to one another. The basis for the ADP induced shape change has remained obscure. In the present study the structural transformations of platelets under the influence of ADP have been examined in the electron microscope. Loss of lentiform appearance is closely related to a marked reorganization of the platelet hyaloplasm. The marginal bundle of microtubules decreases in circumference and is moved into the interior of the platelet. Granules and other organelles are transported to the cell center where they are enveloped within a web of microtubules and microfilaments. These changes are completely reversed after the influence of ADP disappears. The movement of the circumferential bundle of microtubules from its position under the cell wall appears to be the principle cause for the loss of discoid shape. Constriction of hyaloplasmic elements followed by complete recovery of unaltered appearance are indicative of a reversible wave of contraction occurring in the platelet hyaloplasm. Thus the change in platelet surface contour after exposure to ADP is not due to a direct modification of the cell wall by ADP, but to a contractile wave which ADP indirectly triggers in the substance of the cells.
Brief Report: Variations in the Response of Childhood Iron Deficiency Anemia to Oral Iron
Authors: MCNIEL JAMES R.
Published: October 2019

Of 182 infants and children with iron deficiency anemia treated with prescribed oral ferrous sulfate in a dose of approximately 2 mg./kg. body weight two or three times daily 131 (72.0 percent) responded promptly to one month of treatment. Forty-nine (26.9 percent) had a delayed response or responded to an intramuscular iron preparation. The most likely reasons for the delay in the response of this group included the following: (1) The total dose of iron prescribed in 1 month appeared insufficient. (2) The child fought the medication and it was not given properly by the parents. (3) The oral iron caused vomiting or diarrhea and was subsequently not given. (4) The parents appeared unconvinced of the necessity or efficacy of the medication. (5) The response was delayed by repeated infections. Several of these factors were often present in the same patient. Thus many seeming failures to respond to iron may be due to these problems and not to iron being improper therapy.
Preliminary Report: Anticoagulant Therapy in Chronic Idiopathic Thrombocytopenic Purpura
Authors: COHEN RICHARD J. , DENNIS LEWIS H. , CONRAD MARCEL E.
Published: October 2019

The response of a patient with chronic severe idiopathic thrombocytopenic purpura (ITP), refractory to all forms of therapy, to the controlled use of anticoagulation is described. A significant elevation of the platelet count and clinical improvement accompanied the use of heparin and was sustained for a two-week period. In addition, a short-lived response was obtained with warfarin sodium. Studies of the patient’s coagulation factors during the trial of heparin therapy indicated that accelerated intravascular coagulation was not an explanation for the thrombocytopenia or for the response to anticoagulant therapy. These results provide additional evidence that anticoagulant drugs affect blood platelet economy and indicate that further investigation of the underlying mechanisms is needed.
Blood Cell Separation in the Dog by Continuous Flow Centrifugation
Authors: BUCKNER DEAN , EISEL ROBERT , PERRY SEYMOUR
Published: October 2019

A closed continuous flow centrifuge was used to separate and collect large quantities of buffy coat cells from the dog. One hundred fifty-five separate centrifugations of 2-12 hours duration were performed. Up to 61.0 liters of blood, representing 2.2-52 donor blood volumes, were processed. Buffy coat cells with a preponderance of granulocytes or lymphocytes, were collected while plasma and red blood cells were returned to the donor without change in flow or gravitational field. The mean total number of leukocytes, granulocytes, mononuclear cells and platelets removed was 24.0, 17.0, 7.0 and 197.0 x 10,9 respectively, which was 34.0, 28.0, 66.0 and 36.0 percent, respectively, of each cell population entering the centrifuge.

The effect of centrifugation on blood components was evaluated. Granulocytes from buffy coat collections exhibited normal phagocytic ability in vitro. The transfusion of large quantities of granulocytes (15.0 x 109) into leukopenic dogs produced an increment in peripheral granulocyte count (2.7 x 103 per mm.3). Granulocytes labeled with 3H-DFP were also infused with a recovery of 38.6 percent at one hour and a T-½ of 4-6 hours. Machine-separated lymphocytes responded normally to phytohemagglutinin. Prolonged passage of blood through the pumps, tubing and bowl without centrifugation resulted in a decrease in circulating platelet levels (21 percent). A greater decrease in platelets occurred with centrifugation at high g. forces (49 percent). Hemolysis of red blood cells was not a serious problem.
The Ultrastructure of an Abnormal Cell in Sézary’s Syndrome
Authors: LUTZNER MARVIN A. , JORDAN HAROLD W.
Published: October 2019

Sézary described a characteristic cell found in a syndrome which bears his name. This syndrome is manifested by erythroderma, lymphadenopathy, and abnormal circulating cells. The electron microscope was used to study skin, lymph nodes, and blood from three Sézary patients and all demonstrated characteristic cells. The nucleus of this Sézary cell was strikingly irregular, indented, lobulated, and serpentine, often narrowed to a single row of nuclear particles. The cytoplasm exhibited no abnormalities. No abnormal cells similar to those described have been found in any control tissues studied.
Regulation of Erythropoiesis in the Friend Leukemia Mouse
Authors: SASSA SHIGERU , TAKAKU FUMIMARO , NAKAO KIKU
Published: October 2019

Friend leukemia infection in ddO mice produced a marked increase in the erythropoietic activity of the affected mice. By the fact that the increased erythropoietic activity was not suppressed by the transfusion polycythemia and that the plasma and spleen extract of the infected animal showed no erythropoietic activity, it is postulated that erythropoiesis in Friend leukemia is governed by mechanisms other than normal ones. The possible role of the virus in differentiating the stem cell into erythroblasts is discussed.
Leiomyoma and Erythrocytosis: A Tumor Producing a Factor Which Increases Erythropoietin Production. Report of Case
Authors: FRIED WALTER , WARD HARRY P. , HOPEMAN ALAN R.
Published: October 2019

A patient with a leiomyoma of the esophagus and erythrocytosis is reported. Preliminary studies in mice suggest that the tumor contained a substance which was capable of increasing erythropoietin production by the kidneys. Because of the limited amount of tumor available, we were unable to further characterize this substance. We hope that this report will encourage other investigators to repeat and extend these studies.
Brief Report: Intrinsic Factor in Tropical Sprue
Authors: WHEBY MUNSEY S. , BAYLESS THEODORE M.
Published: October 2019

Using an in vitro assay for gastric intrinsic factor, it was shown that seventeen of twenty-three patients with treated and untreated tropical sprue have adequate intrinsic factor in their gastric juice.
Morphologic Evidence for the In Vivo Activity of Transfused Chronic Myelogenous Leukemia Cells in A Case of Massive Staphylococcal Septicemia
Authors: SHOHET STEPHEN B.
Published: October 2019

Morphologic and clinical evidence for the in vivo activity of white blood cell transfusions in a previously well young man with marrow depression and staphylococcal septicemia is presented. No underlying malignancy or chronic immunosuppressive therapy was present.

Characteristics and problems of white blood cell transfusions are discussed with special emphasis on the site and clinical importance of tissue sequestration of the transfused cells.
Tubular Elements in Platelet Granules
Authors: WHITE JAMES G.
Published: October 2019

Improved fixation of platelets has facilitated recognition of tubular elements in the hyaloplasm of the cells. Marginal band microtubules, hyaloplasmic microtubules, and a system of tubular channels have been dealt with in several publications. The purpose of this investigation is to describe a third type of tubular element in platelets which has not previously been reported. Observation of the substructure of hyaloplasmic particles in normal platelets has revealed small, tubelike elements occurring singly or in groups of two or three in many granules. Exposure of platelets to digitonin shock appears to increase the number of tubular elements inside the particles. The tubelike components in granules superficially resemble microtubules, but their origin, nature, and function remain obscure.
Hereditary, X-Linked, Sideroachrestic Anemia. The Isolation of Two Erythrocyte Populations Differing in Xga Blood Type and Porphyrin Content
Authors: LEE G. R. , MACDIARMID W. D. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

1. Two morphologically distinct populations of erythrocytes were found in a mother and in two of her daughters, one of whom (the proband) was anemic. One erythrocyte population was morphologically normal; the other was hypochromic and microcytic.

2. The X-linked blood group antigen, Xga, was present in erythrocytes from the mother and the two daughters, but not in erythrocytes from the father. The daughters were, therefore, heterozygous for the gene controlling this antigen.

3. Separation of the two populations of erythrocytes was accomplished by centrifugation in layered gum acacia solutions of different specific gravity.

4. The microcytic cells from the three affected individuals were Xga-positive. Isolated normal cells were Xga-positive in the mother, but negative in both daughters.

These data suggest that the erythrocyte defect is X-linked and that the phenomenon of X-inactivation applies to genes controlling both the morphologic defect and the Xga antigen.

5. The free protoporphyrin content of the isolated microcytes was lower than that of the normal cells. The capacity of the microcytes to convert delta-aminolevulinic acid to protoporphyrin was unimpaired.

On these bases it is suggested that the hereditary defect lies either at or before the step in which delta-aminolevulinic acid is synthesized.
Functional Cytogenetic and Cytochemical Study of the Leukemic Reticulum Cells
Authors: YAM L. T. , CASTOLDI G. L. , GARVEY M. B. , MITUS W. J.
Published: October 2019

Morphologic, cytochemical, functional, and chromosomal studies were performed on cells from blood and the spleen of a patient with leukemic reticuloendotheliosis. Characteristics of these cells were further defined by histochemical studies, by their removal by the cotton-filtration process, by their negative response to PHA stimulation, and by their poor phagocytic properties. Chromosomal studies in this case showed abnormal patterns in cells from the spleen. This abnormal pattern was characterized by the presence of an abnormal chromosome in A group, extra chromosome in C group, and monosomy in G group.
Hemoglobin JOxford: Effects on Hemoglobin and Erythrocyte Function
Authors: GILCHER RONALD O. , BROMBERG PHILIP A. , FINN FRANCES M. , JENSEN WALLACE N.
Published: October 2019

Hemoglobin JOxford (α215 gly→asp β2A) was found to constitute 20 per cent of the hemoglobin in eight members of an Italian-American family. In the heterozygous state, no clinical stigmata referable to the variant Hb were found. Erythrocyte morphology and survival were normal. No evidence of Hb instability was found. Oxygen-affinity studies of whole blood, whole hemolysates and isolated Hb JOxford were normal. A brief review of the literature on J hemoglobins is included.
Myasthenia Gravis in a Patient with Chronic Myeloid Leukemia Treated by Busulfan
Authors: DJALDETTI MEIR , PINKHAS JACK , DE VRIES ANDRE , KOTT EDNA , JOSHUA HENRY , DOLLBERG LEAH
Published: October 2019

Myasthenia gravis and roentgenologic evidence of a mass in the anterior mediastinum appeared in a patient with chronic myeloid leukemia following busulfan treatment.

X-ray irradiation of the thymic area and subsequent surgical removal of the anterior mediastinal mass were followed by remission from the myasthenia gravis. Histologic examination of the mass showed involuted thymic remnants without evidence of leukemic infiltration or of malignant thymoma.

The possible etiology of the myasthenia gravis in this patient, with special reference to a busulfan-induced autoimmune process, is discussed.
Studies on the Energy Metabolism of Human Leukocytes II. Mechanism of the Pasteur Effect in Human Leukocytes
Authors: BAIERLEIN JEAN L. , FOSTER JOHN M.
Published: October 2019

1. The control of glycolysis by respiration in normal human leukocytes was studied under conditions in which a Pasteur effect was present and under conditions in which this effect was lost.

2. There was a 20-50 per cent Pasteur effect in leukocytes isolated by dextran sedimentation of heparinized blood and suspended in isologous serum. Crossover point analysis of glycolytic intermediates indicate that phosphofructokinase becomes rate-limiting for aerobic glycolysis and that this enzyme is primarily responsible for the Pasteur effect.

3. Studies on the activity of PFK in leukocyte homogenates showed that this enzyme is competitively inhibited by ATP and reactivated by ADP and Pi. The concentrations of these compounds which significantly effect PFK activity in homogenates fall within the range found in intact cells. The differences in PFK activity in intact cells under anaerobic and aerobic conditions can therefore be attributed to allosteric effects caused by an increase in the concentration of ATP on transition to aerobic conditions, with concomitant decreases in the levels of ADP and Pi.

4. Leukocytes isolated by the same procedure but suspended in an artificial medium rather than serum did not show a Pasteur effect. There were no differences between the aerobic and anaerobic concentrations of ATP, ADP, and Pi, and there was no control point at PFK. It is suggested that a change in respiratory function is responsible for the altered control of glycolysis in leukocytes suspended in nonserum media.
A Study of Hematological Complications Occurring in Patients with Polycythemia Vera Treated with 32P (Based on a series of 296 patients)
Authors: TUBIANA M. , FLAMANT R. , ATTIE E. , HAYAT M.
Published: October 2019

Three hundred and three patients with polycythemia vera have been treated with 32P more than five years ago. Seven patients have been excluded because they have been treated by 32P elsewhere before their first visit. Of the 296 other patients, 269 have been followed up regularly for more than 5 years. The median survival after hematologic diagnosis is 14.5 years. It is shorter in older patients and in those patients who had the shortest remissions after the initial 32P treatment. Of 145 patients who had died, death was due in 53 cases to hematologic complications (29 acute leukemia, 4 chronic leukemia, 16 myeloid metaplasia or myelofibrosis, 4 aplastic anemia). The latter complications were seen most commonly in those patients who had received the highest total dose of 32P, those with a high initial white count and those in whom the spleen was palpable at least 2 cm. beneath the costal margin.

The influence of the quantity of 32P given is very significant for equivalent clinical situations, the influence of white cell count and spleen size is significant for equal doses of 32P. This suggests that these two types of factors favor the early occurrence of hematologic complications.
Degradation of Membrane Phospholipids and Thiols in Peroxide Hemolysis: Studies in Vitamin E Deficiency
Authors: JACOB HARRY S. , LUX SAMUEL E.
Published: October 2019

To understand more clearly the hemolytic anemia associated with administration of certain oxidant drugs, the mechanism by which H2O2 causes hemolysis in rat red cells, deficient in vitamin E was investigated. It was demonstrated that the locus of attack by H2O2 was the red cell membrane, in which one phospholipid, i.e., phosphatidyl ethanolamine, was specifically destroyed prior to the onset of hemolysis. No perturbation of intracellular components or metabolism was noted during peroxidative hemolysis. E-deficient red cells incorporated 14C-labelled fatty acids into this phosphatide at nearly twice the rate that in E-supplemented cells, reflecting the continual tendency of phosphatidyl ethanolamine to be destroyed. Young red cells were especially active in this regard and concomitantly were less vulnerable to damage by H2O2 both in vitro and when circulating in rats exposed to hyperbaric oxygenation. If, however, replacement of fatty acids in phosphatidyl ethanolamine was prevented by inhibition of metabolism or if fatty acids were enzymatically removed by a phospholipase-A, H2O2 hemolysis was potentiated. Hemolysis was also associated with, and potentiated by, loss of membrane sulfhydryl activity. It is suggested that hemolytic anemia may occur in patients with vitamin E deficiency (i.e., with steatorrhea) if oxidant drugs capable of generating H2O2 and oxidizing membrane thiols are administered. Two such cases are under investigation.
Regulation of Erythropoiesis
Authors: KUBANEK BERNHARD , FERRARI LUIGI , TYLER WILLIAM S. , HOWARD DONALD , JAY SUSAN , STOHLMAN FREDERICK
Published: October 2019

The effect of hypoxia on red cell production and stem cells, as measured by CFU, was studied in two strains of mice. One of these strains, the CAF1, has been shown to produce relatively little erythropoietin in response to hypoxia; the other, the CF1, produces substantial amounts of erythropoietin. In the studies reported herein the CAF1 mice had an increase of ∼ 30 per cent in red cell mass after 23 days of exposure to either discontinuous (16 hrs./day) or continuous hypoxia equivalent to 23,000 feet of altitude. The CF1 mouse doubled its red cell mass after similar exposure. The splenic CFU decreased to as low as 17 per cent in the poorly responding CAF1 but remained at or near control levels in the CF1. It is suggested that the dissociation between erythroid response and changes in the CFU reflect a secondary effect of hypoxia not directly related to the erythropoietin-induced increase in red cell production.
The Erythropoietin/Hematocrit Relationship in Normal and Polycythemic Man: Implications of Marrow Regulation
Authors: ADAMSON JOHN W.
Published: October 2019

The relationship between erythropoietin excretion and change in hematocrit has been determined in normal and polycythemic subjects. Erythropoietin was measured by a method involving the assay of urinary concentrates in polycythemic protein-depleted mice. Basal erythropoietin excretion in normal subjects ranged from 2.8 to 7.5 Standard B units per day. Studies in subjects made anemic by bleeding demonstrated an inverse relationship between hematocrit and the log of erythropoietin excretion. Patients with hypoxia-induced erythrocytosis had increased levels of urinary erythropoietin when their hematocrit was reduced to normal levels by phlebotomy. Three patients whose erythrocytosis was associated with tumors had an erythropoietin excretion which remained constant over a wide range in hematocrit. In polycythemia vera, erythropoietin output was absent or markedly decreased at high hematocrit levels, but measurable erythropoietin appeared in the urine when the hematocrit was reduced to normal or anemic levels by bleeding.
Analytic Review: Von Willebrand’s Disease-Diagnostic Criteria
Authors: WEISS HARVEY J.
Published: October 2019

Our present criteria for diagnosing von Willebrand’s disease are summarized below and illustrative examples of recently studied patients are shown in Table 1.

A) Prolonged bleeding time and decreased AHG:

When these abnormalities, inherited as an autosomal dominant, are found in several family members, they are considered diagnostic for these patients and for their clinically affected relatives, even though the latter may now show both defects (Case 10). In the absence of family studies, the diagnosis would also be made in individual subjects if a history of bleeding in relatives was consistent with autosomal inheritance (Cases 3,13,18). When family studies are negative (sporadic cases) or no history is attainable, a diagnosis of typical von Wille-brand’s disease would also be made (Cases 1,2,4,14,15,16) unless intrinsic platelet defects were found (see below) or plasma transfusion failed to produce a progressive increase in AHG activity.

B) Prolonged bleeding time, normal AHG:

The diagnosis would be considered "probable" in such a patient if the following criteria were met:

1. There was no evidence of an "intrinsic" platelet abnormality, as indicated by normal values for platelet aggregation, PF-3 availability and ADP release by connective tissue and kaolin

and

2. Platelet adhesiveness, by the modified Salzman test, was abnormal and/or the patient’s bleeding time was shortened by transfusion of plasma in a dosage of 13-15 ml. per Kg. body weight.

C) Normal bleeding time, decreased AHG (Case 17):

A diagnosis of probable von Willebrand’s disease would be made if:

1. An unequivocal pattern of autosomal dominant inheritance, by history, ruled out hemophilia.

2. The Salzman test was abnormal.

3. Transfusion of hemophiliac, as well as normal plasma resulted in a progressive increase in plasma AHG concentration.

D) Normal bleeding time, normal AHG:

The diagnosis would be considered as "possible" if:

1. There was no evidence of intrinsic platelet abnormality (see B 1).

2. The Salzman test was abnormal.

The above criteria are tentative and, undoubtedly, will not satisfy all investigators. To confuse matters even more, some patients who appear to have the "classic" syndrome may also have abnormal platelet factor 338 or fail to "synthesize" AHG after plasma transfusion.13,38 Whether even the "classic" syndrome represents a spectrum of disorders remains to be determined.
Brief Report: Effect of Acute Administration of Acetysalicylic Acid on the Prothrombin Activity of Bishydroxycoumarin-Treated Rats
Authors: COLDWELL BLAKE B. , ZAWIDZKA ZOFIA
Published: October 2019

The administration of a single oral dose of acetylsalicylic acid (100 mg./Kg.) to bishydroxycoumarin-treated male albino rats significantly decreased the one-stage prothrombin time of blood collected 20 hr. after administration of the analgesic. This antagonistic effect of acetylsalicylic acid resulted in a mean increase of 12 per cent in the prothrombin activity of rats given the anticoagulant intraperitoneally compared to an increase of 6 to 7 per cent in those taking it orally. In the latter animals the intensity of the effect seems to be related to the time that elapses between administration of the two drugs.
Porphyrin Synthesis and Heme Synthetase Activity in Pyridoxine-Responsive Anemia
Authors: VOGLER WILLAM RALPH , MINGIOLI ELIZABETH S.
Published: October 2019

Previous in vitro studies had shown that reticulocytes from a patient with pyridoxine-responsive anemia (PRA) incorporated glycine-2-14C into heme at 11-25 per cent of the normal rate. Incorporation of the intermediate compound, δ-aminolevulinic acid-4-14C (ALA), varied from 46 to 81 per cent of normal. These findings suggested two defects in the synthesis of heme: a major one prior to formation of ALA, probably ALA synthetase, and a minor one somewhere between ALA and heme. This minor defect was investigated in a patient with PRA during a period of repeated phlebotomies resulting in a 30 gram reduction in iron stores. Porphyrin synthesis from ALA was measured in vitro and found to be normal. Heme synthetase activity in particulate fractions of reticulocytes measured by radioiron incorporation into heme was 50 per cent less than normal when the iron stores were high and significantly improved when the iron stores were reduced to normal. Repeat studies showed that incorporation of ALA-4-14C into heme by intact reticulocytes equaled the normal rate. Glycine incorporation was still reduced. Concomitant with the improvement in heme synthetase activity was an improvement in anemia. These results suggest that excess iron is a significant cause of the reduced heme synthetase activity observed in this patient with pyridoxine-responsive anemia.
Genetics of the Bombay Phenotype
Authors: YUNIS EDMOND J. , SVARDAL JANET M. , BRIDGES ROBERT A.
Published: October 2019

Seven individuals with the Bombay phenotype have been found among the thirty-three members of an Indian family spanning three generations. This is the first report of children resulting from the union of an individual of the Bombay phenotype hh and an individual heterozygous Hh at the Bombay locus. This family again demonstrates the effective suppression of the A-B-O phenotype by the Bombay genotype. Three Bombay individuals of this family were shown to be heterozygous at the Lewis locus. This had not been determinable in previously reported cases. This is consistent with the concept that there are two kinds of Bombay genotypes. We propose that the Lewis gene has evolved from a duplication of the H gene. Such duplication predisposes to both higher orders of duplication and to deletion. Deletions in this system would then provide the genetic basis for the Lewis-negative and the Bombay phenotype. In order to explain the rarity of the Lewis-negative Bombay phenotype by the proposed mechanism, we postulate that it would only arise by crossing over at the position determining the active site of the transferase enzymes which determine the Lewis and the H specificities.
Hemolytic Transfusion Reaction Occurring in a Patient with Acute Renal Failure
Authors: HOFFSTEN PHILLIP E. , CHAPLIN HUGH
Published: October 2019

An acute hemolytic transfusion reaction due to ABO-incompatibility occurred in a patient during the fifth week of oliguria secondary to post-traumatic acute renal failure. Resort to "plasma-exchange" transfusion to reduce the high level of free hemoglobin in the circulation was considered and rejected. Sequential measurements of free and haptoglobin-bound hemoglobin documented rapid disappearance of both components from the patient’s plasma in the absence of hemoglobinuria. Within one week, the patient entered the diuretic phase, and ultimately stabilized at normal levels of urine volume, with a creatinine clearance of 53 ml per minute. The implications of free hemoglobinemia in the oliguric phase of acute renal failure are discussed.
Paroxysmal Nocturnal Hemoglobinuria with Acute Leukemia
Authors: HOLDEN DOROTHY , LICHTMAN HERBERT
Published: October 2019

In a case of paroxysmal nocturnal hemoglobinuria, documented since 1955, the features of acute leukemia became evident in 1962, leading to quick death. Between 1960 and 1962, indications of PNH became greatly diminished and a slight, nonspecific leukocytosis developed. No apparent etiologic agent either for the PNH or the acute leukemia could be elicited.
Studies in Chronic Lymphocytic Leukemia: Further Studies of the Proliferative Abnormality of the Blood Lymphocyte
Authors: RUBIN ARNOLD D. , HAVEMANN KLAUS , DAMESHEK WILLIAM
Published: October 2019

Peripheral lymphocytes from patients with chronic lymphocytic leukemia were exposed to phytohemagglutinin in culture. Quantitative assessment of the proliferative response provided an in vitro test of lymphocyte function. The results were correlated with several clinical parameters, both hematologic and immune. Lymphocytes from patients with modestly elevated lymphocyte counts and mild disease manifested slightly delayed and depressed reactions to PHA. All immunoglobulin levels in these patients were also moderately reduced. Further delay and depression of the PHA response showed a rough correlation with progressive lymphocytosis and reduction in circulating immunoglobulins.

Kinetic and autoradiographic analyses have suggested that late-reacting lymphocytes formed distinct populations of abnormal cells which did not seem to be appreciably contaminated with normal lymphocytes, even in instances of mild disease. Only in a patient with splenic lymphosarcoma were multiple circulating populations of normal and late reacting lymphocytes detected simultaneously. In that case, at least some of the late-reacting lymphocytes appeared to originate in parenchymal lymphoid masses.

A definition of CLL could well include, not only the findings in the blood and bone marrow, but a statement of the reaction of the lymphocytes to phytohemagglutinin and of the immunoglobulin characteristics.
Food Iron Absorption: A Comparison of Vegetable and Animal Foods
Authors: LAYRISSE M. , COOK J. D. , MARTINEZ C. , ROCHE M. , KUHN I. N. , WALKER R. B. , FINCH C. A.
Published: October 2019

Iron absorption measurements have been made in 131 individuals relating the absorption of nine different foods tagged biosynthetically with radioiron. Relatively low absorption, ranging from 1.7-7.9, was found with wheat, corn, black beans, lettuce and spinach. Higher values of from 15.6-20.3 were observed with soybeans, fish, veal and hemoglobin. When these values were related to the absorption of ferrous ascorbate determined simultaneously in each subject, food iron absorption could be predicted over the spectrum of normal to iron deficient states.
The Effects of Radio-Opaque Contrast Media on the Structure, and Solubility of the Fibrin Clot
Authors: VEREBELY KARL , KUTT HENN , TORACK RICHARD M. , MCDOWELL FLETCHER
Published: October 2019

Radio-opaque contrast media interfered with the normal process of fibrin and plasma clot formation. The morphologic changes included a decrease of the fibrin fiber diameter and an increase of protein aggregates. These appeared amorphous in the light microscope and showed a linear relationship with the concentration of contrast agents in the reaction mixture. Above a threshold concentration, which was different for each contrast media, no clot formed. With increasing concentrations of contrast medium between 3.5 x 10-3M and 2.0 x 10-2M, the optical density of the clots decreased rapidly while the incorporation of fibrin monomers into the polymer structure of the clots stayed within normal limits. This indicated that the spatial arrangements of the clots was altered. Electron micrographs confirmed that the fibrin fibers were reduced by 70 per cent to 90 per cent of the control fiber diameter in the presence of 6.1 x 10-2M sodium diatrizoate. The fibrin stabilizing enzyme (FSF, LLF or Factor XIII) catalyzed covalent cross links despite the structural changes in the clot.
Erythrocyte Volume, Plasma Volume, and Lean Body Mass in Adult Men and Women
Authors: RETZLAFF JOHN A. , TAUXE W. NEWLON , KIELY JOSEPH M. , STROEBEL CHARLES F.
Published: October 2019

Erythrocyte volume, plasma volume, hematocrit, lean body mass (from total body water), skinfold thickness (at three sites), arm circumference, height, and weight were measured in 40 normal males, 38 normal females, and 12 obese females. From these data on the normal subjects, equations for estimating erythrocyte and plasma volumes were derived. Equations utilizing combined height-weight, surface area, height-weight-skinfold thickness, or lean body mass were found to be the most accurate for predicting erythrocyte and plasma volumes in normal and in obese subjects. The body:venous hematocrit ratio (BH:VH) and the variability of this ratio in our subjects were determined and discussed. Errors in indirect estimates of blood volumes based on this ratio are presented. Erythrocyte and plasma volume standards based on height-weight regression equations or surface area ratio equation are suggested for use in clinical laboratories. Tables and a nomogram based on these equations have been prepared and are available on request.
G-6-PD Bangkok: A New Variant Found in Congenital Nonspherocytic Hemolytic Disease (CNHD)
Authors: TALALAK PHUMARA , BEUTLER ERNEST
Published: October 2019

A new variant of G-6-PD was found in a Thai boy who had typical clinical and hematologic findings of congenital nonspherocytic hemolytic anemia. This mutant has normal electrophoretic mobility, normal affinity for G-6P and NADP, and is very labile to heat. It has an activity of about 5 per cent of normal and shows increased utilization of 2-deoxyglucose-6-phosphate and NAD and decreased utilization of deamino NADP. It is different from previously described mutants, and is named G-6-PD Bangkok.
In Vitro Detection of Platelet Antibody in Patients with Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus
Authors: KARPATKIN SIMON , SISKIND GREGORY W.
Published: October 2019

Two technics have been developed, which make possible the in vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura (ITP), and systemic lupus erythematosus (SLE). The dextran-platelet agglutination technic takes advantage of the enhancement of platelet agglutination in the presence of dextran which brings about a threefold increase in simple agglutination. The Platelet-Factor-3 test measures the ability of platelet antibody to injure platelets and in so doing, make Platelet Factor 3 available to the coagulation cascade, thus accelerating the fibrin clotting time. This technic, when compared to the simple platelet agglutination test, increases the detection sensitivity of antiplatelet factor(s) twenty-fivefold.

The antiplatelet factor(s) as measured by these technics was found to be an immunoglobulin of the IgG class. The antiplatelet factor(s) was present in the sera of 85 per cent of patients with ITP and 88 per cent of patients with SLE. This antiplatelet factor(s) was absent in 25 consecutive healthy controls and in 22 out of 26 patients with thrombocytopenia not due to ITP or SLE.

Although 88 per cent of patients with SLE had demonstrable antiplatelet activity in their serum only 2 out of 33 were thrombocytopenic. These observations suggested that a compensated thrombocytolytic state was present in these patients. This conclusion was consistent with the good correlation between an elevated large platelet index and the presence of antiplatelet factor in these patients.
The Heterogeneity of the High Molecular Weight B12 Binder in Serum
Authors: LAWRENCE CHRISTINE
Published: October 2019

The binding of vitamin B12 by serum proteins was studied by separating Co57B12-enriched serum by Sephadex gel filtration, column chromatography with DEAE-cellulose, and paper electrophoresis. Each method of separation yielded two discrete B12-binding fractions. However, the analysis of each serum by all three separation technics indicated that one of the fractions was, in each case, bipartite.

The "high" molecular weight B12-binding fraction defined by Sephadex gel filtration consisted of transcobalamin I and just part of the transcobalamin II fraction. The remaining portion of transcobalamin II was eluted from Sephadex gel in a "low" molecular weight fraction. Thus, transcobalamin II, equivalent to the β-globulin B12-binder, consisted of both "high" and "low" molecular weight components.

This suggests that there are at least three serum proteins that can bind vitamin B12: two β-globulins, together comprising the transcobalamin II fraction and differing in molecular weight; and transcobalamin I.
Polycythemia Rubra Vera With Pernicious Anemia Some Observations on Vitamin B12 Metabolism
Authors: SAGE ROBERT E.
Published: October 2019

A patient with polycythemia rubra vera developed symptoms and signs of pernicious anemia three years after institution of therapy for the polycythemia. This is the first satisfactorily documented report of this sequence. Strict criteria utilized make both diagnoses unequivocal. Autoantibody studies, the first performed in such a patient, show the presence of parietal cell and intrinsic factor autoantibodies but no antibodies to other tissues. Vitamin B12 requirements have been excessive despite high or high normal serum levels and extreme marrow sensitivity to withdrawal of the Vitamin is evident in the presence of these high serum levels. Studies on Vitamin B12 binding proteins showed an elevation in α binding globulin with reversal of the α to β ratio. It is suggested that this protein is physiologically abnormal. The literature is briefly reviewed regarding the pathogenesis of the two disorders with the conclusion that their appearance in the one patient represents purely a chance phenomenon.
The Use of the Supravital Method in a Study of Cells Susceptible to Damage in Smears of Normal and Regenerating Bone Marrow
Authors: ROSSE C.
Published: October 2019

Cells susceptible to damage during smearing were identified in the different cellular compartments of normal and regenerating bone marrow of the guinea pig by comparing differential counts on fixed dry smears and on supravitally stained wet preparations. The comparisons are considered valid since 1) the number of damaged cells was negligibly low in supravital preparations; 2) it could be shown that cell classification and 3) cell distribution corresponded on the two types of preparations. In smears of normal marrow the majority of damaged cells were myeloid cells, although the most fragile cell appeared to be the monocyte. In normal marrow, erythroblasts and lymphoid cells did not damage in significant numbers. During recovery from sublethal irradiation the number of damaged cells increased significantly in each cell compartment at the time when that compartment commenced its regeneration.

In contrast to normal marrow, at the time of lymphoid regeneration 60 per cent of transitional cells had damaged and at the start of erythroid and myeloid regeneration 40-50 per cent of erythroid and myeloid cells were concealed on smears by damage. Labeling with 3H-thymidine indicated that in smears of normal as well as of regenerating marrow, a large proportion of cells susceptible to damage in the various cell compartments was capable of proliferation.
Studies of the Fate of Platelets in Rats and Man
Authors: ASTER RICHARD H.
Published: October 2019

The tissue distribution of 51Cr-labeled platelets and erythrocytes was determined in normal and asplenic rats. Two hours after injection, the distributions in tissues of RBC and platelet 51Cr were not significantly different except in the spleen which contained platelet 51Cr (12 per cent), significantly in excess of red cell 51Cr (1.4 per cent). As labeled platelets were removed from the bloodstream, 80.2 per cent of the injected 51Cr was deposited in the spleen, liver and marrow of normal animals. During the same interval, radioactivity in all other sites examined diminished to less than 10 per cent of initial values. In splenectomized animals, hepatic uptake of radioactivity was twice that observed in normal animals.

Studies in normal human subjects using external scintillation scanning suggest that similar quantitative considerations apply to man in that, normally, one-third of total platelets are sequestered in the liver and one-third in the spleen while in asplenic individuals two-thirds are destroyed in the liver.

These observations suggest that the majority of platelets are cleared from the circulation by the reticuloendothelial system after becoming "senescent" but they do not elucidate the nature of "senescence" or the circumstances leading to it.
Brief Report: Effect of Incubation Time on the L. Casei Bioassay of Folic Acid in Serum
Authors: STREETER A. M. , O’NEILL B. J.
Published: October 2019

It has been shown that the growth rate of L. casei differs in PGA and serum enriched media. Since the serum folic acid level is derived from a comparison of the optical densities in these media it follows that this comparison will yield changing results until growth has stopped due to exhaustion of the available folate. If the assay is terminated before this stage is reached, then nonreproducible results can be easily obtained. Variations in the number of viable organisms in the inocula from assay to assay (which are not easily avoidable) accentuate the possible error. Both these problems appear to be controlled if the usual incubation period is extended to the stage at which growth of the organism has ceased. Our normal range under these conditions is 4.5 ng./ml. to 12.4 ng./ml. with a mean of 7.1 ng./ml.