bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Erythropoietin. I. Demonstration of Erythropoietin in Normal Plasma
Authors: REICHLIN MORRIS , HARRINGTON WILLIAM J.
Published: October 2019

1. A modification of a technic wherein hypertransfused rats are used for the bioassay of erythropoietin is described, and some kinetics of iron incorporation following transfusion are presented.

2. It was possible to detect activity in normal plasma and demonstrate that plasma of animals whose erythropoiesis is depressed below normal by hypertransfusion possesses less erythropoietin than normal plasma.

3. The variation of response under standardized conditions is sufficiently small and sufficiently predictable so that within certain limits, quantitation is possible. A dose-response analysis is presented.

4. Plasma from normal rats possesses approximately 25 per cent of the activity found in rats rendered acutely anemic by a standardized blood loss.
The Amino Acid Composition of Hemoglobin. II. Analytical Technics
Authors: CHERNOFF AMOZ I. , LIU JEVONS C. , Battle E. , Bond M.
Published: October 2019

A detailed description of our current methods of "fingerprinting" and of amino acid analysis of the hemoglobins has been presented. They differ in several respects from comparable technics used elsewhere. Preliminary results of analyses of several human hemoglobins are briefly described.
pH Dependent Hemolytic Systems. I. Their Relationship to Paroxysmal Nocturnal Hemoglobinuria
Authors: YACHNIN STANLEY , LAFORET MITSUKO T. , GARDNER FRANK H.
Published: October 2019

1. Treatment of normal human red cells with various proteolytic enzymes, cholera vibrio filtrate, influenza virus, and periodate ion results in red cells susceptible to acid hemolysis in compatible normal human serum.

2. The kinetics of hemolysis of these artificially altered red cells resembles in many respects those observed in paroxysmal nocturnal hemoglobinuria (PNH).

3. While the observed differences in behavior between these artificially altered cells and PNH cells do not allow direct comparison, it is felt that these models may offer some clues in the understanding of PNH cell hemolysis, and some insight into the nature of the red cell lesion in paroxysmal nocturnal hemoglobinuria.
A New Method for the Preparation of Human Cadaver Bone Marrow for Transfusion
Authors: RAY R. N. , CASSELL M. , CHAPLIN H.
Published: October 2019

1. A simple, economical and effective method has been described for obtaining cadaver bone marrow following a routine autopsy.

2. Individual vertebral bodies are dissected free of soft tissue and their surfaces are sterilized by immersion of the entire bone in 70 per cent ethyl alcohol.

3. Following surface sterilization, the bones are placed in a modified sterile plastic container and the nucleated marrow cells are expressed from the bone by compression of the bag in a vise.

4. After the marrow particles have been dispersed by massaging the bag, the marrow suspension is filtered and the fat is separated following gentle centrifugation.

5. Sterile yields were obtained from 70-90 per cent of cadavers which were judged suitable in terms of freedom from gross evidence of bacterial infection at the time of autopsy.

6. High yields of nucleated hematopoietic cells were obtained, averaging more than 50 x 109 cells as the investigators became more experienced with the procedure.

7. Thirteen transfusions of cadaver marrow were administered to eight patients. Minor symptoms and low-grade febrile responses were experienced on three occasions; in four additional patients entirely asymptomatic temperature elevations of 0.5-2.2 F. were observed. The remaining six transfusions were unaccompanied by fever or symptoms of any kind.

8. The possible value of the technic for definitive study of the therapeutic usefulness of bone marrow transfusion has been discussed.
Mononuclear Cells, Hyaline Bodies and the Plasma: An Analytic Review
Authors: SHIELDS JACK W.
Published: October 2019

Published reports have been analyzed and integrated so as to suggest that various types of mesenchymally derived mononuclear cells in hematopoietic tissue, by shedding fragments of their own gelatinous protoplasm (hyaline bodies) and by dissolving, give rise to a sol which is the blood plasma. The presentation is in accord with the concept that the mesenchyme and its derivatives are truly the perpetual source of the whole blood, i.e., the blood plasma as well as the blood cells.
The Morphology of Buffy Coat from Cord Blood of Normal Human Newborns
Authors: EFRATI P. , ROZENSZAJN L. , SHAPIRA E.
Published: October 2019

The morphology of buffy coat from cord blood of normal human newborns was investigated and the results were compared with our previous observations in adults.

Direct smears from cord blood were examined. Increased alkaline phosphatase activity was found in the granulocytes.

Hotchkiss PAS staining was positive in up to 2 per cent of normoblasts.

The examination of buffy coat revealed 28 normoblasts per 1000 granulocytes. Nuclei and/or nuclear fragments of megakaryocytes were encountered 27 times more frequently in newborns than in adults. Myelocytes and/or metamyelocytes were seen 16 times more often in newborns. Atypical mononuclear cells were found in all the subjects examined. Giant metamyelocytes and staff cells were encountered in 10 cases.
A Case of Juvenile Pernicious Anemia: Study of the Effects of Folic Acid and Vitamin B12
Authors: CLEMENT DAVID H. , NICHOL CHARLES A. , WELCH ARNOLD D.
Published: October 2019

Observations on a 4-year-old boy with Addisonian pernicious anemia have been presented. Noteworthy clinical features included the onset of glossitis at the age of 4 months, followed by anemia severe enough to require hospitalization at the age of 1 year. Relapse occurred in the absence of specific therapy with vitamin B12 and was completely unaffected by the administration of folic acid.

Studies with radioactive vitamin B12 demonstrated that almost all of the compound administered by mouth was unabsorbed and was recovered in the stools. When the vitamin was given simultaneously with a concentrate of intrinsic factor, however, approximately 70 per cent was absorbed. Furthermore, the child’s gastric juice, when mixed with radioactive vitamin B12 and fed to an adult with pernicious anemia in relapse, failed to enhance the latter’s absorption of the vitamin. The failure of our patient to absorb the vitamin alone, but his ability to do so when it was administered with intrinsic factor concentrate, was also confirmed by the "Schilling test," in which a proportion of the absorbed radioactive vitamin was "flushed" into the urine by parenteral injection of one milligram of conventional vitamin B12.

Of special interest was the occurrence in the urine of an unidentified derivative of tetrahydrofolic acid, derived from orally administered pteroylglutamic acid. The presence of this compound in the urine was demonstrated chromatographically when the patient was critically ill with his disease prior to treatment with vitamin B12. Subsequent to therapy with vitamin B12, while the administration of folic acid was continued, the abnormal metabolite of folic acid could not be found in the urine. Similarly, the administration of folic acid did not lead to the appearance of this metabolite in the urine at a time when, after more than two years without specific therapy, a hematological relapse occurred that was much less severe than that previously observed. The implications of these observations, with respect to the metabolic interrelationships of folic acid and vitamin B12, are discussed.

Of further interest were the findings of strongly acid gastric juice containing much mucus and free hydrochloric acid. A fairly normal gastric mucosa was demonstrated by biopsy. The meaning of these unusual findings is discussed and an hypothesis to account for them is offered. The probable sequence of events in these patients from childhood to the development of anemia, usually in later life, is set forth.
The Intercellular Substances of Bone Marrow. I. Preliminary Studies of the Physical and Chemical Character of the Intercellular Bone Marrow Substances in Normal Rabbits
Authors: CARTER ROBERT E. , FLEISHACKER BARBARA , JACKSON WILLIAM L.
Published: October 2019

Separation of cellular and noncellular fractions of rabbit bone marrow was accomplished by mechanical disruption of the marrow stroma and centrifugation. Viscosity studies performed on the intercellular substances showed a decreasing viscosity with increasing age of the animals. Chemical analyses confirmed the presence of mucopolysaccharide material in the intercellular substance of the marrow, but neither this material nor the fat present in the stroma could account for the viscosity measured or the changes in viscosity observed.
A Chromosomal Female With Hemophilia A
Authors: MELLMAN WILLIAM J. , WOLMAN IRVING J. , WURZEL HAROLD A. , MOORHEAD PAUL S. , QUALLS DONALD H.
Published: October 2019

An eight year old female is presented with hemophilia A with hemorrhagic symptoms since three months of age. Family studies revealed sex linked transmission through the maternal lineage.

Chromosome analysis revealed a normal complement with two X chromosomes. Possible genetic mechanisms for this apparent homozygous hemophilic state derived from a carrier woman and normal father are presented.
"Pseudo-Abnormal" Hemoglobins
Authors: PEARSON HOWARD A. , MCCOO JAMES V. , LEIKIN SANFORD L.
Published: October 2019

Three examples of artefactual "pseudo-abnormal" hemoglobins were observed in the course of starch block electrophoresis analysis of over 400 specimens. In fresh samples from the same patients, these components were no longer demonstrable. It is suggested that repeated examination with different blood specimens should be done before an unusual component is accepted as a true hemoglobin variant.
Brief Note: The Use of Desoxyribonuclease As an Aid to the Identification of Primitive White Blood Cells
Authors: GARDNER EDWARD , WRIGHT CLAUDE-STARR , WILLIAMS BETTIE Z.
Published: October 2019

A standard solution of purified desoxyribonuclease in phosphate saline effectively duplicates the differential action of urine on the nuclei of white blood cells. This procedure is a valuable aid to the identification of primitive cell types in bone marrow and peripheral blood films.
Hookworm Anemia: Iron Metabolism and Erythrokinetics
Authors: LAYRISSE MIGUEL , PAZ ALFREDO , BLUMENFELD NORMA , ROCHE MARCEL , Dugarte Iris , Ojeda Adelina
Published: October 2019

Iron metabolism, balance of red cell production and destruction and iron absorption from hemoglobin were determined in 11 patients with heavy hookworm infection and severe anemia.

The plasma iron, total iron binding capacity, bone marrow hemosiderin and plasma Fe59 clearance are in agreement with the idea that the anemia associated with hookworm infection is of the iron deficiency type.

The rate of red cell production measured by the E/M ratio, absolute reticulocyte count and plasma iron turnover showed an increase to about twice normal, while the rate of destruction estimated by the T ½ erythrocyte survival showed a destruction about 5 times normal. This unbalance between production and destruction could explain the severity of the anemia.

The increase of fecal urobilinogen output to twice normal was interpreted as due to the metabolism of the hemoglobin lost into the intestine rather than to an increase of hemolysis.

The estimation of fecal blood loss in the patients whose red cells were tagged with Cr51 and Fe59, showed that the radioactivity counted with Fe59 was only about 63 per cent of the radioactivity counted with Cr51. This difference was interpreted as due to iron absorption from the hemoglobin lost into the intestine.

The mean daily fecal excretion of iron reaches 4.7 mg. Since the iron metabolism in these patients is in equilibrium, we have concluded that the iron loss is replaced by the iron from food; this is in addition to the 3 mg. hemoglobin iron which is reabsorbed from the blood lost into the gut.
Separation of Platelets from Whole Blood by the Use of Silicone Liquids
Authors: MORGAN MARY C. , SZAFIB JEAN J.
Published: October 2019

A method of separating platelets from whole blood has been developed. The method involves simple centrifugation with blended silicone fluids. Quantitative recovery of platelets is achieved. Platelets appear to have no loss of ability to promote clot retraction in platelet poor plasma.
Red Cell Filtration and the Pathogenesis of Certain Hemolytic Anemias
Authors: JANDL JAMES H. , SIMMONS RICHARD L. , CASTLE WILLIAM B.
Published: October 2019

Studies were made of the filterability of normal and abnormal red cells through an inert membrane-type (Millipore) filter having uniform non-branching capillary pores 5 µ in diameter. With this filter it was possible to remove selectively certain kinds of abnormal red cells from mixed suspensions of normal and abnormal red cells.

The red cells of patients with sickle cell anemia were selectively trapped by the filter under low oxygen tensions. Such sickled red cells were unable to pass through the filter even under a pressure differential across the filter (perfusion pressure) of over 120 mm. Hg.

Red cells agglutinated by anti-A were completely retained by the filter at perfusing pressures of 4 mm. Hg., but were partially disagglutinated and forced through the filter when the pressure was increased. Red cells coated with an incomplete (Rh) agglutinin and red cells from a patient with acquired hemolytic anemia were retained by the filter only in the presence of rouleaux-producing agents such as P.V.P. or fibrinogen and only at low perfusion pressures.

A small fraction of the red cells of patients with hereditary spherocytosis were trapped by a single passage through the filter; the trapped cells were largely derived from the minor population of hyperspheroidal cells.

The relevance of these findings to the mechanisms of red cell sequestration in vivo is discussed.
Relation Between Severity of Anemia and Erythropoietin Titer in Human Beings
Authors: VAN DYKE DONALD C. , LAYRISSE MIGUEL , LAWRENCE JOHN H. , GARCIA JOSEPH F. , POLLYCOVE MYRON
Published: October 2019

Patients with severe hematologic disorders may have elevated erythropoietin titers in plasma or urine at higher hemoglobin concentrations than those associated with elevated titers in experimental animals or patients anemic as a result of simple blood loss. Patients with "primary" hematologic disease may have a measurable titer of erythropoietin in the plasma and urine at hemoglobin concentrations up to 8 Gm./100 ml., but patients with iron-deficiency anemia show elevated titers in the urine only with hemoglobin concentrations at or below 4 Gm./100 ml. and in the plasma below 5 Gm./100 ml. The abruptness with which the titer rises and the severity of the anemia required before measurable titers appear are similar in man and in rabbits, sheep and dogs. The fact that no measurable erythropoietin titer can be demonstrated when the hemoglobin concentration is well below that required for intense stimulation of erythropoiesis and the abruptness of the rise at hemoglobin concentration of 4 Gm./100 ml. or less suggest that erythropoietin may not be an important factor in the control of erythropoiesis except in extreme circumstances. On the other hand, these facts may be explained more simply by the insensitivity of the assay methods used.
Studies on the Fetal Hemoglobin in the Persistent High Hb-F Anomaly
Authors: THOMPSON R. B. , MITCHENER J. W. , HUISMAN TITUS H. J.
Published: October 2019

Three generations of a Negro family having herditary persistence of fetal hemoglobin in conjunction with the hemoglobins A and S were studied.

Genetic studies did not exclude the possibility that this anomaly is allelic with the genes responsible for the hemoglobins A, S, and C.

Structural investigations of the isolated abnormal hemoglobin fraction offered evidence that this component is identical with the fetal hemoglobin of the newborn child.

No striking clinical or hematologic abnormalities were found in members of the family who had high percentages of fetal hemoglobin in conjunction with either Hb-A or Hb-S. The per cent of Hb-A2 in the persistent high Hb-F carriers was found slightly below normal, while the total amount of circulating hemoglobins was increased. Previous reports of the complete absence of Hb-A in cases heterozygous for Hb-S as well as for the persistent high Hb-F anomaly have been confirmed by using refined technics available for hemoglobin analyses.

The fetal hemoglobin was distributed almost equally in all erythrocytes of individuals having this inherited anomaly. In this respect, the S-F abnormality differs from homozygous sickle-cell disease in which a mixed population of red blood cells, some with and most without Hb-F, has been demonstrated. It is suggested that the presence of some Hb-F in all erythrocytes of the individual with the S-F condition is the factor that protects the cells from sickling and from destruction.

The distribution of fetal hemoglobin in the red blood cells of persistent high Hb-F carriers was also different from that found in patients with thalassemia major and thalassemia-Hb-E disease. Two distinct cell populations, one with and the other without fetal hemoglobin, were found to be present in the blood of the thalessemia patients.
Bone and Marrow Transplants in the Rat
Authors: DORR ANDREW D. , MOLONEY WILLIAM C. , DOWD GERALDINE , BOSCHETTI ANTONIO E.
Published: October 2019

A simple method for transplantation of autologous bone and marrow to the rat kidney is described and the usefulness of this preparation for research on bone and marrow growth is pointed out.

While an induction mechanism cannot be conclusively ruled out by these studies, the histologic evidence strongly supports the concept that growth of implanted bone and marrow is due to survival of small islands of active bone and marrow cells and from these foci, repopulation takes place.
Studies on the Production of Erythropoietin by Isolated Perfused Organs
Authors: KURATOWSKA Z. , LEWARTOWSKI B. , MICHALAK E.
Published: October 2019

(1) Isolated organs of rabbits (kidney, liver, spleen and lungs) were perfused with rabbit blood. Experimental conditions of hypoxia and full oxygenation were applied.

(2) It could be shown that under these conditions only the kidney produces the erythropoietic factor.
Alkaline Phosphatase Activity of Exudative Leukocytes in Acute Leukemia
Authors: PERILLIE PASQUALE E. , FINCH STUART C.
Published: October 2019

A method for studying the leukocyte alkaline phosphatase activity in patients with acute leukemia is described. The technic overcomes the problem of obtaining sufficient numbers of mature granulocytes for study in such patients. Seven of 11 patients with acute monocytic leukemia were shown to have elevated levels of alkaline phosphatase activity. It is suggested that this method may be of assistance in classifying the stem cell forms of leukemia.
Leukocyte Drumsticks in Chronic Granulocytic Leukemia and Related Disorders
Authors: TOMONAGA MASANOBU , MATSUURA GEN , WATANABE BUNRO , KAMOCHI YASURO , OZONO NOBORU
Published: October 2019

1. The drumstick and other nuclear appendages of the nuclei of polymorphonuclear neutrophils from patients with chronic granulocytic leukemia (CGL), leukemoid reactions and inflammatory leukocytoses were studied.

2. The drumstick counts of the leukocytes of patients with CGL were abnormally low. In contrast, the counts in the leukocytes from patients with the other disorders were not reduced. The low counts increased rapidly in response to treatment and were maintained at normal levels during remission.

3. The normalization of drumstick counts in CGL paralleled the leukocyte alkaline phosphatase and catalase concentrations.

4. The number of sessile nodules and small clubs in each of the disorders studied was moderately reduced. Following treatment, the counts returned to normal. This suggests a relationship between the development of these appendages and hyperproliferation of neutrophils.
The Effect of "Minute" and "Titrated" Amounts of Folic Acid on the Megaloblastic Anemia of Tropical Sprue
Authors: SHEEHY T. W. , RUBINI M. E. , PEREZ-SANTIAGO E. , SANTINI R. , HADDOCK J.
Published: October 2019

A therapeutic trial with "minute" and "titrated" doses of folic acid was performed in 30 patients with the megaloblastic anemia of tropical sprue. Eleven patients responded hematologically to 25 µg. daily doses of the vitamin; nine patients responded to "titrated" doses ranging from 75 to 250 µg. daily. Eleven patients failed to respond to either "minute" or "titrated" doses of the vitamin. The implications and possible reasons for the success or failure of microdoses of folic acid in sprue were discussed.
Case Report: Leukemia and Pregnancy: Observation of a Case Treated with Busulfan (Myleran)
Authors: REYES GUILLERMO RUIZ , PEREZ RUBEN TAMAYO
Published: October 2019

The case of a 28 year old woman with chronic myelocytic leukemia, who conceived while under treatment with busulfan, is reported.

Pregnancy, delivery, and the infant were normal. The child died one month later of a Staphylococcus infection. Autopsy disclosed a few minor and commonplace anomalies which the authors believe cannot reasonably be attributed to busulfan.

A review of the literature on pregnancy and leukemia is cited.
The Measure of Erythropoiesis in Anemias. II. The Immediate and Subsequent Loss of Transfused Erythrocytes in Healthy Subjects
Authors: STRUMIA MAX M. , DUGAN ANN , COLWELL LOUISE S. , Munroe Helen
Published: October 2019

1. Fresh and stored red cells, transfused in healthy subjects, disappear from the circulation during the first 24 hours at a rate in excess of that prevailing in subsequent 24 hour periods. When fresh red cells are transfused the excess first day loss is approximately 3 per cent.

2. Comparative survival studies using the nonagglutinable red cell method of Ashby have indicated that this excess immediate loss is not due to elution of Cr51, but to actual loss of red cells.

3. When red cells are stored improperly or for an extended period of time, the excess loss occurs very rapidly, and at one hour is approximately 50 per cent of the total loss at 24 hours. The limitations to the use of the dilution data of transfused stored cells to establish the 100 per cent value for the measure of the survival of the transfused red cells are implicit.

4. When the first 24 hour loss of transfused red cells is approximately 30 per cent or more, paradoxically the rate of loss in subsequent days is less than when fresh, undamaged red cells are transfused. This observation raises the question of interpretation of the measure of the red cell survival expressed as T ½.
The Role of the Kidney in the Erythropoietic Response to Hypoxia in Parabiotic Rats
Authors: ROSSE WENDELL F. , WALDMANN THOMAS A.
Published: October 2019

1. Parabiotic rats, in which one partner was either nephrectomized or ureter ligated, have been used to determine the role of the kidney in the stimulation of erythropoiesis by hypoxia as measured by iron59 incorporation into the peripheral RBC.

2. The radioiron incorporation into peripheral red blood cells was less in pairs in which the nephrectomized partner was hypoxic than in the pairs in which the unoperated or ureter ligated partner was hypoxic, suggesting that the kidney is important in the stimulation of erythropoiesis in response to hypoxia.

3. The iron incorporation in pairs in which the nephrectomized partner was hypoxic was greater than in those pairs in which one partner was nephrectomized but neither was hypoxic, suggesting that tissues other than the kidney contribute to the erythropoietic response to hypoxia.
Pyridoxine Responsive Anemia
Authors: BICKERS JOHN N. , BROWN CHARLES L. , SPRAGUE CHARLES C. , Karst Katherine
Published: October 2019

A patient is reported with pyridoxine responsive anemia superimposed upon a chronic hypochromic anemia with excess iron storage. A specific response to pyridoxine was demonstrated on several occasions with restoration of the blood picture to its original state. Dietary estimates of vitamin B6 intake demonstrated an increased requirement for the vitamin, approximately 2.5 mg. per day being required for hematologic remission. Splenectomy was followed by high circulating siderocyte levels and severe thromboembolic problems. The possible mechanisms for the development of pyridoxine responsive anemia are discussed briefly.
Metabolic Balance Study of Plasmapheresis in a Case of Waldenström’s Macroglobulinemia
Authors: SKOOG WILLIAM A. , ADAMS WILLIAM S. , COBURN JACK W.
Published: October 2019

A metabolic balance study was undertaken to evaluate the results of plasmapheresis in a case of Waldenström’s macroglobulinemia with an associated cryoglobulinemia. Balances of nitrogen, P, Ca, Cl, and Na and K were carried out. Additional observations were made on serum and urinary protein and uric acid. After a control period of 15 days, the subject was bled 500 cc. per day for 15 days. The plasma was separated by centrifugation and erythrocytes reinfused. A total of 500 Gm. of protein in 5,700 cc. of plasma were removed by this technic. A final control period was continued for 10 days. Plasmapheresis was observed to lower the abnormal plasma protein fraction from 7.5 Gm. per cent to 4.5 Gm. per cent whereas the concentrations of the other plasma proteins remained unchanged. By the last day of the final control period, however, the abnormal protein concentration had risen to preplasmapheresis levels. The patient’s pronounced retinal venous dilatation and "sausage" segmentation were less marked at the end of the plasmapheresis period. The negative nitrogen balance during plasmapheresis was rapidly counteracted by diminished urinary nitrogen excretion. At the same time, urinary protein excretion also fell. Na and Cl urinary excretion responded similarly to that of nitrogen. P and K balances were slightly negative during plasmapheresis, probably reflecting tissue breakdown. Ca balance remained in equilibrium and urinary uric acid levels were unchanged. The study demonstrated that the elevated plasma paraprotein levels in a case of Waldenström’s macroglobulinemia may be lowered by plasmapheresis. Preplasmapheresis levels were rapidly reestablished following discontinuance of the procedure.
Changes in the Group A Antigen in a Case of Acute Myeloblastic Leukemia
Authors: BARTOVA ADELA , NOVOTNY Z. , SLEPICKA J.
Published: October 2019

1. The authors describe a case of acute leukemia in a man of 36 years. During the course of his illness, a change in the agglutinability of the red cells was observed. The cells, originally A1, changed continuously so that in some samples it was possible to detect as many as three populations of red cells, namely, A1, weak A, and so-called non-A. In the course of the illness, fluctuations in the numbers of these cells in the whole population could be observed.

2. The clinical course and the results of detailed isoserologic examinations are presented.

3. Possible causes of these changes are discussed: (a) Somatic mutation; (b) chromosome abnormalities; (c) metabolic changes of the hemopoietic tissue.
Histology of Platelet-Plasma Clots from Normal Subjects and Patients with Abnormal Coagulation
Authors: JAMES THOMAS N. , JOHNSON SHIRLEY A. , MONTO RAYMOND W. , DIAB GEORGE , CALDWELL JUNE
Published: October 2019

Microscopic study of platelet-plasma clots has demonstrated certain structural defects in clots from patients with diseases manifest by abnormal coagulation. Abnormally formed clots were found from patients with polycythemia vera, macroglobulinemia, Christmas disease, AC-globulin deficiency and fibrinolytic syndrome. Some of the problems imposed by the method are discussed.
LECITHIN AND THE ERYTHROCYTE FACTOR IN THE BLOOD SEDIMENTATION PHENOMENON
Authors: HIRSCHBOECK JOHN S.
Published: October 2019

1. The erythrocyte factor in the blood sedimentation phenomenon is not influenced by changes in size or shape of the erythrocytes unless the surface is altered by a hemolytic agent.

2. The erythrocyte factor varies considerably in health and disease. It is depleted when blood is stored under refrigeration.

3. Egg lecithin emulsions and particles of cinnabar covered with lecithin are flocculated by gelatin solutions. The phenomenon is similar to the formation of rouleaux in gelatin solutions.

4. An attempt to explain rouleau formation as a flocculation reaction between plasma proteins and the lecitho-protein surface of the erythrocyte is made.
Evidence for Folic Acid Deficiency in the Genesis of Anemic Sickle Cell Crisis
Authors: PIERCE LAWRENCE E. , RATH CHARLES E.
Published: October 2019

Two cases are presented of sickle cell anemia demonstrating evidence of folic acid deficiency during a period of anemic crisis.

One patient had acute hypoplastic crisis associated with megaloblastic erythropoiesis not in conjunction with acute infection, dietary inadequacy, gastrointestinal malabsorption or chronic alcoholism. An increased excretion of urinary formiminoglutamic acid of 8.8 µM/hr. after histidine stimulation was observed in association with more severe anemia than had been noted previously during nine years observation. Prompt reticulocytosis and rise in hematocrit to previous levels occurred when 1 mg. oral daily folic acid was administered. Improvement was accompanied by a fall in FIGlu excretion to normalcy. Since the observation of folic acid responsiveness in this patient, it has not been necessary to transfuse him for a period in excess of 15 months whereas his previous average requirement approached one unit each month for the past seven and one-half years.

A second patient demonstrated increased formiminoglutamicaciduria coincident with anemic sickle cell crisis following bilateral bronchopneumonia with pulmonary thrombosis. There was a beneficial hematologic response to oral folic acid supplementation in physiologic doses. Previously determined control urinary FIGlu levels had been within normal limits.

Increased urinary FIGlu has been observed in five additional sickle cell patients not in anemic crisis. One of these (V. K.) was tested for sensitivity to higher dosage levels of folic acid (5 mg. each day) without improvement.

Low levels of FIGlu-like material persisted in some patients with sickle cell anemia after treatment with folic acid. Indirect evidence would indicate that this material is urocanic acid and may be related to the chronic liver dysfunction frequently present in sickle cell disease.

Evidence has been presented which indicates that folic acid may be a limiting factor in the development of and recovery from anemic sickle cell crisis.
Mitotic Activity in Vitro of Erythroblasts Previously Exposed to Erythropoietin
Authors: MATOTH YEHUDA , KAUFMANN LILY , Hershkowitz Edith
Published: October 2019

The proliferative activity of rabbit erythroblasts previously exposed to erythropoietin was studied in clot cultures containing colchicine.

Erythroblasts exposed to erythropoietin in vivo (in the anemic animal) or in vitro (by shaking with anemic serum) showed high mitotic rates when subsequently cultured in an erythropoietin poor medium.

These findings indicate that erythropoietin is taken up by erythroblasts from serum. Intracellular erythropoietin stimulates erythroblasts to increased mitotic activity. The direct effect of erythropoietin on the ability of erythroblasts to proliferate constitutes a mechanism by which erythropoietin regulates erythropoiesis.
Glutathione Instability in Normal Blood
Authors: DESFORGES JANE F.
Published: October 2019

Studies have been carried out in vitro to determine whether normal erythrocytes may be made to appear glutathione unstable. Results demonstrate that constant agitation in air or oxygen will cause a drop in reduced glutathione upon incubation of normal blood with an oxidant drug in concentrations which have no significant effect during quiet incubation.

The results are consistent with the fact that drug-induced hemolysis may be seen in nonsensitive individuals and that sensitive individuals may have a mild hemolytic state without exogenous drug.
Hemoglobin Zürich. I. A New Hemoglobin Anomaly Associated with Acute Hemolytic Episodes with Inclusion Bodies after Sulfonamide Therapy
Authors: FRICK PAUL G. , HITZIG WALTER H. , BETKE KLAUS
Published: October 2019

A new abnormal hemoglobin was observed in 15 members over four generations of a large Swiss family and has been termed "Hemoglobin Zürich." The discovery of this hemoglobin was prompted by a severe hemolytic crisis in two members of the family after sulfonamide therapy. During this episode, virtually all erythrocytes and reticulocytes contained a single large inclusion body which was visible with Giemsa and brilliant cresyl blue stains. Outside the hemolytic episode, the erythrocytes revealed no morphologic abnormalities. The results of enzyme studies were all within normal limits. The association of a hemoglobinopathy with a drug-induced inclusion body anemia without any demonstrable enzyme defect is a new entity. The anomalous hemoglobin is inherited as a dominant character and affects both sexes. Thus far, only the heterozygous form has been observed.
Hemoglobin Zürich. II. Physicochemical Properties of the Abnormal Hemoglobin
Authors: BACHMANN FEDOR , MARTI HANS R.
Published: October 2019

The physicochemical properties of Hgb Zürich were investigated. This new hemoglobin is characterized by an electrophoretic mobility between Hgb A and Hgb S at pH 8.6. Similarly it runs between Hgb A and Hgb S on amberlite IRC 50 and on carboxymethylcellulose chromatography. Fingerprints of the tryptic digests revealed three unusual peptides; their existence may be explained by the replacement of one histidyl group by an arginyl group in peptides 20, 21 of the β-chain. At 70 C. Hgb Zürich is destroyed three times faster than Hgb A. The erythrocytes and hemolysates of Hgb Zürich carriers show an increased tendency to form methemoglobin. When incubated with acetylphenylhydrazine, the erythrocytes behave like glucose-6-phosphate dehydrogenase-deficient red cells. Carriers of Hgb Zürich tend to develop severe hemolysis after the ingestion of primaquine and a variety of sulfonamides. Glucose-6-phosphate dehydrogenase activity, glutathione stability and methemoglobin reduction tests have been found normal.
Inhomogeneity of Hemoglobin. VI. The Minor Hemoglobin Components of Cord Blood
Authors: HORTON BENNETT F. , THOMPSON ROBERT B. , DOZY ANDREE M. , NECHTMAN CARL M. , NICHOLS EVAN , HUISMAN TITUS H. J.
Published: October 2019

In a survey of over 300 cord bloods of Negro babies, some 54 cases were selected at random to study the occurrence of the minor hemoglobin components Hb-Bart’s, Hb-H, and Hb-A2. The relationship of these components to Hb-F is discussed. Seven cases with moderate amounts of Hb-Bart’s and Hb-H were studied more intensively, along with the respective parents when possible. The findings suggest the absence of expression beyond infancy of any abnormality responsible for α chain-lacking hemoglobin types of cord blood.

The physiology of Hb-Bart’s reveals its high oxygen affinity to be approximately 8-10 times that of Hb-A, its lack of a Bohr effect and an oxygen dissociation curve showing no heme-heme interaction.

The discovery of a minute amount of a Hb-Gower II-like component in a cord blood sample of a prematurely born white baby of 7.5 months is also presented.
The Intercellular Substances of Bone Marrow. II. Variations in Granulocytic and in Erythrocytic Hyperplasia
Authors: CARTER ROBERT E. , JACKSON WILLIAM L.
Published: October 2019

Rabbits were injected with turpentine to produce granulocytic marrow hyperplasia, or were bled to produce erythrocytic marrow hyperplasia. Both granulocytic and erythrocytic marrow hyperplasia were associated with decreased marrow lipid content. The viscosity of the intercellular substances and the mucopolysaccharide content of this material were significantly increased in granulocytic marrow hyperplasia. in erythrocytic marrow hyperplasia, the viscosity of the intercellular substances was markedly reduced, while the mucopolysaccharide content was slightly elevated compared with control animals.
Clinical Evaluation of an in Vitro Test for Radiosensitivity of Leukemic Lymphocytes
Authors: SCHREK ROBERT , LEITHOLD STANLEY L. , FRIEDMAN IRVING A. , BEST WILLIAM R.
Published: October 2019

A recently developed slide-chamber method was used to test the radiosensitivity of blood lymphocytes from 80 patients with chronic lymphocytic or lymphosarcoma-cell leukemia. The objective of this study was to determine whether these in vitro tests on sensitivity to x-rays had any clinical significance.

Two objective criteria were used to measure the clinical reactions of the leukemic patients. The first was the duration of survival of patients following the in vitro test. The second was the minimal leukocyte count of a patient following x-ray therapy; the minimal count was expressed as a percentage of the count before therapy.

The in vitro radiosensitivity was measured by the 10 per cent survival time of lymphocytes irradiated with 1000 r. Blood lymphocytes from non-leukemic individuals were highly radiosensitive with indices of 1.1 to 2.2 days. In initial tests, the lymphocytes of 61 leukemic patients had the same high sensitivity to x-rays as lymphocytes from non-leukemic individuals. In contrast, the lymphocytes of 19 leukemic patients were radioresistant to irradiation with indices of 2.5 to 11 days.

The 61 patients with radiosensitive lymphocytes had a median survival time of 22 months after the in vitro test. In contrast, the 19 patients with radioresistant lymphocytes had a median survival time of only 4 months. Clinical x-ray therapy caused a greater decline in leukocyte counts in patients with radiosensitive lymphocytes than in those with radioresistant cells.

A significant index of 0.60 was obtained for the correlation of in vitro radiosensitivity of lymphocytes and the in vivo decrease in leukocyte counts of patients after x-ray therapy.

It is concluded that an in vitro finding of radioresistant lymphocytes is correlated with a poor response of the leukocyte count to x-ray therapy and a short survival time of the patient.
A Simple Method for Detection of Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency (G-6-PD Spot Test)
Authors: FAIRBANKS VIRGIL F. , BEUTLER ERNEST
Published: October 2019

A method is described for detection of erythrocyte glucose-6-phosphate dehydrogenase deficiency, based upon the reduction of the tetrazolium dye, MTT, by reduced triphosphopyridine nucleotide. The method is highly reliable and correlates well with established methods of enzyme assay. The test is sufficiently simple to perform that it may be done in any routine clinical laboratory or physician’s office. The reagents may be prepared in mailable, stable form at minimal expense.
Blood Coagulation and Vascular Integrity: Effects of Heparin
Authors: YOSHIMURA HIROKO , DJERASSI ISAAC
Published: October 2019

The administration of large and repeated doses of heparin to normal rats resulted in increased output of red blood cells into the lymph, comparable to that associated with x-ray induced thrombocytopenia. A considerable lapse of time was observed between the inhibition of blood coagulation and the increase of vascular permeability to red blood cells. The latter was not decreased by return of the blood clotting to normal.
Döhle Bodies and Other Granulocytic Alterations during Chemotherapy with Cyclophosphamide
Authors: ITOGA TAKASHI , LASZLO JOHN
Published: October 2019

Morphologic alterations following cyclophosphamide chemotherapy have been described in 25 patients having different types of malignant disease. Significant findings included: 1) An increased number of Döhle bodies in the granulocytes of untreated patients with cancer. 2) A marked increase in the number of Döhle bodies during therapy, approaching normality during the second and third month following initiation of chemotherapy. 3) A "shift to the left" of nuclear maturation during the initial stages of chemotherapy and a return toward normal in a manner similar to that seen with Döhle bodies. 4) The appearance of coarse cytoplasmic granulation in all leukocytes, and of giant platelets during chemotherapy.

The presence of Döhle bodies, nuclear immaturity, "toxic" cytoplasmic granulation, and giant platelets may indicate, at least in some measure, a general metabolic disturbance of the hematopoietic system.
Congenital Orotic Aciduria: Demonstration of an Enzyme Defect in Leukocytes and Comparison with Drug-induced Orotic Aciduria
Authors: FALLON HAROLD J. , LOTZ MYRON , SMITH LLOYD H.
Published: October 2019

1. Leukocytes from presumed heterozygotes of congenital orotic aciduria have been found to exhibit a partial defect in the metabolism of orotic acid. In disrupted cell preparations, orotidylic decarboxylase activity was reduced. Assay of orotidylic pyrophosphorylase activity proved to be unsatisfactory in leukocyte preparations.

2. Orotic aciduria and orotidinuria were produced by the administration of 6-azauridine to patients with chronic myelocytic leukemia. This drug-induced impairment of pyrimidine nucleotide biosynthesis has been compared to the genetically determined disorder.

3. A summary of enzymatic defects previously demonstrated in hemic cells in human genetic disorders has been presented.
Afibrinogenemia and Thrombocytopenia in Guinea Pigs Following Injection of Echis Colorata Venom
Authors: RECHNIC JADWIGA , TRACHTENBERG POLA , CASPER JULIAN , MOROZ CHAJA , DE VRIES ANDRÉ
Published: October 2019

Intravenous injection into the guinea pig of lethal doses of Echis colorata venom or of each of its two chromatographic fractions, separately, caused hemorrhage, afibrinogenemia, factor V deficiency and thrombocytopenia. Sublethal venom doses caused afibrinogenemia, factor V deficiency and thrombocytopenia in the absence of hemorrhage.

Early intravascular clotting was observed following injection of high lethal doses of both whole venom and of procoagulant-containing fraction II, but not of fraction I which was devoid of procoagulant activity.

The afibrinogenemia produced by fraction I was due to its fibrinogenolysin, whereas the afibrinogenemia produced by fraction II, which also had fibrinogenolytic activity, was due chiefly to its procoagulant.

Anti-Echis colorata venom rabbit serum inhibited the fibrinogenolytic, the procoagulant and the thrombocytopenic activities of the venom.
The Red Cell Chromium Elution Rate in Patients with Some Hematologic Diseases
Authors: CLINE MARTIN J. , BERLIN NATHANIEL I.
Published: October 2019

1. The erythrocyte Cr51 elution rate was determined in 38 patients with hematologic diseases.

2. In four patients with finite red cell life spans, two exponential Cr51 elution rate constants could be calculated. In the remaining 34 patients, the data were consistent with a single exponential elution rate constant from day 1 to day 30-40 following Cr51 administration.

3. The single elution rate varied from 0.62 to 2.27 per cent per day.

4. In two patients, the chromium elution rates determined on two separate occasions were not significantly different. In a third individual, the chromium elution rate constant was 0.75 per cent per day when the red cell life span was 66 days and 1.07 per cent per day when red cell life span was 79 days.
Infusion of Marrow in the Mouse and Dog after Thio-TEPA
Authors: LOCHTE H. L. , KASAKURA S. , KARETZKY M. , FERREBEE JOSEPH W. , THOMAS E. DONNALL
Published: October 2019

In mice and in dogs, the usefulness of infusions of marrow in reducing the toxicity of thio-TEPA is limited to a very narrow range of dose of drug in which prompt restoration of hematopoiesis seems critical to survival. Below this range, control animals recover spontaneously; above this range, damage to other organ systems precludes survival.
Differentiation between Vitamin B12—deficient and Folic Acid—deficient Megaloblastic Anemias with C14—Histidine
Authors: FISH MATHEWS B. , POLLYCOVE MYRON , FEICHTMEIR THOMAS V.
Published: October 2019

Intermediary metabolism of the monocarbon pool and histidine in normal subjects and patients with megaloblastic anemia was studied by continuous measurement of pulmonary excretion of C14O2 and urinary excretion of C14 after injection of L-histidine-2(ring)-C14. Cumulative pulmonary and renal excretion of C14 for 1 month by two normal subjects approximates 45 per cent of the amount injected. Within 4 months after injection of the dose used in this study, the resultant average tissue radiation decreases below the average natural terrestrial and cosmic radiation level.

Simultaneous determination of two parameters, (1) cumulative 1-hour pulmonary C14 excretion and (2) the time of occurrence of maximum C14O2specific activity (Tmax), may permit rapid and unequivocal differentiation between folic acid deficiency and vitamin B12 deficiency in the pathogenesis of megaloblastic anemia. Folio acid deficiency results in marked diminution of pulmonary C14 excretion (approximately 0.1 per cent of injection C14 in 1 hour) and marked prolongation of C14O2-specific activity Tmax (approximately 3 hours), while both parameters are normal (approximately 1 per cent and less than 1 hour, respectively) in patients with vitamin B12 deficiency and megaloblastic anemia.

Measurement during periods of reticulocyte response to either folio acid or vitamin B12 demonstrate normal C14O2-specific activity Tmax but decreased pulmonary C14 excretion. These observations suggest that prolongation of C14O2-specific activity Tmax is a sensitive index of folic acid deficiency or block and that if Tmax is normal, pulmonary C14 excretion is a sensitive index of the relative partition of the active monocarbon pool between pathways for oxidation and pathways for nucleic acid synthesis.

This type of breath analysis seems to provide a quantitative dynamic representation of metabolic function which may be particularly useful in differentiating between the alterations of intermediary metabolism that occur in patients with folic acid-deficient megaloblastic anemia and in patients with vitamin B12-deficient megaloblastic anemia.
Evaluation of the Anemia of Rheumatoid Arthritis
Authors: ROBERTS FRANK D. , HAGEDORN ALBERT B. , SLOCUMB CHARLES H. , OWEN CHARLES A.
Published: October 2019

Thirty-six patients with active rheumatoid arthritis in whom anemia was slight were investigated, in part with radioiron and radiochromium, for abnormalities which might lead to anemia.

The primary defect appeared to be a pronounced reduction of ability to absorb iron from the intestinal tract. There was an equally marked reduction in the serum concentration of iron which could not be attributed to the slight reduction in the iron-binding capacity of the serum. Despite the reduction level of iron in the serum, the apparent turnover of iron was so rapid that the total clearance per day was normal or moderately elevated. However, the fraction of the iron cleared from the blood and appearing in the circulation in newly synthesized erythrocytes was slighfly depressed. Erythrocyte survival was normal or very slightly shortened; hemolysis seems to play no important role. The fecal excretion of radioiron, not associated with erythrocytes, was greatly increased in two patients in whom there was no evidence of intestinal bleeding. A moderate increase in plasma vohime was common.
Acute Promyelocytic Leukemia Associated with Hypofibrinogenemia
Authors: ROSENTHAL ROBERT L.
Published: October 2019

This study of 17 cases further establishes acute promyelocytic leukemia with hypofibrinogenemia as a distinct entity. This disease has a rapid course characterized by severe hemorrhagic manifestations and a poor response to therapy. The distinctive features of this disease are the presence of abnormal promyelocytic cells in the bone marrow and an unexplained hypofibrinogenemia. No fibrinolysin could be demonstrated in our cases. Fibrinogen and coagulation studies in patients with other acute leukemias are presented.