bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Nature of the Circulating Anticoagulant Directed against Antihemophilic Factor: With Notes on an Assay for Antihemophilic Factor
Authors: BRECKENRIDGE ROBERT T. , RATNOFF OSCAR D.
Published: October 2019

Modification of the kaolin clotting time has produced a reliable, simple assay system for antihemophilic factor. This system has been utilized for an investigation of the nature and mode of action of the circulating anticoagulant directed against antihemophilic factor.

The anticoagulant has been shown to be present in equal amounts in plasma and serum, to be associated with fractions II and III of plasma prepared by the method of Cohn, to be relatively heat stable and to be stable for prolonged periods at -20 C.

Investigation of the kinetics of the anticoagulant-antihemophilic reaction has demonstrated its temperature, time, pH, and substrate concentration dependency. The anticoagulant is not inactivated during the reaction with antihemophilic factor, and there is a proportional relationship between the anticoagulant and the antihemophilic factor during their interaction.

No antigen-antibody manifestations could be detected during the anticoagulant-antihemophilic factor reaction. These characteristics support the hypothesis that the inactivation of antihemophilic factor by specific circulating anticoagulants is enzymatic.
Heterogeneity of Hemin
Authors: TOALSON L. D. , LUCAS FRED V.
Published: October 2019

A method for the separation of the hemin of hemoglobin into three fractions by ascending paper chromatography is presented. The relative concentration of each fraction of hemin in normal dog and human hemoglobin is fairly constant. The relative concentration of the three fractions varies in induced anemia in dogs and in various types of human anemia.
Adrenal Steroids and Neutrophil Mobilization
Authors: FRUHMAN GEORGE J.
Published: October 2019

Rats were challenged to mobilize neutrophils by intraperitoneal injection of a bacterial extract. Adrenalectomized rats were able to accomplish this as well as their sham-operated controls. Furthermore, pretreatment of intact animals with moderate doses of cortisol injected subcutaneously did not produce a detectable effect upon neutrophil mobilization. On the other hand, when massive, pharmacologic doses were injected subcutaneously, significantly fewer neutrophils appeared in the peritoneal fluid. Inhibition of neutrophil accumulation was noted when the steroid was injected locally; this was accomplished with relatively small doses when calculated in terms of body weight. The relative ineffectiveness of subcutaneous injection compared with topical administration suggests a direct effect of the hormone, probably upon small blood vessels.
The Effect of Chloramphenicol in Human Bone-marrow Cultures
Authors: VAS MAGDALENE R. , BAIN BARBARA , LOWENSTEIN LOUIS
Published: October 2019

1. The effect of chloramphenicol on Fe uptake and Fe incorporation, using Fe59, was studied in human bone-marrow cultures.

2. Choramphenicol, in a concentration of 500 µg. per ml., resulted in a slight depression of uptake of iron by the erythroid cells and in a marked depression of the incorporation of iron into heme.

3. The results suggest that one toxic effect of chloramphenicol upon the bone marrow may involve direct interference with heme synthesis.

4. Under certain experimental conditions the inhibitory effect of chloramphenicol upon iron uptake and heme synthesis by the erythroblast is reversible.
Vitamin E Deficiency in the Monkey. IV. Further Studies of the Anemia with Emphasis on Bone Marrow Morphology
Authors: PORTER F. STANLEY , FITCH COY D. , DINNING JAMES S.
Published: October 2019

Nuclear abnormalities were observed in all the erythroid precursors in the bone marrow of vitamin E-deficient monkeys. Many of these cells were multinucleated. The remainder of the marrow elements appeared normal. Reasons for considering the anemia to be primarily due to inadequate erythropoiesis are given.

Serum iron, glutathione stability of the erythrocytes, hemoglobin electrophoresis, osmotic fragilities and platelet counts were all found to be normal in the vitamin E-deficient monkey.
Studies in Iron Metabolism. IV. Iron Absorption in Experimental Iron Deficiency
Authors: BANNERMAN R. M. , O’BRIEN J. R. P. , WITTS L. J.
Published: October 2019

1) Whole body counting by means of a large phosphor well scintillation counter has been used to measure the absorption of Fe59-tagged inorganic iron, and shown to compare favourably with other methods.

2) There is a delay in the fecal elimination of the unabsorbed portion of the dose of Fe59 by iron-deficient rats on iron-deficient diet. The cause of this delay is unknown but it may be associated with the marked cecal enlargement which exists in these animals.

3) It is confirmed that iron deficiency is associated with striking enhancement of absorption of ferrous and ferric inorganic iron.

4) When a series of doses of ferrous iron of increasing size from 5 to 1,000 µg. was given, there was a progressive increase in absorption for each increase in dose in both iron-supplemented and iron-deficient rats. The relationship between amount of iron given and amount absorbed suggests that two processes may be involved: 1) simple diffusion, and 2) a carrier mechanism.

5) The effect on iron absorption of a sudden change in iron intake has been investigated. Switch from a low to high iron diet reduces absorption, and from a high to a low iron diet increases absorption, too rapidily for hemoglobin level or body iron stores alone to be the most important governing factors and this finding emphasizes the importance of local changes in the intestine.
Transferrin and the Absorption of Iron
Authors: POLLACK SIMEON , BALCERZAK STANLEY P. , CROSBY WILLIAM H.
Published: October 2019

A loop isolated in situ has been used to study iron absorption in the dog. An infusion of iron salt into the artery supplying the isolated loop fails to stop the absorption of iron from the lumen of the gut. Iron absorption appears to be independent of the relative saturation of iron-binding protein.
Familial Hypohaptoglobinemia
Authors: GOTTLIEB ARLAN , WISCH NATHANIEL , ROSS JOHN
Published: October 2019

1) A family is presented with an inherited deficiency of glucose-6-phosphate dehydrogenase and serum haptoglobin.

2) The inheritance patterns observed are consistent with those postulated for two genetically determined, independently segregating traits.

3) The presence of a benign metabolic defect, familial hypohaptoglobinemia, in individuals with Hp 2-1 and Hp 2-2 phenotypes and the lack of involvement to date of Hp 1-1 phenotypes is consistent with the hypothesis that some modification of the Hp2 allele is responsible for the low levels of haptoglobin observed.

4) The term hypohaptogiobinemia, rather than anhaptoglobinemia, is suggested for individuals who manifest a genetically determined depression in the level of circulating haptoglobin.
Leukapheresis in Man. III. Hematologic Observations in Patients with Leukemia and Myeloid Metaplasia
Authors: BIERMAN HOWARD R. , MARSHALL G. J. , KELLY K. H. , BYRON R. L.
Published: October 2019

Eleven patients with leukemia and one patient with myeloid metaplasia underwent leukapheresis on 18 occasions for 94 to 275 minutes during which 93 to 1668 x 109 leukocytes were removed. All patients exhibited a significant and continued decline of peripheral leukocyte concentration during or after the procedure. In 12 of the 18 instances, the leukocyte concentration returned slowly to the initial leukocyte level within 1 hour to 22 days. The number of leukocytes withdrawn represented 16 to 247 per cent of the initial circulating volume removed at a rate of 0.13 to 1.14 leukocyte blood volumes per hour. The RAR was 1:1 to 12:1 to the circulating leukocyte number. Rate of replenishment of the circulating immature leukocyte numbers were 4.0 x 107 to 52.2 x 109/Kg./day. The PMN’s were replaced at rates of 10 x 106 to 7.05 x 109/Kg./day which were equal to or slower than in normal subjects. Changes in number occurred in the dominant leukemic cell types without significant shifts in the differential counts. No changes in marrow population other than a slight decrease in cellularity were observed.

The data indicate that in the leukemic patient the peripheral leukocyte concentration was not maintained or replenished promptly following the withdrawal of sizeable quantities of leukocytes, demonstrating a block in transfer of leukocytes from the tissues to the blood. This is in marked contrast to the leukocytosis and marrow stimulation observed in hematopoietically normal subjects following leukaphereses.

The platelet counts fell promptly during leukapheresis, returning toward control levels in eight studies within 7 hours following the procedure. In four studies the platelet counts returned to control levels in 3 to 9 days. The changes in platelet concentrations were similar to those observed with hematologically normal subjects. The size of the platelet reservoir in these leukemic patients is about twice that of the circulating blood.
Brief Note: A Technic for Sampling Bone Marrow from the Living Mouse
Authors: PILGRIM H. IRA
Published: October 2019

A technic for sampling bone marrow from the living mouse has been described and illustrated.
Hereditary Persistence of Fetal Hemoglobin: A Study of 79 Affected Persons in 15 Negro Families in Baltimore
Authors: CONLEY C. LOCKARD , WEATHERALL DAVID J. , RICHARDSON STUART N. , SHEPARD MARGUERITE K. , CHARACHE SAMUEL
Published: October 2019

Hereditary persistence of fetal hemoglobin is an anomaly of hemoglobin production apparently caused by a mutant gene that inhibits synthesis of hemoglobins A and A2. Alkali-resistant hemoglobin indistinguishable from hemoglobin F of umbilical cord blood is produced, presumably as a compensatory phenomenon, so that neither anemia nor hypochromia of the red cells occurs. The data summarized are compatible with the hypothesis that function of the loci of the β and δ chains of globin is wholly suppressed, quite possibly by a mutant "operator" gene affecting linked structural loci. Heterozygotes for the anomaly have high concentrations of hemoglobin F in the erythrocytes, with a remarkably uniform distribution of fetal hemoglobin throughout the red cell population. Erythrocytes of persons with the anomaly resemble adult red cells with respect to the non-hemoglobin proteins and the oxygen dissociation curve. Experience with 79 affected Negroes in Baltimore is compared with that reported by other investigators. The occasional difficulty in differentiating the anomaly from other conditions, particularly thalassemia, is emphasized.
Cellular Localization of Profibrinolysin (Plasminogen)
Authors: BARNHART MARION I. , RIDDLE JEANNE M.
Published: October 2019

A previously unrecognized property of the human eosinophil is described; namely, profibrinolysin localization within the eosinophilic granules of bone marrow cells. For this demonstration the fluorescent antibody technic was employed. Highly specific fluorescent antiprofibrinolysin marked all members of the eosinophilic series. As maturation proceeded, the profibrinolysin content increased with the greatest intensity of fluorescence seen in the mature eosinophils. These findings are compatible with the view that the bone marrow eosinophil is the site of profibrinolysin synthesis.

Mature eosinophils in peripheral blood smears consistently stained less intensely. Apparently profibrinolysin is tranported from the marrow and released to the circulation and tissues when needed. These findings may be interpreted as indicating a role of the eosinophil in clot lysis and in maintaining the fluidity of the blood.
The Reduction of Methemoglobin in Erythrocytes of a Patient with Congenital Methemoglobinemia, Subjects with Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency, and Normal Individuals
Authors: JAFFÉ ERNST R.
Published: October 2019

The pathways for the reduction of methemoglobin to hemoglobin that are dependent upon the generation of reduced pyridine nucleotides were studied in normal human erythrocytes, in erythrocytes deficient in G-6-PD activity and in erythrocytes of a subject with congenital methemoglobinemia. Reduction of methemoglobin, produced by treatment with nitrite, occurred at equivalent rates in normal and G-6-PD deficient erythrocytes, but failed to occur in the erythrocytes of the patient with congenital methemoglobinemia upon incubation with glucose or inosine. The DPNH-utilizing diaphorase-like system was normal in hemolysates of G-6-PD deficient erythrocytes, but was markedly deficient in hemolysates of erythrocytes of the subject with congenital methemoglobinemia. The marked acceleration of methemoglobin reduction that occurred upon the addition of methylene blue to normal erythrocytes and to the erythrocytes of the woman with congenital methemoglobinemia did not occur with G-6-PD deficient erythrocytes. The TPNH-utilizing methemoglobin reductase system was normal in hemolysates of erythrocytes of the patient with congenital methemoglobinemia, but was reduced to about 50 per cent of normal activity in hemolysates of G-6-PD deficient erythrocytes.

The reduction of methemoglobin to hemoglobin in intact normal and G-6-PD deficient human erythrocytes probably proceeds by way of a DPNH-utilizing, diaphorase-like system that is deficient in the erythrocytes of one type of congenital methemoglobinemia. The TPNH-utilizing methemoglobin reductase appears to be a reserve system that requires an artificial electron carrier, such as methylene blue, to become fully effective in reducing methemoglobin to hemoglobin. The TPNH-methemoglobin reductase system is impaired in G-6-PD deficient erythrocytes not only because of a deficient source of TPNH, but, perhaps, also because of a defect in this methemoglobin reductase system itself.
Effects of Local Irradiation (Co60 Teletherapy) on the Peripheral Blood and Bone Marrow
Authors: GOSWITZ F. A. , ANDREWS G. A. , KNISELEY R. M.
Published: October 2019

1. Local Co60 teletherapy caused a reduction in leukocytes and lymphocytes in the peripheral blood.

2. The bone marrow demonstrated no morphologic change in nonirradiated control sites.

3. Local irradiation produced a pronounced and persistent hypoplasia in the treated sites during and after irradiation, with a great reduction in the numbers of megakaryocytes and precursors of red and white cells. During the period of greatest radiation effect the persistent cells were chiefly plasma cells, "mononuclear cells," and lymphocytes.

4. Even after "cancerocidal" radiotherapy, irradiated bone marrow shows some capacity to regenerate as evidenced by appearance of precursors of various cell series and their ability to incorporate tritium-labeled thymidine.

5. Hemosiderin increased in varying degrees in irradiated sites but showed no change in the control sites.

6. Satisfactory marrow samples can be aspirated from the pubic bone.
Energy Metabolism in the Erythrocytes of Premature Infants Compared to Full Term Newborn Infants and Adults
Authors: GROSS RUTH T. , SCHROEDER ELEANOR A. R. , BROUNSTEIN SUSAN A.
Published: October 2019

1. The following aspects of energy metabolism have been compared in the erythrocytes of premature infants, full term newborn infants, and adults: levels of activity of the enzymes involved in the generation and utilization of ATP, and measurements of the content of ATP and of ADP.

2. The levels of activity of hexokinase, phosphoglyceric acid kinase and pyruvate kinase are significantly increased in the erythrocytes of premature and full term newborn infants compared to adults.

3. The level of activity of phosphofructokinase is significantly decreased in the erythrocytes of premature and full term newborn infants compared to adults.

4. In the erythrocytes of premature infants the content of ATP is significantly increased compared to both full term newborns and adults. The content of ADP is not increased. The percentage content of ADP is significantly below the values found in full term newborn infants and adults.

5. In the erythrocytes of full term newborn infants the content of both ATP and ADP is significantly greater than in adults. The ratio of ADP to the total amount of ATP plus ADP does not differ from the adult value.
Reutilization of Iron in Anemia Complicating Malignant Neoplasms
Authors: HAURANI FARID I. , YOUNG KENT , TOCANTINS LEANDRO M.
Published: October 2019

A study of reutilization of iron by means of Fe59-tagged hemoglobin solution given to normal individuals yielded a rate of reutilization of 70 per cent or more, evidence perhaps that the active storage pool of iron at a given moment is not larger than the plasma iron compartment. Reutilization of iron in patients with anemia complicating malignancy disease has shown a significant decrease which correlates well with the severity of the anemia.
Humoral Regulation of Erythropoiesis. XI. The Pattern of Response to Specific Therapy in Iron Deficiency Anemia
Authors: MOORES RUSSELL R. , STOHLMAN FREDERICK , BRECHER GEORGE
Published: October 2019

Short-lived macrocytes were produced in response to specific therapy in severely iron-deficient rats and in two patients. These findings add weight to our hypothesis that the production of defective, short-lived macrocytes is a phenomenon common to states in which there is marked erythroid hyperactivity in the presence of adequate nutrients.
Ferritin-Containing Bodies in Human Small Intestinal Epitheliuin
Authors: HARTMAN ROBERTA S. , CONRAD MARCEL E. , HARTMAN RICHARD E. , JOY ROBERT J. T. , CROSBY WILLIAM H.
Published: October 2019

Ferritin was identified in the absorptive cells of human jejunum from normal iron-replete subjects by the demonstration of the tetrad form of the iron hydroxide micelle of the ferritin molecule. In a few sections ferritin molecules were observed to be dispersed in the cytoplasm, but usually they were within inclusion bodies found in the apical cytoplasm. These ferritin-containing bodies were oval in profile and 0.5-1.5 µ long. They were not bounded by membrane but did have a moderately dense background substance which made a sharp boundary with the cytoplasmic ground substance. A few clues suggest that the body itself, but not necessarily its substance, is formed within the Golgi apparatus.
The Rate of Iron Accumulation in Iron Storage Disease
Authors: CROSBY WILLIAM H. , CONRAD MARCEL E. , WHEBY MUNSEY S.
Published: October 2019

1. By means of phlebotomy to recover and measure accumulated iron and by determining the rate of replenishment of hemoglobin after induction of iron-deficiency anemia, it is possible to compute the rate at which iron is accumulated by absorption from the diet. Normal humans are presumed to be in iron balance and absorb iron only to replace what is lost; under these conditions they accumulate none. During recovery from induced iron deficiency a normal human accumulated iron at the rate of 5 to 6 mg. per day.

2. Patients with hemochromatosis were found to accumulate iron at the rate of 1.5 to 5 mg. per day. With iron deficiency the rate increased to 8 to 10 mg. per day. Because of uncertainty concerning the manner of onset of iron accumulation in hemochromatosis, whether gradual or abrupt, it is not possible by extrapolation to establish the time of onset in these patients. However, at the rates of accumulation established in this study there was an insufficient excess of iron to permit a conclusion that such rates had existed throughout the patient’s life. If the disease began early, the initial or interim rates were less than those found. If the disease began and continued at the rate found, its onset was 10 to 17 years prior to this study.

3. In a patient with hypochromic iron-loading anemia the rate of accumulation was about 2.5 mg. per day. It was not appreciably increased by iron deficiency except when the deficiency was severe and the plasma iron was quite low. While this patient was iron deficient the plasma iron became abnormally high even before the hemoglobin mass was completely reconstituted.

4. A patient with transfusion siderosis who had recovered from his anemia was phlebotomized to remove the accumulated iron. When iron deficiency finally developed the total amount of iron which had been recovered was less than half of the 32.5 Gm. given in the transfusions some years before. It was computed that during those years the patient was losing iron at a rate of about 4.0 mg. per day. The rate of iron accumulation during his recovery from the induced iron deficiency was the same as the normal: 5 to 6 mg. per day.

5. The ability to lose iron which is in excess of requirement is implicit in the demonstration of iron-laden deciduous cells such as the glandular epithelium of the stomach and duodenum and macrophages in the intestinal villi.

6. In hemochromatosis there is a failure of the intestinal mucosal block to prevent absorption of unneeded iron. When absorption exceeds the capacity of the iron excretory mechanisms, iron accumulation occurs. In iron deficiency the excretory mechanisms become less active so that the rate of iron accumulation is further increased.
Quantitative Assay of Fibrinogen and Fibrinolytic Activity
Authors: PERKINS HERBERT A. , ROLFS MARY R.
Published: October 2019

A variety of technics for assay of fibrinogen were investigated. Greatest accuracy was obtained with a slightly modified Ratnoff-Menzie procedure. One hundred presumably normal blood donors had an average fibrinogen level of 225 mg. per 100 ml. of plasma, with a range from 147 to 319 mg. The levels were not appreciably influenced by age, sex or "reactions" to donation of blood.

Using this assay, over-all fibrinolytic activity was estimated by duplicate assays employing 4-hour incubation of the diluted clot, lysis being inhibited in one of the tubes by epsilon amino caproic acid. The technic showed significant degrees of fibrinolytic activity in the plasma of most patients after open heart surgery as compared with the normal controls.
Cell Antigens and Cell Specialization. III. On the H Antigen Receptors of Human Epidermal Cells
Authors: YUNIS EDMOND , YUNIS JORGE J.
Published: October 2019

This article describes the application of the mixed agglutination method to demonstrate the H antigen receptors on human A1, A2, B and O epidermal cells, and also the presence of A and B antigen receptors in different spatial locations than the H receptors in A and B epidermal cells.
The Recovery of Lethally Irradiated Dogs Given Infusions of Autologous Leukocytes Preserved at -80 C
Authors: CAVINS JOHN A. , SCHEER STUART C. , THOMAS E. DONNALL , FERREBEE JOSEPH W.
Published: October 2019

Nine normal mongrel dogs were exposed to 1200 r whole-body irradiation at 4 to 5 r per minute. They were then given intravenous infusions of 2.12 to 20 x 109 autologous leukocytes that had been previously stored at -80 C. in 10 per cent dimethyl-sulfoxide.

Three dogs survived with delayed but complete hematopoietic recovery. Three showed beginning marrow regeneration but died within 3-4 weeks of irradiation. Three given less than 6 x 109 cells died within 21 days. The number of leukocytes infused was critical since there was no survivor among the dogs receiving less than 9 x 109 cells.

It is concluded that peripheral blood contains primitive cells capable of repopulating marrow spaces and restoring marrow function.
Isoimmune Neonatal Thrombocytopenic Purpura
Authors: PEARSON HOWARD A. , SHULMAN N. RAPHAEL , MARDER VICTOR J. , CONE THOMAS E.
Published: October 2019

1. Serologic tests utilizing complement fixation have allowed differentiation of isoimmune neonatal thrombocytopenia from other forms of congenital thrombocytopenia.

2. The pathogenesis of the isoimmune disease involves fetal-maternal incompatibility of platelet antigens, and destruction of fetal platelets by a transplacental transfer of maternal antibody.

3. Three different platelet antigens have been implicated in neonatal purpura. None of these antigens correspond to known erythrocyte antigens, but two of the platelet antigens are shared by granulocytes and lymphocytes.

4. Review of the literature of probable isoimmune neonatal purpura and our own cases reveals that in untreated cases death occurs in approximately 12 per cent of cases, and platelet counts usually do not remain below 60,000/ mm.3 longer than 21 days.

5. In two of three instances in which neonatal thrombocytopenia was anticipated as a result of serologic tests done on the mothers, antepartum steroids may have benefited the infant.

6. Steroid therapy to the infant appears to shorten the duration of thrombocytopenia, and in one instance exchange transfusion led to immediate cessation of hemorrhage and rapid return of platelets to normal.
Hematopoietic Graft Detected by a Change in ABO Group
Authors: BRONSON WILLIAM R. , MCGINNISS MARY H. , MORSE EDWARD E.
Published: October 2019

A change in blood group was discovered in a group O boy with acute lymphocytic leukemia. Fifty-six per cent of his red cells were of group AB 6 weeks after he received white cell-rich plasma from a group AB donor with chronic myelogenous leukemia. It is concluded that hematopoietic cells in the peripheral blood of the donor survived and divided in the recipient, and were then rejected 6 weeks after transfusion. Factors favoring the acceptance of the graft, consideration of the type of cell or cells that proliferated, and the relation of this finding to recently published reports of survival of cells containing the Ph1 chromosome are discussed.
Use of Testosterone and Busulfan in the Treatment of Myelofibrosis with Myeloid Metaplasia
Authors: SILVER RICHARD T. , JENKINS DAVID E. , ENGLE RALPH L. , Fuller Cynthia Q.
Published: October 2019

Clinical, hematologic, and isotope data from 10 patients with myelofibrosis with myeloid metaplasia, before and after treatment with testosterone and busulfan, are presented. Of the 10 patients treated with testosterone, five showed a good response, three a slight response, and two, no response. The best therapeutic responses were seen in five women who either had a previous splenectomy or in whom the spleen was not massively enlarged. Of the five patients treated with bulsufan only, one beneficial response was observed. The indications for and the consequences of the use of these drugs are discussed.
Chronic Granulocytopenia in Childhood
Authors: ZUELZER WOLF W. , BAJOGHLI MEHDI , Evans Ruth M.
Published: October 2019

Observations in five cases of chronic benign granulocytopenia are reported. The disorder appears to be a true entity occurring in early life. Despite severe depression of the circulating granulocyte count, the course is benign because a reserve of immature granulocytes is available in the bone marrow. Depletion of the leukocyte storage pool by increased peripheral destruction, possibly enhanced by sequestration, rather than a maturation arrest at the penultimate stage is the probable mechanism. This process appears to be of moderate intensity, permitting the maintenance of a "steady state" of low efficiency, resulting in increased susceptibility but not total lack of resistance to infection. The disorder represents a natural model of a special disturbance in leukokinetics. Its ultimate cause remains unknown but is probably related to age-determined factors.
Hereditary Hemolytic Disease Secondary to Glucose-6-Phosphate Dehydrogenase Deficiency: Report of Three Cases with Special Emphasis on ATP Metabolism
Authors: MOHLER DANIEL N. , CROCKETT CHARLES L.
Published: October 2019

1. Three cases of hereditary hemolytic disease secondary to G-6-PD deficiency are described. Two of the cases were first cousins of Scotch-Irish-English descent and the mode of inheritance was believed to be sex-linked. The third case was of Turkish origin; no family studies were availale.

2. The mothers, who were heterozygous for G-6-PD deficiency, showed only minimal expression of the defect, which was manifested by a slightly decreased red cell survival in both mothers and an abnormal methemoglobin reduction test in one of them.

3. All three cases showed a more pronounced fall in erythrocyte ATP after incubation with phenylhydrazine than that observed in primaquine-sensitive Negroes whose red cells were less deficient in G-6-PD.

4. It is suggested that the inability of the G-6-PD-deficient erythrocyte to maintain adequate levels of ATP may be an important factor in the pathogenesis of the hemolytic process.
Effects of Intensive Plasmapheresis on Normal Blood Donors
Authors: KLIMAN ALLAN , CARBONE PAUL P. , GAYDOS LAWRENCE A. , FREIREICH EMIL J.
Published: October 2019

Plasmapheresis was performed in normal blood donors using simple plastic equipment. Removal of plasma in amounts up to 1.0 liter at a single venipuncture proved feasible and produced no major changes in the donor’s blood counts and serum protein levels. Chronic plasmapheresis for periods up to 23 weeks with maximal rates not exceeding 1.5 liters of plasma withdrawn per week, produced no changes in formed elements and only minor changes in serum protein levels. Five donors were subjected to acute plasmapheresis with removal of 5 liters of plasma in 5 days. In this group, serum protein depletion was observed with particular depletion appearing at the end of the 5-day period.

From calculations of protein replacement, the presence of a ready extravascular protein reserve, of a size somewhat less than the intravascular pool, was suggested. An average maximal protein replacement of 49 Gm. per day was observed during the most intensive plasmapheresis, and the data suggest that protein withdrawals should not exceed this amount if serum protein levels are to be maintained. Although no rebound of serum protein was observed, recovery after depletion required at least 2 to 4 weeks.
Brief Note: A Note Concerning the "100 Per Cent Value" in Iron Absorption Studies by Whole Body Counting
Authors: SCHIFFER LEWIS M. , PRICE D. C. , CUTTNER J. , COHN S. H. , CRONKITE EUGENE P.
Published: October 2019

The 4-hour whole body count is found to be clinically valid as a "100 per cent value" in iron absorption studies performed with a whole body counter. Measurement of iron absorption can be made 2 weeks after ingestion of radioiron, but not prior to this period.
Hematologic Studies on Erythropoietic Porphyria: A New Case with Severe Hemolysis, Chronic Thrombocytopenia, and Folic Acid Deficiency
Authors: GROSS SAMUEL , Keefer Vicki
Published: October 2019

An unusual case of erythropoietic porphyria with a severe hemolytic component and thrombocytopenia has been presented. The relationship between the porphyria and the thrombocytopenia, although unclear, showed definite evidence of persistent megakaryocytic hypoplasia. Additional information emphasizing the severity and chronicity of the anemic process included elevated F and A2 hemoglobins, hyperferremia and extramedullary hematopoiesis. The nature of the hemolytic process appeared to be intracorpuscular and not correctible by normal plasma, glucose or ATP. The abnormal in vitro hemolysis, coupled with the appearance of the abnormal nucleated and mature red cells, are suggestive of the defect in heme synthesis seen in some of the hypochromic hypersideremic anemias. A description of therapeutic attempts as well as the appearance of a folate deficiency are included in the report.
Multiple Chromosomal Aberrations in a Patient with Acute Granulocytic Leukemia Associated with Down's Syndrome and Twinning
Authors: KIOSSOGLOU KOSMAS A. , ROSENBAUM ERNEST H. , MITUS W. J. , DAMESHEK WILLIAM , Sheehan Carol
Published: October 2019

1. A case of Down's syndrome (G 21 trisomy) in a boy, age 4, associated with twinning and AGL is described. Multiple chromosomal aberrations were found prior to and during antileukemic chemotherapy.

2. The initial modal number ranged from 47 to 53 and subsequently 49 to 53, and 42 to 52 chromosomes respectively. The overwhelming leukemic cell population was represented by 51 chromosomes on three occasions (74.2, 80 and 79.5 per cent respectively).

3. The autosomal aberrations—trisomies and polysomies—were constant, involving predominantly the chromosomes of the G, F and D series.

4. Heterokaryotic twinning with one normal and one affected was encountered twice in this family (G 21 trisomy and normal) and (normal and mentally affected) sets of twins.

5. A possible tendency to nondisjunction has been demonstrated in three healthy members of the family.

6. Multiple mitotic nondisjunction anomalies might be of etiologic importance in the leukemic process.

7. The implication of different injurious agents and factors, such as ionizing radiation, x-ray exposure, chemicals and parental age in the development of trisomic syndromes and/or neoplasia are briefly discussed.
A Comparative Study of Porphyrin Biosynthesis in Different Tissues
Authors: SARDESAI VISHWANATH M. , WALDMAN JORDAN , ORTEN JAMES M.
Published: October 2019

A comparative study has been made of the ability of nucleated erythrocytes (chicken) and of different tissues, as homogenates of fresh tissues (dog and human) and as "acetone powders" of tissues (several species) to synthesize porphyrinogens-porphyrins from either glycine and acetate or succinate or from ALA.

With the exception of the nucleated erythrocytes, the tissues studied had no measurable ability to form copro- and protoporphyrins from glycine and acetate or succinate

However, the various tissues can form copro- and protoporphyrins from ALA, and in the following order: nucleated erythrocytes > liver > adrenal > spleen > kidney > heart > skeletal muscle > brain. The spleen of the human infant was extremely active. Non-nucleated erythrocytes (dog) are active to the coproporphyrin(ogen) stage.

Acetone powders of the same tissues show similar porphyrin-forming capacities.

Little variation in porphyrin-forming activity was found among tissues from different mammalian species, but avian (pigeon) tissues appear to be more active in this respect.

From these results it appears that different tissues, with the exception of the nucleated erythrocyte, may synthesize porphyrinogens-porphyrins from ALA, but only to a limited extent from glycine and acetate or succinate. ALA may probably be supplied to these tissues preformed, this apparently occurring primarily in the nucleated erythrocyte (bone marrow).

The porphyrinogen-porphyrin-forming capacity of a given tissue appears to be related to the heme content and/or turnover rate in that tissue.
Erythropoietin in Vitro. II. Effect on "Stem Cells"
Authors: ERSLEV ALLAN J.
Published: October 2019

The in vitro effect of sheep erythropoietin on bone marrow cells was studied in order to elucidate its point of action. It was concluded that erythropoietin in vitro acts primarily or exclusively on stem cells and does not have a measurable effect on differentiated nucleated red blood cells or on reticulocytes. Attempts to isolate and study stem cells by freezing or by long or short term culture were not successful.
Implications of Long-Term Survival in Acute Stem Cell Leukemia of Childhood Treated with Composite Cyclic Therapy
Authors: ZUELZER WOLF W.
Published: October 2019

The results of 9 years’ experience with acute stem cell (lymphoblastic) leukemia treated with a combination of steroids and antimetabolites, designated as "composite cyclic therapy" (CCT), are described and their theoretical implications are discussed. In 175 patients surviving at least one month after diagnosis the per cent survivals were: 17.2 months (50 per cent), 27.5 months (25 per cent), and 45.0 months (10 per cent). Six patients were alive in uninterrupted remission at the close of the study, from 4-9 years after diagnosis. The mean survival of the expired patients was 17.7 months, with a median of 14.5 months. The mean duration of the first remission was 15.2 months with a median of 12.5.

The therapeutic response in terms of remission rate and total survival was significantly better in stem cell leukemia, as defined cytologically at the time of original diagnosis, than in other types, suggesting that the effect of steroids on the former is at least in part specific for malignant cells of lymphoid origin.

A highly significant difference within the group of stem cell leukemia was observed between patients with initially low as compared to high white blood count, the dividing line being at 20,000 cells/mm.,3 the latter having twice the mean survival of the former. Of the 44 patients achieving survival of 2 years or more only one had an initial white count of more than 20,000. In conjunction with chromosome studies published elsewhere these findings suggest that the initial white count is a parameter, possibly of immunologic nature, indicative of the partial retention or complete loss of control over leukemic mutant cells. The possibility is discussed, on the basis of theoretical considerations and the observed role of long first remissions in the total survival time, that conditions and measures taken in the early stages of therapy may be decisive for the ultimate course. The current evidence for the mutational nature of acute leukemia permits the theoretical distinction between remission as the temporary suppression of a mutant stem line as opposed to a "cure" representing its permanent elimination, and to explain occasional apparent cures, including some observed in the present series, on that basis.

Clinically, combined cyclic therapy or CCT appears to be superior to the use of single antimetabolites. The withholding of steroids until these drugs become ineffective does not at present appear justified.
Cell Antigens and Cell Specialization. IV. On the H Blood Group Antigen of Human Platelets and Nucleated Cells of the Human Bone Marrow
Authors: YUNIS EDMOND J. , YUNIS JORGE J.
Published: October 2019

This article describes the specific agglutination of normoblasts, recitulocytes, megakaryocytes and platelets of human bone marrow with anti-H sera. It also describes the erythrocyte-platelet mixed agglutination reactions demonstrating H antigen receptors on all human platelets regardless of the ABO group of the donor with the exception of the Bombay blood.
Differences in Proliferative Activity between Normoblasts and Pernicious Anemia Megaloblasts
Authors: RONDANELLI E. G. , GORINI P. , MAGLIULO E. , FIORI G. P.
Published: October 2019

The mitotic behavior of pernicious anemia and normal erythropoietic cells in vitro was studied by means of phase contrast microphotography and cinema-photograph. Direct measurements showed that the duration of mitosis is significantly shorter in megaloblasts than in normoblasts at every stage of maturation. Maturation induces an elongation of mitosis in both the normal and the pathologic series. The mitotic index being practically the same in normoblasts and megaloblasts, the weighted average generation time in megaloblasts, calculated according to the formula tG = tM/IM, resulted in a shorter time than in normoblasts. This indicates that there is a higher than normal proliferative activity of p.a. cells since the generation time appears inversely proportional to the frequency by which new mitoses are entered in a cell population. The role of each single mitotic phase in shortening the total duration of mitoses has been investigated. Possible alterations in the mitotic mechanisms involved have been discussed.
The Characterization of Hemoglobin Shimonoseki
Authors: HANADA M. , RUCKNAGEL D. L.
Published: October 2019

Hemoglobin Shimonoseki, discovered in western Japan in 1960, has been further characterized as a mutant with abnormal α-polypeptide chains on the basis of:

(1) The presence of a minor hemoglobin component migrating cathodally at pH 8.6 to Hb A2, presumably α2Shσ2A2.

(2) Hybridization studies.

(3) Fingerprinting of isolated α-polypeptide chains.

Hemoglobin Sh is characterized by the substitution of arginine for glutamine at residue 54 and can therefore be designated as α254Argβ2A.
Brief Report: The Electrophoretic Mobility of Erythrocytes of Patients with Malignant Tumors
Authors: NADELL JUDITH , CREGER WILLIAM P. , Amendola Kathryn
Published: October 2019

The electrophoretic mobilities of erythrocytes of 123 patients with benign surgical conditions and 55 patients with malignant disorders were determined. There was no appreciable difference between the mobilities of the two groups. In our hands microelectrophoresis of washed, untreated erythrocytes is not a useful tool in the diagnosis of human malignancies.
Brief Report: Clearance of Iron from Hemochromatotic and Normal Transferrin in Vivo
Authors: WHEBY MUNSEY S. , BALCERZAK STANLEY P. , ANDERSON PEARL , CROSBY WILLIAM H.
Published: October 2019

The iron transport function of transferrin from normal subjects and patients with idiopathic hemachromatosis has been studied using the radioisotopes Fe59 and Fe55. It was concluded that transferrin from hemochromatotic patients functions in a normal manner in vivo.
Chronic Erythrocytic Hypoplasia Following Pernicious Anemia
Authors: GOLDSTEIN CARLOS , PECHET LIBERTO
Published: October 2019

A case of chronic erythrocytic hypoplasia of the bone marrow following Addisonian pernicious anemia, treated for 30 years, is reported. Treatment with different erythropoietic agents was completely unsuccessful. The possibility of a causal relationship is suggested.
The Excretion of Urocanic Acid and Formimino Glutamic Acid in Megaloblastosis Accompanying Kwashiorkor
Authors: ALLEN DONALD M. , WHITEHEAD ROGER C.
Published: October 2019

1. Children with both kwashiorkor and megaloblastic anemia when first tested excreted urocanic acid in their urine but no formimino glutamic acid (FIGLU).

2. Treatment with a high protein diet eliminated the block in urocanic acid metabolism. Urocanic acid was no longer excreted and the expected abnormal FIGLU appeared in the urine.

3. Treatment with PGA, but not vitamin B12, corrected the second metabolic block. The excretion of FIGLU stopped and the bone marrow became normoblastic.
Dry Mass Distribution Changes in Mouse Bone Marrow Cell Population during the First 24 Hours after X—Irradiation as Determined by Interfereometry
Authors: LEE HUN , RICHARDS VICTOR , MAICHLE MARIA
Published: October 2019

LAF1 mice were treated with a total-body dose of 800 r. x-ray. The dry mass distribution of the femur bone marrow cells was determined at different intervals postirradiation. The nonproliferating cells showed no significant dry mass change, whereas the proliferating cells of the myelocyte series had a steady increase in mean dry mass per cell. Few cells with the maximum dry mass increase survived at the end of 48 hours postirradiation. The dry mass distribution formed characteristic patterns for each postirradiation interval studied as the proliferating cells shifted to higher dry mass values with accompanied increase in cell sizes.
Life Span of Reticulocytes in Paroxysmal Nocturnal Hemoglobinuria
Authors: KAN S. Y. , GARDNER FRANK H.
Published: October 2019

Two patients with PNH were transfused with young and old Cr51-labeled red cells. The young red cells (reticulocytes) were destroyed more rapidly than the older red cells. In vitro studies also revealed that the reticulocyte was more susceptible to acid hemolysis in acidified serum.

In contrast the Cr51-labeled reticulocytes in 3 patients with pernicious anemia responding to cyanocobalamin showed a normal life span.

In the patients with PNH and pernicious anemia, no sequestration of Cr51-labeled reticulocytes was noted in the liver or spleen by surface scanning.
The Eosinophil as a Source for Profibrinolysin in Acute Inflammation
Authors: RIDDLE JEANNE M. , BARNHART MARION I.
Published: October 2019

The emigration sequence and cytology of acute inflammation produced by a variety of stimulants was studied in dogs using a modified skin window procedure. Control lesions revealed the typical acute inflammatory cycle with an early influx of polymorphonuclear neutrophils and a later increase in lymphocytes, hypertrophied lymphocytes and macrophages.

Either fibrinogen, fibrin or proteolytic enzymes that promote fibrin formation selectively attracted eosinophils into the inflammatory site. Neither histamine nor albumin produced significant eosinophil migration in the 10 hours under study.

The fluorescent antibody technic was employed to assess the level of cellular profibrinolysin. Only inflammatory eosinophils and bone marrow eosinophils were marked with rhodamine antiprofibrinolysin. Staining was confined to intra- and extracellular eosinophil granules and coalesced masses. The intensity of fluorescence varied somewhat and perhaps reflected profibrinolysin release into the inflammatory exudate.

Exudative eosinophils like all members of the bone marrow eosinophilic series contain profibrinolysin localized in the specific granules. Eosinophils which migrate and collect at an inflammatory site clearly transport profibrinolysin to an area of fibrin deposition. Granule release of profibrinolysin provides one mechanism for fibrinolysis that likely facilitates wound repair.
Extraction of Erythropoietin from Kidneys of Hypoxic and Phenylhydrazine-Treated Rats
Authors: CONTRERA JOSEPH F. , CAMISCOLI JAMES F. , WEINTRAUB ARTHUR H. , GORDON ALBERT S.
Published: October 2019

1. Significant amounts of ESF have been extracted from kidneys of anemic and hypoxic rats by the use of hypotonic phosphate buffer at pH 6.8.

2. A minimum of 50 per cent of the ESF extracted from the kidneys was not due to activity contained in the trapped residual plasma.

3. Bioassay of sheep and rat plasma ESF and the kidney extracts by the radioiron-polycythemic mouse method indicated that the above preparations were parallel in their log-dose regressions, suggesting that these substances are similar in physiologic behavior.
Platelet Levels in Infectious Mononucleosis
Authors: Carter R. L.
Published: October 2019

Platelet levels in 57 patients with infectious mononucleosis are recorded. Approximately 50 per cent of cases show some degree of thrombocytopenia during the first 4 weeks of the disease. Possible mechanisms for the change are reviewed and other acute infections complicated by thrombocytopenia briefly discussed.
Hemoglobin Hope: A Beta Chain Variant
Authors: MINNICH VIRGINIA , HILL ROBERT J. , KHURI PHILIP D. , ANDERSON MARY E.
Published: October 2019

A new hemoglobin, hemoglobin Hope, with a beta chain abnormality has been found in three generations of a St. Louis Negro family. The abnormal hemoglobin in the heterozygous state caused neither clinical stigmata nor abnormality in the red blood cells. Hemoglobin Hope was detected by agar gel electrophoresis at pH 6.2, but could not be differentiated from hemoglobin A by starch block electrophoresis at pH 8.6. Also, it could not be separated from hemoglobin A by paper, or starch gel electrophoresis employing a range of buffers from pH 6.2 to 8.6. Amino acid analysis showed that aspartic acid was substituted for glycine at position 136 of the beta chain. Hemoglobin Hope may be formulated as α2Aβ2136 gly-asp.
Rapid Charcoal Assay for Intrinsic Factor (IF), Gastric Juice Unsaturated B12 Binding Capacity, Antibody to IF, and Serum Unsaturated B12 Binding Capacity
Authors: GOTTLIEB CHESTER , LAU KAM-SENG , WASSERMAN LOUIS R. , HERBERT VICTOR
Published: October 2019

The principle of the dialysis assays for intrinsic factor (IF) and antibody to IF was integrated with the demonstration that protein-coated charcoal adsorbs only free and not bound B12, in a single rapid method for 4 separate assays: (1) assay of IF, (2) assay of gastric juice unsaturated B12 binding capacity, (3) assay of serum antibodies to IF and (4) assay of serum unsaturated B12 binding capacity. The method is sensitive, accurate, reproducible, and can easily be completed within an hour. The simplicity and ready availability of reagents and equipment lends itself to ready adoption in any clinical laboratory using radioisotopes.

The charcoal particle is considered as a solid microsponge, and its coat of albumin, other protein, carbohydrate, or other large molecule as a molecular sieve surrounding the sponge. The whole constitutes a system of "instant dialysis," with a wide range of applications in the separation of large from small molecules.