bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure and Composition of Rat Reticulocytes
Authors: HALLINAN T. , EDEN E. , NORTH R.
Published: October 2019

1. Fixed, sectioned rat reticulocytes, embedded in araldite, have a regular outer limiting margin like that of erythrocytes; however, unlike erythrocytes they contain cytoplasmic organelles similar to those in erythroblasts and other mammalian cells. These include mitochondria, ribosomes and a sparse endoplasmic reticulum consisting of rounded vesicles and occasional small cisternae. The endoplasmic reticulum appears to consist wholly of "rough-surfaced" elements.

2. Many mitochondria have disorientated cristae or ruptured outer membranes. The possible origin of these alterations is discussed.

3. Ribosomes appear as electron-opaque granules 10-20 mµ in diameter in sections of whole cells. Most of them occur free in the cytoplasm while a few appear to be attached to the surface of vesicles and cisternae of the endoplasmic reticulum. They can be isolated from ruptured cells by high speed centrifugation and have a similar chemical composition to ribosomes from other mammalian tissues.
Alpha-chain Thalassemia and Hydrops Fetalis in Malaya: Report of Five Cases
Authors: ENG LIE-INJO LUAN
Published: October 2019

Five cases of severe hydrops and erythroblastosis fetalis in association with a large amount of Hb "Bart’s," all of Chinese origin, are described. The following characteristic clinical and hematologic symptoms were found. There were generalized hydrops, ascites and gross enlargement of the liver. The spleen, however, was not always enlarged. The placenta was large and friable. Severe erythroblastosis of the blood was always found, with reticulocytosis, many target cells and thin cells. The MCV of the red cells was very high. The cells showed an interesting sickling phenomenon. No evidence of isoimmunization was found. In eight parents examined, no abnormal hemoglobin was detected, and alkali-resistant hemoglobin and hemoglobin A2 were not found to be increased. Their blood showed microcytosis of the red cells except in one father and one mother. In this mother, however, the blood was examined after a blood transfusion. It is thought probable that these were cases of homozygous α-chain thalassemia.
Leukocytic Inclusions—Döhle Bodies—Associated with Platelet Abnormality (The May-Hegglin Anomaly)
Authors: OSKI FRANK A. , NAIMAN J. LAWRENCE , ALLEN DONALD M. , DIAMOND LOUIS K.
Published: October 2019

A six-year-old girl with thrombocytopenia was found to have the May-Hegglin anomaly, consisting of Döhle bodies in the leukocytes in association with giant platelets. This was also observed in the patient’s mother and brother who had normal platelet counts. The familial nature of this anomaly is again confirmed, and the world literature reviewed. Its morphologic and clinical features are contrasted with those seen in the leukocytes of the Chediák-Higashi anomaly.
Report of a Three-Year Study of Red Cell Mobility and the Slowing Factor in Serum of Persons with Lymphoma
Authors: ROTTINO ANTONIO , ANGERS JOHN W. , Dool Agnes
Published: October 2019

1) A variety of pathologic conditions retard the electrophoretic mobility of the red blood cell.

2) Two retarding factors have been found in the blood serum, one that reduces the mobility of the red cell from normal (1.33µ/cm./sec./volt) to 0.89µ and one that reduces it to 1.14µ.

3) The "0.89" factor and the "1.14" factor can be differentiated and identified.

4) The 0.89-factor has been found in the serum of 99 per cent of patients with cancer and Hodgkin’s disease studied and has been lacking from the serum of all persons with benign tumor.

5) The 0.89-factor has also been found in patients with infectious mononucleosis.

6) A few physical characteristics that enable differentiation of the two slowing factors are described.

7) Clarification of the role played by the 0.89-factor in malignant neoplasm is deemed important.

8) Determination of the presence or absence of the 0.89-factor in the blood serum may become of value in differential diagnosis of malignant neoplasm.
Reactivation of Erythropoiesis by Cobalt after Radiation Injury
Authors: SAIKKONEN JOUKO , MARTTINEN EINO
Published: October 2019

The ability of cobalt chloride to prevent the anemia following total body irradiation injury was tested. Laboratory albino rats were exposed to a single x-ray dose of 250 or 350 r. After the exposure, one-half of the rats were treated with daily subcutaneous injections of cobalt while the others were given saline injections at the same time. The first injection was administered 1 hour after the exposure and the daily dose consisted of 0.8 mg. of cobalt per Kg. of body weight. The treatment was continued over a period of 8 weeks. Hemoglobin and the erythrocyte count were measured once a week.

Rats exposed to 250 r and thereafter treated with cobalt showed reactivation of erythropoiesis after 1 to 2 weeks and the animals then rapidly developed polycythemia, in contrast to the similarly irradiated rats afterwards treated with saline, which after 8 weeks still had blood values below the original level. In rats irradiated with 350 r, the same phenomenon was seen, although the effect of cobalt became apparent slowly. The findings observed in the peripheral blood were confirmed by checking the bone marrow of rats given 350 r.

Besides the erythropoietic effect, toxic symptoms were observed. The toxicity and made of action of cobalt are discussed.
Deficient Activity of DPNH-dependent Methemoglobin Diaphorase in Cord Blood Erythrocytes
Authors: ROSS JEAN D. , Bevan-Pritchard Stephen
Published: October 2019

Activity of DPNH-dependent methemoglobin diaphorase was measured in the erythrocytes obtained from 54 cord bloods and 54 adult controls. There was a significantly lower mean level for this enzyme in the cord bloods and the defect was occasionally severe. Mean diaphorase values of smaller infants was less than that of larger infants, suggesting a greater degree of metabolic immaturity in the former group, even in the absence of prematurity. This transient deficiency of methemoglobin diaphorase is probably a major cause for the increased susceptibility of young infants to the development of acquired methemoglobinemia.
The Effect of Foreign Protein on the Blood and Reticuloendothelial System of the Hamster
Authors: FRIEDELL GILBERT H. , SHERMAN JOSEPH D. , RIGBY PERRY G.
Published: October 2019

The injection of human plasma into hamsters over a period of 14 to 68 days induced splenomegaly, accompanied histologically by reticuloendothelial hyperplasia, plasmacytosis, increased erythropoiesis and hemosiderosis. These findings suggest both an antigen-antibody response and an abnormal increase in splenic hemolysis. The demonstration of positive erythroagglutination reactions when red cells from plasma-injected hamsters are tested also suggests an immunologic response by these animals. Mild anemia was present in some animals during the course of this study but at the termination of the experiment anemia was not present and the animals were apparently in a compensated state. It is clear that the reticuloendothelial system of the hamster is capable of responding to foreign protein. Apparent immunologic tolerance in this animal should not be attributed to inactivity of the reticuloendothelial system.
Occurrence of Leukemia and Lymphoma in Patients with Agammaglobulinemia
Authors: PAGE ARTHUR R. , HANSEN† ARILD E. , GOOD ROBERT A.
Published: October 2019

1) Two case reports of children with congenital agammaglobulinemia who later developed malignant lymphoma are presented.

2) Two additional cases of malignant lymphoma developing in adult patients with hypogammaglobulinemia are reviewed.

3) The occurrence of diseases of this group among patients with this immunologic defect appears to be a greater-than-chance association. Possible reasons for the association are discussed.
Brief Note: Acute Promyelocytic Leukemia?
Authors: GHITIS JACOBO
Published: October 2019

A case of promyelocytic leukemia is presented. It was characterized by 1) a clinical picture of acute leukemia, 2) predominance of promyelocytes in the bone marrow smear, 3) predominance of promyelocytes (as the abnormal leukocyte) in the peripheral blood, 4) a rapidly fatal course and 5) necropsy findings of acute myelogenous leukemia. Unfortunately, the patient died before plasma fibrinogen and other clotting factors could be determined. Promyelocytic leukemia has only recently been considered as a distinct clinical entity. Fibrinogenopenia seems to be a constant finding. The use of 6-mercaptopurine plus corticosteroids apparently produced remissions in two of the 24 patients reported in the last 4 years.
Intranuclear Inclusions in Multiple Myeloma and Macroglobulinemia
Authors: BRITTIN GEOFFREY M. , TANAKA YASUKAZU , BRECHER GEORGE
Published: October 2019

Inclusion bodies in plasma cell nuclei of six patients with multiple myeloma and of three patients with macroglobulinemia have been studied histochemically. In three cases they have been studied with the electron microscope. The inclusions are readily identified in Giemsa stained smears of bone marrow and in paraffin sections. Their PAS positivity may be related to the hexose content of the patient’s abnormal serum protein. Evidence is presented that the inclusions are true nuclear inclusion bodies, that they represent nuclear elaboration of glycoprotein, and that they may be found in all three immunoelectrophoretic varieties of multiple myeloma, as well as in macroglobulinemia.
The Red Cell Chromium Elution Rate in Patients with Some Hematologic Diseases
Authors: CLINE MARTIN J. , BERLIN NATHANIEL I.
Published: October 2019

In the paper entitled "The Red Cell Chromium Elution Rate in Patients with Some Hematologic Diseases," by Martin J. Cline and Nathaniel I. Berlin (January BLOOD, pp. 63-69), equation (4), page 64, was printed incorrectly. The equation should read:

See PDF for Equation
Immunohistologic Localization of Gamma-1-Macroglobulins, Beta-2A-Myeloma Proteins, 6.6 S Gamma-Myeloma Proteins and Bence Jones Proteins
Authors: SOLOMON ALAN , FAHEY JOHN L. , MALMGREN RICHARD A.
Published: October 2019

The cellular localization of 6.6 S γ-globulins, β2A-globulins, γ1-macroglobulins and Bence Jones proteins was studied by immunohistochemical procedures in 21 patients with multiple myeloma or macroglobulinemia.

Each type of protein was identified by specific immunofluorescence in a variety of morphologic forms of malignant cells. Some cells were typically plasmacytic, some were lymphoid cells and others were immature forms. It was clear that γ, β2A, γ1M, and Bence Jones proteins were not associated exclusively with a single morphologic form of malignant cell. The variety of immunofluorescent positive cells in each patient was more restricted, however, than in a group of patients with a specific protein abnormality.

In patients with anomalous proteins, all or almost all of the malignant cells were found to contain the specific anomalous protein. The malignant cells contained either γ-myeloma protein, β2A-myeloma protein or γ1-macroglobulin in patients with these types of anomalous protein. Only one class of globulin was found in individual cells. In patients with Bence Jones proteins as the sole anomalous protein, all the malignant cells appeared to have Bence Jones protein. Where an anomalous serum globulin coexisted with Bence Jones proteins, indirect evidence indicated that the Bence Jones proteins and the larger globulin were formed in the same cells.
Variation in the Amount of Hemoglobin S in a Patient with Sickle Cell Trait and Megaloblastic Anemia
Authors: HELLER PAUL , YAKULIS VINCENT J. , EPSTEIN ROBERT B. , FRIEDLAND SIGMUND
Published: October 2019

A patient with sickle cell trait and nutritional megaloblastic anemia was found to have a much smaller proportion of hemoglobin S during the megaloblastic phase than after recovery. This observation suggests preferential synthesis of hemoglobin A by megaloblastic bone marrow in the presence of the A-S trait.
Sickle Cell—Hemoglobin C Disease
Authors: MOVITT ELI R. , MANGUM JACK F. , PORTER WILLIAM R.
Published: October 2019

Quantitative determinations of iron kinetics and hemoglobin synthesis were made on five patients with sickle cell-hemoglobin C disease. The anemia was mild in all patients but one who had the hemoglobin of 10.1 Gm. per cent. All patients were in a steady state during the period of this study.

The ferrokinetic determinations demonstrated a hemolytic process in all cases. The mean erythrocyte life span in these patients was 18, 20, 29, 46 and 56 days respectively (normal range, 110-130 days). The hemoglobin synthesis was increased in all. Reduced to terms of daily hemoglobin production per liter of blood, the values were 2.2 Gm., 2.9 Gm., 3.6 Gm., 5.8 Gm. and 6.6 Gm. The latter figure represents a five fold increase over the normal mean value of daily hemoglobin synthesis of 1.3 Gm. (normal range, 1.0 to 1.6 Gm. of hemoglobin per liter of blood per day).

The results of the in vivo organ counts demonstrated a significant degree of sequestration of red blood cells in the spleen of two patients. The question of advisability of splenectomy in such patients was discussed.
Erythrocyte Glutathione Reductase
Authors: BEUTLER ERNEST , YEH MARY K. Y.
Published: October 2019

1. The physiologic roles of glutathione in the red cell and of glutathione reductase are reviewed briefly.

2. The partial purification of glutathione reductase by a combination of salting out, heating and chromatographic procedures is described.

3. Throughout purification, no appreciable change in the ratio of activity of the enzyme with DPN and TPN as a coenzyme has been found.

4. Potassium chloride and sodium chloride increased markedly the enzymatic activity when TPNH served as hydrogen donor. However, when DPNH was the hydrogen donor these salts caused a decrease in enzyme activity. Potassium phosphate buffer increased enzymatic activity with TPNH but produced little change with DPNH.

5. Michaelis-Menten constants were computed for the purified enzyme preparations.

6. The DPN-linked system did not result in GSSG reduction when lactate served as a substrate in intact erythrocytes.
Hemolysis and Erythropoiesis
Authors: SÁNCHEZ-MEDAL LUIS , LABARDINI JUAN , LORÍA ALVAR
Published: October 2019

The effect of RBC hemolysates on the recovery from anemia due to blood removal was studied in four dogs. For that purpose each dog was bled on two occasions to obtain similar degrees of anemia, and the erythrocytic production was measured during the 14- to 18-day lapse following each bleeding. A 2- to 3-month interval was allowed between bleedings. The erythrocytic production was evaluated by Cr51 determinations of the circulating erythrocyte volume (EV) after each bleeding and at the end of the 14- to 18-day lapse. During the control study, the dogs received iron intramuscularly and saline intraperitoneally; the latter was substituted by hemolyzed RBC during the test study. The erythrocytic production, in terms of ml. of EV gained per Kg. and per day, in every animal was higher during the test study: 1.126 to 2.411 (mean, 1.568) times the production of the same dog during the control study.

The results furnish strong evidence that the products of erythrocytic destruction have an enhancing effect on the recovery of anemia induced by bleedings in dogs.
Clinical Studies with Vincristine
Authors: CARBONE PAUL P. , BONO VINCENT , FREI EMIL , BRINDLEY CLYDE O.
Published: October 2019

Forty patients with malignant neoplastic disease received vincristine in an effort to define the toxicity, the tolerated dose, the effect of varying dose schedules, and the antitumor properties. The toxicity of vincristine is dose related, and the tolerated dose for the weekly schedule is 0.05 mg. per Kg. for the majority of patients. The tolerated dose per unit time is independent of the schedule of administration. The toxic manifestations relate primarily to the neuromuscular system and the gastrointestinal tract. At the tolerated dose or below, these manifestations are reversible and not accumulative. Hematologic toxicity is rare, and thrombocytosis occurs in some patients. Vincristine produces tumor regression in the majority of the patients with lymphoma where its activity compares favorably with that of the alkylating agents and vinblastine. There is suggestive evidence that cross-resistance between vincristine and the alkylating agents and between vincristine and vinblastine does not occur.
A Case of Autoimmune Hemolytic Anemia with Circulating Cold Agglutinins Presenting for Many Years as "Hypersplenism" and Terminating in Leukemia
Authors: BEN-ISHAY D. , FREUND M. , GROEN J. J.
Published: October 2019

A case of splenomegaly of unknown origin with autoimmune hemolytic anemia, leukopenia and thrombocytopenia (clinically classified as "hypersplenism") has been observed for 18 years. The blood showed a high sedimentation rate, hyperglobulinemia, cold agglutinins, cryofibrinogen, a false positive Wassermann reaction, a positive Coombs test and contained leukoagglutinins in high titer. The patient died of acute leukemia for which it is suggested that the preceding hematologic condition may have prepared the soil, possibly by a process of autoimmunization.
Purified Platelet Phospholipids and Blood Coagulation
Authors: FERGUSON JOHN H. , MARCUS AARON J. , ROBINSON A. JEAN
Published: October 2019

Pure platelet phosphatidylserine (PS) and phosphatidylethanolamine (PE) are compared with brain cephalin (Ceph) in clotting-tests; (1) two-stage, using (a) stypven, (b) trypsin, (c) autoprothrombin-C; (2) PTT (partial thromboplastin time); (3) TGT (thromboplastin generation test); all showing "prothromboplastic" activity, except PE in the unmodified TGT. In validated bioassays (1a), log-log plots of end point clotting-times against phosphatide concentrations are rectilinear and parallel. End points related to equivalents of prothrombin-activated (EPA), or thrombin yield (ETY), make possible computation of reactivities in mixtures. Unlike brain PS ("antithromboplastic"), platelet P-lipids show no inhibitor but summate quantitatively with each other or with Ceph. Alterations in lipid reactivities include: (i) decrease during storage, (ii) increase in desoxycholate, (both assayable), (iii) anomalous ("oxidative") increase, in thromboplastic enzyme tests, invalidating bioassays. TGT’s (3) do not show (iii), but can quantitate certain reactivities. Besides suggesting the basis for a physiologic thromboplastic role of platelets, these methods offer means to explore biochemical bases of reactivities in identifiable lipids. These may be partly related to certain enzymes or intermediates in blood clotting reactions.
A Method of Reducing the Incidence of the Secondary Syndrome in Allogenic Marrow Transplantation
Authors: MATHÉ GEORGES , AMIEL JEAN-LOUIS , SCHWARZENBERG LÉON , MERY ANNE-MARIE , Lapeyraque F.
Published: October 2019

Preservation of a graft of lymph node cells or semi-allogenic bone marrow cells at 37 C. in Tyrode’s solution for 2 hours, which reduces the percentage of cells not permeable to eosin by half, has a statistically significant reducing effect on the frequency of acute or chronic secondary syndromes which occur in irradiated recipients. Preservation at 18 C. for 6 hours, which in the same way increases the percentage of cells permeable to eosin, does not have the same effect.

These two methods of preserving bone marrow cells do not appreciably reduce the myeloid-restoring capacity of compatible or incompatible irradiated recipients.

Application of these results to bone marrow grafting in clinical medicine is discussed.
Possible Errors in the Use of P32 Orthophosphate for the Estimation of Platelet Life Span
Authors: GROSSMAN CHARLES M. , KOHN RICHARD , KOCH RITA
Published: October 2019

Specific activities of platelet lecithin, plasma lecithin, and plasma inorganic phosphate were followed in patients for 4-5 weeks following a single therapeutic injection of P32 orthophosphate, and were found to be of the same order of magnitude at any one specific time. Platelets labeled in vivo with P32 orthophosphate were incubated with non-radioactive plasma, and lost some of the labeled phosphatides to the plasma. Platelets incubated in vitro with P32 orthophosphate incorporated the label into some phosphatides. The findings suggest there is some intrinsic platelet metabolism, and that this must be considered when estimates of platelet life span are made using a P32 orthophosphate label.
The Binding of Cr51 to Hemoglobin I. In Vitro Studies
Authors: PEARSON HOWARD A.
Published: October 2019

By a number of different technics, confirmatory evidence has been obtained that Cr51 activity of Hb A1 tagged with Na2Cr51O4 in a ratio of approximately 1 mole chromium to 1000 mole of hemoglobin is largely associated with the β polypeptide chains. No significant difference in the site or strength of chromium binding could be demonstrated in abnormal hemoglobins resulting from point amino acid substitutions (Hbs S and C).

The results obtained with Hb F were very suggestive of γ chain binding, but an apparently weak Hb F-Cr51 bond or increased elution rate markedly hampered such studies.

The propensity of Cr51 for preferential tagging of β chains was seen not only when hemoglobin was tagged intact, but also when isolated β chains were tagged. This may indicate that there is a specific locus or chemical configuration within the β chains where Cr51 tagging occurs. Knowledge of the exact total amino acid sequence of α, β, and γ chains should soon be available and may permit a precise identification of such a Cr51 binding site.

Whether the results of this type of highly artificial manipulation of hemoglobin has significance in Cr51 red cell survival studies in clinical situations where large amounts of Hb F occur is uncertain. Conflicting results of red cell survival studies of the fetal red cells suggests that it may.27,28 Further investigation of this problem is currently in progress.
In Vitro Studies on Erythrophagocytosis
Authors: GREENDYKE ROBERT M. , BRIERTY ROBERT E. , SWISHER SCOTT M. , Trabold Norma , Ryser Richard
Published: October 2019

1. Two systems for the quantitative study of erythrophagocytosis in vitro are described.

2. The effects of a number of physical factors, cations, anticoagulants, and metabolic poisons in these systems are reported.

3. Existing views on the mechanism of action of factors influencing phagocytosis are briefly reviewed. The importance of the state of energy metabolism of the phagocyte is stressed.

4. The importance of physical, chemical, and metabolic aspects of erythrophagocytic systems is emphasized in connection with the use of erythrophagocytosis as a serologic tool in immunohematology.
Metabolism of Heterogenic Hemoglobins
Authors: LEVERE RICHARD D. , LICHTMAN HERBERT C. , Levine Joan
Published: October 2019

The relative rates of incorporation of Fe59 into heterogenic hemoglobins was studied in four patients with sickle cell trait. Three of the patients were free of superimposed disease, while one had active pulmonary tuberculosis. In all subjects there was a significantly greater incorporation of radioiron, per milligram of hemoglobin, into hemoglobin S than into hemoglobin A.

The data indicate that in sickle cell trait the rates of synthesis of the heterogenic hemoglobins are not proportional to their circulating concentrations. Two interpretations appear possible. Since the size of the intra-marrow pool of hemoglobin S was not known, it is possible that there exists a smaller preformed pool of the abnormal hemoglobin, with the isotope making its appearance first in hemoglobin S. However, it is also possible that hemoglobin S is synthesized at a rate which is greater than that reflected by its circulating concentration. This implies that the relative concentrations of hemoglobin S and hemoglobin A vary from erythrocyte to erythrocyte, and that those cells with the greatest proportion of hemoglobin S are selectively destroyed.
The Gastrointestinal Tract and Iron Absorption
Authors: WHEBY MUNSEY S. , CROSBY WILLIAM H. , Merrill Betty , Lawson Natalie
Published: October 2019

1. Using Fe59 and whole body counting, various aspects of gastrointestinal absorption of iron salts were studied in normal, iron-loaded, and iron-deficient rats.

2. Following a single intragastric dose of iron, peak small intestinal uptake was observed by 30 to 60 minutes with subsequent gradual loss over 24-hour period.

3. Iron absorption showed two phases, an initial period of rapid absorption lasting up to 2 hours during which 60 to 80 per cent of total absorption into carcass took place. The remainder took place at a slow rate over the subsequent 12 to 20 hours.

4. Depending on the relationship between body iron stores and dose of administered iron, the intestine may take up more iron than is ultimately transferred to plasma. A variable amount of this iron is lost when the epithelial cell is sloughed into the gastrointestinal lumen.

5. Regulation of iron absorption appears to involve two steps, mucosal uptake and transfer to the blood.
Identification of Catalase Following Electrophoresis on Acrylamide Gels
Authors: BAUMGARTEN ALEXANDER
Published: October 2019

During the performance of haptoglobin typing by a new technic described by the author, a clear zone was observed in the acrylamide gels used for electrophoresis. Investigations to determine the identity of this zone have shown it to be associated with catalase activity. Consequently, a new technic is presented for identifying catalase following electrophoretic separation of hemolysates. Twenty-five hemolysates from normal human subjects were investigated by this method and were found to contain catalase activity which had the same electrophoretic mobility in all cases. Six normal human sera did not contain this activity under the conditions employed. The catalase activity was found to migrate immediately behind the haptoglobin type 1-1 band.
Transformation of Lymphocytes in Cultures of Human Peripheral Blood
Authors: TANAKA YASUKAZU , EPSTEIN LOIS B. , BRECHER GEORGE , STOHLMAN FREDERICK
Published: October 2019

Previous tracer studies have demonstrated the lymphocytic origin of proliferating cells in blood cultures. Detailed morphologic observations are reported on the transformation of small lymphocytes into larger cells capable of division in tissue culture of human peripheral blood. The large cells have ample cytoplasm with multivesicular bodies, well-developed Golgi apparatus, scanty endoplasmic reticulum, ample ribosomes, and variable fat-laden vacuoles as well as peculiar granular inclusions, large and occasionally bizarre nuclei with prominent nucleoli. Under the condition of culture no further differentiation of these cells has occurred.

The potentialities of the small lymphocyte are discussed in the light of recent radiobiologic and cytogenetic investigations.
Pseudouridine Metabolism. IV. Excretion of Pseudouridine and Other Nitrogenous Metabolites in Chronic Leukemia
Authors: WEISSMAN SHERMAN M. , LEWIS MARVIN , KARON MYRON
Published: October 2019

Urinary pseudouridine, uric acid, and creatine have been estimated in a group of patients with chronic lymphocytic leukemia, chronic myelogenous leukemia, and other diseases. The results indicate that there is a selective and specific overproduction of pseudouridine in patients with chronic lymphocytic leukemia.
The Identification and Synthesis of Activated Plasma Thromboplastin Component (PTC')
Authors: SCHIFFMAN SANDRA , RAPAPORT SAMUEL I. , PATCH MARY JANE
Published: October 2019

1. An activated form of PTC (PTC') which incorporates the properties of both native PTC and activated PTA (PTA') has been identified in BaSO4 eluates of intact citrated plasma.

2. PTC' has been synthesized from partially purified reagents in a reaction shown to require only PTA' and native PTC. Calcium ions greatly accelerate this reaction, but PTC' synthesis occurs slowly in their absence.

3. Kinetic and chromatographic analyses have shown that PTA' functions as an enzyme catalyzing the conversion of native PTC to PTC'.

4. On DEAE-cellulose chromatography, PTC and PTC' were found to elute at the same salt concentration.
Subnormal Serum Folate and Macrocytosis Associated with Anticonvulsant Drug Therapy
Authors: KLIPSTEIN FREDERICK A.
Published: October 2019

Hematologic studies and microbiological assay of serum folate levels with L. casei and serum vitamin B12 concentrations with L. leichmannii were performed on 60 subjects receiving anticonvulsant drug therapy and five epileptics receiving no treatment. Subnormal serum folate levels of less than 5.0 mµg./ml. were observed in 58 per cent of 53 subjects receiving Dilantin and one of seven patients on other anticonvulsant agents. The incidence of subnormal serum folate values was greater in those subjects who had been taking Dilantin for periods of time greater than 5 years, but did not appear to bear any correlation to the dosage of the drug. Slight or moderate macrocytosis was observed in 71 per cent of subjects receiving Dilantin who had subnormal serum folate levels and in 18 per cent of subjects with normal levels. Serum B12 concentrations were within the normal range.

The growth of L. casei was not inhibited by anticonvulsant drugs when added to culture media containing folic acid or serum from patients on Dilantin with normal or low folate concentrations. Folic acid clearance studies were abnormally rapid in three of nine patients studied who were receiving Dilantin.

Possible sites of metabolic inhibition resulting in disturbances in folic acid metabolism during therapy with anticonvulsant medications are discussed.
Protein Metabolism and Erythropoiesis. I. The Anemia of Protein Deprivation
Authors: REISSMANN KURT R. , Dietrich Mary Ruth , Kennedy Myrle Jean
Published: October 2019

(1) Protein deprivation in rats resulted in a rapid depression of iron incorporation. The depression reached its maximum within 6 days. Realimentation with protein was followed within 3 days by a return of iron incorporation to normal values.

(2) Red cell mass declined during protein starvation in a linear fashion, indicating a removal of senescent red cells after a life span of 70 days. The increasing severity of the anemia of protein starvation is the cumulative result of this removal in the absence of any significant replacement.

(3) Daily injections of 1.3 units of erythropoietin prevented a decrease in red cell mass over an observation period of 28 days of protein starvation.

(4) Diminished erythropoietin formation or retardation of protein synthesis in erythroid precursors due to lowered substrate concentration are considered as possible causes of erythropoietic depression.
Sickle Cell Anemia with Two Adult Hemoglobins—Hb S and Hb GPhiladelphia/S
Authors: PUGH REGINALD P. , MONICAL THOMAS V. , MINNICH VIRGINIA
Published: October 2019

Hemoglobin studies have been presented on a patient with clinically typical sickle cell anemia who was found to possess two major adult hemoglobins, Hb S and hybrid Hb GPhil./S. Four hemoglobins were demonstrated in his mother, Hb A, GPhil., S and GPhil./S, in somewhat unexpected and as yet unexplained proportions. To our knowledge the propositus represents the first description of an individual with a homozygous β chain defect accompanied by a heterozygous α chain abnormality.
Radiation Protection of Mice with Bone Marrow and Spleen Preserved at Low Temperature Using Polyvinylpyrrolidone
Authors: PERSIDSKY MAXIM D. , RICHARDS VICTOR
Published: October 2019

The previously reported results11-13 of low-temperature preservation of bone marrow with 10 per cent polyvinylpyrrolidone were re-evaluated on the radiation protection basis. The lethally irradiated mice show 80 per cent recovery after the transplanation of PVP-preserved isologous bone marrow, when compared to the recovery rate of the mice receiving fresh marrow. Slightly higher recovery resulted from the marrow preserved with glycerol. The spleen cells preserved with PVP also induce high recovery in irradiated mice.
The Treatment of Iron-Deficiency Anemia with Intravenous Iron Dextran
Authors: MARCHASIN SIDNEY , WALLERSTEIN RALPH O.
Published: October 2019

Iron-dextran, in doses up to 3000 mg., was administered intravenously by single injection to 37 patients with iron deficiency and to 8 additional patients with acute gastrointestinal bleeding. No serious untoward effects were observed. One patient developed chills and mild abdominal cramps 8 hours after injection. Most of the iron could be accounted for in the circulating blood immediately after the injection. Iron was cleared from the plasma slowly for 3 weeks after the administration. Iron-dextran appears to be a safe and well-tolerated intravenous preparation. It is especially useful in the treatment of iron-deficiency in immobilized patients and individuals with small muscle mass.
The Phosphorylated Carbohydrate Intermediates from Erythrocytes in Hereditary Spherocytosis
Authors: SHAFER A. WILLIAM
Published: October 2019

The phosphorylated carbohydrate intermediates of erythrocytes from normal adults and from five patients with hereditary spherocytosis (HS) were labeled in vitro with P32 orthophosphate and then separated on columns of ion exchange resin.

No qualitative or quantitative differences were found between normal and HS erythrocytes.

The relative specific activity of each phosphate of 2, 3 DPG was the same; whereas the phosphate attached to ribose in ADP and ATP was not labeled. The nucleotides were labeled at a much faster rate than DPG. When the erythrocytes were washed 6 or more times, the specific activity of Pi approached that of DPG. No definite difference was found in the rate of labeling of the intermediates from normal and HS erythrocytes.
Protein Synthesis in Rat Lymphocytes: Radioautographic Studies of Availability and Utilization of Labeled Amino Acids in Vivo
Authors: RIEKE WILLIAM O. , SCHWARZ M. ROY
Published: October 2019

Injections of H3-methionine and H3-leucine were combined with radiochemical and radioautographic technics to study the availability time of H3-methionine and the protein synthetic ability of rat lymphocytes in vivo.

Although 98.5 per cent of H3-methionine was removed from the serum 5 minutes after injection, sufficient quantities persisted and/or re-entered the serum from tissues to cause increasing grain counts in radioautographs of large lymphocytes for 1 hour after isotope administration. A small amount of additional labeling occurred during the 2nd hour, but it is calculated that labeling is 97-98 per cent complete by 1 hour.

All of the large and medium lymphocytes were labeled in the thymus, lymph node, and thoracic duct lymph at short intervals after injection of 4 µc./Gm. body weight of H3-methionine. Evidence is presented that protein synthesis occurs in the nucleus as well as in the cytoplasm and that newly formed protein is equally distributed between daughter cells following mitosis. Previous immunochemical studies are combined with information on generation time and disappearance rates of radioactivity to suggest that large and medium lymphocytes are constantly producing and releasing proteins. Large and medium cells in lymph and lymph node are more active in this than are similar cells in the thymus. Evidence of reutilization of labeled metabolites in the lymph node and especially in the thymus is discussed.

Although not all small lymphocytes were labeled by 4 µc./Gm. body weight of H3-methionine, it was shown that larger doses of isotope would label 100 per cent of them. Small lymphocytes in thoracic duct lymph evidenced significant turnover of labeled protein during the 1st day after isotope administration.
Reticulin Fibrosis and Bone Infarction in Acute Leukemia. Implications for Prognosis
Authors: KUNDEL DONALD W. , BRECHER GEORGE , BODEY GERALD P. , BRITTIN GEOFFREY M.
Published: October 2019

Reticulin fibrosis was found in 21 of 40 patients with acute lymphocytic leukemia when marrows were studied sequentially by Vim-Silverman needle biopsies. Reticulin fibrosis frequently occurred early in the development of the disease. Mild degrees were completely reversible with remission, severe degrees usually persisted, even through remissions. Fibrosis appeared to develop during relapse. Duration of the disease in itself had little influence on the degree of reticulin fibrosis, and collagen fibrosis seldom followed reticulin fibrosis even after many months’ duration.

The prognosis of patients with reticulin fibrosis of their marrows was definitely poorer than for the group without increased reticulin. Reticulin fibrosis virtually always prevented successful marrow biopsies by the standard technic of needle aspiration.

Bone necrosis occurred in 11 of 75 patients with acute lymphocytic leukemia, but in none of 53 patients with acute myelogenous leukemia studied by Vim-Silverman needle biopsies during life or at autopsy. Bone necrosis was the major cause of severe bone pain and it was always associated with reticulin fibrosis of the marrow. Bone infarcts were not associated with short survival in all cases, but in general the prognosis of patients with bone necrosis was even poorer than that of patients with reticulin fibrosis but without demonstrable infarction.
Chromosome Studies in Normal and Leukemic Rats
Authors: DOWD G. , DUNN K. , MOLONEY WILLIAM C.
Published: October 2019

1. Adequate chromosome preparations were obtained in 70 per cent of normal rat peripheral blood cell cultures. However, cultures of peripheral blood cells from leukemic rats were almost universally unsuccessful.

2. In x-ray- and 3MCA-induced leukemias direct bone marrow preparations provided adequate metaphases in eight of 12 cases. Failures were attributed in four cases to scanty material obtained from fibrotic marrows.

3. No consistent chromosome abnormalities, such as those reported in human myelogenous leukemia, were found in these leukemic rats. However, the series of cases is small, and species differences and other factors may have influenced the results of these studies.
The Granulocyte Response to Endotoxin in Patients with Hematologic Disorders
Authors: MARSH JOHN C. , PERRY SEYMOUR
Published: October 2019

Sixty patients with disorders involving the bone marrow were tested with a purified bacterial endotoxin given intravenously. Their leukocyte and granulocyte responses were evaluated based on criteria established in normal individuals and in patients with leukocytosis.

Results in patients with chronic myelocytic leukemia, untreated or in relapse, suggest that adequate granulocyte mobilization may still occur if the disease has been of recent onset or if the count has recently started to rise in spite of therapy. Patients in remission demonstrated adequate granulocyte reserves.

Most patients with chronic lymphocytic leukemia in this study responded well with an increase in the number of granulocytes. Patients with multiple myeloma as a group showed inadequate granulocyte mobilization.

This study demonstrates that endotoxin testing is useful for the evaluation of bone marrow granulocyte reserves in patients with hematologic disorders.
Thalassemia Intermedia
Authors: PEARSON HOWARD A. , NOYES WARD D.
Published: October 2019

Biochemical, genetic, and clinical studies of two adult Negro brothers with clinical thalassemia intermedia are presented. Their hematologic disease appears to have been caused by interactions of thalassemia with another gene which had no phenotypic expression or was non-allelic to the thalassemia locus. These men had striking differences in the proportions of the minor components Hb A2 and F. It is considered unlikely that these differences were genetically determined. Rather, it is suggested that environmental or individual factors can modify this biochemical expression of thalassemia genes.
Mitotic Indices of Human Bone Marrow Cells. III. Duration of Some Phases of Erythrocytic and Granulocytic Proliferation Computed from Mitotic Indices
Authors: KILLMANN S.-AÅ. , CRONKITE E. P. , FLIEDNER T. M. , BOND V. P.
Published: October 2019

1. Weighted average mitotic time of human bone marrow cells is estimated. Mitotic time is about 0.75 hours in red cell precursors and about 0.58 hours in neutrophil precursors.

2. Estimated weighted average DNA-synthesis time is about 9 hours in red cell precursors and about 24 hours in neutrophil precursors.

3. Upper and lower limits for compartment transit times of proerythroblasts, basophilic normoblasts, polychromatic normoblasts, myeloblasts, promyelocytes and myelocytes are presented (table 2).

4. Total mass of nucleated red cell precursors is estimated at 3.5 x 109/kg. and total mass of neutrophils and their precursors in the marrow at 8.8 x 109/kg.
Microspectrophotometric Studies of Individual Erythrocytes from Thalassemia Patients. I. A Case of Double Heterozygosity for β-Thalassemia and Panglobinopenia?
Authors: MATIOLI GASTONE , ZUCKERKANDL EMILE
Published: October 2019

Microspectrophotometric hemoglobin determinations on individual red cells from the peripheral circulation of a patient clinically characterized as a case of thalassemia major show the presence of two main cell populations, one normochromic and one hypochromic, with a ratio of total hemoglobin per cell of 2 to 1, a subnormal β-chain production in all cells, at mean levels that are in a ratio of 4 to 1 in the two cell populations, and a strongly stimulated γ-chain production in both cell populations with no bimodality of distribution. The mean cellular content of δ-chain is augmented. The ratios of 2 to 1 for total hemoglobin production is explained on the basis of the hypothesis that the case is one of heterozygosity for a β-thalassemia gene and a panglobinopenia gene with a mosaic condition realized at least in the case of the panglobinopenia gene. "Panglobinopenia" is described as a condition leading to a general inhibition of hemoglobin synthesis, perhaps through an inhibition of heme synthesis. To account for the observed cellular mosaic, it is proposed that panglobinopenia and perhaps thalassemia are examples of the well known phenomenon of variegation. This interpretation is now to be tested by applying the same methods to the study of further cases of thalassemia patients.
Group-C Trisomy in Myeloid Metaplasia with Possible Leukemia
Authors: SANDBERG AVERY A. , ISHIHARA TAKAAKI , CROSSWHITE LOIS H.
Published: October 2019

A chromosomal abnormality in marrow and blood cells has been found in only one patient out of a group of 20 subjects with myeloproliferative disorders other than leukemia. The abnormal karyotypic finding consisted of group C9 trisomy in a patient with myeloid metaplasia and an acute leukemia-like picture and indicates a definite relationship to acute leukemia. The latter has been shown to be not infrequently accompanied by C9 trisomy. The trisomy was accompanied by the presence of a substantial number of hypertetraploid cells in the marrow but not in the cultured blood cells. As a matter of fact, the blood culture yielded predominantly metaphases with 47 chromosomes (C9 trisomy) on the first examination and metaphases with 46 chromosomes and a normal female karyotype on the second occasion. The superiority of bone marrow karyotype analysis over that of blood cells in leukemic states is thus indicated.
Brief Report: Graft-Versus-Host Reaction in F1 Hybrid Mice Injected with Pre-Immunized Parental Thymus Cells
Authors: FIORE-DONATI LUCIANO , CHIECO-BIANCHI LUIGI , DE BENEDICTIS GIUSEPPE , TRIDENTE GIUSEPPE
Published: October 2019

Dissociated thymus cells are capable of initiating graft-versus-host reaction in (C3Hf/Gs x DBA/2)F1 hybrids only when derived from parental donors previously sensitized against the antigens of the other parental strain. The lower immunologic activity of thymus cells as compared with other lymphoid cells is presumably due to quantitative rather than qualitative differences in immunologically competent cells.
Excess Hemolysis in Subjects with Severe Iron Deficiency Anemia Associated and Nonassociated with Hookworm Infection
Authors: LAYRISSE MIGUEL , LINARES JESÚS , ROCHE MARCEL , Ojeda Adelina , Carstens Alvaro , Dugarte Iris
Published: October 2019

An excess hemolysis was found in subjects with iron deficiency anemia associated with hookworm infection. Red cell survival, measured with Cr51 and DFP32 in the subjects before deworming, showed a marked disproportion between the decrease of the survival and the amount of daily intestinal blood loss in most cases. Excess of hemolysis was still present after more than 90 per cent of the parasites were removed. Red cell survival became normal after correction of anemia through iron treatment. Excess of hemolysis was also present in noninfected subjects with iron deficiency anemia due to other causes.

The reduction in the survival of the erythrocytes from infected subjects transfused into normal recipients shows that the hemolytic process is due to an intrinsic defect of the red cells. The low values of hemoglobinemia and the presence of haptoglobins in the plasma indicate that hemoglobin has not been liberated in excess intravascularly. Finally, the fact that the red cells from an infected patient taken after deworming survived normally in splenectomized recipients indicates that the spleen is probably the principal site of the red cell destruction. The clinical and autopsy findings suggest that splenic function is not pathologically increased, but rather that this organ is acting physiologically at a more rapid rate, "culling" the abnormal circulating red cells and thus leading to a decrease in red cell survival.

The studies presented here also indicate that the hookworm infection per se does not induce hemolysis.
The Course of Experimentally Induced Hemolytic Anemia in a Primaquine-Sensitive Caucasian
Authors: PANNACCIULLI IVO , TIZIANELLO ALBERTO , AJMAR FRANCO , SALVIDIO EMANUELE
Published: October 2019

Two severe hemolytic crises, in a month’s period, were induced by primaquine in a glucose-6-phosphate dehydrogenase deficient Sardinian male.

Young red blood cells tagged with Fe59 10 to 16 days earlier were destroyed in the second hemolytic episode.

The implications of these experiments on the nature of drug-induced hemolysis in Caucasians are briefly discussed.