bluuebunny/crossref_metadata_2025 huggingface dataset:
Critique of the Concept of the "Pre-L.E." Cell
Authors: PASCHER FRANCES , BOROTA ALEXANDER
Published: October 2019

1. Cells with morphologic features apparently identical with the so-called pre-L.E. cell were demonstrated in L.E. preparations in healthy subjects and in individuals suffering from diverse cutaneous and visceral disorders, as well as in patients with systemic lupus erythematosus.

2. These cells appear to be decomposition forms without diagnostic significance, resulting from nonspecific autolytic process that sets in and progresses in the course of setting up the L.E. preparation.
Inhibition of Leukocyte Agglutination by Serum from Patients with Systemic Lupus Erythematosus: A Manifestation of the L.E. Cell Phenomenon
Authors: LEE STANLEY L. , Schultz Florence
Published: October 2019

Dying leukocytes suspended in normal serum tend to agglutinate spontaneously into a firm "clot." This phenomenon is associated with cell lysis and the formation of long fibrous strands of DNA-protein. It seems likely that nuclear DNA-protein actually combines in some way with a fraction of the serum proteins (possibly mucoprotein).

Such leukocyte agglutination is inhibited by serum containing the L.E. cell factor. LAI is associated with nuclear changes which are characteristic of the L.E. cell phenomenon, and it is most probable that it is an expression of the L.E. cell phenomenon.

An understanding of the chemistry of LAI may lead to useful information as to the fundamental mechanism of the L.E. cell phenomenon. Without such understanding, LAI has been used to obtain collateral information concerning the L.E. cell phenomenon: namely, to rule out any important role for DNA-ase, and to confirm the importance of blood platelets. It has also been used to prepare "pure cultures" of L.E. bodies for cytochemical study.

On a clinical level, LAI may prove a useful adjunct to the standard L.E. cell tests. However, its lower level of sensitivity and occasional "false positive" reactions make it inadequate as a primary test in systemic lupus.
Acquired Hemolytic Anemia with Polyagglutinability of Red Blood Cells Due to a New Factor Present in Normal Human Serum (Anti-Tn)
Authors: DAUSSET JEAN , MOULLEC JEAN , BERNARD JEAN
Published: October 2019

A case of acquired hemolytic anemia of 12 years’ duration showing a permanent polyagglutinability for at least 9 years, is presented.

1. Polyagglutinability is due to the presence on the surface of the patient’s erythrocytes of an antigen unknown up to the present time, which is independent of antigens T and H and does not behave like a normal antigen modified by proteolytic enzymes. It has been designated by the letters Tn. The Tn substance is not secreted in saliva. This antigen has not been found on the erythrocytes of 25 members of the patient’s family.

2. The substance which induces agglutination (natural anti-Tn) was found to be present in the serum of 473 white adults and 33 adult Negroes. It was absent or weak in 28 sera from cord’s blood. It acts like a complete antibody, being active in saline at the temperature of laboratory and then inducing massive clumping of Tn red cells. Through absorption and elution studies and through sensitization in rabbits, we have been able to demonstrate that anti-T and anti-Tn are distinct.

3. There are in our patient’s serum: (a) a substance specifically active against Tn erythrocytes treated by trypsin; this may be an immune anti-Tn; (b) a nonspecific incomplete antibody weaker than the anti-Tn and active against all varieties of red cells treated by trypsin; (c) an incomplete anti-E; (d) a cold antiplatelet substance; and (e) an immune antileukocyte antibody.

These three last antibodies are very probably due to transfusions.

4. To explain the combination of an acquired hemolytic anemia and polyagglutinability, two hypotheses are presented: (a) The acquired hemolytic anemia has no relationship to the existence in the patient of a very rare group antigen, perhaps confined to one family. (b) The hemolytic anemia is directly related to the existence of the Tn antigen on our patient’s red cells and is due to the development of an immune anti-Tn antibody against the Tn antigen, this last antigen being either a group antigen or an antigen revealed or modified by the causal agent of the disease.
A New Property of Iso-Agglutinins of the ABO Blood Group System
Authors: JONES A. RICHARDSON , KANEB LORRAINE
Published: October 2019

A new agglutination phenomenon in the ABO group system is described. This phenomenon consists of the development of agglutinates by interaction between a single specifically sensitized cell and other unsensitized, nonantigenic cells. Aggregates of cells formed in this way are tentatively described as "anomalous mixed agglutinates."

Some of the properties of anomalous mixed agglutinates have been investigated, and the impact of these properties on the current theories of agglutination is briefly discussed.
Leukemia and Exposure to X-Ray: A Report of 6 Cases
Authors: MOLONEY WILLIAM C.
Published: October 2019

1. Six cases of leukemia occurring in patients exposed to varying doses of x-ray are reported in this article.

2. The difficulties in evaluating the dosage of radiation is well illustrated in most of these cases.

3. Latent periods were variable and difficult to estimate accurately. It is pointed out that the latent periods in radiation-induced leukemia usually are from three to 10 years in length.

4. All cases in this group were acute leukemias; in four the onset simulated aplastic anemia and diagnosis was verified only after bone marrow aspiration or biopsy.

5. The difficulties in establishing criteria for the diagnosis of radiation-induced leukemia in the present inadequate state of our knowledge are pointed out. In all cases of leukemia attributed to ionizing irradiation it is urgently necessary to publish all information in as complete detail as possible.
Review of Methods for Studying Maturation of Human Erythroblasts in Vitro: Evaluation of a New Method of Culture of Cell Suspensions in a Clot-Free Medium
Authors: BERMAN LAWRENCE , POWSNER EDWARD R. , Davis Mary L. , Fly Marie
Published: October 2019

Characteristics of various tissue and cell culture methods for studying maturation of human erythroblasts were reviewed and the basic assumptions required in their use were examined.

The relationship of maturation and proliferation of erythroblasts in different types of cultures was considered.

Criteria for selection of an in vitro model for studying maturation were established. A new clot-free culture system in roller tubes was found to be superior to those previously described because of convenience, replicability and adaptability to studies of proliferation.

The results of challenging the new culture system with various types of cell-plasma relationships indicated that it was effective in distinguishing among erythroblasts and plasmas of iron deficiency anemia, thalassemia, azotemia and erythrocytosis, and that the deductions arrived at were similar to those derived from the use of less convenient in vitro systems in which different parameters of maturation were used.

Experience with the new method suggests that it may be useful in the study of humoral factors affecting maturation of human erythroblasts.

The chief limitation of the proposed method, as for other in vitro methods, is that only direct effects of humoral agents on erythroblasts can be studied.
Use of the Plasma Thrombin Time to Assess the Adequacy of in Vivo Neutralization of Heparin: Comparative Studies Following Operations Employing Extracorporeal Circulation
Authors: PEDEN JAMES C. , MCFARLAND JAMES A.
Published: October 2019

1. The dosage of protamine necessary for the postoperative neutralization of heparin, used as anticoagulant during extracorporeal circulation, was studied in 25 patients by means of both the protamine titration test and the plasma thrombin time.

2. The plasma thrombin time was found to be far more sensitive in the detection of small quantities of residual heparin than was the protamine titration test, which failed to demonstrate significant quantities of circulating heparin.

3. Adequate neutralization of circulating heparin was achieved when an initial postoperative protamine dose of 1.5 times the calculated residual heparin was given and followed by additional protamine when indicated by the result of the plasma thrombin time.

4. No toxic effects of protamine were noted on such a dosage schedule.
Congenital Deficiency of Proconvertin: A Clinical and Laboratory Report
Authors: MILLER SHERWOOD P. , Patch Mary Jane
Published: October 2019

1. A case of congenital deficiency of proconvertin in a Hopi Indian boy is reported. This is the eleventh case of "pure" proconvertin deficiency and the second reported in the American literature.

2. Laboratory studies revealed normal intrinsic blood coagulation but markedly abnormal tests when coagulation was studied in the presence of tissue extracts.

3. An accompanying mild deficiency of prothrombin was suggested by the results of some tests.

4. The concept that the role of proconvertin in hemostasis is primarily as a co-thromboplastin is supported by the clinical and laboratory studies carried out on this patient. The differentiation of this disorder from other cases with deficiencies of "serum" factors is discussed, and the previously reported cases are reviewed.
Brief Note: The Free Amino Acid Changes in Plasma Following Coagulation and Plasminogen Activation
Authors: COHEN SAUL I.
Published: October 2019

Arginine and lysine are liberated in human blood plasma after plasma plasminogen activation to the protease plasmin as well as after plasma recalcification and subsequent coagulation. Furthermore, digestion of fibrinogen by plasmin results in progressive release of these same amino acids.
Albinism Associated with Hemorrhagic Diathesis and Unusual Pigmented Reticular Cells in the Bone Marrow: Report of Two Cases with Histochemical Studies
Authors: HERMANSKY F. , PUDLAK P.
Published: October 2019

1. A description is given of two unrelated albinos with hemorrhagic diathesis and peculiar, pigmented reticular cells in the bone marrow.

2. On examining hemostasis, the only consistent abnormal laboratory finding was a prolonged bleeding time, so that the hemorrhagic disorder fell into the group of so-called pseudohemophilias.

3. Unusual reticuloendothelial cells in the bone marrow were packed with blackish or greenish blue granules or particles. According to the histochemical study, the substance in the cytoplasm was probably of a lipid nature. These cells could not be identified with similar cells of this kind which have so far been described.

4. The combination of the above described congenital abnormalities (albinism, pseudohemophilia and unusual pigmented macrophages in the bone marrow) in two unrelated patients suggests that a common syndrome is present.
Anemia Following Nerve Resection
Authors: HOLLAN S. R.
Published: October 2019

1. Unilateral sciatic and femoral nerve resection is followed by a marked and lasting fall in the red cell count and hemoglobin value in the albino rat.

2. There are different types in the course of the anemia.

3. A definite parallelism has been observed between the course and severity of anemia and of trophic disturbances developing in the limb almost deprived of its nerve supply.

4. The resection of different peripheral nerves equally results in anemia in the albino rat. The grade of anemia depends on the size of the area supplied by the resected nerve.

5. It is essential in the development of nerve resection anemia that the area with impaired nerve supply and trophic disturbances remain in the organism. Humoral or neurohumoral effects emitted from this area with impaired metabolism are the factors eliciting the anemia observed.

6. Anemia following nerve resection is not due to a change in the distribution of blood cells, nor is it a sequel to loss of blood.

7. Secondary infections, or manifestations of some latent infection (first of all, bartonellosis) are not involved in the development of nerve resection anemia.

8. Chronic tissue destruction induced in areas with intact innervation causes no anemia.

9. Anemia following nerve resection is not due to a deficiency in nutrition.

10. Nerve resections are followed by changes in the entire blood cell system, especially in the formation, maturation and destruction of erythrocytes.

11. Hematologic studies carried out after nerve resections indicate an increased reticuloendothelial activity and the impairment of iron and nucleic acid metabolism.
A Study of Skin Homografting in Patients with Lymphomas
Authors: GREEN IRA , CORSO PHILIP F.
Published: October 2019

Skin homografts were performed on seven patients with lymphomas, three patients with miscellaneous conditions affecting their RE system and four control patients.

The ability to reject skin homograft was impaired in most of the patients with lymphomas, in a patient with bronchogenic carcinoma who had received extensive treatment, and in a patient with multiple myeloma. The presence of normal amounts of gamma globulin and normal response to typhoid antigen did not necessarily indicate a normal response to skin homografts. If marrow homotransplants or other organ homotransplants become a form of therapy in patients with lymphomas, the result of skin grafts from the same donor may be of interest. Our study supports the previous impressions of the immunologic handicaps in patients with lymphomas.
Visual Impairment due to Optic Neuropathy in Pernicious Anemia: Report of a Case and Review of the Literature
Authors: HAMILTON HENRY E. , ELLIS PHILIP P. , SHEETS RAYMOND F.
Published: October 2019

1. A man with optic nerve involvement and pernicious anemia regained normal vision after treatment with vitamin B12.

2. In a search of the literature we found 28 cases with both pernicious anemia and optic neuropathy. The hematologic, neurologic and ophthalmologic findings were analyzed in these cases. In each case, the diagnosis of pernicious anemia was established. Optic atrophy associated with pernicious anemia may be part of the pathologic process of pernicious anemia. If the patient is treated early with vitamin B12 or liver extract, optic nerve function returns.

Sixteen other cases with optic atrophy and possible pernicious anemia in the literature had inadequate information to substantiate the diagnosis.

3. The use of a cobalt60-labelled vitamin B12 absorption test may be helpful in optic nerve disorders of obscure etiology.
A Comparison of Human Leukocyte Phosphatase Activity toward Sodium β-Glycerophosphate, Adenosine 5'-Phosphate and Glucose 1-Phosphate
Authors: FOLLETTE JAMES H. , VALENTINE WILLIAM N. , REYNOLDS JOHN
Published: October 2019

The ability of human leukocyte enzymes to hydrolyze phosphorus is compared in terms of the conventional substrate sodium β-glycerophosphate and the metabolically important phosphate esters, adenosine 5'-phosphate and glucose 1-phosphate. At pH 9.9, there is marked and comparable variation in phosphatase activity toward all three substrates, this being low in chronic myelocytic leukemia and high in the presence of infection and certain "stressful" states. Moreover, substrate mixture experiments show no increased hydrolysis of phosphorus when two substrates are present in the incubation mixture. Increased phosphatase activity toward both glucose 1-phosphate and sodium β-glycerophosphate resulted when corticosteroids were administered in large doses for 72 hours. The data, while not providing absolute proof, are compatible with the hydrolysis of phosphorus at pH 9.9, being due in the case of all three substrates to the activity of the same phosphomonoesterase or group of phosphomonesterases. At pH 5.5, phosphatase activity toward both sodium β-glycerophosphate and adenosine 5'-phosphate was likewise demonstrated, but, in leukocytes, the pH of maximal activity varies from subject to subject and is dependent to a large extent on the amount of the highly variable "alkaline phosphatase" activity present in any given cell population at the time of analysis.
Autologous Bone Marrow Infusion as an Adjunct in Therapy of Malignant Disease
Authors: MCFARLAND WILLIAM , GRANVILLE NORMA B. , DAMESHEK WILLIAM
Published: October 2019

1. Three patients with lymphosarcomatosis and two with disseminated Hodgkin’s disease were treated with massive doses (super-dosage) of nitrogen mustard (over 1.0 mg./Kg.) given intravenously, followed by the intravenous infusion of autologous bone marrow.

2. Two of the five patients succumbed to infection. The remaining three patients recovered within one month and experienced brief remissions.

3. It is suggested that this form of therapy merits further trial. Thus, it may be considered for use earlier in the course of the disease when there is a smaller total amount of tumor tissue, and thus a greater possibility for its complete eradication. Its use in other neoplastic disorders, as following operative procedures disclosing malignancy, is suggested.
Experimental Production of "Grape Cells" and Their Relation to the Serum Gamma Globulin and Seromucoids
Authors: ZLOTNICK AVINOAM , GERICHTER CHAIM B. , NIR ISAAC
Published: October 2019

Hypenimmunization in rabbits with three different antigens produced an elevation of the serum gamma globulin, a plasma cell proliferation and an increase of the seromucoid content of the serum.

Grape cells and intracellular crystals were found in hyperimmune animals, but not in controls. The globules of the grape cells stained positive with periodic acid Schiff and with osmium tetroxide dissolved in a non-polar solution, indicating the presence of a mucopolysaccharide.

It is suggested that there is a relationship between the process of immunization—producing hyperglobulinemia, plasma cell hyperplasia and an elevation of the serum seromucoid content—and the presence of grape cells.
Studies on Erythropoiesis. XIV. The Relationship of Humoral Stimulation to Iron Absorption
Authors: KRANTZ SANFORD , GOLDWASSER EUGENE , JACOBSON LEON O.
Published: October 2019

A new method for the study of gastrointestinal absorption of iron in mice has been described. Phlebotomy, intravenous hemolysis, hypoxia and cobaltous ion increase iron absorption. Transfusion-induced polycythemia depresses iron absorption in mice. Iron-loading by means of Imferon also depresses iron absorption. Under the conditions described for these experiments, exogenous plasma erythropoietin has no direct effect on iron absorption.
Studies of the Production and Life Span of Erythrocytes in Myeloid Metaplasia
Authors: NATHAN DAVID G. , BERLIN NATHANIEL I.
Published: October 2019

1. Four patients with agnogenic myeloid metaplasia and one patient with polycythemia vera and myeloid metaplasia were studied with Fe59, Cr51 and glycine-2-C14.

2. Three of the patients with agnogenic myeloid metaplasia had active splenic, hepatic or renal erythropoiesis. One had deficient erythropoiesis.

3. The red cell life span was short in all of the patients with agnogenic myeloid metaplasia, definite splenic sequestration occurring in two patients. The red cell life span was normal in the patient with polycythemia vera and myeloid metaplasia.

4. The possible indications for splenectomy were discussed.
The Macrocytosis of Hepatic Disease. I. Thin Macrocytosis
Authors: BINGHAM JOHN
Published: October 2019

A macrocytic blood picture was present in 62 per cent of 222 patients with various types of hepatic disease.

Three different types of macrocytes were present in the blood films: a thin macrocyte, a target macrocyte and a thick macrocyte. Just as leukocytosis might be described as neutrophilic, basophilic or eosinophilic according to the predominate leukocyte present, so macrocytosis has been defined according to the predominate macrocyte present: thin macrocytosis, target macrocytosis and thick macrocytosis. This report deals with the first type, thin macrocytosis.

1. Thin macrocytosis is, by definition, the type of macrocytosis in which all the macrocytes are thin macrocytes. It is the commonest type of macrocytosis (59 per cent of all types of macrocytosis).

2. The thin macrocyte is a flattened erythrocyte. It has the same volume as the normal erythrocyte but is broader and thinner. As the diameter of the cell increases its thickness decreases.

3. Thin macrocytosis is caused by an alteration in erythropoiesis in the bone marrow and not by a flattening or swelling of normal erythrocytes in the peripheral circulation, as suggested by various workers, because:

(a) Normal size erythrocytes transfused into the circulation of patients with thin macrocytosis do not become macrocytic.

(b) Anisocytosis is increased.

(c) The nucleated red cells in the marrow are macrocytic.

4.The thin macrocyte is produced by a macronormoblastic (or rarely atypical megaloblastic) type of maturation in the bone marrow.

5. This altered erythrocyte maturation which gives rise to thin macrocytosis is a specific response to nonspecific hepatic parenchymal cell damage. It occurs in a significant percentage of patients suffering from all types of parenchymal and obstructive hepatic disease. It does not occur in patients with simple fatty liver or obstructive jaundice of short duration where hepatic cells are not damaged. A deficiency of any known hematopoietic factor plays no part in the etiology of this disorder.
Homografts of Bone Marrow in Dogs After Lethal Total-Body Radiation
Authors: THOMAS E. DONNALL , ASHLEY CHARLES A. , LOCHTE HARRY L. , JARETZKI ALFRED , SAHLER OTTO D. , FERREBEE JOSEPH W.
Published: October 2019

Twenty-two dogs (20 males and two females) were uniformly exposed over their entire surfaces to supralethal irradiation: 800 to 1,200 roentgens of 250 kv. x-rays measured in air at mid-body position. On the third day and after the last exposure, these irradiated animals were given infusions of normal bone marrow. The marrow for their infusions was taken from female litter-mates, from mothers or from unrelated dogs. Evidence for a return of marrow function and for a successful marrow graft was evaluated on the basis of: (1) the reappearance of formed elements: platelets, leukocytes, and reticulocytes, in the peripheral circulation; (2) the appearance in males of leukocytes bearing the sex-chromatin marker of the female donor; (3) prolonged survival, as compared to six irradiated control animals that were not given marrow; and (4) cellularity of marrow spaces and histologic evidence of marrow function at autopsy.

It was found that marrow transplants usually succeeded after 800 to 1,200 roentgens of total-body irradiation when the infused marrow was taken from litter-mate sisters or from mothers (15 successes in 17 attempts). Marrow transplants between unrelated animals appeared more difficult but were not impossible. One success was obtained in five attempts, and this success was achieved with the coincidental use of splenectomy, ACTH and a large dose of marrow.

Dogs with successful transplants lived longer than did control animals; in this series two to 10 times as long. When they died, they died of common canine infectious diseases and not of marrow failure. Distemper, hepatitis and leptospirosis, with or without superimposed bacterial respiratory disease, were the common causes of death.

The lymph nodes and the splenic follicles of irradiated animals had, in most instances, not regained normal histologic appearance at the time of death from these infectious diseases. The working hypothesis is advanced that infusions of marrow repopulate marrow spaces in the canine after irradiation but are poor sources of the type of cell needed to restore lymphoid function and immunologic effectiveness in lymph nodes and spleen.
The Incidence of Leukemia in Families of Patients with Hypoplasia of the Marrow
Authors: GARRIGA SERGIO , CROSBY WILLIAM H.
Published: October 2019

The authors have reviewed the published cases of Fanconi’s syndrome of hypoplasia of the bone marrow. They have tabulated the features of the syndrome, pointing out that atrophy of the spleen is a common fault and may reflect a generalized dystrophy of the tissues of mesenchymal origin.

Of special interest is the demonstration of a high incidence of leukemia in the families of patients with hereditary hypoplasia of the bone marrow.
Lymph Node Reactivity. III. Lymphomas and Allied Diseases
Authors: BLACK MAURICE M. , SPEER FRANCIS D.
Published: October 2019

A study was made of the ammoniacal silver staining of the cells of Hodgkin’s disease, lymphosarcoma, follicular lymphoma, acute leukemia and chronic leukemia as seen in routine 5 µ. paraffin sections. With the exception of chronic lymphatic leukemia, the cells of lymphomas and allied diseases exhibited minimal staining. These data were compared with the ammoniacal silver staining of normal lymph nodes and the enhanced staining of nonneoplastic proliferations in developing and reactive lymph nodes.
The Cultivation of Mouse Bone Marrow in Vivo
Authors: BERMAN IRWIN , KAPLAN HENRY S.
Published: October 2019

The cultivation of normal mouse bone marrow cells in diffusion chambers implanted into the peritoneal cavity of mice has been described. Mouse bone marrow cells cultivated by this method continue to undergo differentiation and maintain their morphologic identity for a considerable time.
Familial Hemolytic Anemia with Erythrocyte Inclusion Bodies and a Defect in Pigment Metabolism
Authors: SCHMID RUDI , BRECHER GEORGE , CLEMENS TED
Published: October 2019

1. Two patients, a father and his only son, suffered from a severe congenital hemolytic syndrome, which was characterized by the presence of spontaneous inclusion bodies in erythrocytes and by the excretion of dark-brown pigments in the urine.

2. The inclusion bodies present in approximately one-third of the erythrocytes, were indistinguishable from Heinz-Ehrlich bodies. They occurred in reticulocytes and occasionally in normoblasts. In addition to these bodies, many erythrocytes contained basophilic stippling, siderocytic granules and rod-like structures. These morphologic abnormalities are believed to be the result of an inherited metabolic abnormality of the red cells.

3. The urinary pigments were found to have properties which were similar to mesobilifuscin. It is believed that these pigments possessed a dipyrrolic structure and were derived from erythrocyte catabolism.

4. Transfusion of the patient’s erythrocytes into a normal recipient resulted in rapid removal of the heterologous cells from the circulation and in excretion of similar dark pigments in the urine.
Refractory Anemia with Hyperplastic Bone Marrow
Authors: VILTER RICHARD W. , JARROLD THOMAS , WILL JOHN J. , MUELLER JOHN F. , FRIEDMAN BEN I. , HAWKINS VIRGINIA R.
Published: October 2019

1. The hematologic syndrome called refractory anemia with hyperplastic bone marrow, aregenerative anemia, chronic bone marrow failure, pseudo-aplastic anemia, and many other terms, has been separated into five types on the basis of clinical and hematologic studies on 23 patients carried out over a period of 16 years. These groupings are probably highly artificial but are made to facilitate presentation and description. As more is learned of the chemistry of the bone marrow cells in patients with refractory anemia, a more satisfactory classification will be possible.

2. Type 1 is characterized by bizarre chromatin in the normoblasts, mast cell hyperplasia, hemosiderosis or hemochromatosis and a tendency for spontaneous remissions to occur.

3. Type 2 is at first typified by complete or almost complete erythroid aplasia. Hyperplasia of erythroid cells with maturation arrest and bizarre chromatin pattern may occur later, and finally spontaneous remission may appear with considerable frequency. Mast cell hyperplasia, thymoma and hemosiderosis have been noted.

4. Type 3, associated with exogenous toxins and the preleukemia state, is characterized by pancytopenia and a bizarre chromatin pattern in the normoblasts. Some of these patients may he classified as "DiGuglielmo syndrome."

5. Type 4 also is typified by pancytopenia and hyperplasia of bone marrow but with cells of normal appearance. These patients responded partially or completely when splenectomy was performed, and probably represent a variant of the "hypersplenism" syndrome.

6. Type 5 is refractory megaloblastic anemia with typical cytologic changes evident in all cell types similar to those found in pernicious anemia.

7. Hypotheses are proposed to explain these various types of anemia on the basis of abnormalities in the metabolism of nucleic acids, particularly DNA. Deficiencies of metabolites, inhibition of metabolic reactions by exogenous or endogenous toxins, or by immune mechanism in which DNA serves as haptene, are possible explanations.
In Vitro Studies on the Anemia of Tumor-Bearing Hamsters
Authors: SHERMAN JOSEPH D. , RICKARD CARMEN , CHRISTIAN ROBERT S. , FRIEDELL GILBERT H.
Published: October 2019

1. Sterile, cell-free extracts of the viable portion of a methylcholanthrene-induced sarcoma of the hamster were capable of hemolyzing in vitro hamster red blood cells from the donor animals, and from animals with homologous and heterologous tumors.

2. Sterile, cell-free extracts of the necrotic material from this same tumor had little in vitro hemolytic action.

3. Whole tumor extracts varied in their in vitro hemolytic activity depending upon the proportion of viable to necrotic tissue present, with the maximum hemolysis observed when the whole tumor contained more viable than necrotic tissue.

4. Sterile, cell-free extracts of normal hamster liver had a strong hemolytic action on a whole range of red blood cells.

5. Hemolysins elaborated by the viable tissue in transplanted hamster tumors may be one factor contributing to the anemia in hamsters bearing transplantable sarcomas.
Brief Note: A Technic of Bone Marrow Transplantation in Man
Authors: SCHWARZ ROBERT , MISRA DWIJENDRA K. , DAMESHEK WILLIAM
Published: October 2019

A method for the transplantation of bone marrow in man is described. With this technic it was possible to obtain up to 18 billion marrow cells from the posterior iliac crests. The effects of this procedure on the donor and the recipient are discussed in the light of our experience with over 100 such transplants.
The Role of Splenectomy in the Management of Thalassemia
Authors: SMITH CARL H. , ERLANDSON MARION E. , STERN GERTRUDE , SCHULMAN IRVING
Published: October 2019

A group of 58 children with severe Cooley’s anemia, half of them splenectomized, were reviewed from several of the more important clinical and hematologic aspects.

Splenectomy eliminates the extracorpuscular mechanism responsible for the accelerated destruction of normal donor red cells in the patient’s circulation. This represents a lasting improvement and accounts for an increased longevity of normal blood supplements and a striking reduction of transfusion requirements. Less blood was required to maintain at least as good, and at times improved, hemoglobin levels. Estimates of duration of survival of the patient’s own erythrocytes suggest that the basic hemolytic defect is not altered significantly by this operative procedure.

While transfusions and splenectomy promote the patient’s well being, growth in height and sexual development are retarded. Secondary sexual characteristics develop, if at all, later than in normal individuals and normal menses are rare.

Cardiac failure occurred in 10 patients; all but one had been subjected to splenectomy. This group was characterized by cardiac enlargement, multiple arrhythmias and death with refractory heart failure, usually in the second decade of life.

Cardiac complications are likely to be related to the heavy deposition of iron in the myocardium, and are comparable in this respect to a similar incidence in idiopathic hemochromatosis. One of the most serious problems in the management of Cooley’s anemia is the prevention and control of congestive heart failure. This will depend on the discovery of an effective method by which the heart can be made to unload its iron deposits.

The increased susceptibility to infection following splenectomy in patients with severe Cooley’s anemia indicates that the normal immunologic responses inherent in the spleen remain intact despite the stress of a continuous hemolytic process.
Autografts of Bone Marrow in Dogs After Lethal Total-Body Radiation
Authors: MANNICK JOHN A. , LOCHTE HARRY L. , ASHLEY CHARLES A. , THOMAS E. DONNALL , FERREBEE JOSEPH W.
Published: October 2019

1. Four beagles were exposed to supralethal total-body irradiation from a 250 kv x-ray therapy machine. Four were exposed to similar irradiation from a Cobalt-60 teletherapy unit. Dosages administered ranged from 600 to 1500 r, calculated as air dose at theoretical midbody line.

2. After irradiation each dog was given an intravenous infusion of 1.4 to 3.7 billion cells of his own bone marrow. This sample of autologous marrow was aspirated through a surgical window in the femur immediately prior to the animal’s irradiation and was stored in plasma and tissue culture fluid at 4 C. while awaiting use.

3. All dogs survived the acute radiation injury. There were two late deaths, one from intercurrent infection and one from small bowel obstruction.

4. The six surviving dogs are in apparent good health 5 months to 10 months after irradiation. Control dogs in this laboratory have a 100 per cent 15 day mortality after air dose of 600 r total-body irradiation.

5. A comparison with a previous series of dogs grafted with homologous smarrow shows that autologous marrow induces a recovery after lethal irradiation that is superior to the recovery induced by homologous marrow.

6. The superior results observed after autologous marrow appear attributable to a rapid postirradiation recovery of lymphoid tissue as well as bone marrow. Circulating lymphocytes reappear, lymph nodes regain normal histologic appearance, and the serum gamma globulin pattern returns to normal. These latter events do not occur promptly after infusions of homologous marrow.
A Method for Evaluating the Hemostatic Effect of Various Agents in Thrombocytopenic Rats and Mice
Authors: FIRKIN B. G. , ARIMURA GRACE , HARRINGTON W. J.
Published: October 2019

A simple method for measuring the control of blood loss in thrombocytopenic rats and mice is described.

The administration of lyophilized platelets, brain phospholipid extract and soya bean extract failed to correct the blood loss in the thrombocytopenic animal.

The results obtained with this method have failed to support the effectiveness of "platelet substitutes" in in vivo systems and reaffirm the requisites of viability and recirculation for platelet transfusions.
Some Properties of Cross Reacting Antibody of the ABO Blood Group System
Authors: JONES A. RICHARDSON , KANEB LORRAINE
Published: October 2019

An account is given of an experiment in which the use of a "blocking" procedure has enabled the site of action of the cross reacting antibody in group O serum to be shown to be homologous with the A and B antigens of the red cell. In another experiment cross reacting antibody was shown to behave asymmetrically. In both these experiments use was made of the mixed agglutination technic for directly demonstrating the adherence of two cells of differing specificity by cross reacting antibody.

The significance of the results of these experiments is discussed in the light of observations by other workers.
Animal and Human Studies on Ferrous Fumarate, an Oral Hematinic
Authors: BERENBAUM M. C. , CHILD K. J. , DAVIS B. , SHARPE HELEN M. , TOMICH E. G.
Published: October 2019

Ferrous fumarate, an oral hematinic, has been compared with the sulphate, succinate and gluconate for various aspects of toxicity.

In mice, the relative acute oral toxicities were fumarate 1, succinate 1.1, gluconate 2.0 and sulphate 2.7.

In cats, the relative emetic activities were fumarate 1, succinate and gluconate 3, and sulphate 4.

Examination of the stomachs and livers of rabbits given massive doses of the four iron tablets showed that the sulphate and gluconate were much more toxic and irritant than the succinate or fumarate.

Rats dosed for 12 weeks with ferrous fumarate (50 mg. Fe/Kg./day) grew normally, and histologic examination of the major organs revealed no abnormalities that could be attributed to the drug.

Hematinic studies on iron-deficient rats, receiving the four iron compounds orally or iron-dextran intramuscularly, indicated that ferrous fumarate was as effective as the other compounds.

Twenty-two hypochromic anemic patients were dosed with Fersamal (three tablets per day), and all except one showed hematologic improvement. The patient who proved refractory had previously undergone gastrectomy and had not improved on either ferrous sulphate or gluconate.

The tablets were acceptable to all the patients.
Free Serum Vitamin B12 Level in Certain Hematologic Disorders
Authors: BANERJEE D. K. , GHOSE SANDHYA , GHOSH S. K. , CHATTERJEA J. B.
Published: October 2019

The variation of the free fraction of serum vitamin B12 level was studied in certain hematologic disorders. In normals, the mean ratio of free to total vitamin B12 was 10.2 per cent. In leukemias—chronic myeloid, acute myeloid and acute lymphatic—the mean value of free vitamin B12 was higher than normal. In chronic myeloid and acute lymphatic leukemias, the free vitamin B12 level did not on an average exceed 20 per cent of the total. In acute myeloid leukemia, the free fraction was relatively more increased, constituting 31.1 per cent of the total on an average. In aplastic anemia, the mean values of free vitamin B12 and the ratio (31.2 per cent) of free to total vitamin B12 were higher than normal. The patterns presented by acute myeloid leukemia and aplastic anemia appeared to be more or less similar.
Heparin Therapy in Autoimmune Hemolytic Anemia
Authors: MCFARLAND WILLIAM , GALBRAITH ROBERT G. , MIALE AUGUST
Published: October 2019

1. Although a few previous reports suggest a beneficial effect of heparin in autoimmune hemolytic anemia, there has been no general recognition of this form of treatment. Therefore, its striking benefit in a patient with severe autoimmune hemolytic anemia refractory to usual therapeutic measures has been reported.

2. The mechanism of action of heparin in autoimmune hemolytic anemia remains unknown; it does not appear to be due to any anticomplementary activity.

3. Heparin should be tried more widely in autoimmune hemolytic anemia, particularly in situations in which response to corticosteroids and splenectomy has been disappointing.
Induction in Rabbits of Activity Against Human Blood Thromboplastin
Authors: SPAET THEODORE H. , CINTRON JOSE R.
Published: October 2019

Rabbits were injected with sedimented human blood thromboplastin, and two animals developed serum activity against human blood thromboplastin in significant excess over naturally occurring inhibitor. This antithromboplastic activity was specific against human reagent, failed to affect thromboplastin precursors and had no activity against tissue thromboplastin.
Candida-Reacting Antibody in the Serum of Patients with Lymphomas and Related Disorders
Authors: BRODY JEROME I. , FINCH STUART C. , Mcilroy Bettina
Published: October 2019

1. The quantity and characteristics of antibody reacting with Candida albicans was determined in normal subjects and in patients with lymphomas and leukemias by the immune-adherence technic.

2. Little antibody to Candida albicans is present in infants during the first few months of neonatal life; a progressive increase in antibody occurs during adolescence, and antibody is present in high titer in the serum of normal adults.

3. No significant decrease in antibody titer was found in the sera of patients with advanced leukemia or lymphoma, most of whom had had extensive specific therapy.

4. This antibody was characterized by lack of cross absorption with rice starch polysaccharide, complete absorption with Candida albicans and by increased serum reactivity following active antigenic stimulation in rabbits.

5. It is apparent from this study that production of the "natural antibody" of this type is maintained despite the progression of neoplastic disease and the use of antineoplastic agents.

6. It is probable that alteration of tissue defense mechanisms rather than humoral antibody account for the increased incidence of disseminated monilial infections in patients with lymphomas and leukemias.
Renal Hemosiderosis in the Hemolytic Anemias: Diagnosis by Means of Needle Biopsy
Authors: LEONARDI P. , RUOL A.
Published: October 2019

Renal hemosiderosis has been ascertained by needle biopsy in eight patients. Two of them were affected by paroxysmal nocturnal hemoglobinuria, three by autoimmune hemolytic anemia, one by paroxysmal cold hemoglobinuria, one by thalassemia minor, and one by hereditary spherocitosis. Although the extent of the hemosiderin infiltration of the kidney varied, the distribution of this pigment was limited almost exclusively to the proximal convoluted tubule in all cases. Only one patient with autoimmune hemolytic anemia, who had previously received numerous blood transfusions, had hemosiderin infiltration of the liver and spleen. In all other cases hemosiderosis limited to the cells of the proximal convoluted tubule appears to be a histologic sign of hemoglobin reabsorption. This was more evident when intravascular hemolytic episodes were recorded or when a moderate degree of hemoglobinemia suggested the occurrence of a slight, persistent intravascular hemolysis. No significant impairment of tubular function was found, even in patients with most marked hemosiderosis.
On the Etiology of "Meat Anemia" in Mice
Authors: ILAN JUDITH , KENDE M. , GUGGENHEIM K.
Published: October 2019

Young mice kept on a diet consisting of meat only develop an anemia which is accompanied by depressed growth and high fatality.

Treatment of mice while subsisting on the meat diet with para-aminobenzoic acid, folic acid, vitamin B12, liver extract, pyridoxine, iron, vitamin A, penicillin, aureomycin or a combination of some of these substances neither prevents the anemia nor the mortality, nor does it improve growth. Some of these substances have, however, a slight effect in preventing anemia.

Replacing one of four parts of meat by beef liver or an isocaloric-isonitrogenous mixture of casein, cornstarch, salts and water almost completely prevents the anemia but does not improve, or only slightly improves, the stunted growth. Dilution of meat with liver but not with the casein mixture has a striking therapeutic effect in mice rendered anemic by the meat diet.

It is assumed that the anemia is caused by the presence in meat of a hematopoiesis-inhibiting factor and/or by the lack of some unknown hematopoietic factor(s) possibly produced by the intestinal flora and present in liver.
An Inheritable B-like Character in Persons of Blood Group A
Authors: ANDERSEN JØRGEN
Published: October 2019

In a previous paper the author reported investigations of a blood sample (Co) whose blood cells contained, in addition to a normal A antigen, a weak, atypical B-like antigen. The present paper deals with two blood samples, El and Do, which probably possessed the same weak, atypical B-like character. A study of El’s family showed that this blood group character, provisionally designated as Ab, may be inheritable, as it was found in two children and one grandchild of El’s.

The serologic studies of the 5 Ab samples are reported, and on the basis of the family material the possible origin of the Ab character is discussed.
Volume and Cellular Constitution of Bone Marrow in Guinea Pigs Hypoxic from Birth
Authors: HUDSON G.
Published: October 2019

A quantitative study of the volume and cellular constitution of the bone marrow was carried out in 10 guinea pigs of approximately 400 Gm. body weight, which had been born and reared at a simulated altitude of 14,000 feet, and in 10 normal controls.

The hemopoietic marrow of the experimental group was more cellular and showed a marked increase in the number of erythroid cells per unit volume. No significant changes were demonstrated in the absolute counts of other cells, but fat vacuoles appeared less numerous. The fatty (yellow) marrow occupied its normal centrifugal position in the skeletons of both groups.

No absolute increase in the volume of bone marrow was detected in the experimental group, but the red marrow volume formed a significantly greater proportion both of the volume of the skeleton containing it and of the total marrow volume.

It was concluded that the marrow of the hypoxic animals had a total population of erythroid cells about 40 to 50 per cent greater than normal; this increase was largely accommodated by closer packing of cells in the red marrow.
Congenital Hemolytic Disease Associated with Red Cell Inclusion Bodies, Abnormal Pigment Metabolism and an Electrophoretic Hemoglobin Abnormality
Authors: SCOTT J. L. , HAUT A. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

1. A fourth case of the syndrome of congenital hemolytic anemia with abnormal pigment metabolism and red cell inclusion bodies following splenectomy is described.

2. In this case an abnormality was found on paper and starch electrophoresis of the red cell hemolysate at pH 8.6. A similar abnormality has not been reported previously.

3. An increased rate of erythrocyte autohemolysis was found during in vitro incubation, Partial correction of this defect occurred in the presence of glucose or purine ribosides.

4. Genetic transmission of the defect could not be demonstrated.
Morphological and Histochemical Studies of the Leukemic Cells from a Patient with Atypical Myeloblastic Leukemia with Special Reference to Intracytoplasmic Mucopolysaccharide Vacuoles and Fibrillar Formation
Authors: ACKERMAN G. ADOLPH , GRASSO JOSEPH A. , KNOUFF RALPH A.
Published: October 2019

A detailed study (phase contrast, bright field and electron microscopy) of the primitive leukemic cells from a patient with atypical myeloblastic leukemia has been presented. An unusual mucopolysaccharide-containing vacuole has been observed and characterized both morphologically and histochemically. In addition, this study has yielded considerable information concerning the structure and chemical composition of the fibrillar formations, fat droplets and the alterations in erythrocytes following their ingestion by the leukemic cells. Intramitochondrial structural alterations have been observed and characterized in many of the primitive myeloblasts. Changes in the mitochondria and endoplasmic reticulum may reflect impaired or altered metabolism in these abnormal leukemic cells.
Evaluation of a New Chemotherapeutic Agent in Patients with "Advanced Refractory" Acute Leukemia. Studies of 6-Azauracil
Authors: FREIREICH EMIL J. , FREI EMIL , HOLLAND JAMES F. , PINKEL DONALD , SELAWRY OLEG , ROTHBERG HARVEY , HAURANI FARID , TAYLOR ROBERT , GEHAN EDMUND A.
Published: October 2019

6-Azauracil was studied in patients with "advanced" acute leukemia, refractory to standard chemotherapy. Under the conditions of the study this compound was found to have no significant antileukemic activity. As a result, these data have defined the natural history of this phase of acute leukemia. A significant proportion (30 per cent) of these patients showed objective hematologic improvement even in the absence of effective specific therapy, which might be ascribed to a prospective new agent. The median survival from the onset of the study of this group of patients was two months, and survival patterns for adults and children were similar.
Febrile Response to Bacterial Pyrogens in Leukemia
Authors: BRAUDE ABRAHAM I. , BECK JAY , ZALESKY MARGARET
Published: October 2019

1. The intravenous injection of 50,000,000 dead typhoid-paratyphoid bacilli produced a greater febrile reaction in nonbeukemics than in patients with chronic lymphocytic leukemia.

2. These results suggest that granulocytes may contribute to the production of the fever that follows injection of bacterial pyrogens.