bluuebunny/crossref_metadata_2025 huggingface dataset:
RETICULOCYTE RIPENING IN EXPERIMENTAL ANEMIA AND HYPOPROTEINEMIA
Authors: NIZET A. , ROBSCHEIT-ROBBINS F. S.
Published: October 2019

Ripening time of reticulocytes has been measured in dogs with an experimental hemorrhagic anemia and in "doubly depleted" dogs (anemia plus hypoproteinemia).

In dogs submitted to hemorrhagic anemia alone, receiving a basal protein containing diet low in iron, the ripening time is the same as in nonanemic dogs, regardless of the potency for hemoglobin synthesis of any supplementary diet.

In anemic and hypoproteinemic dogs, i.e., "doubly depleted" dogs, a close relationship exists between the rate of hemoglobin regeneration and the ripening time of reticulocytes. Feeding a basal nonprotein diet results in a block of the ripening effect; however, if a potent diet for hemoglobin regeneration is given, the ripening time becomes normal.

Measurement of the ripening time in a "doubly depleted" dog provides a gross evaluation of the potency of a diet, as it concerns hemoglobin synthesis.

The block of reticulocyte ripening in doubly depleted dogs may be lifted by addition of amino acids to the blood in vitro. Only the ten amino acids essential for growth and glycine are necessary. It appears therefore that the block in double depletion is caused essentially by the depletion of some protein factor or factors.

The significance of these experimental results is discussed, relative to the problem of in vivo and in vitro synthesis of hemoglobin.
REFRACTORINESS IN HEMOPHILIA TO COAGULATION-PROMOTING AGENTS: WHOLE BLOOD AND PLASMA DERIVATIVES
Authors: FROMMEYER WALTER B. , EPSTEIN ROBERT D. , TAYLOR F. H. L.
Published: October 2019

Frommeyer, Epstein and Taylor: Refractoriness in hemophilia to coagulation-promoting agents: Whole blood and plasma derivatives. Blood 5: 401-420 (May), 1950. The authors wish to note that the following changes should have appeared in the article:

Page 402, first line: "Lawrence and Johnson, 1941,8 reported" (instead of "Lawrence and Johnston, in 1946,8 reported").

Page 402, second sentence of same paragraph: "In this instance the patient had received whole blood and plasma in therapeutic management prior to the appearance of resistance to therapy." (instead of ". . . had received chemically prepared plasma fractions in the form of Fraction I of Cohn in addition to whole blood and plasma in therapeutic management prior to . . . ").

Page 420, reference 8. To this reference should be added: "(Presented before the American Clinical and Climatological Society, October 1941.)".
Immunochemical characterization of a polyclonal human antibody to factor IX
Authors: Reisner HM , Roberts HR , Krumholz S , Yount WJ
Published: October 2019

Inhibitors of clotting factors occuring in humans are often antibody molecules synthesized in response to exogeneous proteins used in replacement therapy. Extensive studies of inhibitors to factor VIII indicate such antibodies may be monoclonal or polyclonal in nature. To date, only one factor IX inhibitor has been subjected to detailed immunochemical analysis and it appears to be a monoclonal IgGA lambda antibody. We have discovered a second inhibitor of factor IX in a patient with severe hemophilia B and have subjected it to immunochemical analysis. Studies on this second inhibitor have been carried out before and after an anamnestic response. Column chromatography, preparative zone electrophoresis, and specific inhibitor neutralization assays using monospecific heterologous antisera to human immunoglobulin classes, subclasses, and light-chain types indicate that the antibody is of the IgG class and contains both kappa and lambda light chains and probably all four IgG subclasses. Thus, the inhibitor appears to be polyclonal by immunochemical and structural criteria. In addition, preparative isoelectric focusing of pre- and postanamnestic inhibitor samples indicates that recruitment of new clones of IgG antibody occurs as a result of anamnesis. It is conceivable that an antibody initially restricted in immunoglobulin subclass became polyclonal following an anamnestic response.
Low molecular weight intracellular iron transport compounds
Authors: Jacobs A
Published: October 2019

Evidence is presented for the existence of an intracellular pool of low molecular weight iron compounds which acts as an intermediate between extracellular iron and a wide variety of intracellular processes. It is in equilibrium with storage iron and iron enzymes and is of major importance in iron toxicity and chelation therapy.
Erythrocyte cellular and membrane deformability in hereditary spherocytosis
Authors: Nakashima K , Beutler E
Published: October 2019

In order to determine whether the relative rigidity of the hereditary spherocytosis (HS) red cell is due to membrane rididity or merely to an altered surface/volume ratio, we investigated the deformability of resealed red cell membranes from patients with HS. Whereas the osmotic fragility of intact red cells of HS patients showed the expected increase, the osmotic fragility of resealed HS membranes was normal, thus indicating that their surface/volume ratio was normal. Measurements with an ektacytometer showed that deformability of intact HS cells was markedly diminished, whereas deformability of resealed HS membranes was normal. These findings indicate that the HS red cell membrane is not intrinsically abnormally rigid, as has been suggested, but that the lack of deformability of the erythrocyte is primarily a function of the altered surface/volume ratio.
The Normal Megakaryocyte Concentration in Aspirated Human Bone Marrow
Authors: EBAUGH FRANKLIN G. , BIRD ROBERT M.
Published: October 2019

1. A practical chamber method has been devised for enumerating the megakaryocyte concentration of aspirated bone marrow.

2. Marrow aspirations from 23 healthy young adults had a mean megakaryocyte concentration of 4.0 ± 1.1 per 10,000 total nucleated cells or 6.1 ± 1.6 per 10,000 granulocytes.

3. Of the three principal cell types in marrow, i.e. granulocytes, erythrocytes and lymphocytes, the megakaryocyte content seemed to parallel most closely the granulocytes.
Effect of Transfusion Polycythemia upon Bone Marrow Activity and Erythrocyte Survival in Man
Authors: BIRKHILL FREDERICK ROSS , MALONEY MARY A. , LEVENSON STANLEY M.
Published: October 2019

1. The effect of transfusion polycythemia upon bone marrow activity and erythrocyte survival has been studied in 4 normal young adult males.

2. Plasma volumes did not change significantly throughout the period of study.

3. Total red cell masses increased to the "expected" levels, i.e., to the total of the subjects’ cells plus the transfused cells immediately after the transfusions. Thereafter these fell progressively, reaching the control levels in about forty days.

4. Survival of the infused cells was normal.

5. The subjects’ own red cell masses fell progressively at first. This was due to decreased erythropoiesis rather than to increased destruction. This is indicated by (a) no consistent significant elevation in hemolytic indexes; (b) change of the myeloid-erythroid ratio from normal values of 4 to 7:1 to about 20:1 two weeks post-infusion; (c) consistent decrease in circulating reticulocytes.

6. The depression of erythropoiesis was directly related to the quantity of red cells infused; almost complete cessation of red cell synthesis followed an increase of the red cell mass by forty per cent.

7. The depression of erythropoiesis was only temporary. As soon as the total circulating red cell mass returned to the pre-injection level, erythropoiesis proceeded at a normal rate.

8. No consistent changes in the circulating white blood cells, totals and differentials were noted.

9. Mild abnormalities in some liver functions were observed. Whether these should be attributed to the effects of the transfusions directly, or to the mild febrile responses experienced by the subjects shortly after the infusions cannot be stated with certainty at present.
Hereditary Spherocytosis
Authors: YOUNG LAWRENCE E. , IZZO MARY JANE , PLATZER RICHARD F.
Published: October 2019

Clinical, hematologic and genetic data on 28 cases of hereditary spherocytosis are presented for the purpose of characterizing this disorder as completely as possible. On the basis of this experience it is recommended that the following typical laboratory findings be sought in establishing a diagnosis in suspected cases: (1) Presence of spherocytes or abnormally thick red cells in peripheral blood; (2) greater than normal osmotic fragility of the red cells; in cases in which the fragility of fresh cells is not significantly increased, determinations should be made after sterile incubation of the blood at body temperature for 24 hours; (3) greater than normal mechanical fragility of freshly drawn red cells; (4) negative antiglobulin (Coombs) test; (5) greater than normal lysis of the red cells during sterile incubation at body temperature for 48 hours; and (6) presence of similar abnormalities in relatives.

Abnormality of the erythrocyte persisted in all of the 11 patients in this series followed one or more years after splenectomy. An unusual case of chronic hemolytic anemia is described but not included in the numbered series because (1) both parents were hematologically normal and (2) spherocytosis and abnormally great osmotic and mechanical fragility and autohemolysis could not be demonstrated after the fifth postoperative month. Classification of this case is deferred pending further experience.

Demonstration in a parent, sibling or offspring of red cells showing the afore-mentioned abnormalities is necessary for an unequivocal diagnosis, but this requirement cannot always be met because relatives may not be available for examination. Moreover, when parents and/or several siblings are examined without positive findings, low gene expressivity, gene mutation and illegitimacy may be considered as explanations. Evidence is cited to suggest the possibility of a low degree of penetrance or expression in some cases and to illustrate the need for still more sensitive laboratory tests that might aid in diagnosis of the mildest forms of this disease. The lower incidence of spherocytosis in siblings of propositi than in offspring of propositi is cited as evidence bearing on the theory of gene mutation in some propositi.

A simplified "qualitative" test of osmotic fragility of incubated red cells is described.
Influence of Age and Sex upon Frequency and Cytologic Types of Human Leukemias Evidence of a Myeloid: Lymphoid Antagonism
Authors: DAUSSET JEAN , SCHWARZMAN VLADIMIR
Published: October 2019

1. A series of 212 cases of acute leukemia classified according sex and age is presented. Fifty-eight out of 212 were diagnosed by means of phase contrast microscopy.

2. In addition to this personal series, other series collected from the literature tile reviewed. These include both acute and chronic leukemia.

3. The thorough analysis of maximal frequency of the disease according to age, shows that there is, in the course of life, an inverse relation between lymphoid and myeloid leukemias as to the period of life in which they appear. This relation favors the view that a particular ratio of equilibrium must exist between the two systems: lymphoid and myeloid.

4. It is suggested that such an equilibrium might depend upon endocrine factors.
The Effects of Combined Folic Acid and Liver Extract Therapy
Authors: CHODOS ROBERT B. , ROSS JOSEPH F.
Published: October 2019

1. Folic acid, when administered alone, did not prevent the development or progression of subacute combined degeneration in 12 of 22 patients receiving this agent for from twelve to twenty-five months.

2. One patient with total gastrectomy and a macrocytic anemia developed subacute combined degeneration after five months of folic acid therapy.

3. Neurologic disease did not develop in 6 pernicious anemia patients treated with folic acid and liver extract for three and one-half to thirty-nine months.

4. In 10 pernicious anemia patients with good nutrition, neurologic relapses did not progress when liver extract or vitamin B12 therapy was instituted, even though folic acid therapy was continued. In 2 patients with abnormal nutrition and complicating organic abnormalities, nervous system disease progressed after institution of liver extract therapy.

5. Our observations are best explained by the theory that the hematologic and neurologic manifestations of pernicious anemia and other macrocytic anemias associated with gastro-intestinal tract pathology and inadequate nutrition are due to a deficiency of more than one substance. The administration of folic acid may improve the hematologic status but induce a deficiency of another substance or substances, e.g., vitamin B12, which are essential for the maintenance of a normal blood picture and the integrity of the central nervous system. This deficiency will eventually result in the development of a suboptimal blood picture or subacute combined degeneration of the spinal cord, or both.

6. The hematologic status of patients with pernicious anemia is not maintained in a more satisfactory state by supplementation of liver extract or vitamin B12 therapy with folic acid.

7. Folic acid therapy did not produce neurologic disease in patients with iron deficiency anemia who had free gastric hydrochloric acid in their gastric secretions and presumably sufficient intrinsic factor. It did not influence response to ferrous sulfate therapy.

8. Patients with sprue, nutritional macrocytic anemia and other macrocytic anemias associated with gastro-intestinal tract pathology who are treated with folic acid should also be given supplemental liver extract or vitamin B12 to insure against the development of nervous system disease.
On the Nature of Castle’s Hemopoietic Factor
Authors: CALLENDER SHEILA T. , LAJTHA L. G.
Published: October 2019

1. Normal gastric juice (intrinsic factor) and vitamin B12 together form a thermolabile hemopoietic factor which ripens megaloblasts in vitro, both gastric juice and B12 alone being inactive.

2. The hemopoietic factor in normal serum which ripens megaloblasts in vitro also appears to be thermolabile, heating to 56 C. for 2 hours destroying some of its activity.

3. The relationship of these factors is discussed and an extra-gastric as well as a gastric source of intrinsic factor is postulated.
Limitation of Hemolysis in Experimental Transfusion Reactions Related to Depletion of Complement and Isoantibody in the Recipient
Authors: CHRISTIAN R. M. , STEWART W. B. , YUILE C. L. , ERVIN D. M. , YOUNG L. E.
Published: October 2019

Each of 4 dogs was given two successive transfusions of incompatible dog erythrocytes at intervals of ninety or one hundred and twenty minutes. Measurements were made of the concentration of hemoglobin, complement and isoantibody in the plasma or serum of the recipients and of the rate of disappearance of the donated cells labeled with radioactive iron.

In each experiment the donated red corpuscles were destroyed much more slowly after the second transfusion than after the first, and the hemoglobinemia produced by the first transfusion was not appreciably augmented by the second transfusion. The successive transfusions at short intervals were considered nearly equivalent to single large transfusions but permitted separate study of the effects produced.

The rate of hemolysis was influenced by the initial titers of both antibody and complement. In dogs with high antibody titer, available complement appeared to limit the rate of destruction of incompatible donated cells. In the presence of adequate complement the rate of hemolysis was limited by the disappearance of antibody when the initial titer of antibody was low.

Limitation of the degree of hemoglobinemia due to limitation of the rate of destruction of transfused incompatible erythrocytes and the rather efficient clearance of plasma hemoglobin explains in part the failure of some hemolytic transfusion reactions to produce severe or fatal renal damage.

It is emphasized that most investigations of hemoglobinuric nephrosis in animals have dealt with the injection of hemoglobin solutions which resulted in hemoglobinemia of much greater intensity than it has been possible to produce by transfusion of large volumes of incompatible red corpuscles.
Historical Review: Paroxysmal Nocturnal Hemoglobinuria
Authors: CROSBY WILLIAM H.
Published: October 2019

1. The history of paroxysmal nocturnal hemoglobinuria is reviewed, and attention is called to four case reports published in the 19th century. A bibliography of the disease is appended.

2. The outstanding work of Paul Strübing is reviewed. Strübing identified paroxysmal nocturnal hemoglobinuria as a disease entity in 1882 but failed to give it a distinctive name. He described the disease with great accuracy, calling particular attention to the part played by sleep in precipitating the paroxysms. He cited earlier reports of nocturnal hemoglobinuria and by provocative tests differentiated the disease from the other paroxysmal hemoglobinurias. On the basis of his observations he proposed theories regarding the pathogenesis of the disease which have now been shown to be remarkably accurate.
Experimental Studies on Reticulosarcoma
Authors: SAKAMOTO AKIRA S.
Published: October 2019

1. Five human lymphatic and myeloid reticulosarcomas were transmitted to fowls in series.

2. The pathologic changes produced in fowls consisted in proliferation of reticulo-endothelial cells (reticulosarcoma and allied conditions) or those of immature myeloid cells (myelosarcoma, myelosis or myeloid metaplasia). These different forms of leukosis may occur alternately in subsequent generations or simultaneously in the same bird. Neither erythroleukosis nor lymphatic leukosis was encountered. These observations conform with our earlier experience gained in experimental studies of human leukemia.

3. The blood picture of infected fowls was consistently aleukemic either with marked leukopenia or slight leukocytosis. There was usually an increase in mature granulocytes at the expense of lymphocytes. Anemia was usually slight.

4. The causative agent can pass through a Chamberland L2 filter.

5. The infective agent can be demonstrated in the blood of patients, in fluid from the thoratic cavity, in the enlarged lymph nodes as well as in the human tumors.
A Comparison of the Effects of 4-Amino-N10-Methyl-Pteroylglutamic Acid and 2,6-Diaminopurine upon Sensitive and Resistant Sublines of a Strain of Mouse Leukemia
Authors: BURCHENAL J. H. , WEBBER L. F. , MEIGS G. M. , BIEDLER J. L.
Published: October 2019

1. Further studies contrasting the effect of varying doses of 4-amino-N10-methyl-PGA on a resistant variant (Ak4R) of transplanted mouse leukemia Ak4 have been reported.

2. The usual therapeutic dosage of 4-amino-N10-methyl-PGA prevented the increase in total leukocytes, delayed the visceral infiltration, and increased survival time in the Ak4 strain but was without effect in strain Ak4R.

3. In the Ak4 leukemic mice with high leukocyte counts a marked drop within twenty-four hours could be demonstrated after a single dose of 3 mg./Kg. of this drug. With the Ak4R strain there was sufficient resistance so that a dose of at least 25 mg. Kg. was needed to show the marked leukopenia in twenty-four hours.

4. The Ak4R strain was as sensitive as the Ak4 to the leukotoxic effects of 2,6-diaminopurine. This drug also was effective in prolonging the survival time of mice with Ak4R leukemia.
The Effects of Triethylene Melamine and Related Compounds on the Leukocytes of Mouse Leukemia
Authors: BURCHENAL JOSEPH H. , WEBBER LORRAINE F. , BIEDLER JUNE L. , MEIGS G. MARIE , STOBBE GODFREY D.
Published: October 2019

1. In the usual therapeutic dosage in mice with the Ak4 strain of leukemia, TEM caused a prolongation of survival time, held the total leukocyte count down at severely leukopenic levels, delayed the appearance of immature lymphocytes in the peripheral blood, and caused a marked delay in the appearance of leukemic infiltrations of the liver, spleen, bone marrow and kidney.

2. A single massive dose of TEM, administered on the seventh day of the disease when the total leukocyte count was high, caused a rapid fall in the count and depressed the number of prolymphocytes in the peripheral blood.

3. Single massive doses of such structurally related compounds as hexamethylene diethylenurea, 2,4-diethylenimino-6-amino-s-triazine, and to a lesser degree, 2-ethylenimino-4,6-dimethoxy-s-triazine caused a similar fall in the total leukocyte count when administered on the seventh day of the disease.
Case Report: Sickle Cell Anemia; First Case Reported from Egypt
Authors: ABBASY A. S.
Published: October 2019

Rheumatic fever, rheumatic arthritis, acholuric jaundice were excluded in this case on the clinical and laboratory findings. The history, physical examination and the laboratory studies all supported the diagnosis of sickle cell anemia.

This case presents certain points of interest. It is the first case of sickle cell anemia reported from Egypt. The disease was found in the patient and her father and excluded in the other members of the family. It is, however, possible that the paternal uncle had also suffered and died from the disease.

The patient is a white girl and admixture of Negro blood was reasonably excluded through 6 ancestral generations. This case, therefore, adds to those already described in subjects of the white race from the Mediterranean area. It will be noticed that the patient’s family originates from Algeria, where 3 cases were diagnosed in natives by Smith19 on the basis of the anatomical changes observed in the spleen.
A Semi-Quantitative Study of Bone Marrow in Rats Following Total Body X-Irradiation
Authors: ROSENTHAL ROBERT L. , PICKERING BRYANT I. , GOLDSCHMIDT LEONTINE
Published: October 2019

1. A method has been presented for the quantitative enumeration of the bone marrow cells by adjusting the differential count for the degree of cellularity, which is derived from imprint preparations of femoral marrow.

2. This method has been employed in a study of bone marrow changes at various intervals following 700 r total body x-irradiation in the rat. The findings have been correlated with the peripheral blood counts.

3. On the basis of numerical changes and morphologic observations, the mechanism of the effects of irradiation on the various cell series of bone marrow is evaluated. The erythroid cells show rapid decreases in number due to their marked destruction. The myeloid cells chiefly undergo accelerated maturation resulting in increased segmented forms in both blood and bone marrow. The decreases in megakaryocytes, mast cells and lymphocytes appear to be related to their life spans in the absence of further production. The reticulum cells and plasma cells show neither an absolute increase nor decrease.

4. Formation of new cells, except possibly for plasma cells, from the reticulum cells is completely inhibited for the first nine days following total body irradiation of rats with 700 r. Regeneration is first apparent at twelve days after x-ray as evidenced by areas of erythropoiesis, and to a lesser extent, myelopoiesis. Megakaryocytes reappear in small numbers at fifteen days. Although this regeneration is apparent in only 50 per cent of the animals studied at twelve and fifteen days following irradiation, all these animals showed evidence of transition of reticulum cells to mast cells.
Effect of Urethane (Ethyl Carbamate) on the Mitotic Activity in the Bone Marrow of Normal Mice
Authors: ROSIN A.
Published: October 2019

Normal young albino mice were treated with a single intraperitoneal injection of urethane, and the effect of the drug on the mitotic activity of the bone marrow was studied. A notable increase of the mitotic index was observed from ten to forty-four hours after the administration of the drug. At the same time the percentage of prophases was decreased, while the percentage of metaphases was increased. Abnormal mitoses were frequent. Mitotic figures which might be interpreted as reversions from the meta- and anaphase stages to a resting nucleus were seen. Promyelocytes with highly lobated nuclei of bizarre shape appeared.

No changes were found in the myeloid-erythroid ratio, or in the maturation rate of the white blood cells.
Case Report: Essential Pulmonary Hemosiderosis
Authors: JONSSON B. , VAHLQUIST B. , AGNER K.
Published: October 2019

The authors report a fatal case of essential pulmonary hemosiderosis in a 5 year old boy. The child showed typical signs of the disease with relapsing pulmonary attacks with hemoptysis and pronounced anemia of iron deficiency type. Huge amounts of hydrolyzable iron were found in the lungs.
Splenic Arteriovenous Differences in Blood Cells During the Hematologic Reaction to Adrenal Cortical Stimulation
Authors: SOLOMON DAVID H. , HUMPHREYS STEWART R.
Published: October 2019

1. Arteriovenous eosinophil differences across the spleen were measured in 10 dogs during the development of adrenal-mediated eosinopenia. In 7 instances the stimulus was epinephrine, in 2 ACTH, and in 1 operation alone.

2. In no case was significant net splenic uptake of eosinophils indicated. In 3 out of 7 epinephrine experiments and in 1 ACTH experiment, a significant net splenic output of eosinophils was found. For all 10 experiments averaged, the splenic output of eosinophils was significant.

3. Arteriovenous neutrophil and hematocrit differences were insignificant and were independent of simultaneous eosinophil differences.

4. It is concluded that the spleen is not a significant site of uptake on destruction of eosinophils during the development of adrenal-mediated eosinopenia. Under certain conditions, it actually extrudes eosinophils into the general circulation at a time when other factors are causing eosinophil disappearance.

5. The results suggest but do not establish the presence of a discriminatory splenic mechanism for the control of blood cells, capable of storing cells of one type while it releases others into the circulation.
Prenatal diagnosis of classic hemophilia (hemophilia A) by immunoradiometric assays
Authors: Hoyer LW , Carta CA , Golbus MS , Hobbins JC , Mahoney MJ
Published: October 2019

During the period from 1978 to 1983, 92 pregnancies have been evaluated by fetoscopy for the prenatal diagnosis of hemophilia A. Satisfactory fetal plasma samples were obtained in 80 instances and the diagnosis-- or exclusion--of hemophilia was made by immunoradiometric assay of the factor VIII coagulant protein (VIII:CAg). The accuracy of the diagnosis established by fetoscopy has been verified after delivery or termination, and there have been no misdiagnoses resulting from laboratory error. Additional evidence for the accuracy of the analysis was the observation that the frequency of hemophilia in pregnancies of obligate carriers of the hemophilia gene, and of women whose plasma assays were indicative of the carrier state, was 29 of 59 fetuses at risk. In one case of cross-reacting material-positive hemophilia, samples obtained at fetoscopy and from the newborn infant had normal VIII:CAg levels but the infant had decreased factor VIII procoagulant activity. There were five fetal deaths resulting from fetoscopy in 55 pregnancies not intentionally terminated. Although only a small percentage of pregnant hemophilia carriers in the United States have elected to undergo fetoscopy for prenatal diagnosis, this procedure has allowed a number of pregnancies to go to term with delivery of normal males in families that were not willing to accept the risk of a hemophilic child. In eight instances, fetoscopic evaluation was sought for two successive pregnancies.
Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases
Authors: Michels SD , McKenna RW , Arthur DC , Brunning RD
Published: October 2019

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French- American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with AML.
Treatment of two patients with B cell lymphoma with monoclonal anti- idiotype antibodies
Authors: Rankin EM , Hekman A , Somers R , ten Bokkel Huinink W
Published: October 2019

Mouse monoclonal anti-idiotype antibodies have been used to treat two patients with progressive advanced B cell non-Hodgkin's lymphoma. Transient falls in the level of circulating malignant cells and idiotypic immunoglobulin were produced, and free unbound monoclonal antibody was identified in the serum. Homing of the antibodies to tumor cells in the blood, bone marrow, ascites, and lymph nodes was demonstrated in both patients. Although large amounts of anti-idiotype antibody were given (3.8 g and 5.8 g), no toxic effects were seen, and no antibodies to the foreign mouse protein were made. There was no modulation of the antigen from the tumor cells and no indication of immunoselection. There was evidence of large-scale tumor cell destruction, but only a modest reduction in tumor size. The killing of the tumor cells was mediated by the reticuloendothelial system and not by complement.
High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study
Authors: Wolff SN , Marion J , Stein RS , Flexner JM , Lazarus HM , Spitzer TR , Phillips GL , Herzig RH , Herzig GP
Published: October 2019

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.
Platelet-associated immunoglobulin, platelet size, and the effect of splenectomy in the Wiskott-Aldrich syndrome
Authors: Corash L , Shafer B , Blaese RM
Published: October 2019

Wiskott-Aldrich syndrome (WAS) thrombocytopenia is frequently improved by splenectomy, although the mechanism of the thrombocytopenia and its resolution are unknown. Previous studies in two patients have shown that mean platelet volume, which is characteristically reduced in WAS, increased along with platelet count postsplenectomy. Additional studies in a limited number of patients have also demonstrated that platelet- associated immunoglobulin G (PAIgG) is elevated presplenectomy, but to date no postsplenectomy data have been reported. The present study was performed to more fully evaluate the effect of splenectomy on platelet volume and PAIgG in WAS. Before splenectomy, mean platelet volume was reduced but platelet size was broadly distributed with substantial overlap of the normal range. PAIgG was significantly elevated in 13 of 14 presplenectomy WAS patients (means = 78.9 fg per platelet) and fell to normal levels postoperatively (means = 4.0 fg per platelet). Platelet count and clinical status improved postsplenectomy, and mean platelet volume and platelet volume distribution returned to the normal range. WAS subjects who relapsed with recurrent thrombocytopenia redeveloped elevated PAIgG but maintained normal platelet size. The spleen appears to play a critical role in a process that may be immunologically mediated and results in reduced platelet size.
Megakaryocytopoiesis and granulopoiesis of W/Wv mice studied in long- term bone marrow cultures
Authors: Petursson SR , Chervenick PA
Published: October 2019

Megakaryocytopoiesis and granulopoiesis of marrow cells from W/Wv mice were studied using a continuous liquid marrow culture system. Cells in the suspension phase were assayed weekly over a 16-week period for total nucleated cells, megakaryocytes, granulocytes, megakaryocytes and granulocyte-macrophage progenitor cells (CFU-Ms, CFU-GMs), and spleen colony-forming cells (CFU-Ss). Without hydrocortisone supplementation, proliferation of megakaryocytes, granulocytes, and their progenitor cells was significantly less in W/Wv cultures than in +/+ cultures. These cells became undetectable in both W/Wv and +/+ cultures at seven to 11 weeks in culture, after which only monocytes and macrophages proliferated in the cultures. Treatment of cultures with hydrocortisone improved megakaryocytopoiesis and granulopoiesis in both W/Wv and +/+ cultures. Following an initial lag phase of three to four weeks, proliferation of megakaryocytes, granulocytes, and their progenitor cells in W/Wv cultures equalled that observed in +/+ cultures and was sustained for 16 to 24 weeks. This improvement was associated with a sustained reduction in monocytes and macrophages. Despite improvements in megakaryocytopoiesis and granulopoiesis, production of macroscopic and microscopic spleen colonies by cells from W/Wv cultures remained severely reduced or absent. Studies of DNA synthesis rates of fresh marrow cells indicated that significantly fewer CFU-Ms and CFU-GMs were in cycle in W/Wv mice compared with +/+ mice. However, in hydrocortisone-treated W/Wv cultures, DNA synthesis rates of CFU-Ms and CFU-GMs increased markedly and equalled those observed for +/+ cultures. These results suggest that the improvements in megakaryocytopoiesis and granulopoiesis in hydrocortisone-treated liquid cultures is associated with a reduction in monocytes and macrophages and that progenitor cells of W/Wv mice have a proliferative defect that is correctable by hydrocortisone treatment in vitro.
Hemorrhagic Diathesis Due to a Circulating Anticoagulant Report of Case with Laboratory Observations
Authors: PONS EDUARDO R. , DE TORREGROSA MERCEDES VICENTE
Published: October 2019

1. A case is reported of hemorrhagic diathesis in a woman in which the presence of an anticoagulant in the patient’s blood and plasma could be demonstrated.

2. The anticoagulant was shown to be active in dilutions up to 1:350. It retained its potency after heating to 61 C. for 10 minutes and after storage, either in a refrigerator or at room temperature, for twenty-four hours.

3. The anticoagulant was not neutralized by protamine sulfate or by toluidine blue. Placental plasma corrected the clotting defect in vitro but was ineffective when administered intravenously to the patient.

4. Evidence is presented suggesting that the second and third stages of coagulation in this case are normal, that the patient’s plasma has antithromboplastic activity, and that the anticoagulant may be antithromboplastin.
Studies on Abnormal Hemoglobins
Authors: SINGER KARL , CHERNOFF AMOZ I.
Published: October 2019

1. It could be demonstrated that of the three tested types of human hemoglobin—N (normal adult), S (sickle cell) and F (fetal)—only the reduced S compound shows tactoid and gel formation in sufficiently concentrated solutions. These physico-chemical phenomena may be used for the qualitative identification of S hemoglobin.

2. The alkali resistant hemoglobin fraction, present in sickle cell anemia erythrocytes (but not in trait red cells), was concentrated in purified form. No tactoid or gel formation could be elicited. Therefore, this alkali resistant pigment does not appear to be a variant of S hemoglobin. It seems probable that sickle cell anemia erythrocytes contain two separate types of pathologic hemoglobin (S and F) which are not directly related to each other.
Experimental Production of Nutritional Macrocytic Anemia in Swine
Authors: CARTWRIGHT G. E. , TATTING BETTY , KURTH DORIS , WINTROBE M. M.
Published: October 2019

A total of 20 swine were fed a diet adequate in all known respects except that soybean protein was substituted for casein, succinylsulfathiazole and a folic acid antagonist were added, and vitamin B12 and pteroylglutamic acid were withheld from the vitamin supplement.

The animals developed macrocytic anemia, leukopenia and neutropenia, accompanied by erythroid hyperplasia of the bone marrow. Tue erythroblasts consisted mainly of immature macronormoblasts but a few atypical megaloblasts were also observed.

The anemia responded rapidly and completely to the administration of both vitamin B12 and pteroylglutamic acid. The administration of pteroylglutamic acid alone resulted in an immediate return of the blood and bone marrow to within normal limits but after several months there was a partial hematologic relapse in spite of continued therapy with this vitamin. The administration of vitamin B12 alone resulted in only partial remission of the anemia and the bone marrow remained macronormoblastic although the megaloblasts tended to disappear.

Growth of the animals was stimulated by the administration of either vitamin but the administration of both vitamins simultanseously resulted in the greatest rate of growth.

No manifestations of neurologic disturbances or of inscreased pigment excretion were observed in the deficient swine.
Serologic Properties of a Cold Hemolysin and an Acid Hemolysin Occurring in a Case of Syphilitic Paroxysmal Cold Hemoglobinuria
Authors: PETERSON E. T. , WALFORD R. L.
Published: October 2019

1. Two apparently separate hemolysins observed in a case of syphilitic paroxysmal cold hemoglobinuria are described.

a. One hemolysin (cold hemolysin) is that responsible for the Donath-Landsteiner reaction.

b. The other (acid hemolysin) is a thermolabile antibody requiring a lowered pH for the production of hemolysis.

2. Review of the literature indicates that a similar acid hemolysin may have been encountered in other reported cases of this disease.
The Occurrence of Megaloblastic Erythropoiesis in Patients with Hemochromatosis
Authors: KOSZEWSKI B. J.
Published: October 2019

The occurrence of megaloblastic anemia in hemochromatosis was observed in 9 patients. The anemia was characterized by a macromegalocytic blood picture, a hyperactive macromegaloblastic erythropoiesis as well as a positive response to liver therapy. The bone marrow reticulum was hyperplastic and showed extensive hemosiderin phagocytosis. The hemosiderin was also stored in the plasma cells. This unusual finding was pathognomonic for megaloblastic anemia of hemochromatosis and distinguishes it from the other symptomatic megaloblastic anemias.

Megalocytic anemia occurs relatively frequently in hemochromatosis. Pigment cirrhosis of the liver and hemosiderotic changes in the gastro-intestinal tract seem to be responsible for its genesis. Disturbance in storage, absorption and formation of the antianemic principle favors the accompanying hematologic changes.
Studies on Abnormal Hemoglobins
Authors: SINGER KARL , FISHER BEN
Published: October 2019

1. By transfusing sickle cell anemia erythrocytes with a relatively high concentration of F hemoglobin into normal recipients, it was demonstrated that the disappearance rates of the transfused cells and of their alkali resistant pigment consistently showed great discrepancies. These observations suggest an unequal distribution of the F pigment within the erythrocyte population. A nonuniform distribution of F hemoglobin could also be detected in vitro by exposing sickle cell anemia bloods to mechanical trauma for a longer period of time. The cells most resistant to trauma contained a higher percentage of F hemoglobin than the original blood specimen.

2. The red cell population of patients with sickle cell anemia seems to be composed of three main fractions: (1) cells containing S hemoglobin and no or little F hemoglobin, (2) cells containing both pigments and (3) cells containing F pigment with no or little S hemoglobin.

3. The erythrocytes carrying mostly S hemoglobin have the shortest life span, whereas the red cells containing mostly F hemoglobin have the longest survival time.

4. The significance of these findings in regard to clinical and genetic aspects of sickle cell anemia is discussed. No direct correlation is demonstrable in an individual patient between the absolute amounts of either type S or type F hemoglobin and the severity of the anemia. The latter depends on the variable size of the portion of red cells containing mostly S hemoglobin, and also on the ability of the marrow to replace this particular fraction.
Roles of Prothrombin Activity, Heparin-Protamine Titer and Platelet Concentration in Bleeding of Leukemia
Authors: FREEMAN GUSTAVE , HYDE JOHN S.
Published: October 2019

A test for circulating "heparin-like" anticoagulants neutralizable by protamine has been studied in children with acute leukemia. Bleeding occurred with equal frequency among those with normal and those with elevated heparin-protamine titers. When the protamine titers are calculated on the basis of unit plasma volume, similar distributions of titers for both bleeding and nonbleeding leukemic individuals and identical medians for both groups are observed. The hemorrhagic diathesis in acute leukemia does not necessarily appear to be dependent on coagulation defects demonstrable by prothrombin time, although such defects often are present.

The regular association of circulating platelet levels below 50,000 to 60,000 per cu. mm. with bleeding in acute leukemia has been reaffirmed. Below this critical level, the rate of plasma coagulation is often, but not always, prolonged. Although critical thrombocytopenia appears to be essential to activation of the hemorrhagic diathesis, it seems not to be causative by itself. The relationships among bleeding, thrombocytopenia, and coagulation are discussed.
Blood Destruction in the Polycythemia Induced by Hypoxia
Authors: REISSMANN KURT R. , BURKHARDT WILLIAM L. , HOELSCHER BERNARD
Published: October 2019

The hemoglobin catabolism during the development and during the disappearance of polycythemia induced by hypoxia was studied by measuring the total circulating hemoglobin and the daily bile pigment excretion in bile-fistula dogs before, during, and after prolonged periods of exposure to 20,000 feet simulated altitude.

1. The inscreased erythropoiesis during the first weeks of altitude exposure was accompanied by a signiflcant increase in bile pigment output. The possible sources of this pigment excretion are discussed.

2. The life spans of the red cells during altitude exposure was found to be about 115 days. No differences were observed in the longevity of the cells in animals at ground level and at altitude.

3. The normalization of the polycythemic blood levels took place within six to eight weeks after returns to ground level, and was achieved by the combined effect of a depressed erythropoiesis and of an increased blood destruction. The increase in red cell destruction observed under these conditions demonstrates the existence of an "active" mechanism of blood destrunction by which the organism is able to destroy normal blood cells before their life span is exhausted. This increased red cell destruction, however, accounted for only 21 to 39 per cent of the hemoglobin which disappeared from circulation after return to ground level. The major part of the normalization of altitude polycythemia was brought about by a temporary depression of erythropoiesis which was estimated to amount to 30 or 40 per cent of the normal cell production in the six weeks after the discontinuation of the altitude exposure.
Analytical Review: The Interpretation of Red Cell Survival Curves
Authors: DORNHORST A. C.
Published: October 2019

In the article entitled "Analytical Review: The Interpretation of Red Cell Survival Curves," by A. C. Dornhorst (Blood 6: 1284-1292, 1951), an error in Equation 2, page 1285 occurred. Equation 2 should read:

See PDF for Equation
The Mechanism of Hemolysis in Paroxysmal Cold Hemoglobinuria
Authors: JORDAN WILLIAM S. , PROUTY ROBERT L. , HEINLE R. W. , DINGLE JOHN H.
Published: October 2019

Attacks of hemoglobinemia were induced in 2 patients with paroxysmal cold hemoglobinuria (PCH). The occurrence of slight neutropenia and erythrophagocytosis in the first patient occasioned more detailed observations of these phenomena in the second. The in vivo changes observed in Case 2 following three episodes of chilling were similar to those described by earlier investigators. Marked hemoglobinemia and hemoglobinuria occurred twice; mild hemoglobinemia once. The maximum number of phagocytes was observed at the time of maximum hemolysis. Leukopenia developed promptly during each attack, but the degree of leukopenia was not correlated with either the intensity of erythrocyte destruction or with the extent of phagocytosis.

Neutrophils and monocytes—the phagocytic cells—and eosinophiles were equal1y depressed, all decreasing by from 75 per cent to 80 per cent. Lymphocytes decreased by 33 per cent to 48 per cent. The neutrophils recovered within 2 hours, but the eosinophiles and lymphocytes remained depressed for 5 hours.

When PCH serum was chilled and warmed with complement and homologous or heterologous erythrocytes and leukocytes, erythrophagocytosis occurred, reaching its maximum at a time consistent with the development of leukopenia in vivo. Although PCH antibody was fixed to erythrocytes in the cold phase of the Donath-Landsteiner reaction, phagocytosis did not occur if complement, with the attending hemolysis, was absent in the warm phase.

Erythrophagocytosis was also produced in vitro when human isoantibodies acted as either agglutinins or hemolysins. Phagocytosis was most marked when the sensitized cells were lyzed, the degree of phagocytosis corresponding to the degree of hemolysis.

The in vivo and in vitro observations suggest that leukopenia occurs in persons with cold hemoglobinuria as part of the paroxysm of hemolysis, and that erythrophagocytosis operates to remove damaged erythrocytes and probably promotes the trapping of leukocytes in organ capillaries.