bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 Mutations and Outcome in Patients with Myelodysplastic Syndromes (MDS)
Authors: Al-Issa Karam , Sekeres Mikkael A. , Nielsen Alek d , Jha Babal , Przychodzen Bartlomiej P , Aly Mai , Carraway Hetty E. , Advani Anjali S. , Patel Bhumika , Clemente Michael J. , Mukherjee Sudipto , Gerds Aaron T. , Maciejewski Jaroslaw P , Nazha Aziz 
Published: October 2019

Abstract

Objectives:
TP53, a tumor suppressor gene, is frequently mutated in myeloid malignancies. The negative impact of TP53 mutations in myelodysplastic syndromes (MDS) has been described previously but there is controversy regarding the prognostic impact of the mutation's characteristics (location, type, passenger vs. driver, and others).
Methods:
We sequenced DNA samples from 732 patients (pts) with MDS and related myeloid malignancies for the presence of TP53 mutations and 61 other genes that have been described as recurrently mutated in MDS. Overall survival (OS) was measured from the time of diagnosis to time of death or last follows up. Variant allele frequencies (VAFs) adjusted by zygosity were used to define clonal architecture of driver clones.
Results:
Of 80 mutations detected in 73 (10%) pts, 66 (88%) were missense, 7 (9%) were nonsense, and 7 (9%) were frame shift deletions/insertions. Pts with TP53 mutations had a higher WBC (4.6 vs. 3.9 X 109/L, p = .04), higher bone marrow blast % (median 9 vs. 3, p =0.1), and a higher risk category by revised International prognostic Scoring System (56% vs. 27%, p =.01) compared to pts with TP53 wild type. TP53 mutations were commonly occurred with TET2 (16%), PRPF8 (13%), ASXL1 (11%), DDX54 (8%), DNMT3A (8%), and IDH2 (8%). The mean VAF for TP53 was 41.9 (5-100). TP53 mutations were defined as drivers in 20% of samples, passengers in 40%, and mosaic in 40%. Mutation positions included: 19 (24%) in the DNA binding domain, 2 (3%) in the transactivation domain, 1 (1%) in the tetramerization domain and 58 (72%) other. With a median follow up of 16.4 months, the median OS for the entire group was 8.24 months. Patients with TP53 as driver mutations had a worse OS compared with patients with TP53 as passenger mutations (median, 2.2 vs. 13.0 months, respectively, p =.02). Similarly, OS by TP53 VAF categorized as low (<25%), intermediate (25-50%), and high (>50%) was 12.4, 8.5, and 3.4 months, respectively. Among patients with available treatment data, 29 patients were treated with the hypomethylating agents, azacitidine or decitabine, 17% responded (60% CR, and 40% PR), and OS was similar compared to patients treated with other therapies. Patients treated with Hematopoietic stem cell transplant (HCT) had superior OS compared to pts not receiving HCT (median, 14.9 vs. 8.9 months, respectively, p =.05).
Conclusions:
TP53 mutations are associated with poor outcome in MDS, but the outcome varies depending on the type of mutation and VAF. Treatment with HCT remains a valid treatment option in a subset of patients but novel treatment strategies are desperately needed.

Disclosures
Mukherjee: Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.
Congenital Hemolytic Anemia with Abnormal Pigment Metabolism and Red Cell Inclusion Bodies: a New Clinical Syndrome
Authors: LANGE ROBERT D. , AKEROYD JOSEPH H. 
Published: October 2019

Abstract
1. A case report and special studies of a 14-year-old girl with a congenital hemolytic anemia are reported.
2. Fourteen per cent of her erythrocytes contained unusual inclusion bodies.
3. In addition, the child has been known to pass dark urine since the age of 2½ years. The pigment probably belongs to the bilifuscin and mesobilifuscin group.
4. It is believed that the syndrome is probably caused by an inborn error in erythrocytic metabolism.
5. It has been proposed that the syndrome be named "congenital hemolytic anemia with abnormal pigment metabolism and red cell inclusion bodies."
Rate of Production of P32-Labeled Lymphocytes
Authors: PERRY SEYMOUR , CRADDOCK CHARLES G. , VENTZKE LUTZ , CREPALDI GAETANO , LAWRENCE JOHN S. 
Published: October 2019

Abstract
1. Lymphocytes in dogs have been labeled by means of the DNA-P32 incorporation technic.
2. In the thoracic duct, a high level of lymphocyte DNA-P32 specific activity is reached within two hours. After 24 to 30 hours, the activity falls to a lower level which is then maintained for at least 160 hours.
3. Lymphocyte-granulocyte separations on the blood revealed that DNA-P32 specific activity reached a peak on the fourth day for both lymphocytes and granulocytes.
4. These findings are consistent with a short maturation time for the lymphocyte and a short intravascular time.
Multiple Hemangiomata Associated with Thrombocytopenia: Remarks on the Pathogenesis of the Thrombocytopenia in this Syndrome
Authors: GILON ELIAHU , RAMOT BRACHA , SHEBA CHAIM 
Published: October 2019

Abstract
1. A 13-year-old girl with multiple hemangiomata and thrombocytopenia is described.
2. Complications of surgical treatment included severe bleeding, septicemia and a fibrinolytic event.
3. Simultaneous platelet counts from the tumor and peripheral blood were performed and showed a significantly higher concentration of platelets in the tumor vessels.
4. With the rise in the platelet count, a decreased platelet fragility as well as a persistently abnormal prothrombin consumption could be demonstrated.
5. The possible role of the tumor in the pathogenesis of the thrombocytopenia is discussed.
Some Factors Involved in the Effect of X-Irradiation on the Phosphatase Activity of Hematopoietic Tissues
Authors: UYEKI EDWIN M. , SALERNO PAUL R. 
Published: October 2019

Abstract
Factors which modify lymphoid distribution of tissues were found to modify the adenosine triphosphatase activity of these tissues. Starvation or cortisone injection, which produces destructive changes in lymphoid tissues, was found to increase the enzyme activity of spleen and thymus tissues. The greater increment of enzyme activity of the thymus as compared to that of the spleen was correlated with its normally higher content of lymphoid tissue.
The increase in adenosine triphosphatase activity of hematopoietic tissues appears to be associated with the type of cells present in the assay medium. With respect to peripheral blood leukocytes of the rat, the cell type is confined largely to lymphocytes and granulocytes. The increase in adenosine triphosphatase activity of the leukocytes after total-body x-ray was seen to parallel the increase in granulocytes present in the assay medium. The ratio of granulocytes to lymphocytes is not appreciably altered in dog peripheral blood after exposure to total-body x-ray; the adenosine triphosphatase activity similarly was not significantly altered. After total-body x-ray (390 r and 780 r), cells isolated from the rat bone marrow displayed a fivefold increase in adenosine triphosphatase activity. This increase was seen to correspond with an increase in the ratio of segmented leukocytes and reticuloendothelial cells and a decrease in the immature forms of the erythroid and myeloid cells.
The heterogeneous cell mixtures used for our assay procedures permit the observation that total-body x-irradiation results in an increased enzyme activity of the isolated cells of the peripheral blood, bone marrow and spleen tissue of the rat. The increased enzyme activity was associated with the increased ratio of cells with high enzyme activity present in the assay medium.
Hematologic Changes in Rat Following Administration of Desoxypyridoxine, Aminopterin, Oxythiamine and 6,7-Dimethyl-9-(2'-acetoxyethyl)isoalloxazine
Authors: DOCTOR V. M. 
Published: October 2019

Abstract
1. Administration of aminopterin to rats at a level of 100 γ/Kg./day for a 10 day period produced leukopenia which was rapid in onset and led quickly to death, whereas the leukopenia produced by the administration of desoxypyridoxine at the level of 40 mg./Kg./day for a 2 week period or at 100 mg./Kg./day for a 4 week period was not accompanied by toxic effects such as loss of appetite, diarrhea and hemorrhage and was characterized by lymphocytopenia and granulocytosis.
2. The results of combining the administration of aminopterin (70 γ/Kg./ day) with desoxypyridoxine (40 mg./Kg./day) for a 2 week period indicated an additive effect of the two in the production of lymphocytopenia; the granulocytosis resulting from desoxypyridoxine administration was counter-acted by the granulocytopenic effect of aminopterin. Also, the leukopenia produced by the combined administration of aminopterin and desoxypyridoxine was not accompanied by the toxic effects which follow aminopterin administration.
3. Oxythiamine alone or in combination with desoxypyridoxine or aminopterin did not influence the leukocyte count.
4. Administration of aminopterin with 6, 7-dimethyl-9-(2'-acetoxyethyl)isoalloxazine (U-2112) produced marked lymphocytopenia and granulocytopenia accompanied by toxic effects such as loss of appetite, diarrhea and hemorrhage.
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Thrombocytopenia with a Circulating Platelet Agglutinin, Platelet Lysin and Clot Retraction Inhibitor
Authors: ZUCKER MARJORIE B. , LEY ALLYN B. , BORRELLI JENNIE , MAYER KLAUS , FIRMAT JORGE 
Published: October 2019

Abstract
A case is reported of thrombocytopenia developing suddenly in a patient with metastatic carcinoma. Studies of this patient’s serum revealed a platelet agglutinin presumed to be related to the development of the thrombocytopenia in spite of the failure to demonstrate autoagglutination. In addition, a technique is described for the detection of a platelet lysin and clot retraction inhibitor, both of which could be demonstrated in this patient’s serum. The identity of the lysin and retraction inhibitor is suggested.
Studies on the serums of other patients showed a dissociation between the occurrence of platelet agglutinin on the one hand and of platelet lysin and retraction inhibitor on the other.
Behavior of Total Serum Complement in Hodgkin’s Disease and Other Malignant Lymphomas
Authors: ROTTINO ANTONIO , LEVY ARTHUR L. 
Published: October 2019

Abstract
Using the method of Mayer and collaborators for the determination of complement in the blood serum, 67 normal persons, 72 patients with Hodgkin’s disease, 28 with other types of lymphoma and 65 with cancer involvement of various organs were studied.
Fifty-eight of 72 Hodgkin’s disease patients were found to have an elevated level of complement, 12 a normal level and 2 a below-normal level. Elevated levels were found also in patients with other lymphomas and cancer.
An association between elevated complement, increased sedimentation level, decreased serum properdin, positive C-reactive protein and elevated beta globulin in the serum was noted.
The conclusion reached is that an elevation of complement in the serum indicates that Hodgkin’s disease is in an active phase. As to the nature of the disease, the statistics assembled seem to give no clue.
Distribution of Abnormal Hemoglobins in Puerto Rico and Survival Studies of Red Blood Cells Using Cr51
Authors: SUAREZ RAMON M. , BUSO ROBERTO , MEYER LEO M. , OLAVARRIETA S. T. 
Published: October 2019

Abstract
1. A survey of the incidence of abnormal hemoglobins in different racial groups distributed over the island of Puerto Rico was performed. The relation of the rate of destruction of red cells to the presence of abnormal hemoglobin patterns in the affected population was also studied.
2. The abnormal hemoglobins were classified by the difference in paper electrophoretic mobility. Fetal hemoglobin was measured by its resistance to alkaline denaturation. The red cell life span was determined by measuring the survival of erythrocytes labelled with radioactive sodium chromate.
3. A total of 2,089 inhabitants were studied. There were 1,487 white subjects and 602 Negroes. Forty-two individuals were found to harbor abnormal hemoglobins. All but one were Negroes or Negroid of African descent, and their relative numbers agreed closely with the geographical distribution of ethnic groups in the island. Abnormal hemoglobins were found in 2.01 per cent of the entire series of 2,089 persons, but in those considered Negroes or Negroids the incidence of abnormal hemoglobins was 6.8 per cent.
Of the 42 persons showing abnormal hemoglobins, thirty-four or 81 per cent, had hemoglobin S; only two of these had sickle cell anemia. The incidence of the sickle cell trait among the Puerto Rican Negro population was 5.2 per cent; and the incidence of hemoglobin S disease among those harboring the trait was 5.9 per cent.
Eight, or 19 per cent of the abnormal cases had hemoglobin C; only one of these had hemoglobin C disease with clinical hemolytic anemia. The incidence of the hemoglobin C trait among the Puerto Rican Negro population is 1.3 per cent; and the incidence of hemoglobin C disease among those harboring the trait may reach 12.5 per cent.
4. All 42 cases harboring abnormal hemoglobins showed very small quantities of fetal or alkali-resistant hemoglobin ranging from 0.45 per cent to 3.25 per cent, averaging 1.12 per cent.
5. The "apparent" half-life of the red blood cells was found to be 10 days in sickle cell anemia, 7 days in SC disease, 20.6 days in cases of hemoglobin SA, 18.5 days in one case of hemoglobin C disease and 21.5 days in 2 cases of the combination CA. The normal "apparent" half-life in our laboratory is 24.5 days.
Leukokinetic Studies. I. A Method for Labeling Leukocytes with Diisopropylfluorophosphate (DFP32)
Authors: ATHENS J. W. , MAUER A. M. , ASHENBRUCKER HELEN , CARTWRIGHT G. E. , WINTROBE M. M. 
Published: October 2019

Abstract
1. A method has been presented by which granulocytes can be labeled in vivo with diisopropylfluorophosphate containing radioactive phosphorus. The leukocytes are isolated from blood by dextran sedimentation of erythrocytes and are then treated with gramicidin and lysolecithin to remove remaining red cells. Platelets are removed by differential centrifugation. The isolated leukocytes are placed between two squares of scintillating plastic and counted with a scintillation counter.
2. Leukocytes essentially free of erythrocytes and platelets can be obtained by the method outlined. The efficiency of the plastic scintillation counting method for radioactive phosphorus is about 74 per cent and leukocyte samples obtained from 20 ml. samples of normal blood can be counted with a reproducibility of ±10 per cent.
3. The administration of 2 mg. of diisopropylfluorophosphate either intramuscularly or intravenously is without significant toxic side effects.
4. No evidence has been obtained that the label damages the leukocytes.
5. No evidence has been obtained that the label elutes from leukocytes under the conditions of these studies.
6. Diisopropylfluorophosphate labels granulocytes for a brief period of time following injection. The label is not reutilized after death of the cells.
What Are Normal Blood Values for Leukemia in Remission?
Authors: HYMAN CAROL B. , BORDA C. EDUARDO , DIGUMARTHI GOPALASWAMI 
Published: October 2019

Abstract
1. The values for hemoglobin concentration, total white blood cells, granulocytes, lymphocytes and monocytes at the midpoint of 78 drug-induced remissions in a group of children with acute leukemia have been presented. These values have been compared with those from a group of normal children, and the differences analyzed statistically.
2. Statistical analysis shows that, in general, blood values in remission are reduced by the particular agent employed. White blood cells are more markedly affected than hemoglobin.
3. The effects are essentially the same with 6-M.P. given alone or in combination with azaserine or DON.
4. The reduction in values is greatest with 6-M.P., alone or in combination, less with amethopterin and least with prednisone.
5. The data presented indicate that criteria for complete blood remission should make allowances for the influence of the drug employed.
Congenital Hypoplastic Thrombocytopenia with Skeletal Deformities in Siblings
Authors: SHAW SIDNEY , OLIVER R. A. M. 
Published: October 2019

Abstract
The occurrence of congenital hypoplastic thrombocytopenia with absent radii is described in siblings.
Both presented with hemorrhagic manifestations within a few weeks of birth and the first died at the age of six and a half months.
Reference is made to two other examples in siblings.
These abnormalities are considered as due to a genetic defect and the cases are probably variants of Fanconi’s syndrome.
Total Cell Counts of the Bone Marrow of Normal Albino Rats from 1 to 50 Weeks of Age
Authors: BURKE WILLIAM T. , HARRIS CHARLES 
Published: October 2019

Abstract
A method is described by which the total nucleated cell count of femoral bone marrow of the rat can be estimated and cell population expressed in terms of differential counts. Normal values of total nucleated cell counts and the cellular distributions are given for seven age groups. These data indicate considerable change in bone marrow total cell population in rats one to 10 weeks of age.
Ferritin and Ferruginous Micelles in Normal Erythroblasts and Hypochromic Hypersideremic Anemias
Authors: BESSIS MARCEL C. , BRETON-GORIUS JANINE 
Published: October 2019

Abstract
1. All normal erythroblasts contain some iron in the ferritin form. It may be present in either a dispersed state or in compact clusters. When large enough, these clusters may be observed in the optical microscope: they are the granular particles of the siderocytes.
2. Iron can be found in the mitochondria. It may exist either in the form of ferritin granules or as ferruginous micelles.
3. In thalassemia, large quantities of iron accumulate in the erythroblasts and are even found in the erythrocytes as ferritin, in cluster formation or dispersed. Occasionally, iron is present in great quantities in the mitochondria as ferritin or micelles. It seems that the various disorders encountered in thalassemia may thus be ascertained; the disturbance in hemoglobin synthesis results in the accumulation of the unused iron in the hypochromic erythrocytes.
4. In diseases very similar to thalassemia and in which no fetal hemoglobin is found, i.e., the hypochromic-hypersideremic anemias (sidero-achestic anemia, hypochromic hypersideremic anemia, lead-poisoning ), similar findings are observed.
5. Normally, it is probable that iron metabolism occurs in the mitochondria. In thalassemia and hypochromic hypersideremic anemias, on the other hand, iron metabolism often appears to be "blocked" in the same areas.
Studies on the Biosynthesis of Heme from Iron and Protoporphyrin
Authors: SCHWARTZ H. C. , CARTWRIGHT G. E. , SMITH EMIL L. , WINTROBE M. M. 
Published: October 2019

Abstract
1. Additional evidence has been presented that the formation of heme in vitro from iron and protoporphyrin is enzyme dependent.
2. An enzyme solution was prepared from the active particulate matter of a chicken erythrocyte hemolysate. The enzyme is soluble in 0.15 M KCl and optimally active at pH 7.9.
3. The rate of heme synthesis was constant over the first 30 minutes and approached maximal values at 3 to 4 hours. At optimal concentrations of protoporphyrin and iron the rate of heme synthesis over the first 30 minutes was proportional to enzyme concentration.
4. The enzyme solution was 89 per cent inactivated after heating at 56 C. for 30 minutes. Optimal stability for 3 hours was at pH 7.4. It was unstable when lyophilized or on storage at 5 C. or -30 C.
5. The enzyme was inhibited by 1 x 10-2 M p-chloromercuriphenylsulfonate and 1 x 10-2 M iodoacetamide.
6. There was a 70 per cent loss of activity after dialysis of the enzyme solution for 22 hours against water. The dialyzed enzyme solution was reactivated with either reduced glutathione or cysteine.
7. The enzyme solution augmented heme synthesis in vitro from δ-amino-levulinic acid, porphobilinogen and protoporphyrin, but not from glycine.
The Proportion of Reticulocytes in the Erythrocytes of the Spleen as Compared with Those of Circulating Blood, with Special Reference to Hemolytic States
Authors: BERENDES MARGRET 
Published: October 2019

Abstract
1. Comparative studies of reticulocyte percentages have been made on the spleens of normal dogs, dogs with phenylhydrazine hemolytic disease, and human cases of hemolytic jaundice. Splenic artery and vein blood has been compared in some of these, both before and after adrenalin.
2. No significant differences were found, as between peripheral, splenic arterial and venous blood, with or without the use of adrenalin.
3. Imprint and "squeeze" preparations of splenic parenchyma consistently gave higher percentages ranging from 1.5 to 3.5 times the peripheral values, the most marked differences being noted in the normal dog (11.5 to 27 x).
4. The possible significance of these findings is discussed.
Studies on Erythropoiesis. XI. Reticulocyte Response of Transfusion-Induced Polycythemic Mice to Anemic Plasma from Nephrectomized Mice and to Plasma from Nephrectomized Rats Exposed to Low Oxygen
Authors: JACOBSON LEON O. , MARKS EDNA K. , GASTON EVELYN O. , GOLDWASSER EUGENE 
Published: October 2019

Abstract
Mice with transfusion-induced polycythemia have been used to assay erythropoietic activity in plasma derived from mice and rats subjected to various stimuli and experimental procedures.
1. Anemic, anoxic, or cobalt mouse plasma increased erythropoiesis from the zero baseline to about the normal range after four 0.5 cc. injections. No significant effect is observed from the same number of injections of normal rat or mouse plasma or normal saline. Similarly, plasma from rats starved for 4 days had no erythropoietic activity, but erythropoietic activity was present in the plasma of pregnant mice during the last trimester of pregnancy.
2. Plasma from mice made anemic by phenylhydrazine and then subjected to bilateral nephrectomy contained slight erythropoietic activity (less than 0.2 per cent reticulocytes). The plasma of sham-operated anemic animals had considerably more erythropoietic activity (2.0 per cent). The plasma was collected for assay 10 hours after the operative procedures.
3. Plasma from nephrectomized rats exposed to hypoxic anoxia for 8, 16, or 24 hours, had slight erythropoietic activity when measured by the peripheral reticulocyte response of the recipients (0.18, 0.11, and 0.00 per cent reticulocutes, respectively). The same plasma had no erythropoietic activity when judged by the Fe59 red cell incorporation response in starved rats.
Plasma from rats subjected to bilateral ureter ligation and similarly exposed had an erythropoietic activity (0.7, 1.38, and 1.26 per cent reticulocytes, respectively), comparable with that of the plasma from normal rats exposed to hypoxic anoxia (0.9, 1.71, and 1.78 per cent, respectively). The low and inconstant erythropoietic activity in the plasma of nephrectomized mice and rats subjected to anemic or hypoxic anoxia is more or less comparable with the response occasionally produced by normal plasma. We are, therefore, disinclined to consider the data as evidence against the renal origin of erythropoietins, but the alternative possibilities are discussed.
Hereditary Spherocytosis-Sicklemia in the Negro
Authors: MARTIN WILLIAM W. , KOUGH ROBERT H. , BRANCHE GEORGE C. 
Published: October 2019

Abstract
1. A case of coexistent hereditary spherocytosis and sicklemia in a Negro female is reported. Hematologic and clinical amelioration followed splenectomy.
2. Study of three generations of the family of the propositus revealed one additional case of hereditary spherocytosis-sicklemia and 10 cases of hereditary spherocytosis in the Negro.
3. Further evidence is adduced that the combination of this heterozygous hemoglobinopathy with the red blood cell defect of hereditary spherocytosis produces an illness which is not grossly different from hereditary spherocytosis associated with normal hemoglobin.