bluuebunny/crossref_metadata_2025 huggingface dataset:
Methotrexate-Cytarabine-Dexamethasone Combination Chemotherapy with or without Rituximab in Patients with Primary Central Nervous System Lymphoma
Authors: Liu Jing , Sun Xuefei , Bai Xueyan , Chen Yuedan , Qian Jun , Zhu Hong , Wang Yaming , Ji Nan , Sun Shengjun , Wang Yajie , Liu Yuanbo
Published: October 2019

High-dose methotrexate (HD-MTX) based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because as a large protein limits its penetration to blood brain barrier (BBB). We aimed to investigate the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL from Beijing Tiantan Hospital, Capital Medical University. Twenty-four patients received 3-6 courses of methotrexate 3.5 g/m2 on day 1, cytarabine 0.5-1 g/m2 on day 2 and dexamethasone 5-10 mg on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m2 on day 0. All patients repeated the treatment every 3 weeks. Patients who obtained a complete remission (CR) after induction chemotherapy received consolidation chemotherapy, and those with partial remission (PR), stable disease (SD) or progression disease (PD) received rescue whole brain radiotherapy (WBRT). After induction chemotherapy, patients treated with rituximab plus methotrexate-cytarabine-dexamethasone had a CR rate of 66.7%, compared with 33.3% of those treated with methotrexate-cytarabine-dexamethasone alone (p=.011). Seven anaphylaxis and 1 interstitial pneumonitis occured in patients with rituximab. The most common grade 1-3 adverse events were similar in the two groups including neutropenia, anaemia, thrombocytopenia, aminotransferases elevated and gastrointestinal reaction. None of the patients in the two groups experienced any grade 4 toxicity. On multivariate analysis, rituximab was associated with longer progression-free survival (PFS, hazard ratio: 5.23, 95% CI: 1.64-16.70, p=.005). Elevated serum lactate dehydrogenase (LDH) was associated with shorter OS (hazard ratio: 0.06, 95% CI: 0.00-0.97, p=.048) and PFS (hazard ratio: 0.10, 95% CI: 0.03-0.37, p=.001). HD-MTX based chemotherapy with rituximab had a higher rate of CR, and without serious toxicity. PFS but not OS benefited from addition of rituximab. LDH as an independent prognostic factor which predicted poor outcome.

Disclosures

No relevant conflicts of interest to declare.
Cytopenia, Predisposition to Myelodysplastic Syndrome, Immunodeficiency, and Neurological Disease Caused By Gain-of-Function SAMD9L Mutations Is Frequently Ameliorated By Hematopoietic Revertant Mosaicism
Authors: Tesi Bianca , Davidsson Josef , Voss Matthias , Holmes Timothy , Ripperger Tim , Chiang Samuel , Nilsson Lars , Nordenskjöld Magnus , Henter Jan-Inge , Bryder David , Fioretos Thoas , Uusimaa Johanna , Komulainen-Ebrahim Jonna , Möttönen Merja , Niinimäki Riitta , Moilanen Jukka , Rahikkala Elisa , Tedgård Ulf , Cammenga Jörg , Bryceson Yenan
Published: October 2019

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic diseases characterized by impaired hematopoiesis and progression to acute myeloid leukemia (AML). Although rare, several monogenic causes of familial MDS/AML have recently been molecularly defined. We studied two families with variable manifestation of cytopenia, MDS with cytogenetic aberrations involving chromosome 7, immunodeficiency, and neurologic disease consistent with ataxia-pancytopenia syndrome.

Genetic studies uncovered heterozygous missense variants (p.Arg986Cys and p.Ile891Thr) in SAMD9L, a tumor suppressor gene located on chromosome 7. Consistent with a gain-of-function effect, transfection and over-expression of both SAMD9L variants decreased cell proliferation relative to wild-type protein. In the two families, a total of 10 individuals heterozygous for either SAMD9L mutation were identified. Three individuals developed MDS, with monosomy 7 or der(1;7)(q10;p10) as cytogenetic aberrations that encompassed the mutant SAMD9L locus. In an additional five individuals, three of which experienced a spontaneously resolved cytopenic episodes in infancy, we detected mosaic copy-neutral loss of heterozygosity of 7q by uniparental disomy, with loss of the mutated allele, or mosaic cis SAMD9L mutations. By digital PCR, we identified these events in hematopoietic progenitor cell populations, which were further enriched in B and NK cell lineages. Absent in non hematological tissues, these mutations thus represented somatic revertant mosaicism. Clinically, revertant mosaicism was associated with reduced disease severity, although in two individuals neurological manifestations persisted. Of note, two unaffected carriers without revertant mosaicism harbored an additional rare in trans germline SAMD9L p.Thr233Asn missense variant. In cellular assays, the SAMD9L p.Thr233Asn variant increased proliferation, indicating a loss-of-function effect that potentially compensates for the SAMD9L p.Arg986Cys mutation.

Together, our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause a disease with cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with chromosome 7 aberrations, where hematopoietic revertant mosaicism is common and ameliorates the clinical presentation.

Disclosures

Fioretos: Cantargia: Equity Ownership.
Observations on Chimpanzees after Whole-Body Radiation and Homologous Bone Marrow Treatment
Authors: ROTHBERG HARVEY , BLAIR EUGENE B. , GOMEZ ALPHONSE C. , MCNULTY WILBUR
Published: October 2019

1. Three chimpanzees were given 900 r of whole body radiation followed by transfusion of homologous bone marrow. One animal survived for nearly six months.

2. Five chimpanzees were given 1200 r of whole body radiation; three of them were given homologous bone marrow. There was no difference in survival time of treated animals and of controls.

3. Observations were made on clinical, hematologic, bacteriologic and pathologic aspects of acute radiation injury.

4. There was no evidence of a "take" of the homologous marrow. The significance of the findings is discussed.
Plasmoptysis and Gelation of Erythrocytes in Coagulation of Blood of Freshwater Bony Fishes
Authors: WOLF KEN
Published: October 2019

1. A clot-like material which results from very rapid plasmoptysis and hydrophyllic swelling of karyoplasm of erythrocytes from freshwater fish was reported. This attribute was found to a lesser degree in erythrocytes from an amphibian, but it was almost lacking in those of an aquatic reptile.

2. Rapid clotting of fish blood with the usual clinical methods was confirmed in this work. Fish blood clotted more quickly with the slide test than with the capillary tube test. In the presence of water, complete coagulation of fish blood occurred in only 65 per cent of the time required for clotting to be completed in air. This speed is attributed to the water-erythrocyte reaction, and not to a quality of the plasma.

3. An attempt was made to correlate the findings with the need for hemostasis and blood coagulation that is peculiar to aquatic vertebrates.
The Utilization of Protoporphyrin 9 in Heme Synthesis
Authors: GRINSTEIN MOISES , BANNERMAN ROBIN M. , MOORE CARL V.
Published: October 2019

The experiments described in this communication demonstrate that C14-tagged protoporphyrin 9 can be incorporated into the heme during the biosynthesis of hemoglobin.

1. In vitro observations:

(a) C14 protoporphyrin 9 was found to be incorporated into heme by hemolysates of chicken and human blood incubated at 37 C. The degree of incorporation by washed chicken erythrocytes was less, presumably because the protoporphyrin was not readily transferred across the cell membrane. Incorporation by hemolysates was inhibited completely at 1 x 10-2 M KCN at 4 C., markedly by 1 x 10-2 M KCN at 37 C. and partially by 1 x 10-3 M Pb at 37 C.

(b) The degree of incorporation was reduced by the addition of an equivalent quantity of delta-aminolevulinic acid. Furthermore, the incorporation of glycine-2-C14 into heme was reduced by the addition of an equivalent quantity of protoporphyrin 9.

2. In vivo observations:

Intravenously administered C14 protoporphyrin was incorporated into the circulating hemoglobin of two rabbits with a phenylhydrazine-induced hemolytic anemia.

These observations provide support for the view that protoporphyrin 9 itself is a true direct precursor of hemoglobin, in the biosynthetic pathway between porphobilinogen and heme. Comparative studies of rates of incorporation of C14 protoporphyrin 9 and its precursors into heme in vitro may provide a useful tool for the study of heme synthesis in normal and pathologic conditions. For instance, it was shown that hemolysates from the blood of patients with thalassemia major, with poor iron and glycine utilization, rapidly incorporated the tagged protoporphyrin into heme.
Multiple Inherited Erythrocyte Abnormalities in an American Negro Family: Hereditary Spherocytosis, Sickling and Thalassemia
Authors: COHEN FLOSSIE , ZUELZER WOLF W. , NEEL JAMES V. , ROBINSON ABNER R.
Published: October 2019

An American Negro family has been described in which there are found the genes responsible for three inherited abnormalities of the erythrocyte, namely, the genes resulting in spherocytosis, a thalassemia-like trait and the sickling phenomenon. The study of this family provides evidence for the independent segregation of the genes responsible for this type of thalassemia and the sickling phenomenon, and for spherocytosis and the sickling phenomenon. It is noteworthy that the thalassemia gene present in this family is not associated with an increased proportion of hemoglobin A2, and fails to exhibit "factor interaction" with the sickle cell gene, and the question is raised whether these attributes characterize a type of thalassemia gene non-allelic to the sickle cell gene.
Lymph Node Reactivity. II. Fetal Lymph Nodes
Authors: BLACK MAURICE M. , SPEER FRANCIS D.
Published: October 2019

A study was made of the progressive development of structure and metalophilia of the axillary nodes obtained from fetuses of various weights. Metalophil cells were rare in fetuses weighing less than 1000 Gm., while the adult pattern of metalophilia was not observed until the fetus approached 2000 Gm. The findings were discussed in terms of their relationships to perinatal death.
Detection of Leukocyte Antibodies by the Complement Consumption Test
Authors: CHUDOMEL V. , JEZKOVA Z. , LIBANSKY J.
Published: October 2019

A new method for the demonstration of leukocyte antibodies by the complement consumption test is described. For this test active serum and the complement of the examined serum itself is used. In the presence of antibodies against the antigen used, complement consumption takes place during the antigen-antibody reaction. This consumption can be estimated while titrating C' by the difference between the first completely hemolyzed test tube in the lower row (serum to which no antigen had been added), and the test tube with complete hemolysis in the upper row (serum with added antigen).

Two hundred-eighty normal sera, 105 sera of patients suffering from variouts internal diseases and 78 sera from patients with disorders of the blood were examined. The complement consumption test gave positive results more often than did the leukoagglutination method.

The method described was also successful in the demonstration of thrombocyte antibodies. We believe that it is equally suited for the detection of various tissue antibodies.
A Method for the Measurement of Red Cell Dimensions and Calculation of Mean Corpuscular Volume and Surface Area
Authors: HOUCHIN DONALD N. , MUNN JOHN I. , PARNELL BENJAMIN L.
Published: October 2019

Houchin, D. N., Munn, J. I., and Parnell, B. L.: A method for the measurement of red cell dimensions and calculation of mean corpuscular volume and surface area. Blood 13:1185-1191, 1958.

Page 1186: the formula for surface area (ninth line from the bottom of the page) should read:

See PDF for Equation
Dysproteinemia Induced in Vitro by Plasmin Digestion of Fibrinogen
Authors: KOWALSKI E. , BUDZYŃSKI A. , KOPEC M. , MURAWSKI K.
Published: October 2019

1. Electrophoretic investigation of split products of plasmin digestion of pure fibrinogen and of fibrinogen in a plasma medium was performed. It was shown that split products possessed electrophoretic mobilities of alpha, beta and gamma globulins.

2. It could be shown that by digestion of I131-labeled fibrinogen, radioactivity in the range of alpha, beta and gamma globulins is released.

3. Simultaneously with the formation of high molecular intermediates, low molecular, TCA-soluble substances are released.

4. Radioactivity balance calculation of the relative amounts of the newly formed fractions has been performed.

5. A possible influence of plasmin-induced fibrinogen proteolysis on the electrophoretic pattern of plasma proteins in dysproteinemia has been suggested.

6. The electrophoretic pattern of plasma proteins, obtained in the above experiments is similar to those seen in patients with dysproteinemia.
Neonatal Neutropenia Due to Maternal Isoimmunization
Authors: LALEZARI PARVIZ , NUSSBAUM MURRAY , GELMAN SIDNEY , SPAET THEODORE H.
Published: October 2019

A family is reported with multiple cases of neonatal neutropenia. The first child died of severe infection, the second was asymptomatic, the third and the fourth children had a benign course of agranulocytosis which lasted about 10 weeks and was followed by spontaneous recovery. A potent leukoagglutinin was found in the maternal serum which agglutinated leukocytes obtained from the father and all three available children but failed to agglutinate the mother’s own cells. Identical leukoagglutinin was found in the last baby’s serum; it disappeared after the baby recovered. The disorder is tentatively named "isoimmune neonatal neutropenia" and is considered to represent a condition analogous to erythroblastosis fetalis.
Brief Note: Hemoglobin J in a Healthy Hawaiian-Chinese-Caucasian Male
Authors: JIM ROBERT T. S. , YARBRO MARINA T.
Published: October 2019

Hemoglobin J is reported in a 27 year old healthy adult Hawaiian-Chinese-Caucasian male and 3 of his offspring. All were healthy and displayed no hematologic disturbances except for the Youngest offspring, who exhibited mild nutritional iron deficiency anemia.
Variation in the Duration of Survival of Patients with the Chronic Leukemias
Authors: FEINLEIB MANNING , MACMAHON BRIAN
Published: October 2019

Data on 649 white residents of Brooklyn first diagnosed as having chronic leukemia during the period 1943 to 1952 were obtained from hospital records. Diagnosis was based on marrow biopsy or autopsy in 65 per cent. Follow-up to January 1, 1958 was complete for 90.0 per cent (584) of the patients. The life table method and the method of maximum likelihood applied to the three parameter log-normal distribution were used to analyze survival trends of these patients.

The median duration of survival after diagnosis for the total sample was 11.65 months. Sixteen per cent of the patients survived longer than 43 months after diagnosis, and 9 per cent survived for five years. The mean duration of symptoms prior to diagnosis was 5.1 months.

Median durations were somewhat longer for females than for males and for patients with chronic lymphocytic leukemia than for those with chronic myelocytic leukemia. However, neither of these differences was statistically significant.

The duration of survival after diagnosis was significantly shorter for males and females with chronic myelocytic leukemia who were over 60 years of age than for any other age or diagnosis group. For patients with chronic lymphocytic leukemia, duration of survival was independent of age.

Duration of survival after diagnosis was independent of the duration of symptoms prior to diagnosis. The median duration of survival for a group of patients in whom the diagnosis was made during examination for symptoms referable to some other condition was similar to that of those presenting with symptoms clearly referable to leukemia.

Two groups by religion and ABO blood type showed significantly longer median durations of survival after diagnosis than comparable groups. Jewish women with chronic lymphocytic leukemia showed a median duration of survival of 21.1 months compared with 6.4 months for the non-Jewish women. Women with chronic myelocytic leukemia of type B or AB blood had median survivals after diagnosis of about 24 months, compared with about 10 months for the same groups with type A or O blood.
The Ultrastructure and Genesis of Auer Bodies
Authors: FREEMAN JAMES A.
Published: October 2019

The light microscopic morphology, chemical composition, ultrasonic fractionation, ultracentrifugal separation and light absorption characteristics of Auer bodies have all been described. However, since the initial observations by John Auer in 1906 and until the advent of electron microscopy, few data have been added to elucidate the structure of these bodies. With the aid of the electron microscope, Auer bodies have been found to be coacervates of laminated, homogeneous, crystalline plaques with the long axis of the plaques in the same plane as the long axis of the rod. The ultracytologic resemblance between Auer bodies and cytoplasmic granulation supports previous histochemical evidence suggesting the genesis of Auer bodies from cytoplasmic granules.

Existing evidence indicates that the newly discovered fibrillar formation and the recently described granule-vacuole body are the same structure. Although histochemical studies show similarities between these structures and Auer bodies, they are architecturally unrelated and probably have distinctly different pathophysiologic significance.
Hereditary Spherocytosis in the Deer Mouse. Its Similarity to the Human Disease
Authors: ANDERSON R. , HUESTIS R. R. , MOTULSKY A. G.
Published: October 2019

The hematologic and pathophysiologic consequences of a mutant recessive gene in the deer mouse produce features that are indistinguishable from hereditary spherocytosis in man. The syndrome in the mouse was characterized by neonatal jaundice, splenomegaly, spherocytosis and hemolytic disease which could be abolished by splenectomy. Red cell survival was shortened when the spleen was present and was normal or almost normal in splenectomized animals. Affected animals had a marked increase of gallstone formation at a young age. The intensity of neonatal jaundice as well as the tendency to gallstone formation among affected animals appeared to be under control of genetic modifiers. Hereditary spherocytosis in the mouse is identical pathophysiologically with the human syndrome, although inherited as a recessive trait. Biochemical heterogeneity and dominance modification are discussed as possible explanations for this genetic discrepancy.
Motility Studies of Human Postmortem Bone Marrow
Authors: PERRY VERNON P. , STEVENSON ROBERT E. , MCFARLAND WILLIAM , ZINK GEORGE A.
Published: October 2019

The source of an adequate supply of human bone marrow for transplantation purposes presents a distinct problem. The use of cadaver marrow has been suggested.

Studies of 70 human cadaver bone marrow preparations obtained from 1.5 to over 102 hours postmortem were examined by tissue culture and photomicrographic technics to correlate the survival of leukocyte motility with the time postmortem.

Motile cells were present in marrow up to and including 50 hours after death, thus suggesting the possibility of using such marrow as a practical source of viable marrow cells.
Combined Deficiencies of PTA and AHG with Vascular Fragility
Authors: PERRY SEYMOUR , OPFELL RICHARD , BAKER MARY
Published: October 2019

Coagulation studies in a 22 year old Caucasian male have revealed the presence of combined deficiencies of PTA and AHG with vascular fragility. Members of his family have been shown to have isolated deficiencies of PTA, AHG, vascular fragility and various combinations of all three defects. The family studies indicating segregation of the PTA and AHG deficiencies lend support to the concept that these two are clinically separate entities.

The inheritance patterns of PTA deficiencies and AHG deficiencies with vascular fragility are discussed.

The problems encountered in this type of study are mentioned, and the precautions to be observed are indicated.
Studies in Experimental Autoimmune Disorders. I. Clinical and Laboratory Features of Autoimmunization (Runt Disease) in the Mouse
Authors: OLINER HERMAN , SCHWARTZ ROBERT , DAMESHEK WILLIAM , Beldotti Lorraine
Published: October 2019

The graft vs. host reaction (runt disease) was studied in LAF1, BDF1, and BAF1, mice. The disease was induced by the injection of parental splenic tissue into adult recipients.

The F1 hybrid recipients developed weight loss, hair changes, dermatitis, hypothermia and splenomegaly. The laboratory features included hemolytic anemia with a positive antiglobulin test, leukopenia, thrombocytopenia and abnormalities of their plasma electrophoretic patterns.

Certain similarities between runt disease and autoimmune diseases of man were suggested, and their significance was discussed.
Reticuloendothelial Clearance of Blood Thromboplastin by Rats
Authors: SPAET THEODORE H. , HOROWITZ HERBERT I. , ZUCKER-FRANKLIN DOROTHEA , CINTRON JOSE , BIEZENSKI JERZY J.
Published: October 2019

Data have been presented suggesting that blood thromboplastin given intravenously to rats is cleared by the reticuloendothelial system. (1) The reagent given into the jugular vein or aorta caused profound defibrination, whereas injection into the portal circulation caused a milder reaction. These differences were obtained irrespective of the source of phosphatide in the thromboplastin generation mixture. (2) Reticuloendothelial blockade reduced the protective effect of portal administration. (3) Radioactive blood thromboplastin given intravenously was rapidly cleared from the blood, and showed an organ distribution resembling that of agents known to be removed by reticuloendothelial cells. (4) Injection of the blood thromboplastin during a carbon clearance caused depression of the carbon disappearance slope.
Uric Acid Excretion in Patients with Malignant Lymphomas
Authors: PRIMIKIRIOS N. , STUTZMAN L. , SANDBERG A. A.
Published: October 2019

Uric acid blood and urine studies were performed in 12 patients with lymphomas while on a measured low purine diet before, during and after cytotoxic therapy.

Before treatment, urinary uric acid excretion in these patients was significantly higher than in normal subjects, although only 2 patients had clearly elevated blood uric acid levels. There was no correlation between the estimated size of the tumor masses and pretreatment uric acid excretion. The response to treatment could not have been predicted by measurement of the pretreatment uric acid excretion.

In one patient with extensive tumor infiltration of the kidneys, dangerous renal failure, preceded by marked hyperuricemia, developed during therapy. Mechanical hemodialysis resulted in clinical improvement and marked reduction in the blood levels of uric acid and urea.

The finding of a large increase in uric acid excretion during the early days of treatment of a patient with lymphoma is indicative of a responsive tumor. Such data also serve as warning of potential obstructive uric acid nephropathy or uropathy before major increases in serum uric acid appear. Small increases of uric acid excretion in association with treatment could not be correlated with objective clinical response.
Measurement of Absorption of Vitamin B12 by Whole-Body Gamma Spectrometry
Authors: REIZENSTEIN P. G. , CRONKITE EUGENE P. , COHN S. H.
Published: October 2019

A technic is described to measure directly the intestinal absorption of radiovitamin B12 by using a whole-body gamma spectrometer. A double tracer technic is used, and the amounts of free and intrinsic factor bound vitamin B12, respectively, retained in the body after final excretion of unabsorbed radioactivity, are measured. The results are in agreement with those previously obtained by other methods. The present method is simple and quantitative.

The primary advantage of the whole-body counter for measuring absorption of Cobalt-labeled B12 is that it can measure less than 0.1 µc. with a high degree of accuracy. Whole-body counting substitutes a rapid and simple measurement for the difficult and tedious collection and radiochemical analysis of excreta.
Hemoglobin "Pylos": Study of a Hemoglobinopathy Resembling Thalassemia in the Heterozygous, Homozygous and Double Heterozygous State
Authors: FESSAS PHAEDON , STAMATOYANNOPOULOS GEORGES , KARAKLIS ARIS
Published: October 2019

Eight Greek families are reported in which an hereditary hemoglobin abnormality was present. The abnormal hemoglobin is provisionally called Hgb "Pylos" (= Lepore?) and its properties are described. The pattern of inheritance suggests a one gene effect.

In the heterozygous state the abnormality manifests itself by the presence of low amounts of Hgb "Pylos", low amounts of Hgb A2 and mild increase of Hgb F together with quantitative and qualitative alterations of the red cells as observed in thalassemia trait. In one homozygous individual, complete absence of Hgb A and Hgb A2 as well as very high amounts of Hgb F were observed, together with a clinical and hematologic picture resembling overt thalassemia. The combination with A2-thalassemia was observed in five cases and manifested itself by a clinical and hematologic picture of rather moderately severe thalassemia, by complete absence of Hgb A and by predominance of Hgb F. In both the homozygote and the double heterozygotes the amount of Hgb "Pylos" was within the range found for heterozygotes. The findings are discussed and it is concluded that the abnormal gene is allelomorphic to the gene controlling synthesis of β-chains; however, it appears to affect concomitantly the synthesis of δ-chains. The possible interpretations of this double effect are presented.
Autoimmune Thrombocytopenic Purpura ("ITP" Type) with Chronic Lymphocytic Leukemia
Authors: EBBE SHIRLEY , WITTELS BENJAMIN , DAMESHEK WILLIAM
Published: October 2019

Five cases of chronic lymphocytic leukemia complicated by thrombocytopenic purpura are presented. They differed from the usual cases with this complication in that megakaryocytes were plentiful in spite of leukemic involvement of the bone marrow. Hypersplenism did not appear to be a factor.

The evidence suggests that the thrombocytopenia was of an autoimmune nature, due to antiplatelet antibodies. Brief platelet survival times, the presence of a platelet agglutinin, staining of megakaryocytes by fluorescein-labeled anti-human globulin, and responses to corticosteroids were demonstrated.
Myelogenous Leukemia in the Rat
Authors: MOLONEY WILLIAM C. , DORR ANDREW D. , DOWD GERALDINE , BOSCHETTI ANTONIO E.
Published: October 2019

Observations on growth and other characteristics of subcutaneously transplanted chloroleukemia in non-inbred rats have been described in this report. This chloroleukemia cytologically is an acute or subacute, not chronic, myelogenous leukemia. Because of serious immunologic differences, the experimental usefulness of subtransferred chloroleukemia is greatly limited. However, myelogenous leukemia in the rat, induced by chemical agents or ionizing radiation, may offer a valuable approach to the study of leukemogenic mechanisms.
Thrombotic Thrombocytopenic Purpura in Childhood
Authors: MACWHINNEY JAMES B. , PACKER JAMES T. , MILLER GERALD , GREENDYKE ROBERT M.
Published: October 2019

(1) Two cases of thrombotic thrombocytopenic purpura (TTP) occurring in childhood are described. Case 1 is unique in that the patient survived for 12 years.

(2) The clinical features of 19 reported cases of TTP in children are reviewed.

(3) The presence of morphologic abnormalities of red blood cells and the regular occurrence of kidney involvement in this disorder is emphasized. In one patient (Case 2), histologic changes of the disease were limited to the kidney.

(4) Certain hematologic and histologic features shared by TTP and eclampsia are described.

(5) Unusual histologic lesions of renal vessels are described.
The Morphologic Responses of the Lymphoid System to Homografts. I. First and Second Set Responses in Normal Rabbits
Authors: ANDRÉ JANINE A. , SCHWARTZ ROBERT S. , MITUS W. J. , DAMESHEK WILLIAM
Published: October 2019

The morphologic responses of the lymphoid system of the rabbit were studied. The results demonstrated: (a) the proliferation of a characteristic cell, the "hemocytoblast", within lymphoid centers; (b) architectural changes in lymph nodes and spleen, at first characterized by enlargement of follicles and germinal centers, later by effacement of normal landmarks and finally by reconstitution of lymphatic structures; (c) a barely perceptible plasmocytic response, especially in the first set reaction.

These changes, although most pronounced in the lymph node proximal to the homograft, were also found later in distant lymph nodes and in the spleen.

They arose more rapidly, were of greater intensity and were more persistent in the second set reaction than in the first set reaction. These findings indicated that transplantation immunity eventually invokes generalized morphologic changes in the lymphoid system. The events which followed a second set graft suggested that the second set phenomenon had the features of an anamnestic response.
The Effect of Phytohemagglutinin on Leukocyte Cultures as Measured by P32 Incorporation in the DNA, RNA, and Acid Soluble Fractions
Authors: MCINTYRE O. ROSS , EBAUGH FRANKLIN G. , Vaules Martha P.
Published: October 2019

PHA, when added to human leukocyte cultures, results in DNA synthesis and cell mitosis. The addition to these cultures of fetal calf serum, indole-acetic acid, kinetin, estrogens, or a small clot did not duplicate the effect of PHA. Concentrations of chloramphenicol 3.05 x 10-3 M, diphenylhydantoin 5 x 10-5 M, and 6-mercaptopurine 1.3 x 10-3 M resulted in inhibition of growth. Possible mechanisms of action of PHA have been considered. In addition, the possible use of the method described as an in vitro means of evaluating drug sensitivity in leukemia has been suggested.
Hemoglobin Electrophoresis in Acrylamide Gel
Authors: FERRIS THOMAS G. , EASTERLING ROBERT E. , BUDD RICHARD E.
Published: October 2019

A method for hemoglobin electrophoresis is described, using acrylamide gel as the supporting media. The advantages and characteristics of this gel are mentioned. Clear and distinct separations of hemoglobin types obtained after 60 minutes electrophoresis in a vertical cell are illustrated. It is felt that the use of this gel affords a simple and rapid method for the detection and quantitation of hemoglobin abnormalities.
THROMBOCYTIC ACROANGIOTHROMBOSIS (PLATELET THROMBOSIS OF THE CAPILLARIES, ARTERIOLES, AND VENULES)
Authors: FITZGERALD PATRICK J. , AUERBACH OSCAR , FRAME EUGENE
Published: October 2019

It is believed that there is a definite disease syndrome characterized clinically by fever, marked anemia, purpura, thrombocytopenia, central nervous system involvement, and a progressive fatal course of a few weeks’ duration. Histologically the presence of platelet thrombi in the capillaries, arterioles, and venules is pathognomonic. Only by histologic demonstration of the platelet thrombi can the disease be definitely differentiated from idiopathic thrombocytopenic purpura.

The data of 9 previously reported cases of this rare disease are summarized and 2 additional cases reported.

Diagnosis of the disease probably can be made by bone marrow biopsy or, possibly, by skin biopsy. If a case be diagnosed and the patient is not responding to conservative treatment it is suggested that splenectomy be considered.

Spleens removed for thrombopenic diseases should be examined for platelet thrombi in the possibility that unrecognized cases of the disease have been treated by this procedure. Proper evaluation of splenectomy in this disease might be aided by follow-up study of any cases showing platelet thrombi.

The name "thrombocytic acroangiothrombosis" is suggested for this disease.
Congenital hypoplastic anemia associated with multiple developmental defects (Fanconi syndrome)
Authors: ESTREN S. , SUESS JOHN F. , DAMESHEK WILLIAM
Published: October 2019

The following information has been received from Dr. Solomon Estren. On page 92, volume II, Blood (January 1947) in the article, "Congenital hypoplastic anemia associated with multiple developmental defects (Fanconi syndrome)," by Estren, Suess, and Dameshek, the second paragraph on the page concludes with the statement: "Death here also occurred three years later." This should have read: "This patient is living and well seven years after the operation (personal communication, Dr. J. V. Dacie5)."
Regulation of Erythropoiesis. I. Erythropoietin Assay as a Clinical Tool
Authors: NOYES WARD D. , DOMM BILL M. , WILLIS LORETTA C.
Published: October 2019

An erythropoietin assay using hypertransfused rats and radioiron utilization has been evaluated in regard to modifying factors and its variability. It is proposed that the dose-response relationship may be regarded as an adsorptive process which suggests new investigative approaches in terms of hormone binding sites and erythropoietin inhibition.

Elevated levels of erythropoietin were found in 14 of 16 patients with refractory anemia indicating a basic defect in the response of the erythroid marrow. The two exceptions are of great theoretical interest, but insufficient information limits further conclusions. Patients with hypoxic polycythemia demonstrated increased levels only when their compensatory equilibrium had been modified by phlebotomy. Seven patients with polycythemia vera had erythropoietin levels within the normal range whether or not therapy had modified their red cell mass. This is further evidence that polycythemia vera is a proliferative disorder usurping the normal regulation. The clinical use of erythropoietin assay may provide the most information when correlated with alterations of oxygen-carrying capacity as a functional test of the patient’s erythropoietic regulatory mechanism.
Studies in Bisalbuminemia: Binding Properties of the Two Albumins
Authors: SARCIONE EDWARD J. , AUNGST C. WILLIAM
Published: October 2019

1. An abnormal serum protein pattern in a patient with Wegener’s granulomatosis and five of his relatives was identified as bisalbuminemia by electrophoretic and immunochemical methods.

2. With the exception of the patient with Wegener’s syndrome, the presence of bisalbuminemia was not associated with a significant change in total serum proteins, total albumin, serum components other than albumin, or any disease.

3. Addition of I131-thyroxine to bisalbumin sera resulted in thyroxine binding by albumin B but not by albumin A. The failure of albumin A to bind added I131-thyroxine leads to speculation that, in this family, neither albumin A nor B are identical to normal human serum albumin.
The Antigenicity of the Rho (Du) Blood Factor
Authors: SCHMIDT PAUL J. , MORRISON ELEANOR C. , SHOHL JANE
Published: October 2019

The antigenicity of the Rh variant Rho(Du) was investigated by the transfusion of 45 Rh negative (cde/cde) patients with 68 units of "low grade" Rho (Du) blood of the phenotypes Rho(ccDuee) or Rh2(ccDuE). The donor red cells had normal viability; none of the patients made antibodies to Rho(D) or Rho(Du).

The results indicate that the inherited, "low grade" Rho(Du) factor is far less antigenic than Rho(D). It was also less antigenic than Kell or rh'' (E) in this study. It remains possible that this variant will prove to be antigenic in some recipients, but the hazard from this is undoubtedly much less than has been expected.
The Use of Radioactive Antiglobulin for the Detection of Erythrocyte Sensitization
Authors: COSTEA NICOLAS , SCHWARTZ ROBERT , CONSTANTOULAKIS MATTHEW , DAMESHEK WILLIAM
Published: October 2019

Red cell sensitization by either agglutinating or incomplete antibodies was detected with an I131 labeled rabbit antihuman globulin serum (RAG). Nonspecific absorption of RAG by red cells was reduced to a minimum by the addition of 6 per cent bovine albumin. The reactions between RAG and the sensitized erythrocytes were typical of antigen-antibody reactions and the sensitivity of the test was found to be greater than the standard Coombs test. Quantitative studies of the degree of erythrocyte sensitization by isoimmune or autoimmune antibodies were possible with this technic.
The Chediák-Higashi Syndrome
Authors: PAGE ARTHUR R. , BERENDES HEINZ , WARNER JOHN , GOOD ROBERT A.
Published: October 2019

1. Two siblings with the Chediák-Higashi syndrome are reported. One, a three-year-old boy, died with malignant lymphoma; the other, a six-year-old girl, is alive and well.

2. Results of studies of white blood cell function and antibody production were normal, indicating that the increased susceptibility to infection of some Chediák-Higashi syndrome patients is probably not attributable to abnormal leukocytes or to deficient antibody production.

3. Results of investigations of some aspects of tryptophan metabolism indicated an interesting, unique, and as yet unexplained absence of 5-hydroxytryptamine in the peripheral blood.

4. A review of the reported cases of Chediák-Higashi syndrome indicates that these patients have a striking predisposition to a peculiar type of malignant lymphoma.

5. An unusual perivascular infiltrate of histiocytes has been noted in postmortem sections of brain of patients with this anomaly. It is not clear whether this is a manifestation of the malignant lymphoma or a reflection of the basic disease process.
An Electron Microscopic Study of the Changes in Platelets during Viscous Metamorphosis
Authors: CASTALDI P. A. , FIRKIN B. G. , BLACKWELL P. M. , CLIFFORD K. I.
Published: October 2019

Viscous metamorphosis of platelets has been studied with the light microscope, and ultra-thin sections have been prepared at progressive stages for examination in the electron microscope.

The phase contrast light microscope reveals rapid aggregation and distortion of platelets and gives the impression of their fusion into structureless aggregates during viscous metamorphosis.

Sectioned material collected during viscous metamorphosis of platelets and examined in the electron microscope reveals a remarkable degree of retention of structure in a majority of the platelets. All become deficient in granules and devoid of vesicular spaces, but most retain intact cell membranes, and the structureless masses seen with the light microscope are found to consist of densely aggregated platelets. Fusion and complete loss of identity occurs in the minority.

The retracted clot was found to contain densely aggregated, distorted and elongated platelets, empty of granules and intimately related to fibrin particles.
Plasma Concentration of Chloramphenicol and Bone Marrow Suppression
Authors: MCCURDY PAUL R. , Gieschen Mona M.
Published: October 2019

The appearance of reticulocytopenia and of vacuolated marrow blast cells has been correlated with elevated plasma levels and prolonged marrow exposure to free chloramphenicol. It is suggested that chloramphenicol may have produced bone marrow suppression in these patients in part by acting as an antimetabolic agent.
Homologous Bone Marrow Transplantation in Dogs Receiving X-Radiation plus Urethan or 6-Mercaptopurine
Authors: COLE LEONARD J. , ALPEN EDWARD L. , Maki S. , Lacina F.
Published: October 2019

Mongrel dogs were treated with 6-mercaptopurine (6-MP) or urethan prior to x-irradiation (900 r, delivered at a dose rate of 15 r/min.). The marrow dose was 7-11 x 109 cells, given on the day following irradiation; urethan (175 or 350 mg./Kg.) and 6-MP (12.5 or 25 mg./Kg.) were administered at three or four daily intervals during the week prior to irradiation. Mean survival time (MST) in this group of 13 dogs was 23 days, with a maximum of 63 days. MST in a group of dogs given homologous marrow after 900 r, but not treated with the chemicals, was 10 days The treated animals characteristically showed good recovery of peripheral blood granulocyte count by 8-10 days, together with objective evidence of marrow "take"; recovery of mononuclear cell count was not observed, except in the single case which survived for 63 days. None of the control animals showed any rise in the peripheral blood count after initial depression, and all died with marrow aplasia. Secondary disease in treated dogs was characterized by anorexia, weight loss, infection, and lymphoid tissue aplasia in all the animals; skin atrophy, liver lesions, jaundice and anemia were seen in some of the animals. The marrow showed active hematopoiesis and moderate to good cellularity in most of the treated animals, although megakaryocyte activity was deficient in some. Pneumonia and pulmonary edema were found in many of the dogs at autopsy. It is evident that the use of these antimetabolites permits the successful transplantation of homologous marrow in dogs at a dose of x-radiation (900 r) which, by itself, is insufficient. These compounds (urethan and 6-mercaptopurine) are, therefore, additive to x-radiation with respect to suppressing the homograft reaction in dogs, as well as in rodents.
Sulfhemoglobinemia and Acute Hemolytic Anemia with Heinz Bodies Following Contact with a Fungicide— Zinc Ethylene Bisdithiocarbamate—in a Subject with Glucose-6-Phosphate Dehydrogenase Deficiency and Hypocatalasemia
Authors: PINKHAS JACK , DJALDETTI MEIR , JOSHUA HENRY , RESNICK CHAIM , DE VRIES ANDRÉ
Published: October 2019

Sulfhemoglobinemia associated with Heinz body formation and acute hemolytic anemia following contact with a fungicide, zinc ethylene bisdithiocarbamate, is described in a Persian Jew whose red blood cells had low glucose-6-phosphate dehydrogenase activity with low and unstable reduced glutathione and low catalase activity.

The fungicide, similarly to acetylphenylhydrazine, was capable of decreasing in vitro the reduced glutathione of the patient’s red blood cells, as well as of those of other subjects with the same enzymatic defect.

The sulfhemoglobinemia and the hemolytic anemia are considered to have been produced independently by the fungicide, the glucose-6-phosphate dehydrogenase deficiency having played a role only in the latter. The possibility that the hypocatalasemia was a factor in rendering the patient’s red blood cells sensitive to the hemolysis- and sulfhemoglobin-producing action of the fungicide is discussed.

The importance of zinc ethylene bisdithiocarbamate as a sulfhemoglobin-producing and hemolytic agent is stressed, in view of the widespread use of this fungicide.
Chronic Granulocytic Leukemia and Cancer
Authors: ANGUS HELEN B. , GUNZ FREDERICK W.
Published: October 2019

A man of 34 with chronic granulocytic leukemia survived for 7¼ years from diagnosis and died from carcinoma of the pancreas. It appears possible that this tumor was caused by the treatment given for the control of the leukemia.
The Amount of Sr90 in the Bones of People Who Have Died of Leukemias
Authors: ALEKSANDROWICZ J. , TUTAJ L. , WAZEWSKA-CZYZEWSKA M. , MARCHAND B.
Published: October 2019

The authors have compared the amounts of Sr90 in the bones of persons who have died of leukemias and in the bones of those deceased from causes other than tumors or hemocytopathic diseases.

The first group shows an abnormally low level of Sr90 which the authors believe to be due to disturbed calcium metabolism.
Studies on Hemoglobin
Authors: IZAK G. , RACHMILEWITZ E. A. , NELKEN D.
Published: October 2019

Immune sera produced against adult human, fetal, canine and rabbit hemoglobin solutions were found to agglutinate specifically the papain-treated red cells of the respective donors to a high titer. Intact red cells were also specifically agglutinated by the same antibody-containing sera in the presence of dextran, suggesting that the antibodies produced are incomplete ones.

A marked shortening of the life span of rabbit erythrocytes followed the intravenous injection of anti-rabbit hemoglobin serum into normal rabbits.

The possible implications of the above findings in human pathology are discussed.
Radioautographic Studies of Bone Marrow Lymphocytes in Vivo and in Diffusion Chamber Cultures
Authors: OSMOND D. G. , EVERETT N. B.
Published: October 2019

Radioautography with tritiated thymidine has been utilized to examine the turnover rate and origin of small lymphocytes in the bone marrow of the guinea-pig.

Very few marrow lymphocytes were initially labeled by a single injection of tritiated thymidine, but thereafter the number of labeled lymphocytes rapidly increased to high maximum levels at 3 days. Analysis of the labeling curves and grain counts indicates that the population of marrow lymphocytes is maintained in a dynamic steady state with an average turnover time of 3 days or less.

Suspensions of bone marrow cells were isolated from the circulation within intraperitoneal diffusion chambers after short-term labeling with tritiated thymidine in vivo. Although very few small lymphocytes were labeled when introduced into the diffusion chambers, a considerable percentage became labeled during the subsequent culture period.

Tritiated thymidine was also administered intravenously whilst excluded from one hind limb by the application of an occlusive compression bandage for 20 minutes. Very few labeled small lymphocytes were found after 72 hours in the tibial marrow of the initially occluded limb, whereas the normal high percentage was labeled in the control tibial marrow.

These experiments do not demonstrate any large-scale influx of small lymphocytes from the blood stream into the marrow parenchyma. They suggest that newly formed small lymphocytes appear in the marrow as a result of the division of locally situated precursor cells, but the mechanism of intramedullary lymphocytopoiesis is uncertain. "Transitional" cells, intermediate in morphology between blast cells and small lymphocytes, synthesize DNA and are actively proliferative, but they do not appear to account fully for the rate of lymphocyte production.

Certain large, undifferentiated labeled cells appeared in the bone marrow as a result of hematogenous migration. Some implications of these findings are discussed.
Effect of Thymectomy on the Golden Hamster (Mesocricetus Auratus)
Authors: SHERMAN JOSEPH D. , ADNER MARVIN M. , DAMESHEK WILLIAM
Published: October 2019

Thymectomy in our hamster colony produced two major changes: (1) wasting disease, and (2) impaired immune response. Wasting occurred in 36 per cent of all males of all ages and was noted even when thymectomy was performed at 4 weeks of age. Lymphoid atrophy was profound and lymphocytopenia sustained. In the non-wasted hamster, the lymphoid atrophy was less striking and there was only transient lymphocytopenia. Experiments in this study were limited to the non-wasted animals. An impaired immune response was demonstrated in both humoral antibody production and in delayed hypersensitivity (heterograft rejection). Male and female hamsters thymectomized at 2 weeks showed an impaired ability to make antibodies against HGG and exhibited prolonged survival of mouse (AJAX) skin. In animals thymectomized at 4 to 8 weeks of age, impaired humoral antibody production could not be demonstrated. Antigen administered on the day of thymectomy was not associated with impaired humoral antibody production. Splenectomy appeared to be more effective than thymectomy in the adult (8-week) hamster in inhibiting humoral antibody production. From these studies, it is evident that the thymectomized, non-wasted male and female hamster has an impaired immune mechanism for both humoral antibody production and heterologous skin rejection.