bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Allogenic Bone Marrow Transplantation in Man: Chimerism, Induced Specific Tolerance and Possible Anti-Leukemic Effects
Authors: MATHÉ G. , AMIEL J. L. , SCHWARZENBERG L. , CATTAN A. , SCHNEIDER M. , DE VRIES M. J. , TUBIANA M. , LALANNE C. , BINET J. L. , PAPIERNIK M. , SEMAN G. , MATSUKURA M. , MERY A. M. , SCHWARZMANN V. , FLAISLER A.
Published: October 2019

A patient suffering from acute lymphoblastic leukemia in the third progressive phase, refractory to the majority of available treatments, was given total-body irradiation of 800 r. dosage, after administration of methyl-nitro-imidazolyl-mercaptopurine (300 mg. daily for 4 days). One week after irradiation, he received an infusion of a mixture of equal parts of bone marrow from six donors (mother, sister, father and three brothers), a total of 5.8 x 1010 nucleated cells.

Myeloid restoration began 2 weeks after the infusion and continued to progress rapidly. The reality of the graft was demonstrated by study of the erythrocytic antigens. Nearly all the erythrocytes found in the blood after 6 months belonged to the phenotype of one of the male donors.

Studies of chromosomes and leukocyte sex chromatin suggested that a small proportion of leukocytes were being produced by the cells of one of the female donors. The patient was found to produce beta 2A, beta 2M and gamma globulins of the Inv type of the donors, suggesting that lymphoid cells may also have been successfully grafted.

A skin graft from the male donor whose marrow graft had apparently been accepted was still perfectly intact 7 months after grafting, whereas the grafts from other donors were rejected, indicating a specific tolerance to tissues from this donor. Previous studies of compatibility between the recipient and the various donors by a histocompatibility test described by us, or by means of similarities in leukocyte antigens, indicated that the accepted donor had been antigenically more nearly compatible than the others.

What appeared to be a secondary syndrome became manifest 1 week after marrow transfusion; it consisted of weight loss, digestive disorders (anorexia, nausea, vomiting, diarrhea), hepatic disturbances (hepatomegaly, increased serum concentrations of various enzymes), transient polyadenopathy (histologically composed of histiocytic proliferation and lymphocytic aplasia), desquamative erythrodermia, eosinophilia exceeding 50 per cent, and superinfection (including a probable miliary tuberculosis). The syndrome was controlled by careful symptomatic treatment; its intensity gradually abated.

Reactivation of the secondary syndrome was accomplished by reinjection of leukocytes from the donor whose graft had been tolerated. This was controlled by Δ-1-cortisone and symptomatic treatment.

The patient was still alive and in apparently complete hematologic remission from the leukemia 12 months after the treatment described above. Particular reasons for this success possibly include the absence of previous blood transfusions and the use of multiple marrow donors.
The Site of Absorption of Co58-Labeled Vitamin B12 in Man
Authors: RØNNOV-JESSEN VAGN , HANSEN JACOB
Published: October 2019

Intestinal intubation was performed with a tri-bore tubing in ten subjects without signs of gastrointestinal disease. After administration of a test meal containing Co58-labeled vitamin B12 and with polyethylene glycol as a marker substance, samples of intestinal juice were collected from the upper, middle and anal thirds of the small intestine.

During the passage of the test dose from the upper to the middle third of the gut a modest, but significant, absorption of about 6 per cent was discovered. During the passage from the middle to the anal third of the intestine a considerably larger absorption took place, on an average of about 25 per cent of the oral dose.

These results agree entirely with those obtained from experiments performed in animals and with clinical observations in man after operations on the small intestine. The most outstanding feature was that, contrary to the generally accepted view, our study seems to indicate that in certain cases the absorption of B12 begins far up in the jejunum. This seemed to be the case in 3 out of 9 experiments. The study throws no light on the cause of this.
Peripheral Leukocyte Infusion into Lethally Irradiated Guinea Pigs
Authors: MALININ THEODORE I. , PERRY VERNON P. , KERBY CAREY C. , DOLAN MICHAEL F.
Published: October 2019

Homologous peripheral blood leukocytes were injected into lethally irradiated guinea pigs. Histologic examination of these showed a rapid recovery of the bone marrow and the lymphatic tissue following an injection of a sufficient number of leukocytes. All control animals died with a hypoplastic bone marrow. Protected animals did not develop "secondary" disease during 9 months of observation.
Immunologic Studies of Platelet Protein
Authors: NACHMAN RALPH L.
Published: October 2019

Antigens were demonstrated in platelets which were not detectable in plasma. One of these antigens was detected in serum and was presumed to be released during the process of coagulation. Plasminogen and fibrinogen were detected in platelets, and the fibrinogen appears to be part of the intracellular structure. Thrombin was found to act not only on fibrinogen but also on at least one other unidentified platelet protein.
Starch Block Electrophoresis of Plasma and Serum Clotting Factors. Separation of Activated PTC (PTC’)
Authors: SCHIFFMAN SANDRA , RAPAPORT SAMUEL I. , PATCH MARY JANE
Published: October 2019

1. Plasma clotting factors separate into two groups on starch block electrophoresis. The contact activation factors—Hageman factor, PTA, and activated PTA—remain around the origin, whereas the vitamin K-dependent factors— prothrombin, proconvertin, Stuart factor, and PTC—migrate between the α-globulins and albumin. AHG, proaccelerin, and thrombin are not recovered.

2. The electrophoretic pattern of serum differs from that of plasma mainly in the absence of prothrombin and in the presence of activated PTC (PTC’).

3. The electrophoretic mobility of PTC’ is found to differ from that of native PTC. This difference may be exploited to separate PTC’ from its native form and from Stuart factor.
Brief Report: Utilization of Iron by Scorbutic Guinea Pigs
Authors: BANERJEE SACHCHIDANANDA , CHAKRABARTY ARDHENDU SEKHAR
Published: October 2019

Administration of iron to guinea pigs during the progress of development of scurvy did not check the onset of anemia but enhanced it. Iron treatment also could not correct hypoferemia observed in the scorbutic condition although absorption of iron from the intestinal tract was not defective. The absorbed iron was deposited in tissues as hemosiderin. Ascorbic acid seems to be necessary for utilization of iron in the synthesis of hemoglobin.
Brief Case Report: Syndrome of Erythremia di Guglielmo after Lightning Injury with Autoimmune Antibodies and Terminating in Acute Monocytic Leukemia
Authors: ENG LIE-INJO LUAN , SINNADURAI C.
Published: October 2019

A case of lightning injury is described associated with changes of the hemopoietic system resembling di Guglielmo’s syndrome. Megaloblasts were found in the peripheral blood and bone marrow, resistant to folic acid and vitamin B12 treatment. The presence of auto-immune antibodies in this patient was accompanied by a hemolytic condition not responding to treatment with high doses of prednisolone. Towards the end of the disease the most bizarre-looking erythroblasts were seen in the peripheral blood. Shortly before death the condition suddenly changed into an acute monocytic leukemia. Although it was not proved that the lightning injury caused or precipitated the blood changes, it is thought not to be improbable.
Immunohistochemical Study of Thrombolytic Mechanisms
Authors: BACK N. , HIRAMOTO R. , AMBRUS J. L.
Published: October 2019

The indirect immunofluorescent staining technic has been employed to study the localization onto fibrin clots of components of the fibrinolysin system and its activators. Immunodiffusion technics revealed the heterogeneity of the various enzyme preparations used. The activated fibrinolytic enzyme preparations were found to localize onto and diffuse into the matrix and core of the clots. High degree of localization was seen with streptokinase-, urokinase- and spontaneously activated human plasmin, as well as human plasminogen. Chloroform-activated bovine plasmin localized to a lesser extent. No differences were observed in the results whether the fibrin clots were of human, canine or bovine origin.
Sickle Cell Disease. A Serum Defect in the Thromboplastin Generation Test
Authors: HENSTELL HENRY H. , KLIGERMAN MIRIAM , IRWIN LOWELL E.
Published: October 2019

1. A defective ability of sickle cell disease (SCD) serum to support thromboplastin generation was demonstrated.

2. The serum defect was associated primarily with homozygous SCD, although defects of varying severity were also noted in the heterozygous forms.

3. The deficiency appears to be due to an accelerated loss of thrombin or thrombin-like factors from serum.
Ultrastructural Studies of the May-Hegglin Anomaly
Authors: JORDAN S. W. , LARSEN W. E.
Published: October 2019

One case of May-Hegglin’s anomaly has been described with characteristic findings present also in the mother of the reported case. The propositus showed typical stigmata of the condition: characteristic crescentic, pyroninophilic cytoplasmic patches in a high proportion of polymorphonuclear leukocytes, thrombocytopenia, and giant platelets. The patient’s mother, however, had characteristic patches in only 6 per cent of polymorphonuclear leukocytes and had giant platelets, but was not thrombocytopenic. This is the first patient reported to have such a small proportion of affected polymorphonuclear leukocytes, and suggests that there is variable expression of this genetically determined error of cell differentiation. Other family members did not show hematologic abnormalities.

The ultrastructure of leukocytes and platelets from the propositus was investigated, and it was found that:

1. No ultrastructural abnormalities were identified in the lymphocytes and monocytes.

2. Polymorphonuclear neutrophiles had irregular cytoplasmic areas which lacked specific granules and which contained small granules probably glycogen, 50 Å. diameter filaments, and amorphous densities.

3. The fibrils found in the characteristic patches probably consist of RNA.

4. Platelets have apparently normal ultrastructure, but are twice the normal diameter.
Iron Metabolism in Rats with Phenylhydrazine-Induced Hemolytic Disease
Authors: CONRAD MARCEL E. , WEINTRAUB LEWIS R. , CROSBY WILLIAM H.
Published: October 2019

Increased absorption and excretion of iron were observed in AcPh-treated animals. Enhanced absorption was related to a decrease in the iron content of intestinal epithelial cells and an accelerated plasma iron turnover. Increased excretion of iron from AcPh-treated rats was attributed to an enhanced biliary loss of iron and an increased rate of turnover of the small intestinal epithelium. The balance established between absorption and loss of iron would prevent the accumulation of a massive iron store in this hemolytic disorder.
The Carbohydrate Intermediates of Erythrocytes Deficient in Glucose-6-Phosphate Dehydrogenase
Authors: SHAFER A. WILLIAM
Published: October 2019

The carbohydrate intermediates of erythrocytes were studied before and after incubation for 6 hours at 37 C. A comparison was made between a case of NSHA with G-6-PD deficiency, his mother, a Caucasian and a Negro with G-6-PD deficiency (so-called primaquine sensitivity), and a normal case.

An abnormality of ATP metabolism manifested by a distinct fall in concentration of ATP after incubation was found in the case of NSHA but not in the other cases. This is another demonstration of the heterogeneity of the cases of deficiency of G-6-PD.
Immunologic and Cytogenetic Studies of Chronic Lymphocytic Leukemic Cells
Authors: OPPENHEIM JOOST J. , WHANG JACQUELINE , FREI EMIL
Published: October 2019

The lymphocyte transformation response of 17 chronic lymphocytic leukemia patients when tested in the short-term tissue culture with PHA-M, and PPD was found to be significantly decreased when compared to normal subjects. Serum factors were not found to be responsible for this cellular hyporesponsiveness. The proportions of immunoresponsive lymphocytes found in the patients’ peripheral circulation decreased as their white blood cell count increased. The transformation response to PHA-M was generally better than to PPD. Neither the PPD negative patients nor the normal PPD negative subjects’ cells responded to PPD stimulation in vitro.

Monocytes usually would phagocytize particles added to the cultures and could thus be distinguished from the nonphagocytic proliferating lymphocytes which were the only cells that incorporated thymidine H3. Radioautographs of tritiated thymidine also revealed the rate of PPD lymphocyte transformation to be slower than with PHA-M. There were no significant differences in the proportions or the degree of leukemic and normal transformed lymphocyte labeling with tritiated thymidine.

Cytogenetic studies revealed that the patients’ mitotic indices both in vivo and in vitro were markedly depressed. The modal chromosome number was 46 in each patient, and no cytogenetic abnormalities other than those due to exposure to radiation were found.
Studies of the Reticuloendothelial Mass and Sequestering Function of Rat Bone Marrow
Authors: KEENE WILLIS R. , JANDL JAMES H.
Published: October 2019

Quantitative studies were made in rats of the total reticuloendothelial cell content of bone marrow and of the ability of marrow to sequester antibody-treated red cells, immature red cells and carbon particles. Although normal marrow played a relatively minor role in clearing cells and particles from the blood stream, its clearing activity increased markedly when the marrow was depleted of its blood-forming cells. The greatly enhanced ability of hypoplastic marrow to trap immature red cells suggests that this may be a homeostatic mechanism for repopulating the depleted marrow.

Carbon blockade resulted in decreased liver and spleen uptake of sensitized red cells, but enhanced the marrow uptake. This suggests that marrow sequestration of cells, in contrast to that in the liver and spleen sequestration, is not affected by phagocytic activity.

In their functions and reactions the RE cells of the marrow usually acted in parallel with those of the liver and reciprocally with those of the spleen.
The Action of Two Sulfhydryl Compounds on Normal Human Red Cells
Authors: SIRCHIA GIROLAMO , FERRONE SOLDANO , MERCURIALI FRANCESCO
Published: October 2019

In the paper by G. Sirchia, S. Ferrone and F. Mercuriali: "The Action of Two Sulfhydryl Compounds on Normal Human Red Cells. Relationship to Red Cells of Paroxysmal Nocturnal Hemoglobinuria," published in BLOOD 25:502, 1965, a misprint appears. The first line on page 503 reads "for exactly 19 minutes" instead of "for exactly 9 minutes."
Morphologic and Developmental Differences between the Cells of the Chicken’s Thymus and Bursa of Fabricius
Authors: PETERSON RAYMOND D. A. , GOOD ROBERT A.
Published: October 2019

Apparent functional differences between the chicken’s thymus and bursa, two lymphoepithelial organs considered similar in many ways, have prompted an evaluation of the morphologic and developmental differences between the cells of these two organs. Thymic lymphocytes are well developed prior to the time of hatching, whereas bursal lymphocytes remain large and possibly relatively immature for the duration of the bursa’s existence. These differences may provide a reasonable explanation for the functional differences observed between the bursa and thymus.
The Effect of Differing Demands for Blood Cell Production on DNA Synthesis by Hemopoietic Colony-Forming Cells of Mice
Authors: BECKER A. J. , MCCULLOCH E. A. , SIMINOVITCH L. , TILL J. E.
Published: October 2019

A technic capable of estimating the fraction of hemopoietic colony-forming progenitor cells in DNA synthesis in vivo has been described. The technic is based on the ability of tritiated thymidine to inhibit the growth of those colony-forming cells which, by virtue of their presence in the S-phase during a 20-minute incubation in vitro, in the presence of 500 µc./ml. of H3TdR, have incorporated large amounts of the nucleoside. The method has been applied to transplanted colony-forming cells proliferating in spleens of heavily irradiated recipients as well as to cells from normal fetal liver, normal marrow, and normal spleen. In situations where the hemopoietic system is expanding (fetal liver and regenerating transplants), a large fraction, 40-65 per cent, of the stem cells are in DNA synthesis. In the steady-state situations (adult marrow and spleen), the fraction of cells in DNA synthesis is almost imperceptible using this technic. It is concluded that control mechanisms which govern the rate of hemopoiesis operate, at least in part, by altering the generative cycle of blood-forming progenitor cells.
Analytical Review: Leaky Red Cells
Authors: JANDL JAMES H.
Published: October 2019

The normal survival of red cells requires maintained regulation of cell size and shape. This regulation is to a large extent dependent upon membrane permeability and the active transport of cations. Agents such as C' that affect permeability markedly by creating large holes in the membrane lead to rapid cell death. Most hemolytic disorders thus far studied involve lesser increases in membrane permeability and hemolysis occurs more gradually by the sequence of colloid osmotic swelling, loss of cell surface, and spherocytosis. With very mild permeability changes, as in hereditary spherocytosis, the cell may compensate for an increased leak-rate for cations by increased active transport. This compensation requires increased glycolysis and optimal metabolic conditions, however, and the cell rapidly decompensates during glucose deprivation or metabolic stress. The interaction between reticuloendothelial tissues and red cells provides such a stress for leaky cells and hastens their destruction.
Effects of Large Doses of Androgen on Rodent Erythropoiesis and Body Composition
Authors: NATHAN DAVID G. , GARDNER FRANK H. , Kan Alvera L.
Published: October 2019

Six weeks treatment of male and female mature Sprague-Dawley rats with 8 mg. testosterone enanthate per week produced varied effects depending upon the sex of the animal. Compared to controls, the androgen-treated female rats exhibited a greater gain in body weight which was predominantly water. There was concomitant renal hypertrophy and fat loss. An accelerated rate of erythropoiesis produced a gain in total red cell volume out of proportion to the accretion of lean tissue. Treated male rats gained somewhat less water and lean tissue and much less fat than controls. Definite evidence of acceleration of erythropoiesis was not observed. It is concluded that the female rat is more sensitive to the erythropoietic effects of large doses of androgen than is the male. The erythropoietic response to androgen in the female rat appears to be independent of the effects of the hormone on body composition.
The Philadelphia Chromosome in an Unusual Case of Myeloproliferative Disease
Authors: HEATH CLARK W. , MOLONEY WILLIAM C.
Published: October 2019

In an unusual case of myeloproliferative disease, the Ph1 chromosome was found in association with persistently elevated levels of LAP activity. Clinical findings in this case included marked thrombocytosis, basophilocytosis, absence of splenomegaly and a preceding history of untreated ankylosing spondylitis. Cytogenetic findings were compatible with the existence of the Ph1 chromosome in erythroid and megakaryocytic as well as granulocytic marrow precursors.

This case illustrates the difficulties currently encountered in the clinical differentiation of myeloproliferative disorders and in interpreting the diagnostic significance of the Ph1 chromosome. The co-existence in this case of the Ph1 chromosome and elevated LAP does not support the concept of a direct relationship between Group G chromosomes and LAP activity.
Reticuloendothelial Phagocytic Function in Patients with Leukemia, Lymphoma and Multiple Myeloma
Authors: GROCH GEORGE S. , PERILLIE PASQUALE E. , FINCH STUART C.
Published: October 2019

Reticuloendothelial phagocytic function was studied in a group of patients with leukemia, lymphoma and myeloma utilizing I131-aggregated human serum albumin. The majority of patients with acute leukemia were found to have diminished RES phagocytosis. Increased RES phagocytosis was demonstrated in some patients and appeared to be related to accelerated erythrocyte destruction. Chemotherapy per se had little demonstrable effect on RES phagocytic function.
An Assay for the Mitogenic Activity of Phytohemagglutinin Preparations
Authors: TORMEY DOUGLASS C. , MUELLER GERALD C.
Published: October 2019

The addition of increasing levels of phytohemagglutinin to amethopterin-treated cultures of human lymphocytes results in the induction of DNA synthesis which can be measured by the incorporation of exogenous radioactive thymidine. The graded nature of this response permits the assay of mitogenic activity of such preparations as well as the assessment of antimitogenic factors in sera.
Erythroid Homograft Following Leukocyte Transfusion in a Patient with Acute Leukemia
Authors: LEVIN ROBERT H. , WHANG JACQUELINE , CARBONE PAUL P. , FREIREICH EMIL J.
Published: October 2019

A patient with acute lymphocytic leukemia developed a functioning erythroid homograft after transfusion of leukocytes from donors with chronic myelocytic leukemia. Two donor populations were observed cytogenetically, by examination of the recipient’s marrow for sex and Philadelphia chromosomes. The cells from a female donor of different blood group eventually repopulated the entire bone marrow and were exclusively responsible for the function of the homograft. Although the donor was anemic and required periodic transfusions, her transplanted cells caused normal erythropoiesis in the recipient for a prolonged period. During this time the recipient enjoyed remission of acute leukemia but expired as a result of overwhelming infection. It is proposed that multiple transfusions of leukocytes is a useful technic for treatment of infection, for increasing knowledge of factors influencing hematopoiesis, and for studying approaches to effective immunotherapy of leukemia.
The Effectiveness of Combinations of Antileukemic Agents in Inducing and Maintaining Remission in Children with Acute Leukemia
Authors: FREI EMIL , KARON MYRON , LEVIN ROBERT H. , FREIREICH EMIL J. , TAYLOR ROBERT J. , HANANIAN JULIET , SELAWRY OLEG , HOLLAND JAMES F. , HOOGSTRATEN BARTH , WOLMAN IRVING J. , ABIR ESSHAGH , SAWITSKY ARTHUR , LEE STANLEY , MILLS STEPHAN D. , BURGERT E. OMER , SPURR CHARLES L. , PATTERSON RICHARD B. , EBAUGH FRANKLIN G. , JAMES G. WATSON , MOON JOHN H.
Published: October 2019

1. Combinations of effective agents produce at least an additive increase in complete remission rates over that which can be achieved when the agents are used individually.

2. Patients who do not achieve complete remission with initial treatment have a significantly shorter survival.

3. Alternating MTX and 6-MP at 28-day intervals during remission does not prolong the duration of remission over that of combined concurrent 6-MP and MTX.

4. The administration of folic acid antagonists intrathecally at 28-day intervals during antimetabolite maintained remission did not prolong the duration of remission. Meningeal leukemia, however, occurred significantly less frequently in these patients.

5. The duration of combined 6-MP and MTX maintained remission is not greater than that of 6-MP maintained remission.

6. The toxicity of 6-MP and MTX in combination in patients in remission is additive.

The above conclusions were drawn from this comparative study of combinations of chemotherapeutic agents in children with acute lymphocytic leukemia.
Effect of Anticoagulant and ABO Incompatibility on Recovery of Transfused Human Platelets
Authors: ASTER RICHARD H.
Published: October 2019

The effects of anticoagulant solutions on the recovery of transfused platelets were studied. Citrate anticoagulants at pH 7.4 or pH 6.5 were found to be equally effective in preserving the viability of platelets when centrifugation of the cells was not required. When centrifugation is required, as in most platelet survival studies, citrate at pH 6.5 gives maximum recoveries. Ethylene diamine tetraacetate (EDTA) caused temporary sequestration of nearly all transfused platelets and reduced maximum recoveries by about 50 per cent.

Platelet recovery was lowered by ABO-incompatibility between donor platelets and recipient serum, but survival time of remaining platelets was not altered. Lowest platelet recoveries resulted when group A1 or A1 B platelets were given to group O recipients with high isoagglutinin titers.

It is suggested that ABO-compatible platelets prepared in citrate should be used where possible in the treatment of thromboctyopenic disorders.
A Clinical and Experimental Study of Acquired Inhibitors to Factor VIII
Authors: ROBERTS HAROLD R. , SCALES MARGARET B. , MADISON JOHN T. , WEBSTER WILLIAM P. , PENICK GEORGE D.
Published: October 2019

Factor VIII inhibitors which developed in four patients with hemophilia A are described. These inhibitors are apparently specific for Factor VIII and are capable of inducing a transient hemophilic state when injected into dogs. The genesis, properties, and mode of action of these inhibitors can be explained on an immunologic basis and it seems most likely that they represent an antibody to Factor VIII. One hemophilia A patient, with retroperitoneal hematoma and a potent Factor VIII inhibitor, was successfully treated by an exchange transfusion followed by administration of purified porcine Factor VIII.
The Production of γG-Globulin by Lymphocytes in Chronic Lymphocytic Leukemia
Authors: GAMBLE CHARLES N. , CUTTING HUNTER O.
Published: October 2019

A case of chronic lymphocytic leukemia associated with the excessive production of a monoclonal γG-globulin has been investigated by immunofluorescent technics. Gamma globulin was demonstrated within the cytoplasm of young and mature lymphocytes and these cells were interpreted as the cells of origin of the monoclonal protein. The finding of gamma globulin within the cytoplasm of mature small lymphocytes in the absence of any apparent morphologic relationship with the occasional plasma cells present was interpreted as indicating a population of gamma globulin forming cells distinct from plasma cells, and suggested that a small number of lymphocytes may also contribute to the formation of immunoglobulins under normal conditions. The distribution of the fluorescent lymphocytes in sharply defined small and large cells groups within a lymph node supports the concept of the clonal origin of single molecular species of gamma globulin.
"Hairy" Cells in Blood in Lymphoreticular Neoplastic Disease and "Flagellated" Cells of Normal Lymph Nodes
Authors: SCHREK ROBERT , DONNELLY WILLIAM J.
Published: October 2019

During examinations of viable leukocytes from many leukemic and nonleukemic patients, peculiar cells called "hairy" cells were seen in the blood from 2 patients. These cells were characterized by numerous short, thin villi projecting from the surface of the cells. In one patient, some of these cells had one or more cytoplasmic masses. The nuclei were oval or crescentic, eccentrically placed, and some had small nucleoli. The cells did not flatten on glass, did not phagocytize latex particles, and were resistant to irradiation with 2000 r. The cells were considered to be identical to the neoplastic lymphoid reticulum cells of Mitus et al.1

Both patients with hairy cells had large spleens, moderate anemia, and thrombocytopenia. Radiotherapy of the spleen of one patient resulted in a prompt leukopenia and a delayed decrease in the size of the spleen. This patient is alive and asymptomatic 21 months after diagnosis. The second patient’s thrombocytopenia was relieved by splenectomy. He is asymptomatic now, 11 months after diagnosis. Hairy cells are still present in small numbers in the blood of both patients.

The pathologic hairy cells in the blood were similar to "flagellated" cells seen in suspensions from several hyperplastic lymph nodes. The flagellated cells were relatively few in number, large, with numerous long, thin cytoplasmic projections and round, oval or crescentic nuclei, some of which had small nucleoli. The flagellated cells were resistant to irradiation and probably were identical to the "phagocytic reticular cells" of Sundberg.12
Brief Report: Urinary Excretion of 5-Methyl-Tetrahydrofolate in Man
Authors: McLEAN ANNE , CHANARIN I.
Published: October 2019

Tritium-labeled folic acid was given intravenously to normal male volunteers and the nature of the folate compounds appearing in the urine was studied by column chromatography and microbiologic assay.

Three peaks of activity were obtained and these were due to (a) N10-formyl folate and p-amino-benzoylglutamate, (b) N 5-methyl-tetrahydrofolate, and (c) pteroylglutamic acid. Peaks (a) and (c) were tritium-labeled, but peak (b), containing 5-methyl-tetrahydrofolate, was not tritium-labeled.

It was concluded that between one-quarter to one-third of the folic acid activity in urine following a small parenteral dose was due to 5-methyltetrahydrofolate, but that this arose by displacement from the tissue (presumably liver) and not from the administered dose of folic acid.
Brief Report: B12 Binding Protein Deficiency in Pernicious Anemia
Authors: LAWRENCE CHRISTINE
Published: October 2019

When radioactive B12 was added to normal serum, it was bound predominantly to beta globulin. Deficient binding was observed in the serum of five of ten patients with untreated pernicious anemia. Treatment of these patients with B12 restored the beta globulin B12 binding capacity toward normal.

In one of the five patients there was virtually no beta globulin binding of added B12 before treatment. This patient exhibited a malabsorptive pattern Schilling test when first seen. Treatment with B12 was attended by an increase of beta globulin binding capacity, and by return of the ability to absorb oral B12 when given with intrinsic factor. It is possible that these two abnormalities are related in that the beta globulin may have an important role in the absorption and transport of B12.
Inhibition of Erythropoiesis by a Factor Present in the Plasma of Patients with Erythroblastopenia
Authors: JEPSON JOANNE H. , LOWENSTEIN LOUIS
Published: October 2019

An erythropoietic inhibitor was found in the plasma of each of two patients with erythroblastopenia. Because these plasmas exhibited similar biological behavior to that of antisera to ESF, it is postulated that the inhibitory effect of these plasmas may be due to the formation of antibody directed against ESF.
Origin of Auer Bodies
Authors: FREEMAN JAMES A.
Published: October 2019

Evidence accrued by electron microscopic study of in vitro tissue-cultured leukemic cells supports Ackerman’s histochemical evidence that Auer bodies are formed from azurophilic granules, a circumstance first postulated by Nakashima in 1924. The enzymatic content and structure of these granules conforms to that of lysosomes, according to deDuve’s concept. Therefore the Auer body actually represents an unusual form, or abnormal development, of lysosomes.
Immunofluorescence of Megakaryocytes in the Thrombocytopenic Purpuras
Authors: PIZZI F. , CARRARA P. M. , ALDEGHI A. , ERIDANI S.
Published: October 2019

The fluorescent antibody technic was applied to the study of thrombocytopenic purpuras with a presumable immunologic pathogenesis.

The results of the investigation suggest the hypothesis that some plasma protein material is strongly adherent to the surface of megakaryocytes in more than 50 per cent of cases of chronic ITP.
Studies on the Metabolism of Adenosine and Adenine in Stored and Fresh Human Erythrocytes
Authors: LOWY BERTRAM A. , WILLIAMS MARJORIE K.
Published: October 2019

The metabolism of adenosine-8-C14, at relatively high and low concentrations, was studied in human erythrocytes freshly obtained and after 6 and 9 weeks of storage in ACD. At high adenosine concentration (3.6 µM/ml. cells), considerable conversion to ATP was found in fresh and stored cells, suggesting that direct phosphorylation of adenosine occurred, a reaction that is minimal at low (0.36 µM/ml. cells) adenosine concentration because of extensive rapid deamination. Incorporation of the label via hypoxanthine or adenine is unlikely, since at high adenosine concentration no dilution of ATP labeling in the presence of unlabeled inosine (hypoxanthine) was found, nor was free labeled adenine detected in erythrocyte extracts.

A study of the metabolism of adenine-8-C14 in fresh and stored erythrocytes suggests that the presence of a suitable nucleoside (e.g., inosine) is required for efficient utilization of adenine-8-C14 for ATP formation in the erythrocytes of blood stored for prolonged periods.
Elimination of Chromosome Aberrations from Human Lymphocytes
Authors: NORMAN AMOS , SASAKI M. S. , OTTOMAN R. E. , FINGERHUT A. G.
Published: October 2019

The frequency of chromosome aberrations in the lymphocytes of 36 hematologically normal women who had received radiation therapy for cervical carcinoma was measured. The decrease with time in the frequency of cells with acentric fragments, of cells with a single dicentric, and of quasidiploid cells can each be represented by a single exponential with an average lifetime, respectively, of 530 ± 64 days, 788 ± 98 days, and 5.55 ± 1.23 x 103 days. Aneuploid cells fall into two classes: One contains no chromosomes with structural aberrations and shows a stable frequency of about 5.8 per cent; the other contains chromosomes with structural aberrations and is eliminated at the same rate as cells with acentric chromosome fragments. The distribution of dicentrics among the lymphocytes at the end of the radiation therapy period is similar to that shown by a population of lymphocytes exposed in vitro to a single dose of about 300 rads.
Cytogenetic and Morphologic Abnormalities in Human Bone Marrow Cells during Cytosine Arabinoside Therapy
Authors: BELL WILLIAM R. , WHANG JACQUELINE J. , CARBONE PAUL P. , BRECHER GEORGE , BLOCK JEROME B.
Published: October 2019

The cytogenetic and morphologic abnormalities arising in the bone marrow following therapy with 1-β-D-arabinofuranosylcytosine hydrochloride (cytosine arabinoside) were studied with 10 patients with various neoplasms. A 5-day course of daily, rapid administration of the drug was employed at a dose of 150-200 mg./m2 body surface area. Within 24 hours there was a high incidence of chromosomal aberrations in both granulocytic and erythroid marrow cells. These aberrations consisted of chromatid breaks, erosions, despiralization, precocious separation of the chromatids at the centromeric region, and extensive fragmentation. Prominent morphologic abnormalities were seen in nondividing cells of the erythroid series, but were absent from the granulocytic precursors. Following cessation of cytosine arabinoside therapy, the morphologic and cytogenetic abnormalities rapidly returned to normal. These features were discussed in relation to the known pharmacology of cytosine arabinoside.
Studies on Several Genetic Hematologic Traits of Mexicans
Authors: LISKER RUBÉN , ZARATE GRACIELA , LORIA ALVAR
Published: October 2019

The distribution of abnormal hemoglobins and erythrocytic glucose-6-phosphate dehydrogenase deficiency in 2000 Mexican Indians is described. It is pointed out that the frequency of hemoglobin S and G-6-PD deficiency is low and directly related to Negro admixture. On the other hand, two rare mutants were encountered: hemoglobins Mexico and Chiapas, the former in 2 unrelated subjects. The clinical, hematologic, genetic and biochemical characteristics of Hb Chiapas are described.
Analytical Review: Hemostatic Homeostasis
Authors: SPAET THEODORE H.
Published: October 2019

Preservation of the blood fluidity is a primary prerequisite for the maintenance of the circulation and consequently of life itself. The protection against loss of this fluidity is accordingly most effective. Since blood coagulation is a sequential process involving the successive activation of multiple proenzymes79,80 and since each activated enzyme is subject to neutralization in the plasma and cellular clearance, it must be extremely difficult to achieve a significant degree of activation of the later clotting factors in circulating blood. This interpretation of hemostatic homeostasis provides a theoretical basis for doubting blood coagulation as a continuous generalized process in vivo; it buttresses experimental evidence against the generalized coagulation hypothesis.81 Seen from a different perspective, the above concept of hemostatic homeostasis provides a teleological reason for the complexity of the coagulation process: Since so many steps are required, a great variety of independent mechanisms is available for controlling them, and there is corresponding safety in having the control mechanisms unavailable to total destruction by a single disrupting pathway.
Plasma Cells Containing Iron
Authors: GOODMAN JOSEPH R. , HALL SHIRLEY G. , Gonsalves Mary , Wharran Gordon
Published: October 2019

The presence of iron in plasma cells was demonstrated by light and electron microscopy. The iron compound was identifiable as ferritin in at least one patient. Possible modes of origin, function, and fate of iron in these cells was discussed.
Observations on Certain Enzyme Activities of Normal Human Red Cells Treated with Sulfhydryl Compounds
Authors: SIRCHIA GIROLAMO , FERRONE SOLDANO , MILANI ROBERTO , MERCURIALI FRANCESCO
Published: October 2019

Some enzyme activities of normal human red cells treated with AET and cysteine have been investigated. Treated red cells showed low acetylcholinesterase activity and low O2 uptake in the presence of methylene blue; on the contrary, glucose-6-phosphate-dehydrogenase activity and lactic acid production in the presence of glucose were found to be normal. Results are briefly discussed.
Leukocyte Response following Simultaneous Ionizing and Microwave (Radar) Irradiation
Authors: THOMSON R. A. E. , MICHAELSON S. M. , HOWLAND J. W.
Published: October 2019

Simultaneous microwave and x-irradiation at a sublethal x-ray dose level modify the hematologic response to x-irradiation. Earlier neutrophil recovery and delayed lymphocyte and hematocrit recovery resulted following simultaneous microwave and x-ray exposure.
The Effects of Phytohemagglutinin on Mouse Spleen Cells in Vivo
Authors: GAMBLE CHARLES N.
Published: October 2019

The intravenous injection of absorbed (erythroagglutinin free) PHA in mice resulted in a marked increase in spleen weights, numbers of nucleated spleen cells, and spleen cells in mitosis. The morphologic changes induced in the splenic lymphocytes were striking and closely paralleled the changes observed following the addition of PHA to cultures of human and animal leukocytes. Observations on the absolute numbers of mature lymphocytes and immature lymphoid and blast cells suggest that the proliferative effect of PHA on spleen lymphocytes is due in part to mitosis following blast cell transformation of mature small lymphocytes. PHA also stimulated the normoblasts and granulocytes present in the mouse spleen to proliferate. The normoblasts showed a single early peak of proliferative activity. The granulocytes showed a similar early increase in numbers, but remained elevated for the duration of the experiment. The lymphoid cells showed an early, primary peak of proliferation as well as a later, secondary, smaller peak which preceded the appearance of serum antibody directed against PHA. The findings suggest that PHA acts as both a nonspecific or nonantigenic stimulus and as an antigenic stimulus to the proliferation of spleen lymphoid cells in vivo.
Erythrocyte Mucoids in Acquired Autoimmune Hemolytic Anemia
Authors: TISHKOFF GARSON H.
Published: October 2019

Erythrocyte membrane mucoid composition has been quantitated in 13 normal subjects, 11 subjects with Coombs’ negative hemolytic or blood-loss anemia with reticulocytosis and 7 subjects with acquired autoimmune hemolytic anemia. The stromal protein value was increased in all subjects with anemia and reticulocytosis. The increase in protein paralleled the reticulocyte count. An abnormality of the erythrocyte mucoid composition was observed in acquired autoimmune hemolytic anemia as evidenced by a significant decrease in the fucose to protein ratio. A lesser change was observed in the sialic acid to protein ratio. It is speculated that these changes in membrane mucoid composition may be related to the selective modification of certain red cell, fucose-containing receptors by endogenous enzymes, possibly activated by antigenantibody interaction.
Fast Hemoglobin in Lead Poisoning
Authors: CHARACHE SAMUEL , WEATHERALL DAVID J.
Published: October 2019

1. An electrophoretically fast hemoglobin was found in approximately 40 per cent of preschool children with elevated blood lead levels.

2. Fast hemoglobin was found more often in lead-poisoned patients with hypochromic anemia than in patients with normochromic red cells.

3. Fast hemoglobin differed from hemoglobins produced in vitro by incubation with chromate or oxidized glutathione. It had electrophoretic properties similar to that found in a few patients receiving tolbutamide.

4. Fast hemoglobin could not be differentiated from normal hemoglobin A3 by any technic utilized.

5. Both lead and A3 hemoglobins were heterogeneous molecular species.

6. The mechanisms leading to the production of hemoglobin A3 and lead hemoglobin remain unknown.
The Development of Hodgkin’s Disease and Lymphoma during Anticonvulsant Therapy
Authors: HYMAN GEORGE A. , SOMMERS SHELDON C.
Published: October 2019

1. Six patients in whom Hodgkin’s disease or lymphosarcoma developed during the use of anticonvulsant agents (Dilantin, phenobarbital, Mysoline, Celontin) are reported.

2. The differential diagnosis from pseudolymphoma, the course of these malignant lymphomas, and their therapeutic management are discussed.

3. Based upon information presently available, it could not be determined whether the atypical hyperplasia sometimes observed during anticonvulsant drug therapy is precancerous, or whether these agents may be carcinogenic in certain sensitive individuals.

4. Patients with a seizure disorder who develop lymphoma require standard therapy for both conditions. The anticonvulsant drugs had no evident adverse effect on the course of the lymphoma, although substitution of another agent seems warranted, if possible, for the offending drug.
Characteristics of Cell Proliferation in Four Patients with Untreated Acute Leukemia
Authors: MAUER ALVIN M. , FISHER VIRGINIA
Published: October 2019

The characteristics of proliferation of leukemic cells in four children with untreated acute leukemia have been studied. In all four of these children a population of marrow leukemic cells was found which were dividing with a generation time of about 15 to 20 hours. In two of these patients it was possible to demonstrate that these dividing cells after one or more mitotic divisions became smaller and stopped dividing. In all of these patients 70 per cent or more of the leukemic cells of the marrow and almost all leukemic cells of the blood were nonproliferative at the time of these studies. These nondividing cells would be relatively unaffected by chemotherapeutic agents designed to inhibit cell division.
Brief Report: Factor VIII (AHF) Concentration in pH 6.5 Citrate-Plasma
Authors: MORRISON FRANCIS S.
Published: October 2019

A by-product of the preparation of platelet concentrates, by recently proposed methods, is fresh citrate-plasma at pH 6.5. Because this plasma might be a useful source of Factor VIII, the activity was investigated. Compared to unaltered citrate-plasma, the activity was found to be 54 per cent. However, after incubation with washed fresh erythrocytes the "acidified" plasma had the same Factor VIII activity as the control.

This suggests that, after infusion, pH 6.5 plasma is probably as effective a source of Factor VIII as ordinary ACD-plasma. This conclusion was supported by observations on Factor VIII concentrates prepared by cryoprecipitation. In such preparations additional ACD and pH are eliminated as factors in the assay system. Factor VIII concentration in the precipitates prepared from acidified plasma was found to be as high as in precipitates prepared from untreated plasma.
Erythropoietin in the Urine of Normal and Erythropoietically Abnormal Human Beings
Authors: VAN DYKE DONALD , NOHR MARY LOU , LAWRENCE JOHN H.
Published: October 2019

A standard method of concentrating urinary erythropoietin and a standard assay procedure can be used to demonstrate the hormone in the urine of normal human beings. The eythropoietically active material recovered produced increasing response to increasing dose and was completely neutralized by rabbit serum containing antibodies to human urinary erythropoietin. The average normal man excretes approximately 1 standard A unit of erythropoietin per day and the average normal woman excretes approximately 0.4 units per day. With the exception of one patient with a renal allograft, and normal subjects living at extremely high altitude, the recovery of erythropoietin from the urine has not been found to exceed normal in patients with polycythemia, whether the polycythemia is primary or secondary to renal pathology. Markedly elevated levels of erythropoietin were found in subjects living at extremely high altitude.
A Series of New Screening Procedures for Pyruvate Kinase Deficiency, Glucose-6-Phosphate Dehydrogenase Deficiency, and Glutathione Reductase Deficiency
Authors: BEUTLER ERNEST , Halasz Agnes
Published: October 2019

A new type of screening procedure for the detection of enzymatic defects of the red cell has been described. The blood or red cell sample is added to the reaction mixture. After a suitable period of incubation a drop of the mixture is spotted on filter paper, permitted to dry, and examined for fluorescence under UV light. In this way the oxidation of reduction of pyridine nucleotides is readily evaluated. Reaction mixtures for the detection of glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and glutathione reductase deficiency are described. The same general procedure should be readily adaptable to the detection of other enzymatic deficiencies of red cells, such as phosphogluconate dehydrogenase deficiency or triosephosphate isomerase deficiency.
Cytogenetic and Cytochemical Studies on Marrow Cells in B12 and Folate Deficiency
Authors: MENZIES ROSA C. , CROSSEN PETER E. , FITZGERALD PETER H. , GUNZ FREDERICK W.
Published: October 2019

In order to define the functional defect in marrow cells in B12 and folate deficiency, ten patients were investigated. Chromosome studies showed alterations similar to those produced experimentally by agents interfering with DNA metabolism. Measurements of the DNA content of individual cells in the resting and synthetic stages of the mitotic cycle suggested arrest of DNA synthesis in a proportion of cells, or alternatively prolongation of the S and G2 phases. It was concluded that in these deficiency states changes in the cellular DNA metabolism may cause disturbances during both the mitotic and intermitotic stages of the cell cycle, and that these may account for the deficient production of the various classes of blood cells.