bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphologic and Autoradiographic Observations of H3-Thymidine-Labeled Thoracic Duct Lymphocytes Cultured in Vivo
Authors: SCHOOLEY JOHN C. , BERMAN IRWIN
Published: October 2019

1. The behavior of mouse and rat thoracic duct lymphocytes cultivated in diffusion chambers implanted into the peritoneal cavity of recipient mice and rats has been described.

2. The temporal pattern of labeling of cultured thoracic duct lymphocytes labeled with H3-thymidine has been described. From an analysis of this pattern and the changes in the mean grain count of the different classes of lymphocytes a maximum generation time for large and medium lymphocytes of 15 and 24 hours has been calculated. The results of these experiments favor an origin of small lymphocytes from the division of large and medium lymphocytes.

3. Some evidence for the transformation of thoracic duct lymph cells into monocytoid cells was found. In homologous cultures of labeled thoracic duct lymph cells and unlabeled bone marrow apparent evidence for transformation of labeled cells into plasma cells was found. The data suggest that neither the monocytoid cells nor the plasma cells arose necessarily from small lymphocytes. It was concluded that some unidentified cells, presumably the largest cells which are normally present in thoracic duct lymph, can be transformed into these other cell types when appropriately stimulated.
Carbohydrates of Human and Bovine Platelets
Authors: WOODSIDE E. E. , KOCHOLATY W.
Published: October 2019

1. Average values for the total carbohydrate content of human and bovine platelets were 8.47 and 8.77 per cent of the dry weight, respectively. On a dry weight basis, human platelets were calculated to be approximately one-third larger than bovine platelets. By chemical and chromatographic analysis, glucose, galactose, mannose, fucose, ribose, glucosamine, galactosamine, glucuronic acid and sialic acid were detected in both human and bovine platelets.

2. Glucose and ribose were found to be the only monomers present in the 5 per cent TCA-soluble fractions of both human and bovine platelets. The TCA-insoluble residue contained glucose, galactose, mannose, fucose, ribose, glucuronic acid, glucosamine, galactosamine and sialic acid. The acid mucopolysaccharide fraction of both human and bovine platelets contained galactosamine and glucuronic acid monomers as well as galactose, glucose, and ribose.

3. Glycogen was found in both human and bovine platelets. Total glycogen was extracted by 5 per cent TCA from sonorated human and bovine p1atelets; however, subsequent ethanol precipitation of tile glycogen was incomplete. In contrast, 30 per cent KOH extraction followed by ethanol precipitation resulted in complete recoveries of the glycogen.

4. Variations ill both total hexose and glycogen contents were found in both human and bovine platelets. These variations were partially dependent on the length of storage of the platelets in whole blood or in 0.85 per cent NaCl after separation from whole blood.
Studies in Experimental Eosinophilia. II. Induction of Peritoneal Eosinophilia by the Transfer of Tissues and Tissue Extracts
Authors: LITT MORTIMER
Published: October 2019

Tissues taken from one guinea pig were transferred into the peritoneal cavity of another, and the total number of peritoneal eosinophils in the recipient was determined 24 hours after transfer. Peritoneal eosinophilia resulted in the recipients when peritoneal lining, lungs, blood or serum were taken from an animal previously prepared by repeated injections of foreign protein and transferred along with some of the same protein. With lung, but not with peritoneal lining, some eosinophil responses were noted when the protein used to prepare the donor was omitted, and when either the donor or recipient was a normal animal.

Extracts of peritoneal lining or lung also induced peritoneal eosinophilia. Isolated instances of activity occurred in extracts of normal tissues, but most of the positive responses were induced when extracts from animals previously prepared with foreign protein were accompanied by the same protein.

Eosinophilotactic activity remained inside dialysis bags. It was stable to 56 C. for ½ hour, 4 C. for 24 hours, and -5 C. for two days. The activity disappeared with the removal of trichloracetic acid-precipitable material.

These experiments support the view that eosinophilia may occur in the absence of actively acquired antibody, and that an eosinophilotactic mechanism may be passively transferred from one guinea pig to another.
The Cytologic Reaction of the Spleen in Experimental Amyloidosis in Mice
Authors: ZLOTNICK AVINOAM , TAL CHLOE
Published: October 2019

Seventy W.-H. Swiss line mice were injected with adjuvant, TAB vaccine and TAB vaccine plus adjuvant. The 61 mice which survived form the subject of this study.

Spleen smears and histologic sections taken after completing immunization revealed a marked deposition of amyloid in 48 of the animals. Varying degrees of plasma cell hyperplasia were observed in 46 animals, and increased granulopoiesis in 37. In 28 of the amyloid-bearing animals some of the plasma cells were transformed into "flame cells" which stained faintly positively with PAS and metachromatically with methyl violet.

Electrophoresis of the pooled sera of animals receiving adjuvant alone, TAB plus adjuvant or TAB alone, compared to normal controls, showed decrease in albumine and an increase in the globulin fraction. Animals receiving adjuvant alone showed an increase in the beta globulins, while animals receiving TAB plus adjuvant or TAB alone showed an increase in the gamma globulins.

The relationship between the production of amyloid, plasma cell hyperplasia and the appearance of "flame cells" is discussed.
Busulfan in the Treatment of Chronic Myelocytic Leukemia. The Effect of Long Term Intermittent Therapy
Authors: HAUT A. , ABBOTT W. S. , WINTROBE M. M. , CARTWRIGHT G. E.
Published: October 2019

1. The observations made during the administration of 114 courses of busulfan to 30 patients over a period of seven years are recorded. The responses to initial courses of therapy corresponded with those reported previously. With repeated courses of therapy, subjective improvement, the decline in the number of leukocytes, decrease of anemia and the subsidence of physical signs of the disease were as satisfactory as during the first course but tended to appear later. Patients were ambulatory and most were symptomatically and objectively improved during and after repeated courses as compared to their status beforehand.

2. Remissions were longest when the leukocyte values were 10,000 per cu. mm., or less, at the time busulfan was discontinued. Among such patients, remissions of six months or longer were seen in 85 per cent after the initial course of busulfan but in only 19 per cent after fifth or later courses.

3. Evidence of partial resistance to busulfan was seen in some cases after multiple courses of treatment. Complete resistance occurred in 15 patients upon development of the acute, myeloblastic phase of chronic myelocytic leukemia. When busulfan failed, 6-mercaptopurine and colcemide were temporarily of value; x-ray was not of benefit. After the onset of the acute phase. the median survival was three months. This mode of termination is probably no more frequent (50 per cent of cases) since the advent of busulfan therapy than before.

4. If anemia was not relieved, or a large spleen was not reduced 50 per cent in size following a course of therapy, the prognosis was poor and the acute phase imminent.

5. Thrombocytopenia in early, untreated cases was not necessarily a bad sign, nor was the use of busulfan precluded because of it. However, when thrombocytopenia appeared in a previously treated patient, without other evidence indicating busulfan toxicity, or when it occurred in a patient with three or more years of known disease, it usually presaged the development of the terminal acute phase.

6. Side effects of busulfan were significant in only one patient; this man received 8 milligrams daily, double the usual dose, for eight months and developed glossitis, anhydrosis and alopecia totalis. The major hazard in the use of the drug was the occurrence of pancytopenia. This could be related to excessive dosage.

7. Morbidity was clearly decreased. Longevity (median 42 months) was greater than in Minot’s untreated cases (median 31 months) and at least as great as that achieved by treatment with radioactive phosphorus and x-ray (median 32-41 months). Repeated courses of busulfan are considered to offer an effective and practical palliative form of therapy for chronic myclocytic leukemia, up to the time of appearance of the terminal acute myeloblastic phase.
The Effect of Hemorrhage on Plasma Iron Turnover
Authors: GIRVIN EB C. , OOI SENG KAH , WONG STANLEY PI SHU
Published: October 2019

The plasma iron turnover rate in rats following a single hemorrhage reaches a maximum in about 48 hours and returns to normal between the seventh and tenth day. There is considerable variation in individual rats in both the maximum rate attained and the time required for recovery. No significant difference in response was observed due to the severity of hemorrhage upon removal of 2.7 to 18 per cent of total red cells.
Inhomogeneities in Alkali-Resistant Hemoglobin. Demonstration of Zone Electrophoretic Differences Using a Cationic Detergent Electrolyte
Authors: HOERMAN KIRK CONKLIN
Published: October 2019

Trimethyloctadecyl ammonium chloride, a cationic active detergent electrolyte, when added to starch gels before electrophoresis, caused selected alteration in the migration rates of alkali-resistant hemoglobin. Other red blood cell pigments were not similarly affected. Electrophoretic inhomogeneity of cord blood and thalassemia hemoglobin was noted. New components of cord blood hemoglobin were revealed by the method. A new component in the hemoglobin of cases of severe thalassemia was demonstrated.
Study of Humoral Factors Regulating the Production of Leukocytes. I. Demonstration of a "Neutropoietin" in the Plasma after Administration of Triamcinolone to Rats
Authors: SHEN SHU CHU , HOSHINO TAKASHI
Published: October 2019

Male Wistar rats were divided into 3 groups:

Group I. Rats given the triamcinolone daily by gastric catheter all developed neutrophilia accompanied by lymphopenia.

Group II. Rats given daily intraperitoneal injections of plasma from normal rats manifested no significant alteration in the peripheral blood elements.

Group III. Rats given daily intraperitoneal injections of plasma from rats given triamcinolone invariably developed neutrophilia without lymphopenia.

Studies of the bone marrow of these groups at the end of the experiments revealed increased myeloid:erythroid ratios in Groups I and III but not II.

It is therefore believed that this experiment suggests the existence of a neutrophilia-promoting factor in the plasma following the administration of triamcinolone.
An Attempt to Produce Hypersplenism in the Dog, Using Methylcellulose
Authors: WEISSMAN S. M. , WALDMANN T. A. , LEVIN E. , BERLIN N. I.
Published: October 2019

(1) Hematological and histopathologic changes were studied in dogs and rats after infusions of solutions of methylcellulose.

(2) After 4 to 8 weeks of daily intravenous infusions of 0.6 Gm. of 400 centipoise methylcellulose, the dogs developed moderate anemia with a reduction of the mean red cell volume to 27 ± 4 cc./Kg., compared with 38.6 ± 3 cc./Kg. in the controls, and a reduction in the apparent red cell life span studied with Cr51 from 24 ± 3 days in the controls to 18 ± 3 in the treated animals.

(3) Following the infusions in the dog there was an increase of the mean blood urea nitrogen from 15 mg. per cent to 96 mg. per cent, with only a small increase in the rat.

(4) At necropsy there was foamy cytoplasmic vacuolization throughout the reticuloendothelial systems of both rat and dog. In the dog, the spleens were pale and moderately enlarged. Large cells with vacuolized cytoplasm largely replaced the normal structures of this organ. In the markedly enlarged rat spleen there were islands of methylcellulose-filled cells, surrounded by a rim of lymphocytes and strikingly engorged red pulp.

In the rat there was vacuolization of the renal glomerular cells but no significant change in the tubules or interstitial tissue. In the dogs sacrificed one week after the termination of the methylcellulose infusions, foamy cytoplasmic distention of the glomeruli and interstitial cells and tubular dilatation and cyst formation were noted. Progressive fibrosis and hyalinization of the glomerulus and fibrosis and calcification and lymphocytic infiltration of the interstitial tissue were seen in the kidneys of dogs sacrificed from 3 months to 3 years after termination of the methylcellulose infusions.

(5) Although methylcellulose infusions produce splenomegaly and anemia in the dog, the associated uremia precludes this preparation as a model for the study of hypersplenism.
Hematologic Findings in Children Exposed to A-Bomb Radiation In Utero in Hiroshima
Authors: TAKAMURA TSUGISO , UEDA SHOICHI
Published: October 2019

1. Hematologic findings in in utero atomic bomb irradiated and nonirradiated children of Hiroshima between the years 1950 to 1957 have been compared, and no changes peculiar to the irradiated group were found.

2. Despite several predisposing factors in Japan toward the development of iron deficiency in children, overt anemia was rare and distribution of hemoglobin levels was only slightly lower than those reported in American and European children.

3. Leukocyte levels, irrespective of age of the children, were found to be progressively falling in the children of Hiroshima, whether or not exposure to irradiation had occurred. Thus, by 1957 the values were distinctly lower than those reported for normal children in Japan and the United States. No cause for this change was apparent.
Staining of Leukocytes by the Tetrazolium Method: Correlation of Results with the Leukocyte Count and with the Clinical Classification
Authors: MARCUSE PETER M. , COCHRAN JOAN
Published: October 2019

(1) A method is described for the supravital staining of leukocytes with neotetrazolium chloride, using EDTA as the anticoagulant.

(2) The reaction, as demonstrated by this method, is not dependent on any particular substrate and cannot be regarded as a function of specific dehydrogenase. It permits, however, the direct visualization of endogenous reductase activity.

(3) The results, expressed as the percentage of leukocytes stained, show a relation to leukocytosis. Readings below 20 per cent are infrequently obtained with nonleukemic specimens when the leukocyte count exceeds 13,000/cu.mm. In leukemia low ratings are the rule, even in the presence of a high white blood count. In other diseases, including malignant lymphomas, the number of stained cells roughly parallels the elevation of the white blood count.
Hereditary Methemoglobinemia: A New Variant Exhibiting Dominant Inheritance of Methemoglobin A
Authors: TOWNES PHILIP L. , LOVELL GEORGE R.
Published: October 2019

1. A case of dominantly inherited methemoglobinemia is described.

2. Despite the pattern of autosomal dominant inheritance, the hemoglobin is thus far indistinguishable from methemoglobin A and is considered to be normal rather than one of the subtypes of hemoglobin M.

3. The primary defect is one in which there is a decreased capacity to reduce methemoglobin via the normal glucose dependent pathway.

4. The nature of the specific defect remains to be more completely elucidated but is considered not to result from a deficiency of TPN or DPN methemoglobin reductase.

5. Hereditary methemoglobinemia and hemoglobin M disease are reviewed.
Phospholipid Accumulation in Histiocytes of Splenic Pulp Associated with Thrombocytopenic Purpura
Authors: SALTZSTEIN SIDNEY L.
Published: October 2019

Accumulation of a lipid, histochemically a phospholipid, in the histiocytes of the splenic pulp was observed in seven patients with thrombocytopenic purpura. Six had classical idiopathic thrombocytopenic purpura with abundant megakaryocytes in the bone marrow. Splenectomy resulted in clinical and hematologic remissions in four of these six, continued thrombocytopenia in the fifth, and in the continued requirement of corticosteroid to maintain a reasonably normal platelet count in the sixth. The seventh patient, who died shortly after splenectomy, had marked hypoplasia of megakaryocytes. Similar lipid accumulation was not seen in more than 700 other spleens, removed for a variety of reasons, reviewed in this study. Platelet phagocytosis has been suggested as a source of the lipid.
On the Possibility of Cure of Malignant Lymphoid Tumors. I. Treatment of Autochthonous Lymphoid Tumors in C57BL Mice with Massive Doses of Lymphocytolytic Agents
Authors: KAPLAN HENRY S. , NAGAREDA C. SUSAN
Published: October 2019

Strain C57B1 mice in which thymic lymphosarcomas had been induced with total-body X-radiation were treated, at various times in the course of tumor development, with either hydrocortisone or local X-irradiation. Their survival was compared with that of placebo-treated controls. In other sacrificed control groups, the incidence and extent of lymphoma development at the time of treatment was established by microscopic examination.

Treatment with single massive doses of hydrocortisone or local thymic X-irradiation at 50 or 100 days after lymphoma induction resulted in permanent cure of half or more of the animals. For a given dose, hydrocortisone was equally effective when given at any time interval up to 100 days after the start of lymphoma induction. However, the therapeutic efficacy of hydrocortisone was a significant function of hormone dose, over the range 0.3 to 3.0 mg. In addition to the cure of many animals, significant prolongation of life was noted in animals dying of lymphomas in all of the treated groups.
Synthesis of M Protein by Mouse Myeloma Tumor: Correlation of In Vitro and In Vivo Methods
Authors: TRUAX WAYNE E. , BRAY JUANITA P.
Published: October 2019

1. In vitro incubation of Potter-Pilgrim No. 5563 and No. 5647 mouse myeloma tumors with tritiated-d,l-leucine produced demonstrable radioactivity in the respective myeloma proteins.

2. In vivo inoculation of H3-d,l-leucine in tumor bearing animals showed similar incorporation and in addition showed incorporation of radioactivity into albumin and alpha globulin.

3. It is suggested that the in vitro studies better serve to identify the isolated tissue function in protein synthesis.

4. Mouse myeloma studies confirm previous results in human multiple myeloma and indicate that in vitro incubation of protein producing tissues with H3-d,l-leucine can demonstrate protein synthesis.
Leukocytic Alkaline Phosphatase in Busulfan Induced Remissions of Chronic Granulocytic Leukemia
Authors: XEFTERIS E. , MITUS W. J. , MEDNICOFF I. B. , DAMESHEK WILLIAM
Published: October 2019

The alkaline phosphatase content of mature neutrophils, characteristically low in chronic granulocytic leukemia, became normal in 7 of 12 cases developing full initial remissions as a result of Myleran therapy. The alkaline phosphatase content was also found to be normal in 2 further cases in which these enzyme levels were first estimated with the patients already in full remission. The data presented suggest that the return of the alkaline phosphatase level to normality may presage a lengthy remission.
Hemolysis In Vitro and the Anemia of Leukemia
Authors: CROSBY WILLIAM H. , VULLO CALOGERO , GARRIGA SERGIO
Published: October 2019

Autohemolysis occurs in vitro in the blood of some patients with leukemia and other disseminated neoplastic diseases. It is known that patients with such diseases are frequently anemic and hemolytic disease frequently contributes to the anemia. The present study has demonstrated that the in vitro autohemolytic phenomenon is not necessarily associated with a short red cell life span. This suggests that the abnormality does not damage the red cells while they are in the circulation.
The Use of FE59 and CR51 for Estimating Red Cell Production and Destruction: An Interpretive Review
Authors: STOHLMAN FREDERICK
Published: October 2019

In surveying some of the limitations of studies with Cr51 and Fe59 my purpose has been not to deny their usefulness but to put them in perspective. These technics have made possible many extensions of the fundamental understanding of red cell physiology and iron metabolism. They will continue to be valuable experimental tools. It is hoped that if some of the limitations of isotope technics are considered, the non-experimental use of these isotopes will be confined to situations in which otherwise unavailable information of diagnostic or therapeutic importance can be obtained. Unfortunately isotope technics are used when more conventional means would be adequate or even preferable. An extreme example is the suggestion24 that repeated Fe59 turnover studies might be used to determine the total dose of parenteral iron (as Imferon or saccharated iron oxide) to be given in iron deficiency anemia, pointing out that in so doing the possibility of iatrogenic hemochromatosis could be avoided. The usual calculations for determining dose25 however are not only safer but more accurate.

The use of Fe59 and Cr51 entails some risk, the main hazards being hepatitis, with the use of donor plasma or cells, and the possibility of untoward effects from radiation. An estimate of the risk of hepatitis can be gained from its incidence after transfusion. The radiation hazard is more difficult to assess. Leukemia has occurred after large doses of radiation but the extent of the radiation hazard is unknown from the much smaller doses of radiation employed in the usual isotopes studies. Certainly the risk is not such as to preclude the use of isotopes to obtain information essential for diagnosis. However, when such information can be obtained by other means or when results cannot be adequately interpreted, the use of isotopes in clinical medicine appears unwarranted. In considering the use of isotopes in the doubtful case, the dose of radiation to be delivered should not be thought of as an isolated event but rather as adding to a total radiation dose, which as shown by the British survey28 may be appreciable.
Repeated Plasmapheresis of Blood Donors As a Source of Platelets
Authors: KLIMAN ALLAN , GAYDOS LAWRENCE A. , SCHROEDER LESLIE R. , FREIREICH EMIL J.
Published: October 2019

Repeated plasmapheresis with simple plastic equipment was performed on six normal donors for the purpose of obtaining platelet-rich-plasma. Plasmapheresis was performed at rates of up to 1000 ml. of plasma per week for periods up to three months. The six donors produced a total of 26.5 liters of platelet-rich-plasma, an amount which would have requried 106 separate blood donations had conventional means been used.

No significant changes in hemoglobin, platelets or white cells were observed in the donors and serum protein depletion was minimal. No reactions to intensive plasmapheresis were encountered even when the procedure was abruptly terminated. Repeated donor plasmapheresis is a convenient method for producing large amounts of platelet-rich-plasma and affords a practical means of controlling donor factors in platelet transfusion studies.
The Colchicine Method in the Study of Bone Marrow Cell Proliferation
Authors: CARDINALI GIUSEPPE , CARDINALI GIULIANA , AGRIFOGLIO MARIA F.
Published: October 2019

The rate of metaphase accumulation in the bone marrow cells of AKR mice treated with colchicine was investigated. The influence of this alkaloid on the differential count of the bone marrow cells in these animals was also studied. It was demonstrated that the stathmokinetic effect of colchicine on the bone marrow cells started almost immediately after the administration of the drug. The number of arrested metaphases increased linearly from one-half hour to six hours after the injection of colchicine, and then fell rapidly.

In rats injected with colchicine, the changes in the bone marrow concentration of this compound were followed for eight hours. The colchicine concentrations increased from the first to the fourth hour, and then fell rapidly, reaching the zero level at the eighth hour.

From the results obtained, it appeared that four hours post-injection was the most convenient time for the study of the bone marrow proliferative activity by the colchicine method when 1.2 mg./Kg. of colchicine per body weight was used. The fact that four hours after the injection, a mild decrease in the percentage of mature bone marrow granulocytes was found, may represent a limiting factor, which is, however, of moderate importance in the application of this technic.
pH Dependent Hemolytic Systems. III. The Physical Properties of the Serum Factors Involved, with Some Observations on Their Occurrence in Various Disease States in Man
Authors: YACHNIN STANLEY , GARDNER FRANK H.
Published: October 2019

Agglutinins for various artificially altered red blood cells belong to the class of 19S macroglobulins, which migrate electrophoretically as fast gamma or slow beta globulins. The agglutinin activity of serum for altered red cells is readily destroyed by sulfhydryl compounds. Hemolysins for altered red cells are not readily recoverable from serum fractions prepared by starch block electrophoresis or density gradient ultracentrifugation, but, when present, are found to have the same properties. This information lends credence to the concept of these serum factors as examples of "natural antibody," although the stimulus to their formation is not understood.

The sera from patients with various types of hemolytic anemias and various dysproteinemias including macroglobulinemia were found to contain normal amounts of altered red cell agglutinins and hemolysins.

The sera from three patients with congenital agammaglobulinemia were studied. Two of these sera contained agglutinins and hemolysins for altered red blood cells, as well as isohemolysins and isoagglutinins. The significance of this finding is discussed.

The "T" agglutinin and the agglutinin for periodate-treated red cells, both of which are macroglobulins, have been shown by other workers to be absent from newborn sera. Their inability to cross the placenta can be explained by their large size.
Influence of Spleen on Thrombocytopenia Induced by Humoral Factor(s) of Experimental Hypersplenism
Authors: PÉREZ-TAMAYO RUY , MEJIA SILVIA , MONTFORT IRMGARD
Published: October 2019

The influence of the spleen on the thrombocytopenia induced in normal rats by intragastric administration of humoral factor or factors [HF(s)] was studied. Splenectomized rats showed the same thrombocytopenia associated with administration of HF(s) as rats with intact spleen. Thrombocytopenia established by two separate and disconnected periods of intragastric administration of HF(s) and followed by splenectomy was not modified. It is concluded that the spleen is not required by HF(s) to induce thrombocytopenia in the normal rat, and also that the spleen does not participate in the maintenance of thrombocytopenia observed after discontinuation of HF(s).
S-C Hemoglobin: A Clinical Study
Authors: RIVER GEORGE L. , ROBBINS ANITA B. , SCHWARTZ STEVEN O. , Feldhake Charlotte
Published: October 2019

1. Seventy-five cases of S-C hemoglobin disease were studied, ranging in age from 14 months to 66 years.

2. Pain in the splenic area was the most common presenting complaint, splenomegaly being readily demonstrable in about two-thirds of the cases.

3. Hematuria, epistaxes and concomitant infections occurred with sufficient frequency to suggest a relationship to the underlying S-C disease.

4. Pregancy was tolerated fairly well.

5. Although a number of clinical and hematologic features are suggestive of S-C disease, the diagnosis must still be based on electrophoretic studies of the hemoglobin.
Porphyrin Concentration and Myeloperoxydase Activity in the Tissues of the Shay Chloroma of the Rat
Authors: KELÉNYI GABRIEL , PONGRATZ JULIUS , ORBAN STEPHEN , DEAK GEORG
Published: October 2019

Previous investigations have shown that when cells of the Shay chloro-leukemia of the rat are inoculated into animals of different age subcutaneously, intraperitoneally or intravenously, various forms of chloromatous and leukemic processes develop.

In the present studies, the porphyrin concentration and the myeloperoxydase activity of these various forms were studied by quantitative methods.

It was found that the porphyrin concentration and the myeloperoxydase activity of the tissues show an inverse relationship; i.e., in tissues with high myeloperoxydase activity, porphyrin concentration was low and in those with low myeloperoxydase activity, the porphyrin concentration was high.

Possible causes of the reverse relationship of the two components of the chloroleukemic tissues are discussed.
Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6-Mercaptopurine and Methotrexate
Authors: Frei Emil , Freireich Emil J. , Gehan Edmund , Pinkel Donald , Holland James F. , Selawry Oleg , Haurani Farid , Spurr Charles L. , Hayes Donald M. , James G. Watson , Rothberg Harvey , Sodee D. Bruce , Rundles R. Wayne , Schroeder Leslie R. , Hoogstraten Barth , Wolman Irving J. , Traggis D. G. , Cooper Talbert , Gendel B. R. , Ebaugh Franklin , Taylor Robert
Published: October 2019

The efficacy of three therapeutic programs for acute leukemia were compared. These programs included (1) Methotrexate (Phase I) followed by 6-mercaptopurine (Phase II); (2) 6-mercaptopurine (Phase I) followed by Methotrexate (Phase II); and (3) Combination Therapy, i.e., 6-mercaptopurine given in combination with Methotrexate.

In children with acute lymphocytic leukemia the remission rate was 59 per cent for combination therapy, 47 per cent for 6-mercaptopurine, and 29 per cent for Methotrexate. The better remission rate for combination therapy is consistent with that predicted if it is assumed that 6-mercaptopurine and Methotrexate act independently. The median duration of complete remissions for the three treatments was not different (4 to 5 months). However, long lasting remissions were more frequent in patients receiving combination therapy. The median survival from the onset of therapy to death was 9 months. There were no differences between the three treatment programs as regards survival.

In adults the remission rate was 15 per cent for combination therapy, 21 per cent for 6-mercaptopurine and 7 per cent for Methotrexate. As regards survival in adults, early deaths were more common in patients who received MTX as initial therapy, whereas after 5 months survival was somewhat better in those patients receiving combination therapy.

In both children and adults there was no evidence that prior treatment with one of the antimetabolites altered response to the other antimetabolite. This result differs from those in animal models, and its effect on our concept of the mechanism of resistance is discussed.

Responsiveness to the second course of antimetabolite therapy (Phase II) was as good as that to the first course of treatment. This was true for the remission rate, remission duration, and even for survival when appropriate corrections were made. Thus, responsiveness to drug therapy is maintained as the disease progresses temporally. It may be concluded therefore that new agents can be effectively studied in patients with "late" disease.

Responsiveness to Phase II therapy was independent of responsiveness to Phase I.

The most common and severe toxic manifestations related to the bone marrow and gastrointestinal tract. There were no major differences quantitatively in the toxicity for the three treatment programs in children in spite of the fact that the drugs were given in full dosage in the combination program. Oral ulcers and a generalized erythematous rash occurred significantly more frequently in patients receiving Methotrexate. Jaundice was significantly more frequent in adults and in patients receiving 6-MP.
Methods: A Microelectrophoresis Chamber of Small Volume for Use with Biological Systems
Authors: SEAMAN G. V. F. , HEARD D. H.
Published: October 2019

A cylindrical microelectrophoresis chamber about 1 ml. in volume incorporating silver/silver chloride/potassium chloride electrode systems separated from the viewing compartment by sintered glass discs is described. The apparatus was designed for biological systems and the determination of mobility of red cells in human serum used as an example of its field of application. The apparatus gives reproducible results in good agreement with previous observations.
The Lymphocyte-Like Cell in the Marrow of Rats
Authors: Harris Charles
Published: October 2019

The lymphocyte-like cell of rat marrow is capable of performing as a multipotential cell. It resembles a small lymphocyte, and reacts to the effects of cortisone and thio-TEPA, as do small lymphocytes in other organs, thus should be called a small lymphocyte.

Its sudden appearance in large numbers to occupy almost 50 per cent of the marrow space in suckling rats fourteen days of age can best be explained on the basis of migration of these cells to the marrow from other organs via the blood stream. The rate at which lymphocytosis of the bone marrow occurs in rats is influenced by the size of the suckling litters, and may be related to a non-caloric factor in mother's milk. The small lymphocyte probably represents the inactive phase of a multipotential cell, a dormant cell which can give rise to other cell forms when appropriately stimulated.
Studies on the Erythropoiesis Inhibiting Factor in the Plasma of Animals with Transfusion Polycythemia
Authors: KRZYMOWSKI TADEUSZ , KRZYMOWSKA HALINA
Published: October 2019

Further investigations of the action of polycythemic plasma filtrate were made using Fe59 and with detailed examination of the blood and bone marrow. These studies confirmed the appearance of an active thermostabile plasma factor (erythropoiesis inhibitor) which depressed erythropoiesis in normal rabbits or rats. The plasma obtained from bilaterally nephrectomized sheep subjected to transfusion polycythemia also contained the erythropoiesis inhibitor. Blockade of the reticuloendothelial system using trypan blue, in sheep, induced production of the active substance similar or identical with the erythropoiesis inhibitor produced after transfusion polycythemia.
Investigation of the Defect in a Variant of Hereditary Methemoglobinemia
Authors: TOWNES PHILIP L. , MORRISON MARTIN
Published: October 2019

1. Further evidence has been presented to confirm the fact that the methemoglobin found in a new variant of hereditary methemoglobinemia was normal methemoglobin.

2. The reduced glutathione content of the red cells of this variant was less than 50 per cent of normal.

3. The total glutathione and oxidized glutathione were proportionally deficient.

4. The low glutathione content did not result from abnormal degradation nor lack of adequate reducing mechanisms. The primary defect was considered to be one of inadequate glutathione synthesis.

5. Various enzymes were assayed, including the following: glucose 6-phosphate dehydrogenase, lactic acid dehydrogenase, triosephosphate dehydrogenase, glutathione reductase, glucose 6-phosphate dehydrogenase-glutathione reductase (coupled system) and catalase.

6. This variant of methemoglobinemia was considered to result from inadequate synthesis of glutathione. The deficiency of this essential co-factor apparently results in an impairment of triosephosphate dehydrogenase activity and consequently insufficient reduction of DPN, an essential component of the DPNH-dependent methemoglobin reductase.
Erythroblastopenia (Pure Red Cell Aplasia) in Childhood in Djakarta
Authors: KHO L. K. , ODANG O. , THAJEB S. , MARKUM A. H.
Published: October 2019

Erythroblastopenia or pure red cell aplasia was encountered in 186 children during an observation period of five years in the Pediatric Department in Djakarta, Indonesia. Twenty cases were of the acute type of erythroblastopenia, distinguished by a sudden drop of the hemoglobin content of the blood, reticulocytopenia, and disappearance of the erythroblasts in the bone marrow. Giant red cell precursors (giant reticular cells and proerythroblasts) appeared in the bone marrow. This condition lasted two days to two weeks.

A subacute type of erythroblastopenia with a duration of two weeks to two months was found in 25 cases. The last group consisted of 141 cases of subchronic or chronic erythroblastopenia with a duration of more than two months. Malnutrition, infections and vitamin deficiencies were the main clinical findings in these children. The authors are of the opinion that erythroblastopenia is a maturation arrest of the erythropoietic system caused by protein deficiency and/or temporary deficiencies of one or more erythrocyte maturation or stimulating factors.
Erythroblastopenia (Pure Red Cell Aplasia) in Childhood in Djakarta
Authors: KHO L. K. , ODANG O. , THAJEB S. , MARKUM A. H.
Published: October 2019

In the list of authors’ affiliations following "Erythroblastopenia (Pure Red Cell Aplasia ) in Childhood in Djakarta," which appeared in the February BLOOD (Vol. XIX, No. 2, pp. 168-180), it was erroneously stated that Dr. S. Thajeb was formerly Director of the Army Blood Center in Djakarta. We have been informed that Dr. Thajeb still holds that position.
Influence of Several Hormones on Erythropoiesis and Oxygen Consumption in the Hypophysectomized Rat
Authors: FISHER JAMES W. , CROOK JERRY J.
Published: October 2019

Adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), adrenocortical extract (ACE), hydrocortisone (F), corticosterone (B), 11-dehydrocorticosterone and 3,5,3'-triiodothyronine (T-3) induced a moderate to marked erythropoietic effect in the hypophysectomized rat as indicated by an increase in both Fe59 incorporation in RBC and total circulating red cell volume. A corresponding increase in oxygen consumption was also observed. Angiotensin increased red cell volume and radioactive iron incorporation in RBC of hypophysectomized rats and stimulated Fe59 incorporation in hypophysectomized-adrenalectomized rats, but did not exert a significant effect on oxygen consumption. Cobalt injections resulted in a significant increase in red cell volume and Fe59 incorporation in RBC of hypophysectomized rats, but produced a significant decrease in oxygen consumption. The significance of these findings is discussed.
Fluorescence of Megakaryocytes in Idiopathic Thrombocytopenic Purpura (ITP) Stained with Fluorescent Antiglobulin Serum
Authors: MCKENNA JAMES L. , PISCIOTTA ANTHONY V. , Hinz Jean
Published: October 2019

1. A technic is described for the direct and indirect visualization of affinity between fluorescein labeled antiglobulin serum and megakaryocytes.

2. Fluorescent megakaryocytes have been found with this technic in the marrow of some patients with chronic ITP, but not in acute ITP. It was possiple to confer fluorescence on normal megakaryocytes by incubating them with sera from patients with chronic ITP, and from a woman who had a child with neonatal thrombocytopenia.

3. Similar reactions were noted in three patients with systemic lupus erythematosus.

4. These findings indicate adherence of a humoral substance (antibody?) for megakaryocytes, which may have etiologic significance in chronic ITP.
The use of photo-electric turbidometry in the determination of red cell counts, hematocrits, and hemoglobin
Authors: WHITLOCK J. H.
Published: October 2019

A communication from Dr. J. H. Whitlock (The use of photo-electric turbidometry in the determination of red cell counts, hematocrits, and hemoglobin. Blood 2: 463, September 1947) states that he has the D.V.M. and M.S., but not the Ph.D. as used erroneously after his name on the title page of the article.
Experimental Studies on Erythropoietin. II. The Relationship between Juxtaglomerular Cells and Erythropoietin
Authors: HIRASHIMA KUNITAKE , TAKAKU FUMIMARO
Published: October 2019

The relationship between erythropoietin production and the juxtaglomerular (JG) cells of the kidney were studied using Harada’s method for staining and Hartroft’s method for estimating JG granularity.

In stimulated erythropoiesis (after bleeding and phenylhydrazine injection), the JG cells also showed hypergranularity. In depressed erythropoiesis, on the contrary, the JG cells showed hypogranularity. Furthermore, from the observation of the chronological change of the JG cell, granularity tended to change in parallel with erythropoietin production. This study gave an indirect evidence of the secretion of erythropoietin by juxtaglomerular cells of the kidney.
The Familial Aplastic Crisis in Hereditary Spherocytosis. Urocanic Acid and Formiminoglutamic Acid Excretion Studies in a Case with Megaloblastic Arrest
Authors: CHANARIN I. , BURMAN D. , BENNETT MYRA C.
Published: October 2019

A case of herditary spherocytosis who presented with an aregenerative crisis is reported. Evidence of megaloblastic hemopoiesis was present and was accompanied by the urinary excretion of large amounts of urocanic acid following oral dose of histidine hydrochloride. The severe illness in this patient was accompanied by a reticulocytopenia in a younger sister who, however, remained well clinically.
Chromatography of Red Cell Hemolysate
Authors: ANGELETTI PIETRO U. , GAYLE R.
Published: October 2019

Column chromatography on DEAE-cellulose has been used to fractionate red cell homolysates. Under the experimental conditions described above, hemoglobin is not bound to the column and is eluted by the starting buffer. Upon gradient salt elution other proteins are fractionated in a number of peaks. Some enzyme activities were localized in the chromatograms; acidphosphatase appeared in three distinct chromatographic forms with different enzymatic properties.
The Determination and Evaluation of Capillary Resistance—A Review of Methodology
Authors: KRAMÁR JENÖ
Published: October 2019

In view of the uncertainty and inadequacy still prevailing in the routine determination and interpretation of capillary resistance, the problem has been analyzed in the hope of contributing to a much needed improvement.

(1) The pressure and suction methods have been compared and a good correlation found. A study of the mechanisms involved reveals that both methods rest upon a common underlying mechanism. The suction method is in reality a miniature pressure method.

(2) Scrutiny of the merits and shortcomings of the two methods leads to the conclusion that the pressure method can serve only for crude estimations of capillary resistance. Detailed clinical studies of capillary resistance requiring repeated accurate measurements at short intervals, as well as experimental animal studies, necessitate the suction method as the obvious method of choice.

(3) The three main causes of the present undesirable situation in this field are discussed: lack of standardization; inadequate realization of the pitfalls of testing; and erroneous interpretation of findings.
Electronic Measurement of Cellular Volumes. I. Calibration of the Apparatus
Authors: LUSHBAUGH C. C. , MADDY J. A. , BASMANN N. J.
Published: October 2019

A 100-channel pulse height analyzer with automatic read-out mechanisms, in conjunction with an electronic particle counter, makes possible the defermination of frequency distribution curves of red cell volumes in individual patients in 6 minutes. The apparatus can be standardized so that pulse heights are converted mathematically and visually into µ3 without the necessity of hematocrits. Conversion factors have been developed which enable the operator to report his results in terms of analyzer channel volume, pulse height, cellular volume, or relative magnification. The method should have the same clinical applications as Price-Jones’ curves.
Comparison of Chromosome Constitution in Chronic Myelocytic Leukemia and Other Myeloproliferative Disorders
Authors: SANDBERG AVERY A. , ISHIHARA TAKAAKI , CROSSWHITE LOIS H. , HAUSCHKA THEODORE S.
Published: October 2019

The frequency of the Ph1 chromosome in freshly aspirated marrow cells of 14 patients with typical chronic myelocytic leukemia processed by a "direct technic" without resort to culture or colchicine was significantly higher (> 75 per cent) than that observed in the cultured blood cells (< 35 per cent) of the same subjects. The karyotypic abnormally of the abbreviated G-group chromosome would appear not to be related to therapy, since the frequency with which it occurred was not materially affected by treatment (including radiation). The Ph1 chromosome was not observed in any of the metaphases of blood or marrow of 12 subjects who had developed a leukemia-like picture complicating either myelofibrosis, polycythemia vera or myeloid metaplasia. A new chromosome abnormality—a shortened D-group chromosome—was observed with about the same frequency in the blood and marrow metaphases of a female patient with treated chronic myelocytic leukemia. This new karyotypic abnormality was associated with the highest frequency of the Ph1 chromosome in cultured blood cells in the group studied. The Ph1 chromosome was observed in the metaphases of a patient with the blastic phase of chronic myelocytic leukemia. The variations of the morphology of the Ph1 chromosome are discussed and illustrated, especially in relation to the Y-chromosome. In four patients with an atypical picture of CML, the Ph1 chromosome was not observed either in the marrow or cultured blood.
"Monocytic" Cells of Normal Blood, Schilling and Naegeli Leukemia, and Leukemic Reticuloendotheliosis in Slide Chambers
Authors: RABINOWITZ YALE , SCHREK ROBERT
Published: October 2019

1. The study of living blood cells in slide chambers by phase microscopy and cinemicrography adds useful morphologic, developmental and physiologic data complementary to other methods for studying blood cells.

2. Normal monocytes were characterized by flattening in fresh serum with minimal ameboid motility, by ectoplasmic veils waving in the medium, and by transformation to fully developed macrophages in 5-7 days.

3. Cells from four patients with acute monocytic leukemia (Schilling type) showed only slight differences in morphology, development and function from normal monocytes in the slide chamber.

4. Monocytoid cells from four patients with myelomonocytic leukemia (Naegeli type), in the slide chamber, resembled those from two patients with leukemic reticuloendotheliosis in morphology, development and function, but differed from normal monocytes and cells of acute monocytic (Schilling) leukemia. The monocytoid cells were labeled "reticulum" cells with the implication that they were related to the primitive hematopoietic reticulum cell.

5. The "reticulum" cell in the slide chamber differed from the monocyte in having a coarse nuclear chromatin pattern with clumping of chromatin, larger numbers of varying sized cytoplasmic granules, less ectoplasm, development of characteristic star-shaped macrophage forms without ectoplasmic veils, and in exhibiting a considerable ameboid motility as opposed to the sluggish veil waving of the monocyte.

6. Speculation as to the significance of the "reticulum" cell has been presented with the suggestion that this cell precedes the blast cell in hematopoiesis. In Naegeli leukemia, unknown factors may cause alterations in the type of cell released from the marrow. There may also be shifts in emphasis between myeloblast and pre-myeloblast proliferation which become reflected in the cells appearing in the peripheral blood.
Red Cell Preservation: Further Studies with Adenine
Authors: SIMON ERNEST R. , Momoda George S.
Published: October 2019

Supplementation of the ACD-preservative with small amounts of adenine (0.5 µM per ml. amounting to 37 mg. of the base or 56 mg. of adenine sulfate per 550 ml. unit of blood) preserved satisfactory viability (post-transfusion survival greater than 70 per cent) of stored human red cells for 5 to 6 weeks. In the concentrations used, the addition of guanine, cytidine or uridine, alone or in combination with adenine, had little or no effect in extending viability. Hypoxanthine, even in large amounts, did not appear to be toxic to the stored cells. Preservation of viability after 6 weeks of refrigerated storage may be somewhat improved by storage in certain plastic containers as compared with glass.