bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF THE PARENTERAL INJECTION OF EPINEPHRIN ON LEUKOCYTE COUNTS IN NORMAL SUBJECTS AND IN PATIENTS WITH ADDISON’S DISEASE
Authors: GABRILOVE JACQUES L. , VOLTERRA MARIO , JACOBS MILDRED D. , SOFFER LOUIS J. 
Published: October 2019

Abstract
Ten normal subjects and 11 patients with Addison’s disease were studied as to their leukocyte response following the subcutaneous administration of epinephrin. The pattern of response was found to be similar in both groups, diphasic curves being noted. In general, the patients with Addison’s disease differ from normal individuals in having: (1) a lower and less labile white count, (2) a lower and less labile neutrophile count, (3) a higher lymphocyte count, (4) a slightly lesser percentage fall in absolute number of lymphocytes, and (5) a higher lymphocyte percentage.
The use of this method to demonstrate adrenal cortical destruction is not feasible with the dosage of epinephrin employed in this study.
STUDIES OF BLOOD PASSED THROUGH AN ARTIFICIAL KIDNEY
Authors: DE LEEUW NANNIE K. M. , BLAUSTEIN A. 
Published: October 2019

Abstract
1. In vitro blood studies using the artificial kidney are discussed in detail.
2. In vitro experiments in which samples of blood in cellophane tubing are rotated on the drum showed a diminution in the red cell volume, leukocyte and platelet counts.
Dilution, caused by the passage of the dialyzing fluid through the cellophane membrane and by the presence of some of the rinsing fluid, and rotation of the drum are factors of importance in this regard.
3. The influence of heparin and the chemotactic role of cellophane on the leukocytes are discussed.
Heparin in concentration of 1 mg./10 cc. of blood causes in vitro agglutination and disintegration of leukocytes after approximately one hour.
Photographs are shown that demonstrate coating of the cellophane by granulocytes. This is in keeping with the findings of Chambers and Grand that cellophane exerts a positive chemotactic influence on the granulocytes.
4. Hypersegmentation of the leukocytes was noted in samples of blood rotated on the drum for fifteen minutes. Exteriorization and slow speed centrifugation probably account for this phenomenon.
A METHOD FOR THE RAPID SEPARATION OF LEUKOCYTES AND NUCLEATED ERYTHROCYTES FROM BLOOD OR MARROW WITH A PHYTOHEMAGGLUTININ FROM RED BEANS (PHASEOLUS VULGARIS)
Authors: LI JONAH G. , OSGOOD EDWIN E. 
Published: October 2019

Abstract
A method is described for rapid and efficient separation of leukocytes and nucleated erythrocytes from blood or marrow. It is based on the rediscovery of a nontoxic hemagglutinin, isolated from common red or navy beans, which agglutinates all human erythrocytes and those of the animals which have been tested with it. The time from drawing the blood to complete separation of the cells is less than ten minutes. The cells remain in suspension in their own plasma and are countable. Negligible amounts of foreign material are introduced, a great advantage in chemical studies. The cells so isolated are living and suitable for culture studies. Any volume of blood from less than 1 ml. to over 500 ml. may be processed. In marrow nucleated erythrocytes are separated with the leukocytes and in their original porportions. The volume, motility, morphology and life span of the cells in cultures are not altered by addition of the bean extract.
A FACTOR IN SERUM WHICH ACCELERATES THE CONVERSION OF PROTHROMBIN TO THROMBIN
Authors: ALEXANDER BENJAMIN , DE VRIES ANDRE , ADDELSON EUNICE 
Published: October 2019

Abstract
The sera from thrombocytopenic blood show abnormally large residual prothrombin activity and small amounts of prothrombin conversion accelerator. The addition of normal platelets or thromboplastin corrects these abnormalities. In one subject the clotting defect persisted despite temporary remission of the thrombocytopenia consequent to splenectomy.
LYMPHATIC LEUKEMIA AND LYMPHATIC LEUKEMOID STATES IN CANCER OF THE STOMACH
Authors: BICHEL JØRGEN 
Published: October 2019

Abstract
The author reports the case of a patient with chronic lymphatic leukemia, who after some years developed dyspeptic symptoms, increasing cachexia, and eventually died. The leukemia had been subleukemic for several years. Necropsy revealed an adenocarcinoma of the pylorus and lymphatic leukemic changes in the lymph nodes, spleen and liver. In two other cases a lymphatic leukemic blood picture and clinical signs of leukemia (including lymph node enlargements and leukemic changes in the bone marrow) gradually disappeared as tumors of the stomach developed, and in both cases the leukemic blood picture was replaced by a state of lymphopenia. In one of them, the necropsy revealed an adenocarcinoma of the pylorus; in the other, necropsy could not be obtained, but the clinical picture and the radioscopic examinations strongly suggested carcinoma of the stomach in this case, too. These last two cases must be interpreted as lymphatic leukemoid states produced by the presence of the carcinomatous neoplasms, though the possibility can not be excluded that certain carcinomas of the gastrointestinal tract may be capable of primarily or secondarily exercising an inhibitory influence on the leukemic processes.
In connection with the report of these cases, the author reviews the cases from the literature, of lymphatic reactions in cancer and of the coexistence of lymphatic leukemia and cancer in the same individual.
LYMPHOCYTIC LEUKEMOID REACTION OF THE BLOOD ASSOCIATED WITH MILIARY TUBERCULOSIS
Authors: GARDNER FRANK H. , METTIER STACY R. 
Published: October 2019

Abstract
Two cases of miliary tuberculosis that were diagnosed clinically as lymphocytic leukemia are presented. Both cases had evidence of chronic tuberculosis which was of 43 years’ duration in Case 1 and of 28 years’ duration in Case 2. Both patients had granulocytopenia and anemia.
Autopsy findings revealed no evidence of leukemic infiltration, but a diffuse miliary tuberculosis, involving all of the hematopoietic tissues, existed in both Cases.
PERNICIOUS ANEMIA AND RELATED ANEMIAS TREATED WITH VITAMIN B12
Authors: JONES EDGAR , DARBY WILLIAM J. , TOTTER JOHN R. 
Published: October 2019

Abstract
Eleven cases treated with vitamin B12 have been presented. Eight patients with pernicious anemia in relapse responded hematologically. Two patients with mild neurologic involvement were relieved by therapy with B12 alone.
Consideration of the quantities of the crystalline vitamin required to promote maximal erythropoiesis in pernicious anemia indicates that less than about 0.75 µg. daily in doses at intervals of several days will not suffice to establish and maintain blood values as high as does adequate treatment with liver extract. Parenteral daily doses of 1.0 µg. promoted good erythropoiesis in one patient, although it appears that the maximum rate of hemopoiesis may require the initial average daily dose of approximately 3.0 µg.
The reticulocyte count is an unreliable quantitative criterion of activity or adequacy of therapy.
It is suggested that hemopoietic factors in addition to PGA and B12 may be required by some patients to obtain maximal erythrocyte levels.
Vitamin B12, as well as PGA, effects a reduction in the fecal urobilinogen output of patients with pernicious anemia. The significance of this finding is discussed.
No change in urinary excretion of pteroylglutamate or of porphyrin was detected in patients treated with vitamin B12.
Production of Erythrogenin by Organ Cultures of Rat Kidney
Authors: Sherwood J. B. , Robinson S. H. , Bassan L. R. , Rosen S. , Gordon A. S. 
Published: October 2019

Abstract
Organ cultures of rat kidney produce a factor capable of stimulating erythropoiesis in exhypoxic polycythemic mice. This material appears to be renal erythropoietic factor or erythrogenin, since biologic activity was observed only after incubation of the culture media with rat serum. Production of this material was similar in cultures prepared from four different anatomic regions of the kidney, suggesting that erythrogenin may be produced diffusely throughout this organ. Production of erythrogenin was usually insignificant during the first 3½ days in culture but became significant in all four anatomic regions during the second 3½ days. Histologic evaluation of the explants revealed primarily autolysis in the early period followed by the development of epithelial elements, many of which comprised renal tubular structures, during the later culture interval. The newly developed cells had a markedly hypertrophic Golgi apparatus, extensive rough-surfaced endoplasmic reticulum, and numerous polyribosomes, findings consistent with active protein synthesis. This organ culture technique provides direct evidence that the kidney produces an erythropoietic factor and represents a promising model for future studies of this problem.
Treatment of Advanced Malignant Lymphomas With Bleomycin
Authors: Rudders Richard A. 
Published: October 2019

Abstract
Bleomycin, a new antitumor agent reported to lack myelotoxicity, was administered to 43 patients with disseminated refractory lymphomas. Either a weekly or daily regimen was used and in order to minimize the possibility of pulmonary toxicity, the total cumulative dose limited to 5 mg/kg. In 37 evaluable patients objective > 50% responses were observed in 18 (49%). Three patients are still in unmaintained complete remission after 6-9 mo and a fourth relapsed after 13 mo. Myelotoxicity was conspicuously uncommon and serious pulmonary toxicity occurred in only one patient. Bleomycin has significant activity in the malignant lymphomas and its unique toxic properties make it ideally suited for combined use with other standard agents or singly in previously treated patients, particularly those with marrow depression.
The Estrous Cycle and the Hemopoietic Stem Cell in the Mouse
Authors: Lord Brian I. , Murphy Martin J. 
Published: October 2019

Abstract
A large variability in the stem cell content of the spleens of female mice by comparison with that of the bone marrow, or with that of the spleen and bone marrow of male mice, is demonstrated. This variability is shown to be associated with the estrous cycle. Stem cells are assayed by the spleen colony-forming test, either exogenously by transplantation to irradiated recipient mice, or endogenously by colony development in sublethally irradiated female mice. It is shown that, for mice in pre-estrus, the spleens contain up to three times as many hemopoietic stem cells (CFU) as during the estrus and post-estrus stages of the cycle. Although the association may be indirect, it is suggested that the changes in splenic stem cell numbers may be related to the hormonal milieu at the time of observation.
Freeze-Etching Studies of Human Platelets
Authors: Hoak John C. 
Published: October 2019

Abstract
The freeze-etching technique was used to study morphologic features of normal human platelets. A well-developed canalicular system was demonstrated within the platelet, with communication to the plasma surface of the platelets and with direct contact of the canaliculi with organelles. Cross-section fractures of granules revealed compartmentalization in some while others appeared homogeneous. Several types of filamentous structures were observed within the matrix of the platelet. Microtubular subfilaments were approximately 80 Å in diameter. Microfilaments were observed in other areas of platelets and had a diameter of 50-70 Å, a size consistent with that described for actinoid filaments. The interior of the platelet membrane contained 85-Å particles, while the membrane surface had a more granular appearance. Earlier morphologic descriptions of platelets prepared by fixation methods have been confirmed and expanded with this technique.
A Light and Electron Microscopic Study of the Lymphomyeloid Complex in Hypervitaminosis A
Authors: Polliack Aaron , Drexler Ruth 
Published: October 2019

Abstract
Prolonged administration of vitamin A to guinea pigs caused lymphomonocytosis and marked changes in organs of the lymphomyeloid complex, with proliferation of atypical mononuclear cells in the spleen, lymph nodes, and liver. In the bone marrow, atypical mononuclear cell proliferation was also encountered and represented 13% of the entire marrow cell population in some animals. Electron microscopic examination of the marrow revealed many lymphocytes and plasma cells with a well-developed rough endoplasmic reticulum (RER), suggesting that these cells are active in protein synthesis and antibody production. The atypical mononuclear cells described appeared to belong to the monocytic series and contained a variety of dense bodies, and a well-developed RER and Golgi apparatus. Vitamin A is mitogenic, labilizes lysosomal and cell membranes, and can act as an adjuvant enhancing immune responses. It has been suggested that vitamin A alters lymphoid cell membranes and enhances the degree of immune response by stimulation of cell division in immunologically competent cells. The lesions described here may well be the morphologic counterpart of an enhanced cellular immune response.
The Effect of Neutropenia on Myeloid Growth and the Stem Cell in an In Vivo Culture System
Authors: Tyler W. S. , Niskanen Eero , Stohlman Frederick , Keane Jane , Edward Donald 
Published: October 2019

Abstract
An in vivo diffusion chamber (DC) culture technique was used to evaluate the role of circulating humoral factors in the control of myelopoiesis. Normal mouse bone marrow cell suspensions sealed in DC’s were implanted intraperitoneally into mice or rats rendered neutropenic by pretreatment with cyclophosphamide, and the growth of cells in the DC’s was evaluated at intervals thereafter. When marrow was cultured in hosts with graded neutropenia, a dose-related augmentation of myelopoiesis was demonstrated. The growth of macrophages and of pluripotent stem cells, measured by the spleen colony-forming technique, was also enhanced by culture in neutropenic hosts. These data provide further evidence that the rate of myelopoiesis is influenced by a circulating humoral factor. They further suggest that a humoral or hormonal factor is important in control of the pluripotent stem cell population.
The Liver as a Source of Extrarenal Erythropoietin Production
Authors: Fried Walter 
Published: October 2019

Abstract
Nephrectomized rats exposed to intense hypoxia produce sufficient erythropoietin (Ep) to detectably increase their plasma Ep titers. Extrarenal Ep production is no longer detectable if nephrectomized rats are also subjected to 80% hepatectomy prior to being made hypoxic at 0.465 atmos and is barely detectable but significantly lower than in nephrectomized rats when exposed to 0.435 atmos. These results suggest that the liver plays an important role in the production of extrarenal erythropoietin.
Incidence of Monoclonal Proteins in a Minnesota Community With a Cluster of Multiple Myeloma
Authors: Kyle Robert A. , Finkelstein Sidney , Elveback Lila R. , Kurland Leonard T. 
Published: October 2019

Abstract
Multiple myeloma was diagnosed in six residents of Thief River Falls, Minn. in 1968 (a rate of 84/100,000). A survey of the normal population for monoclonal serum protein peaks was undertaken in 1969. Serum from 1200 residents of the city, who were 50 yr of age or older, was collected. Fifteen (1.25%) had monoclonal serum protein peaks: IgG in 11, IgA in one, and IgM in three, with kappa in 11 and lambda in four. No clinical, laboratory, or roentgenographic evidence of myeloma or macroglobulinemia was found in any of the patients. The incidence of monoclonal serum protein peaks is similar to that reported from Sweden. It was concluded that there was no significant increase in monoclonal proteins in the population of Thief River Falls. The 1968 socalled epidemic of multiple myeloma in Thief River Falls remains unexplained.
Erythroblastic Differentiation of Stem Cells in Hemopoietic Colonies
Authors: DeGowin Richard L. , Hoak John C. , Miller Suzanne H. 
Published: October 2019

Abstract
An early phase of cellular replication precedes the initiation of erythropoiesis in hemopoietic spleen colonies of mice receiving a supralethal split-dose of irradiation, first with the leg shielded and then followed by leg irradiation 3 hr later. Previous studies indicated that this proliferative phase represents the repopulation of a depleted, endogenous stem cell compartment. To label replicating stem cells, tritiated thymidine (3HTdR) was injected intraperitoneally in mice on days 1-4 after irradiation. Touch preparations and autoradiograms of splenic colony cells were examined with light and electron microscopy from 2 to 4 days after irradiation and 5-8 days later, when erythroblasts and other differentiated cells first appeared. Replicating mononuclear cells that were pulse labeled during the early proliferative phase of stem cell renewal resembled medium- to large-sized leptochromatic lymphocytes. Electron microscopic examination of autoradiograms demonstrated a labeled undifferentiated cell with a thin rim of nuclear heterochromatin. Sequential studies showed that the injection of 3HTdR on days 1-4, when only the mononuclear cells were present, resulted in labeled erythroblasts and other differentiated cells on days 5 and 6. These results confirm the presence of an early proliferative phase in endogenous splenic hemopoietic colonies and strongly suggest that mononuclear cells, replicating during this period of self-renewal of the stem cell compartment, transform to erythroblasts and other cells.
Marrow Transplantation and Iron Therapy in Mouse Hereditary Microcytic Anemia
Authors: Harrison David E. 
Published: October 2019

Abstract
The defective tissues causing the microcytic anemia in mk/mk mice have been studied by transplantation of marrow erythrocyte precursors into lethally irradiated recipients. Microcytic (mk/mk) marrow in irradiated normal mice produced erythrocyte parameters, blood values, spleen/body weight ratios, and reticulocyte percentages characteristic of the microcytic anemia, but splenic iron stores remained high. Normal marrow in irradiated microcytic mice produced erythrocyte parameters intermediate between microcytic and normal and, combined with iron injections, produced normal erythrocyte parameters, blood values, spleen/body weight ratios, and reticulocyte percentages; long-term splenic iron stores remained low. Iron injections did not improve blood values of either irradiated normal mice implanted with microcytic marrow or untreated microcytic mice. Microcytic mice injected with iron recovered more rapidly from repeated severe bleedings than did uninjected microcytic mice, but iron injections made no difference in final blood values reached. Only slightly less 59Fe remained in mk/mk than in normal mice 22 days after injection. These results indicate that not only the erythrocyte precursor cells but also iron supplies to these cells and splenic iron stores are defective in microcytic mice and that iron loss is not responsible for the iron storage defect.
Growth of Human Bone Marrow in Liquid Culture
Authors: Golde David W. , Cline Martin J. 
Published: October 2019

Abstract
A system for the cultivation of normal and malignant human bone marrow cells in liquid medium is described. The apparatus used is an in vitro diffusion chamber in which cells grow in suspension and upon a dialysis membrane. Proliferation and maturation of normal granulocytes and macrophages were sustained in culture for several weeks in the absence of exogenous stimulating substances. Cell replication was documented by a rise in viable counts, 3H-thymidine incorporation, and labeled mitoses. The entire maturational sequence of the granulocyte and macrophage series was identified in culture, and the cells were characterized by light and electron microscopy, cytochemical properties, phagocytic ability, and the presence of surface receptors for IgG. Nucleated red cell precursors were observed in some cultures for up to 11 days. Malignant cells from patients with various hematologic neoplasms were also successfully cultured. With this system human myeloma cells were maintained in culture for up to 3 wk on primary explant, and continued to synthesize immunoglobulin. The in vitro diffusion chamber technique permits the cultivation of normal human bone marrow cells in liquid medium and provides a convenient means for studying normal and neoplastic hematopoietic cell differentiation and function in short-term culture.
The Hemagglutination-inhibition Assay for Thrombopoietin
Authors: McDonald T. P. 
Published: October 2019

Abstract
A sensitive immunoassay procedure for the detection of the thrombopoietic-stimulating factor (TSF) has been developed. This procedure is similar to the hemagglutination-inhibition (HAI) technique that is available for erythropoietin. For the production of TSF, sheep were made thrombocytopenic by the injection of antiplatelet serum. TSF from sheep sera was partially purified by column chromatography and tested for biological activity in thrombocythemic mice. A TSF-rich serum fraction was used to immunize rabbits, and the immune serum was tested for hemagglutinating antibodies. The hemagglutinating antisera were absorbed with normal sheep serum to remove antibodies not specific to TSF. The absorbed antisera containing TSF-specific antibodies were then used to detect TSF in platelet-depleted sheep sera by use of the HAI assay procedure. The data indicate that TSF can be detected and quantified in sheep serum by use of this technique.
Platelet Dysfunction in Glycogen Storage Disease Type I
Authors: Czapek Emily E. , Deykin Daniel , Salzman Edwin W. 
Published: October 2019

Abstract
A hemorrhagic tendency has been observed in patients with glycogen storage disease Type I (GSD-I). We have studied the hemostatic mechanism in six patients with GSD-I who have mild to severe bleeding tendencies. All exhibited abnormalities of platelet function (decreased prothrombin consumption, abnormal aggregation reactions, prolonged bleeding time, and low platelet adhesiveness). The degree of dysfunction correlated with the patients’ general clinical condition: when patients were acidotic and severely lipemic, platelet function was strikingly impaired. Two patients received a course of continuous intravenous alimentation. As their general metabolic state approached normal, abnormal platelet function was corrected. We found normal platelets to contain no glucose-6-phosphatase. There was no consistent increase in platelet glycogen levels in patients with GSD-I. These data indicate that the bleeding disorder in GSD-I is an acquired defect rather than a primary platelet abnormality.
Mechanisms of Immunosuppression: Effects of Cyclophosphamide on Cellular Immunity
Authors: Winkelstein Alan 
Published: October 2019

Abstract
A course of cyclophosphamide administered to guinea pigs after immunization with mycobacteria led to a transient inhibition of cutaneous hypersensitivity to tuberculin protein. This treatment resulted in generalized depletion of lymphoid cells, including lymphopenia, and a substantial reduction in the number of macrophages found in induced peritoneal exudates. Results of in vivo cell transfer studies indicated that cyclophosphamide-treated recipients were rendered transiently unresponsive to purified tuberculin protein (PPD). However, sensitized lymph node cells from drug-treated donors were capable of transferring immunity to normal recipients. In vitro tests of cellular immunity with lymph node cells from drug-treated animals yielded discordant results. The proliferative response to both PHA and PPD was significantly impaired. However, these lymphoid cells functioned normally in assays for migration inhibition factor (MIF). Thus, these data suggest that cyclophosphamide can limit proliferation without impairing intermitotic functions of sensitized lymphocytes, such as the release of MIF. Results of this study suggest that cyclophosphamide does not impair development of a population of specifically sensitized T-type lymphocytes. However, several components of the expression phase are affected; the resultant anergy is probably due to a summation of effects on lymphocytes and macrophages.