bluuebunny/crossref_metadata_2025 huggingface dataset:
Fletcher Factor Deficiency: Family Study and Detection
Authors: Abildgaard Charles F. , Harrison Janet
Published: October 2019

Eight of 11 children of a known Fletcher factor-deficient individual were found to have normal activated partial thromboplastin times, normal levels of factors VIII, IX, XI, and XII, and a mean Fletcher factor level of 53% (range 40%-72%), suggesting a heterozygous state for the genecontrolling Fletcher factor production. All partial thromboplastin time reagents containing celite or kaolin were sensitive to Fletcher factor deficiency, while one reagent containing ellagic acid did not detect this abnormality. The finding of an abnormal partial thromboplastin time that is corrected by a 10-min incubation period is presumptive evidence for Fletcher factor deficiency.
Hydrogen Peroxide and Platelet Function
Authors: Canoso Rosa T. , Rodvien Robert , Scoon Kristine , Levine Peter H.
Published: October 2019

Hydrogen peroxide, at concentrations in the micromolar range, can influence platelet function. Although H2O2 causes no detectable platelet aggregation at these concentrations, it can aggregate platelets which have been previously exposed to any of several aggregating agents. H2O2 can enhance bath aggregation and the subsequent disaggregation of platelets, as initiated by ADP. Preexposure of platelets to H2O2 blunts the subsequent response to ADP. Washed platelets are susceptible to H2O2. Catalase-treated H2O2 has no effect on platelet function. H2O2 does not appear to act by altering either the aggregating agent or plasma thrombin generation. These data suggest that minute amounts of H2O2, which could theoretically be generated in vivo at sites of platelet plug formation, could play a regulatory role in the dynamics of growth and/or dissipation of the hemostatic plug. The blood granulocyte could participate in hemostasis and thrombosis via H2O2 generation.
Production of Colony-stimulating Factor by Malignant Leukocytes
Authors: Golde David W. , Rothman Belina , Cline Martin J.
Published: October 2019

There is considerable evidence supporting a role for colony-stimulating factor (CSF) as a humoral regulator of leukopoiesis. Data on CSF levels in the serum and urine of patients with leukemia and on the in vitro responsiveness of leukemic cells to CSF have suggested a basis for considering leukemia as a primary disorder of leukopoietic regulation. We examined the question of leukemic cell production of CSF. Conditioned medium from cultured leukemic cells was tested for colony-stimulating activity against normal human bone marrow using a two-layer agar colony assay technique. The cells from patients with acute myelogenous leukemia and a patient with chronic myelogenous leukemia in blast crisis did not elaborate CSF nor did acute lymphocytic leukemia cells. CSF production was documented with cells obtained from patients with chronic myelogenous leukemia in the chronic phase and two patients with acute myelomonocytic leukemia. In acute leukemia the cellular production of CSF correlated closely with morphologic and functional maturation along the monocyte-macrophage line. Evidence was obtained that the adherent cells within the leukemic population were primarily responsible for CSF production. We interpret these data to indicate that neoplastic hematopoietic cells may produce CSF in relation to their capacity for mononuclear leukocyte differentiation.
The Value of the Serum Vitamin B12 Level in Diagnosing B12 Deficiency
Authors: Pierce H. Irving , Hillman Robert S.
Published: October 2019

Serum vitamin B12 levels of 2523 individuals were measured using the hemoglobin-coated charcoal assay. In one hospital, the test was performed on 1698 patients under hematologic evaluation for erythrocytic abnormalities of all types, while 825 patients from five other hospitals were studied because of suspected B12 deficiency. The incidence of low serum vitamin B12 was surprisingly low for both groups (2.3% and 3.5%, respectively). The value of the test as a diagnostic tool was further reduced by two characteristics of physician performance. First, with those patients who demonstrated a clear-cut macrocytic anemia and were suspects for intrinsic factor deficiency (pernicious anemia), extensive evaluations for B12 malabsorption were usually carried out prior to the receipt of the low B12 level. Second, when a deficiency state was not suspected, the return of a low value did not reliably stimulate physicians to begin evaluation or institute therapy. This was true despite the presence of clinical evidence of a possible gastrointestinal abnormality in many of the patients.
DNA Polymerases in Normal and Leukemic Human Hematopoietic Cells
Authors: Coleman Mary Sue , Hutton John J. , Bollum F. J.
Published: October 2019

DNA polymerase activities were assayed in bone marrow cells and peripheral leukocytes from normal people and patients with acute myelogenous, chronic lymphocytic, and chronic myelogenous leukemia. Extracts of subcellular components were fractionated by velocity sedimentation through sucrose density gradients and assayed using activated DNA as template. Two major DNA-dependent DNA polymerases were found in human cells with molecular weights of approximately 50,000 and 200,000 daltons, respectively. The DNA polymerase of high molecular weight is located in the soluble cytoplasmic fraction and is inhibited by N-ethylmaleimide. The low molecular weight polymerase is detected in extracts of nuclei and in the soluble fraction. It is resistant to inhibition by N-ethylmaleimide. In all cell types tested, total DNA polymerase activities were much higher in cytoplasmic than in nuclear extracts. Lymphocytes purified from normal peripheral blood had three to four times as much of both the high and low molecular weight polymerase activities per cell as purified granulocytes. Leukemic myeloblasts had 10 to 20 times as much cytoplasmic DNA polymerase activity as more mature leukocytes from normal peripheral blood. In general, immature granulopoietic cells contained higher total DNA polymerase activities than more mature granulocytes, and the major increases in polymerase activities were in the high and low molecular weight cytoplasmic enzymes rather than in the nuclear enzyme.
Platelet Antiheparin Activity: Storage Site and Release Mechanism
Authors: Walsh Peter N. , Gagnatelli Giovanna
Published: October 2019

The platelet storage and release mechanisms for the heparin-neutralizing activity (HNA), adenosine diphosphate (ADP), serotonin, and lysosomal enzymes were investigated in normal human platelets and in platelets with defective storage or release of ADP and serotonin. The time course of release of HNA from normal washed platelets by thrombin and collagen was slower than that of serotonin. Lysosomal enzymes were not released by collagen from normal washed platelets, whereas under the same conditions HNA was released. In four of six patients with storage pool deficiency, the platelets contained normal amounts of HNA but definitely decreased amounts of ADP and serotonin, whereas in the remaining two patients the total contents of ADP, serotonin, and HNA were all definitely lower than normal. In four of six patients with storage pool deficiency, the amounts and per cents of total HNA released by collagen were normal, whereas the amounts and per cents of total ADP released were diminished compared with normal. Platelets from patients with the aspirinlike platelet release defect and from aspirin-treated normal subjects contained normal quantities of ADP, serotonin, and HNA, but HNA and ADP were not released in response to collagen. It is concluded that either HNA is stored in and released from dense granules by mechanisms different from those for ADP and serotonin, or that HNA is stored in and released from granules other than the dense granules, which contain ADP and serotonin and the α-granules, which contain lysosomal enzymes.
Bone Marrow Involvement in Hodgkin's Disease: Pathology and Response to MOPP Chemotherapy
Authors: Myers C. E. , Chabner B. A. , De Vita V. T. , Gralnick H. R.
Published: October 2019

Examination of the bone marrow biopsies of 174 patients with Hodgkin’s disease seen at the National Cancer Institute between 1965 and 1972 revealed tumor involvement of the marrow in 19 cases. Eighteen of the 19 patients were treated with intensive combination chemotherapy (MOPP), and 13 achieved complete remission; the median duration of remission was 25+ mo, and 49% of those at risk remained in continuous remission for at least 3 yr. In all patients with marrow involvement, marrow fibrosis due to increased collagen or reticulin was identified in the pretreatment specimen. Repeat biopsies following therapy revealed entirely normal marrow free of tumor and reticulin or collagen fibrosis in eight patients, although residual collagen was detected in three other patients. Pretreatment leukopenia (WBC less than 5000 cells per cu mm) was present in seven of the 18 patients treated with MOPP, and appeared to be associated with an increased risk of infection and a less favorable response to therapy. These results indicate that nonleukopenic patients with Hodgkin’s disease and bone marrow involvement can be safely and effectively treated with intensive chemotherapy, and that pathologic changes in the marrow, including diffuse myelofibrosis, are often reversible with such therapy.
Intracellular Lysozyme in Mature Neutrophils and Blast Cells in Acute Leukemia
Authors: Karle Hans , Hansen Niels Ebbe , Killmann Sven-Aage
Published: October 2019

Intracellular lysozyme (muramidase) activity was measured in leukemic blasts and mature neutrophilic granulocytes from 20 patients with acute myeloblastic and myelomonocytic leukemia and in 11 patients with acute lymphoblastic leukemia after differential centrifugation of cells in Ficoll and extraction of lysozyme with n-butanol. Considerable abnormalities in cellular lysozyme activity were found both in qualitative and quantitative terms. In contrast to normal myeloblasts, leukemic blasts of the myeloid series contained lysozyme in a considerable number of cases. Although no clear-cut distinction was seen, those patients with positive blast lysozyme reactivity tended to have the highest plasma lysozyme levels, whereas no good correlation was found between morphologic differentiation along myeloblastic or monocytoblastic lines of blasts and lysozyme reactivity. Calculations of the magnitude of lysozyme production in acute leukemias with high plasma lysozyme concentration was compatible with the hypothesis that in these cases lysozyme must be secreted by intact blasts and that, consequently, plasma lysozyme activity reflects the total leukemic cell mass. In mature neutrophilic granulocytes from patients with acute myeloblastic and myelomonocytic leukemia in relapse, the mean lysozyme activity was significantly decreased, although a great deal of variation was found. In remission, neutrophil lysozyme activity seemed to increase; among several possibilities this might be a reflection of different clones being operative in relapse and remission. In acute lymphoblastic leukemia, lysozyme activity in neutrophils was constantly low in relapse and increased to normal following induction of remission, which may be the main explanation of the low plasma lysozyme activity found in this type of acute leukemia. It is unexplained and puzzling why intraneutrophil lysozyme activity is low in a leukemic type where the myeloid cells are not believed to be primarily leukemic; one possible reason might be an effect of cell-to-cell interaction with the leukemic cell population.
Glycogen Metabolism in Glycogen-rich Erythrocytes
Authors: Moses Shimon W. , Bashan Nova , Gutman Alisa , Ockerman Per Arne
Published: October 2019

High concentrations of red blood cell glycogen were visualized by electron microscopy and demonstrated biochemically in amylo-1,6-glucosidase- and phosphorylase-deficient red blood cells. Glycogen concentration decreased as a function of cell age. Similar incorporation rates of 14C-U-glucose into glycogen were observed in amylo-1,6-glucosidase-deficient and normal erythrocytes, characterized by an initial rise, followed by a plateau formation reflecting a steady state between glycogen synthesis and breakdown. A different pattern of kinetics was observed in phosphorylase-deficient cells, which in view of the lack of the degradative enzyme showed a continuous linear increase in radioactive glycogen formation leveling off only after exhaustion of substrate. Evidence that in amylo-1,6-glucosidase-deficient red blood cells the main metabolic activity affects the outer branches of the glycogen molecule was obtained directly by β-amylolytic degradation of the radioactive glycogen molecule and indirectly by a chase experiment substituting radioactive with nonlabeled glucose. Normal glycogen synthetase activity was found in all cases of amylo-1,6-glucosidase examined except in one family in which an unexpected low affinity of the enzyme to glycogen was found. The observation that both amylo-1,6-glucosidase- and phosphorylase-deficient red blood cells retain the capacity to incorporate glucose into glycogen indicates that glycogen synthesis in erythrocytes proceeds along the UDPG glycogen synthetase pathway and is not a result of a reverse activity of any of the degradative enzymes.
Alterations of Granulopoiesis Following Chemotherapy
Authors: Greenberg Peter , Bax Ine , Mara Beth , Schrier Stanley
Published: October 2019

Clonal proliferation of marrow granulocytic progenitor cells (GPC) in vitro and the daily urinary output of granulocytic colony-stimulating factor (CSF) were determined in two patients with acute myeloid leukemia (AML) in remission and one patient with malignant lymphoma receiving monthly pulses of chemotherapy with cytosine arabinoside and 6-thioguanine. During and immediately following therapy, a marked decrease of granulocytic colony-forming capacity (CFC) occurred, with an increase and return to basal levels by 3-4 wk. In the AML patients, the proportion of GPC in DNA synthesis (GPC-S), as determined by the thymidine suicide technique, declined from basal levels (31%-39%) to 0%-26% after 2 days of treatment. This was followed by a sharp rise in GPC-S to 41%-75% 1-3 days posttherapy, with an oscillatory return of GPC-S to basal levels by 3-4 wk. In all courses a marked increase of urinary CSF output occurred during or 1 day posttherapy, concomitant with the rise of the proportion of GPC-S. In the lymphoma patient, an initially high proportion of marrow GPC-S and low CFC anticipated the severe neutropenia which followed therapy. These results provide a basis for determining the efficacy with which cytotoxic drugs destroy proliferative activity of GPC and for assessing the potential for hemopoietic toxicity following chemotherapy.
Effects of Hydrocortisone on the Yield and Bactericidal Function of Granulocytes Collected by Continuous-flow Centrifugation
Authors: Shoji Mamoru , Vogler William R.
Published: October 2019

The usefulness of granulocyte transfusions is in part dependent upon the number of granulocytes transfused. The invention of the continuous-flow cell separator has made it possible to obtain granulocytes from normal donors. Efforts to improve the yield are under study. This controlled study was undertaken to determine the effect of a single dose of hydrocortisone on granulocyte yield from volunteer donors and on granulocyte bactericidal function. Twenty-two normal volunteers were randomized between no therapy or a single intravenous injection of 120 mg/sq m of hydrocortisone 2 hr prior to initiation of a 4-hr leukapheresis using the Aminco cell separator operated at 750 rpm and a flow rate of 41 ml/min. Significant increases in granulocyte yield and reductions in lymphocyte and monocyte yields were obtained in the hydrocortisone-treated group. Granulocytes from each group were equally effective in the phagocytosis of yeast particles and in vitro bactericidal activity.
Polymorphonuclear Leukocytes Prepared by Continuous-Flow Filtration Leukapheresis: Viability and Function
Authors: Harris Michael B. , Djerassi Isaac , Schwartz Elias , Root Richard K.
Published: October 2019

Preparation of granulocytes for transfusion in high yield and relatively free of contamination by other cell types has been made possible by the technique of continuous-flow filtration leukapheresis (CFFL). Since previous work suggested that granulocytes collected in this manner may have impaired viability and function, a detailed study of the bactericidal, metabolic, and chemotactic properties of such cells was performed and compared to control cells obtained from the same donors prior to CFFL. The granulocyte percentage of the cell suspensions obtained by CFFL averaged 94.5% ± 1.5% compared to 82.5% ± 1.8% for the controls (p < 0.001) with viability of the PMNs determined by trypan blue exclusion being 97.5% ± 0.9% and 98.2% ± 0.5%, respectively. The phogocytic, metabolic (14C-I-glucose oxidation and protein iodination) and chemotactic properties of both cell types were equivalent in suspensions equalized for granulocyte content. These findings indicate that CFFL technique employed does not impair granulocyte viability or function in vitro. Studies of the in vivo survival and function of CFFL granulocytes are necessary to evaluate their efficacy in combating infection in severely leukopenic patients.
The Number of in Vitro Stem Cells in AKR Leukemic Mice
Authors: Chevalier Christiane , Gaillard Nadine , Frindel Emilia
Published: October 2019

The total number of in vitro stem cells (CFUc) is lower in AKR leukemic mice than in nonleukemic AKR mice of the same age. This decrease is caused by a drop in the bone marrow CFUcs which is not compensated for by an increase in the number of these cells in the spleen. This decrease in CFUcs is not due to the presence of leukemic cells in the cultures, nor to the age of the mice, nor to a modified response to the stimulating factor (CSF) of CFUcs in leukemic mice.
An Acquired Inhibitor of Fibrin Stabilization Associated With Isoniazid Therapy: Clinical and Biochemical Observations
Authors: Otis Peter T. , Feinstein Donald I. , Rapaport Samuel I. , Patch Mary Jane
Published: October 2019

A patient who bled seriously while taking isoniazid was found to have an inhibitor of fibrin stabilization. The bleeding appeared to cease soon after the isoniazid was discontinued, although the plasma still contained potent inhibitor activity. This activity gradually disappeared over several weeks. The inhibitor was precipitated at 50% saturation with ammonium sulfate, migrated in the beta area on zone electrophoresis, and was found in the second peak on Sephadex G-200 gel filtration. Inhibitor activity persisted after heating to 90°C. Fibrinogen isolated from the patient’s plasma lacked factor XIII activity but did not contain measurable inhibitor activity. When the rate of incorporation of 14C-putrescine into casein was utilized to study the kinetics of the inhibitor, it was shown that the inhibitor acted reversibly and that it competed with the amine donor, 14C-putrescine. The mechanism whereby isoniazid led to the development of the inhibitor is unknown.
Erythroid Colony Formation in Vitro by Dimethylsulfoxide-treated Erythroleukemic Cells
Authors: Goldstein Kenneth , Preisler Harvey D. , Lutton John D. , Zanjani Esmail D.
Published: October 2019

Friend leukemic cells grown in suspension culture with dimethylsulfoxide can be induced to respond to erythropoietin by increased synthesis of hemoglobin. Investigation was undertaken to determine if these erythroleukemic cells could be induced to form erythroid colonies in a plasma-clot system. This study demonstrates that culture for 24-48 hr in suspension in the presence of 2% dimethylsulfoxide affected these cells so that they then produced benzidine-staining erythroid colonies in the plasma-clot culture. The cells responded to erythropoietin in these cultures with an increase in the number of erythroid colonies.
Radiosensitivities of DNA molecules in lymphocytes from the circulating blood of man
Authors: Hashimoto Y , Ono T , Okada S
Published: October 2019

The radiosensitivities of DNA molecules from lymphocytes of human circulating blood were examined by alkaline sucrose gradient centrifugation. The single-strand breaks of DNA per rad, including the breaks formed under the present alkaline condition, were 1.2 plus or minus 0.1 breaks per 10–12 daltons DNA per rad. When the cells were transformed, the number of breaks was found to increase to 1.8 plus or minus 0.2 breaks per 10–12 daltons DNA per rad. The lymphocytes are capable of rejoining radiation-induced single-strand breaks of DNA. The rate of rejoining was dependent upon types of the suspending medium. The rate increased to ten times of that of the non-transformed cells upon transformation.
Impaired T-cell transformation in chronic lymphocytic leukemia (CLL): Demonstration of a blastogenesis inhibitory factor
Authors: Utsinger PD
Published: October 2019

A noncytotoxic serum factor was found in CLL serum which interfered with the response of normal lymphocytes to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). This factor was not produced by B-lymphocytes during short-term culture. This factor may contribute to the impaired lymphocyte responsiveness in CLL. In five of six patients, T- lymphocytes which were purified by passage over nylon wool columns exhibited an impaired response to both PHA and PWM, suggesting that a dilutional effect alone does not fully explain the impaired lymphocyte transformation in CLL.
Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia
Authors: Branda RF , Jacob HS , Douglas SD , Moldow CF , Puumala RR
Published: October 2019

Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.
Human red cells protein kinase in normal subjects and patients with hereditary spherocytosis, sickle cell disease, and autoimmune hemolytic anemia
Authors: Beutler E , Guinto E , Johnson C
Published: October 2019

A somewhat simplified modification of a previously described method for the measurement of red cell membrane phosphorylation by ATP has been devised. Phosphorylation of membranes was linear with time for only 5- 10 min, and linearity with membrane concentration was observed only when assays were limited to short incubation times. Protein kinase activity of hereditary spherocytosis (HS) membranes was found to be normal. However, the average phosphorylation after 60 min incubation was less in HS membranes than in normal membranes. Findings similar to those in HS membranes were observed in sickle cell disease. The Km of red cell protein kinase for ATP is approximately 10(-5) M. Membrane phosphate binding sites are not saturated in either HS or normal membranes after 1 hr incubation with ATP. Approximately 27% of phosphorylating activity is lost after 1 hr incubation at 37 degrees C. GTP is a very inefficient phosphate donor. Under the conditions of measurement employed, the enzyme is slightly stimulated by 1 muM cAMP, but is not stimulated by 1 muM cGMP. Dephosphorylation of red cell membranes after labeling occurs at a similar rate in HS as in normal membranes. Although a mild abnormally in membrane phosphorylation is observed in HS, this could not be demonstrated to be due to a decrease in protein kinase activity or in alterations of its kinetic properties. The abnormally seen is not specific for HS.
Effect of propranolol on platelet function
Authors: Weksler BB , Gillick M , Pink J
Published: October 2019

Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.
PHASE MICROSCOPY STUDIES OF HODGKIN’S DISEASE LYMPH NODES IN RELATION TO HISTOGENESIS OF THE STERNBERG-REED CELL
Authors: HOFFMANN GEORGE T. , ROTTINO ANTONIO
Published: October 2019

1. The free reticulum cell in Hodgkin’s disease undergoes progressive cytologic alterations leading to the formation of Sternberg-Reed cells.

2. The other free cellular components of Hodgkin’s disease nodes are cytologically normal.
FOLIC ACID ANTAGONISTS IN THE TREATMENT OF ACUTE AND SUBACUTE LEUKEMIA
Authors: DAMESHEK WILLIAM , FREEDMAN MILTON H. , STEINBERG LESTER
Published: October 2019

Forty cases of acute and subacute leukemia were treated with one or more of various folic acid antagonists, usually aminopterin. Thirty-two cases were treated for at least one week, remissions occurring in 10. The remissions were of a temporary nature and variable in duration. As of June 1, 1949, two patients were still alive and in good condition, seven and one-half and thirteen months, respectively, after onset of therapy.

Clinical, hematologic, and to lesser extent, marrow remissions were obtained most commonly in the lymphocytic type, none in the 4 monocytic cases. The subacute cases responded far better than did those of the acute, fulminating variety.

The exact mechanism of action of the folic acid antagonists is not known, although one may speculate that anti-PGA, an anti-growth factor which resembles PGA so closely, is readily accepted by the primitive white cell with resultant cell death.

The margin between a therapeutic or effective dose and one causing a toxic reaction is a narrow one. A "toxic" reaction may in fact be an indication of a therapeutic response.

The pattern of therapy was (1) administration of the drug, usually by parenteral injection until a toxic or a pronounced hematologic reaction occurred, at which point (2) the drug was discontinued. With subsidence of the toxic reaction, (3) a maintenance dosage was then given, usually in the form of oral medications, 0.5 mg. daily for adults and 0.25 mg. for children.

Transfusions and antibiotics were administered as indicated. Frequent transfusions were usually very helpful at the time of the initial reaction when anemia was ordinarily severe. Penicillin and other antibiotics were used for supportive therapy. Thrombocytopenia and hemorrhage were exceedingly difficult to control.

The observed remissions appeared to be directly attributable to the action of the drug. Although temporary, they indicate that acute leukemia is not necessarily completely irreversible. Thus, there is hope that more potent anti-growth factors may someday be discovered which will be of value in ultimate control of the disease.
HEMOLYTIC ANEMIA IN MYELOGENOUS LEUKEMIA WITH SPLENECTOMY
Authors: JONSSON ULFAR , HANSEN-PRUSS O.C. , RUNDLES R. W.
Published: October 2019

A patient with chronic myelogenous leukemia developed anemia with evidence of increased red cell destruction. After anemia had persisted for eleven months in spite of 49 blood transfusions, splenectomy was performed. The hemolysis subsided and her health remained good during the following thirty months.
ADDITIONAL EVIDENCE FOR THE ANTI-d: STATISTICAL STUDIES
Authors: HILL JOSEPH M. , HABERMAN SOL , GUY RUTH , DAVENPORT JULIUS W.
Published: October 2019

Additional evidence for the finding of the d agglutinin and antigen are reported. Differential agglutination with key genotype cells, genetic studies in selected families, and statistical analysis of 232 random bloods have confirmed the earlier report on the d antibody and antigen.
HEMOLYSIS WITH ALLOXAN AND ALLOXAN-LIKE COMPOUNDS, AND THE PROTECTIVE ACTION OF TOCOPHEROL
Authors: ROSE CATHARINE S. , GYÖRGY PAUL
Published: October 2019

The production of hemolysis in tocopherol-deficient rats by injection of compounds related to alloxan has been studied. Alloxantin had the same hemolytic action as alloxan; dialuric acid was about twice, ninhydrin about six times as effective as alloxan. Alloxanic acid had no hemolytic action. In tocopherol-treated rats no hemolysis was observed after the injection of alloxantin, dialuric acid and ninhydrin, as well as of alloxan.

Hemolysis of red blood cells obtained from tocopherol-deficient rats could be produced in vitro by dialuric acid and to a lesser extent by alloxantin but not by alloxan or ninhydrin. In the presence of cysteine, glutathione or ascorbic acid, alloxan reacted as dialuric acid. The three reducing agents themselves hemolyzed the cells of deficient rats although to a much lesser extent than did dialuric acid. The red blood cells of tocopherol-treated rats were resistant to hemolysis in vitro as in vivo by all the above hemolyzing compounds. Addition of tocopherol to the reaction mixture protected the cells of deficient animals against the hemolytic action of dialuric acid. The tocopherol was more effective when it was incubated with the cells before the dialuric acid was added.

It is proposed that the hemolysis is linked with the reversible oxidation-reduction system of dialuric acid and alloxan, the actual hemolyzing agent being an intermediate of this reaction. Cysteine, glutathione and ascorbic acid, which are readily oxidized by molecular oxygen may form similar intermediates. The protective action of tocopherol is a function of the red blood cell and may best be explained as an antioxidant effect.
GROUP-SPECIFIC APPEARANCE OF PLASMA CLOTS
Authors: STARK G. J. , STIVEL N.
Published: October 2019

Clots formed on recalcification of citrated plasma show differences in appearance which are specific for the original blood groups.

The differences in appearance are considered to be due to a group-specific factor, some of the properties of which are described.

The group-specific factor is tentatively related to the platelets.

Further lines of investigation are suggested.
STUDIES ON CHARCOT-LEYDEN CRYSTALS
Authors: AYRES WILLIAM W. , STARKEY N. M.
Published: October 2019

1. Synthetic detergents of the anionic, cationic and nonionic types result in the rapid and constant formation of Charcot-Leyden crystals from eosinophils.

2. Charcot-Leyden crystals have a negative crystalline birefringence and form penetration twins.

3. The changes taking place in the eosinophil in the formation of Charcot-Leyden crystals under the influence of wetting agents, utilizing phase and polarizing microscopy, are described.

4. In the formation of Charcot-Leyden crystals with wetting agents, the nucleus of the eosinophil lyses with no appreciable effect on the granules.

5. In the formation of Charcot-Leyden crystals with a wetting agent, there is no change in the lipoid cortex of the eosinophil as demonstrated by staining with sudan black B.

6. Charcot-Leyden crystals undergo changes on standing that affect their solubilities.

7. The staining reactions and solubilities of Charcot-Leyden crystals are described.

8. Oxyhemoglobin crystals constantly form from red cells on exposure to Aerosol MA; on two occasions, tyrosine crystals formed from the blood of a patient with chronic myelogenous leukemia.

9. Evidence is offered that Charcot-Leyden crystals are crystalline proteins derived only from the nucleus of the eosinophil.
MEGALOBLASTIC ERYTHROPOIESIS IN PATIENTS WITH CIRRHOSIS OF THE LIVER
Authors: MOVITT E. R.
Published: October 2019

Three patients with cirrhosis of the liver, macrocytic anemia, and megaloblastic proliferation in the bone marrow have been described. All 3 patients gave histories of grossly deficient diets for many years and all 3 had free hydrochloric acid in the gastric juice. The latter finding was thought to be of particular significance from the diagnostic point of view in that it appeared to exclude the possibility of coexisting addisonian pernicious anemia. The clinical diagnosis of Laennec’s cirrhosis was confirmed by liver biopsies in 2 cases, and in both, the bone marrow morphology reverted to the normoblastic type on appropriate therapy.

The literature on the subject of macrocytic anemia in association with hepatic cirrhosis has been briefly reviewed and various theories as to its pathogenesis briefly discussed. Attention has been called to the fact that despite specific denials by many investigators, megaloblastic bone marrow is seen in some of these patients. The pathogenesis of this phenomenon has remained obscure, and the various etiologic possibilities are discussed.
THROMBOPATHIC THROMBOCYTOPENIA: SUCCESSFUL TRANSFUSION OF BLOOD PLATELETS
Authors: HIRSCH ERWIN O. , FAVRE-GILLY JEAN , DAMESHEK WILLIAM
Published: October 2019

1. A case of thrombopathic thrombocytopenia, a variant of chronic idiopathic thrombocytopenia is described.

2. In addition to the customary studies, the prothrombin consumption test of Quick was used in a study of the physiology of the platelets.

3. The patient’s platelets were not only reduced in number but were morphologically abnormal and physiologically defective. Their abnormality was presumably related to the lack of granularity in the cytoplasm of the platelet-producing cells, namely, the megakaryocytes.

4. Because of the uniformly abnormal appearance of the patient’s platelets, the success of a transfusion of normal platelets could be readily evaluated from inspection of stained blood smears.

5. Transfusion of blood from a polycythemic donor whose platelet count was about eight times the normal level resulted in the recovery of a detectable proportion of these platelets in the patient. Possible mechanisms leading to their relatively low recovery are discussed.

6. The donor platelets survived for five to six days and retained their normal physiologic activity throughout that time.
THE PHOSPHATASES OF HUMAN ERYTHROCYTES
Authors: WOODARD HELEN QUINCY
Published: October 2019

Hemolysates of human erythrocytes begin to liberate inorganic phosphate as soon as they are lysed. In most cases the process takes place most rapidly at pH 9, but some preparations are about equally active over the entire range from pH 5 to pH 9. The process ceases after incubation for twenty-four hours at 37 C.

Hemolysates of human erythrocytes decompose sodium β glycerophosphate and calcium hexose diphosphate about equally. For both substrates there is a well defined maximum of activity at pH 6.0. No other maxima were observed over the range from pH 4 to pH 9.

There is some evidence that erythrocytes from patients with various types of anemia liberate more inorganic phosphate when lysed than do those from normal individuals.
ACUTE INFECTIOUS LYMPHOCYTOSIS
Authors: MOYER JOHN B. , FISHER GEORGE S.
Published: October 2019

1. Case reports are presented of 5 cases of acute infectious lymphocytosis in siblings, ages 2¼-10 years. Symptoms included diarrhea, abdominal pain, vomiting, fever and cough. There was an absolute lymphocytosis lasting about three weeks. All of the cases had elevated eosinophil counts during the course of the disease. Four of the 5 had an eosinophilia lasting several months.

2. The clinical features are reviewed.

3. The morphology of the lymphocytes is discussed in detail.
BLOOD FACTOR IN ACUTE DISSEMINATED LUPUS ERYTHEMATOSUS
Authors: HASERICK JOHN R. , LEWIS LENA A.
Published: October 2019

The gamma globulin fractionated by the Tiselius electrophoretic technic from the plasma of patients with acute disseminated lupus erythematosus was used as an antigen to induce antibodies in rabbits. Similarly, antibodies were induced in control rabbits with normal human serum and with normal human gamma globulin.

The antisera developed in these three groups of rabbits were added to the L. E. gamma globulin solution and, after precipitation, the supernatant fluid was added to bone marrow preparations.

The L. E. phenomenon was not demonstrable after the L. E. gamma globulin was precipitated by anti-L. E. gamma globulin rabbit serum. However, after precipitation of the L. E. gamma globulin by anti-normal human serum rabbit serum, or by anti-normal human gamma globulin rabbit serum, the L. E. phenomenon was still apparent.

These studies suggest that the L. E. factor is an immunologically distinct component of L. E. gamma globulin.
THE NATURE OF PLASMA ANTITHROMBIN ACTIVITY
Authors: KLEIN PETER D. , SEEGERS WALTER H.
Published: October 2019

In plasma antithrombin studies it is essential to recognize two separate effects on thrombin. One is concerned with thrombin disposal, and the magnitude of this effect is determined by finding how much thrombin remains after the antithrombin reaction has gone to completion. The other effect is concerned with interference with the thrombin-fibrinogen reaction, there being no thrombin activity destroyed by this mechanism.

In the disposal of thrombin, plasma antithrombin is not influenced by heparin. The amount of thrombin destroyed is constant for a given amount of defibrinated plasma and is independent of the initial thrombin concentration, provided the initial quantity of thrombin is above the antithrombin capacity of the plasma. For bovine plasma, the antithrombin capacity is about 710 units of thrombin. In contrast, if the initial quantity of thrombin is less that the antithrombic capacity of the plasma, some thrombin may remain after equilibrium conditions have been reached.

In addition to plasma antithrombin, fibrin may remove certain quantities of thrombin activity from solution by adsorption. Heparin increases the amount of thrombin adsorbed on fibrin whereas albumin decreases the amount of thrombin adsorbed. The adsorbed thrombin can be recovered by lysis of the fibrin with fibrinolysin.

The general concept that heparin has an antithrombic effect in conjunction with a plasma cofactor is explained on the basis that this mechanism interferes in the thrombin-fibrinogen reaction. No thrombin is destroyed by this mechanism.
FAMILIAL NONSPHEROCYTIC HEMOLYTIC ANEMIA
Authors: KAPLAN EUGENE , ZUELZER WOLF W.
Published: October 2019

A congenital familial chronic hemolytic anemia not conforming to the known types was observed in 3 members of a French-Canadian family.

The erythrocytes were normochromic, normocytic to macrocytic, and had normal osmotic and mechanical fragility. Spherocytosis. elliptocytosis and sickling were absent but a moderate degree of ovalocytosis was present in many of the patients’ red corpuscles. No acid hemolysis could be demonstrated. The survival of erythrocytes transfused from one of the patients to a normal recipient was significantly shortened, whereas normal erythrocytes transfused into 2 of the patients survived normally, indicating an intracorpuscular defect.

Clinically the condition was characterized by jaundice, hepatosplenomegaly, osseous changes, and a tendency toward the development of mongoloid facies. Typical hemolytic crises have been absent. Despite moderately severe anemia there has been remarkably little interference with normal childhood activity.
The Average Volume of Leukemic Leukocytes
Authors: TIVEY HAROLD , LI JONAH G. , OSGOOD EDWIN E. , DUERST MARIE , KLOBUCHER VICTOR , PETERSON ELEANOR , HUGHES MARGRET E.
Published: October 2019

1. The technic used to determine the average volume per cell of leukocytes from patients with leukemia has been described.

2. The distribution of the average volumes of leukocytes from 15 patients with granulocytic leukemia, based on 52 determinations, has a median value of 450 cu. µ and a mean of 460 cu. µ. 2. The 95 per cent range for this distribution is 340 to 570 cu. µ.

3. Sufficient data are not presently available to determine the Shape of the distribution for the volume of monocytes, but the average value for the leukocytes from 8 patients with monocytic leukemia is 470 cu. µ and the range is 360 to 580 cu. µ.

4. The average volumes of leukocytes from 27 patients with lymphocytic leukemia, based on 74 determinations, have a Poisson-like distribution with a median value of 230 cu. µ and a mean of 250 cu. µ. Ninety-five per cent of the values in this distribution fall in the range of 130 to 410 cu. µ.

5. Although leukocyte volumes from both granulocytic and lymphocytic leukemias follow Poisson-like distributions, the central values of these distributions are significantly different. However, there is an overlap of the distributions with approximately a 15 per cent chance that average lymphocytic volumes will fall into the range of the small granulocytic volumes.

6. For many purposes it may be assumed that two billion cells of the granulocytic or monocytic series or four billion cells of the lymphocytic series equal 1 ml.
Blood Coagulation in Arthropods
Authors: GRÉGOIRE CH.
Published: October 2019

1. Thin films of freshly drawn hemolymph of about 360 insects belonging to 61 different species were observed under the phase contrast microscope and the process of coagulation investigated. Control of the observations by motion picture recordings were performed in a few species.

2. In the hemolymph of all the insects investigated, a category of hyaline hemocytes can easily be recognized under the phase contrast microscope from the other kinds of blood cells. Attempts of identification of these hyaline hemocytes with elements described in the classifications of insect blood cells based on fixation and staining were inconclusive.

3. In the insects in which the blood clotting does not occur, these hyaline hemocytes do not exhibit any important alteration. In species inn which blood coagulation occurs, the cells of this category appear to be highly labile to contact to glass surfaces. They undergo rapid modifications in their structure which play an important if not exclusive part in the initiation of the plasma coagulation. In the present material these alterations are of two kinds, each of them being related to a different appearance of the plasma reaction. They can occur alone or together.

4. In contrast to the hyaline hemocytes, the other categories of blood cells do not take part in the process of coagulation. Scattered or agglutinated at random, they are passively embedded in the coagulum.

5. In the present material, hemolymph coagulation appears to be a continuous process, initiated by alterations taking place in a single category of hemocytes. These alterations are followed by various degrees of plasma coagulation, from a general macroscopic clotting to a limited reaction detectable only under the microscope.

6. The results are at variance with former data in which the coagulation of insect blood was described as being either a cellular agglutination, in which no special part was recognized to be played by a special category of cells, or a plasma coagulation, both considered as two physiologically distinct processes, which can occur independently or together. On the other hand, the present results show an analogy with the type of coagulation described in crustacean blood by Hardy, Tait, Tait and Gunn, in which a special category of cells, Hardy's explosive cells, as distinguished from the other blood cells, has a specific and important part to play.
Microspectrophotometric Determination of Desoxyribosenucleic Acid in Megaloblasts of Pernicious Anemia
Authors: REISNER EDWARD H. , KORSON ROY
Published: October 2019

1. In 9 patients with various types of megaloblastic anemia responding to treatment with vitamin B12, folic acid or liver extract, no significant deviations from the normal amounts of total or polymerized DNA were observed in the nuclei of red blood cells in marrow smears.

2. During the maturation of megaloblasts in the bone marrow there is a gradual loss of nuclear DNA.

3. This pattern is quantitatively and qualitatively similar for normal marrow and for that of pernicious anemia in relapse and after treatment.
Deficiency of Plasma Prothrombin Conversion Accelerators in the Postoperative State with a Description of a Simple Method of Assay
Authors: WARREN RICHARD , BELKO JOHN S.
Published: October 2019

1. A simple method for distinguishing between prothrombin and prothrombin conversion accelerators has been described.

2. A deficiency in prothrombin conversion accelerators in the early days after major surgical operations has been observed.
Inhibition by Rutin of Capillary Injury by Alpha-Radiation in Rats
Authors: GRIFFITH JOHN Q. , COUCH JAMES F.
Published: October 2019

Rutin administered subcutaneously or by implantation can protect the rat against increased capillary fragility due to irradiation with alpha particles.
Idiopathic Hypoprothrombinemia Associated with Hemorrhagic Diathesis, and the Effect of Vitamin K
Authors: LEY ALLYN B. , READER GEORGE G. , SORENSON C. W. , OVERMAN RALPH S.
Published: October 2019

Two cases of hypoprothrombinemia of unknown cause are presented. In each case there was a marked hemorrhagic diathesis which, in Case 1, led to death. In each there were additional findings (clinical or necropsy) which suggested that the prothrombin deficiency was only one manifestation of a generalized disease.

The pertinent literature is reviewed and a classification of the previously reported cases of "idiopathic hypoprothrombinemia" into "congenital" and "acquired" types is offered. Both of our cases fall into the "acquired" group. The treatment of the condition is discussed and it is pointed out that vitamin K1 oxide in large doses restored the prothrombin time to normal after the apparent failure of large doses of water soluble menadione. A rationale for this difference in response is suggested.
The Effect of Dicumarol on Co-Thromboplastin, a Factor in Blood Concerned with the Conversion of Prothrombin to Thrombin
Authors: MANN FRANK D. , BARKER NELSON W. , HURN MARGARET
Published: October 2019

The deficiency in the conversion of prothrombin to thrombin which develops after administration of dicumarol appears to be due largely to decreased cothromboplastin activity. Both the development of this deficiency and the recovery from it tend to precede the accompanying changes in prothrombin itself, as measured by the two-stage method. In terms of deviation from normal, the deficiency in conversion often exceeds in magnitude the deficiency of prothrombin itself.