bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of the carrier state for classic hemophilia using an enzyme- linked immunosorbent assay (ELISA)
Authors: Fishman DJ , Jones PK , Menitove JE , Ratnoff OD , Everson B 
Published: October 2019

Abstract
A high proportion of carriers of classic hemophilia can be identified in the laboratory because, in comparison to normal women, the concentration of antigens related to antihemophilic factor (AHF, factor VIII) that are detected in their plasma by heterologous antiserum (factor VIIIR:Ag) is relatively higher than the titer of AHF that is measured in clotting assays (factor VIII:C). Enzyme-linked immunosorbent assay (ELISA) appears to overcome some of the technical difficulties associated with measurement of AHF-like antigens. The results of ELISA correlated closely with those obtained by semiquantitative immunoelectrophoresis, except in patients with von Willebrand's disease. In which ELISA appeared to provide a more quantitative estimate of AHF-like antigen. Utilizing the ELISA technique and a revised method of logarithmic discriminant analysis, we were able to distinguish all of 37 obligate carriers of hemophilia at the level of certainty that would have misclassified 5% of normal women as carriers. The relative simplicity of ELISA suggests its utility in the diagnosis of the carrier state in the female relatives of hemophiliacs.
Evolution of Sezary syndrome in the course of hairy cell leukemia
Authors: Zucker-Franklin D , Amorosi EL , Ritz ND 
Published: October 2019

Abstract
A patient with a history of “leukemia” for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sezary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sezary cells (SC) also belonged. Both types of cells contained tartrate- resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sezary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases.
Staging of chronic lymphocytic leukemia
Authors: Baccarani M , Cavo M , Gobbi M , Lauria F , Tura S 
Published: October 2019

Abstract
One-hundred and eighty-eight patients with chronic lymphocytic leukemia were analyzed for prognosis based on Rai's staging system. It was found that stages I and II were not homogeneous as to prognosis. Stage II patients presenting with isolated splenomegaly had a long survival and were pooled with stage 0 patients (low risk group, 30% of cases, relative death rate 0.24, median survival greater than 10 yr). Stages I and II patients with a lymphocyte count higher than 40 x 10(9)/liter had a short survival and were pooled with stages III and IV patients (high risk group, 39% of cases, relative death rate 1.91, median survival 3.3 yr). Stages I and II patients with a lymphocyte count lower than 40 x 10(9)/liter made up an intermediate or standard risk group (31% of cases, relative death rate 1.00, median survival 6.2 yr). This modified staging system applied successfully to both old and young patients (more and less than 60 yr old, respectively).
Relationship of pretreatment lymphoblast proliferative activity and prognosis in 97 children with acute lymphoblastic leukemia
Authors: Dow LW , Chang LJ , Tsiatis AA , Melvin SL , Bowman WP 
Published: October 2019

Abstract
We have analyzed the pretreatment 3H-thymidine labeling indices in blood and marrow blast cells from 97 children with acute lymphoblastic leukemia (ALL) and circulating blasts. The median marrow labeling index (LI) was 6.2% (range 0.8%--32.7%) and the median blood LI, 3.2% (range 0.3%--20%). Blood LI was significantly correlated with leukocyte count and rosette-forming (E+) lymphoblasts but not with central nervous system leukemia or thymic mass at diagnosis. Marrow LI was related to E+ blasts only. In children with E+ leukemia, both blood and marrow LIs were significantly higher than values for other ALL subtypes (p less than 0.01) excluding undifferentiated ALL, which was characterized by an increased blood LI. Eighteen patients had a blood LI that either equaled or exceeded the marrow LI; apart from age, the clinical features, blast phenotypes, and treatment responses of this group were similar to those of patients with blood LI less than marrow LI. Among 51 patients assessed for treatment response, the estimated median length of remission was significantly shorter for those with a blood LI greater than 4% (p = 0.002) or a marrow LI greater than 6% (p = 0.011). By Cox-regression analysis, the pretreatment proliferative activity of blood and marrow blasts, unlike other initial features studied, added significant prognostic information to leukocyte count in these patients with circulating blasts. The findings provide a cogent explanation for the differential clinical responsiveness of commonly recognized ALL subclasses.
Activation of plasma complement by perfluorocarbon artificial blood: probable mechanism of adverse pulmonary reactions in treated patients and rationale for corticosteroids prophylaxis
Authors: Vercellotti GM , Hammerschmidt DE , Craddock PR , Jacob HS 
Published: October 2019

Abstract
Perfluorocarbons have shown promise as clinical blood substitutes. Although early experience in Japan with one such product--Fluosol-DA-- has been uncomplicated, we observed an adverse pulmonary reaction in the first American patient to receive it and know of similar reactions in two other Americans so treated. Postulating that activation of plasma complement (C) by the perfluorocarbon emulsion might have caused the reaction, we tested the product to determine if it is an activator of complement. Incubation of Fluosol with plasma led to C3 conversion, decrement in CH50, and generation of C5a-related PMN aggregating activity; EDTA prevented such activation, while EGTA did not, suggesting that it proceeded via the alternative C pathway. Infusion of Fluosol into rabbits produced hypoxemia, neutropenia, thrombocytopenia, and pulmonary leukostasis, mimicking abnormalities previously demonstrated in rabbits receiving infusions of zymosan-activated plasma C. These deleterious responses to Fluosol were diminished by premedicating rabbits with corticosteroids (which had seemed to benefit when used empirically in our patient). In vitro and in vivo, Fluosol's effects were reproduced by Pluronic F-68, the nonionic detergent used to maintain the emulsion stability of Fluosol-DA. We conclude that adverse reactions to Fluosol are probably mediated by C activation and that steroid premedication may prevent them in susceptible patients.
Synthesis of fibronectin by the isolated perfused rat liver
Authors: Owens MR , Cimino CD 
Published: October 2019

Abstract
The major site(s) of synthesis of plasma fibronectin is unknown. Using the isolated perfused rat liver and anti-rat fibronectin antiserum, we have measured net hepatic synthesis of fibronectin during 10-hr perfusion periods. We calculated the circulating plasma fibronectin pool of a 195-g rat with body surface area of 300 sq cm to be 3.3 mg: net hepatic synthesis of 3.75 +/- 1.0 mg/300 sq cm body surface area of the rat liver donor was seen in liver perfusions of 10 hr. When the hormones cortisol and insulin were added to the liver perfusate, net synthesis of 5.05 +/- 0.82 mg/300 sq cm was seen. Synthesis of two known acute phase reactant proteins, fibrinogen and alpha-2 acute phase globulin, was also substantially greater in the presence of cortisol and insulin. Plasma fibronectin levels measured in intact rats that had abscess produced by subcutaneous turpentine injection were 0.57 +/- 0;05 mg/ml compared to 0.38 +/- 0.02 mg/ml in normal control animals. Our studies indicate that hepatic synthesis contributes substantially to the plasma fibronectin pool and show that such synthesis is enhanced by the hormones cortisol and insulin. In the intact rat, inflammation was associated with elevated levels of plasma fibronectin.
Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells
Authors: Tarella C , Ruscetti FW , Poiesz BJ , Woods A , Gallo RC 
Published: October 2019

Abstract
Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.
Hematologic Manifestations of Vitamin B12 Deficiency in Swine
Authors: CARTWRIGHT G. E. , TATTING BETTY , ROBINSON JEAN , FELLOWS N. M. , GUNN F. D. , WINTROBE M. M. 
Published: October 2019

Abstract
In an effort to produce a deficiency of vitamin B12 a total of 70 pigs were fed a purified diet containing soybean alpha protein in place of casein. One group of animals was started on the diet at 2 to 7 days of age. A second group began at 21 to 28 days of age. Methionine, iodinate casein, desiccated thyroid and pteroylglutamic acid were added to the diet of certain animals and! omitted from the diet of other pigs. In addition, 9 pigs were gastrectomized. Forty-three of the animals survived for a sufficiently long period of time for adequate evaluation of the results of the experiment.
Severe liver damage was observed in 24 of the 25 animals autopsied. The only animal not showing liver damage received vitamin B12 from the beginning of the experiment. Necrosis of the liver cells, fatty infiltration, or both, occurred in the presence of a high fat diet containing apparently adequate amounts of protein, choline, vitamin E and methionine. These pathologic changes were apparently prevented but not reversed by the administration of vitamin B12.
Growth of the animals on the above diets without added vitamin B12 was retarded as compared with the growth of animals on the same diet supplemented with this vitamin. The administration of vitamin B12 to the deficient animals resulted in rapid growth.
Of the 39 animals not receiving vitamin B12 13 failed to develop anemia, 16 developed a mild anemia and in 10 a moderately severe anemia was present. When present the anemia was normocytic and in 24 pigs was accompanied by a moderately severe neutropenia. Differential cell counts on the sternal marrow were normal except for a slight increase in the proportion of normoblasts. These hematologic alterations were neither consistently or completely corrected by the administration of vitamin B12 in spite of the fact that definite and sometimes marked reticulocyte increases followed.
When methionine deficiency was associated with vitamin B12 deficiency, anemia appeared to be more severe.
The administration of aureomycin, an "animal protein factor," did not stimulate growth and failed to induce a hemopoietic response.
There was no macrocytic anemia, the bone marrow was not megaloblastic, and neurologic disturbances or morphologic alterations in the neutrophils were not observed.
These results are in contrast to those obtained in pigs with an experimentally produced deficiency of pteroylglutamic acid. Such animals develop macrocytic anemia, leukopenia and a macronormoblastic type of bone marrow.
It is not possible to give with any assurance the reason why megaloblastic anemia was not produced in the "B12-deficient" animals. This may have been due to the fact that (1) the deficiency was not sufficiently severe to result in such a change in the hemopoietic system; or (2) because pteroylglutamic acid prevents the development of megaloblastic anemia even in the absence of vitamin B12.
In vitro proliferation of hematopoietic stem cells in the absence of an adherent monolayer
Authors: Eastment C , Denholm E , Katsnelson I , Arnold E , Ts'o PO 
Published: October 2019

Abstract
Experiments on long-term murine bone marrow cultures indicate that the production and maintenance of the hematopoietic stem cell is dependent on the establishment of an adherent monolayer and a secondary repopulation of the culture with fresh marrow. In contrast, we have found that bone marrow cultures derived from the Syrian hamster do not require a repopulation step and produce stem cells that proliferate and differentiate for more than 12 wk in the absence of an adherent layer. Stem cells were grown in Fisher's medium (pH 7.0–7.2) containing 20% horse serum in a fully humidified atmosphere of 5% CO2 in air at 37 degrees C. Cultures were fed twice weekly by removal of half of the medium and supernatant cells and replacement with an equal volume of fresh medium. No hormones or exogenous growth factors were required for the maintenance of myeloid cells, monocytes, and megakaryocytes in either the adherent or suspension cells cultures.
Isolation of myeloid progenitor cells from peripheral blood of chronic myelogenous leukemia patients
Authors: Griffin JD , Beveridge RP , Schlossman SF 
Published: October 2019

Abstract
Myeloid progenitor cells (colony- and cluster-forming cells in semisolid medium, CFU-GM) were purified from the peripheral blood of chronic myelogenous leukemia (CML) patients. Lymphocytes, monocytes, and most immature myeloid cells were simultaneously depleted with specific monoclonal antibodies using an erythrocyte rosette technique for cell separation. Cells expressing Ia-like antigen were then selected from the residual cell population. Day 7 CFU-GM were enriched 44--116-fold in the IA+ cell fraction, when compared to the unseparated cells, and up to 47% of the cells could form a myeloid colony or cluster in culture. This cell fraction contained up to 92% undifferentiated blasts, with the remainder mostly promyelocytes. The enriched CFU-GM cells were dependent on an exogenous supply of colony- stimulating factor for growth, and colony formation was linear with cell concentration over a large range (10(4)-10(1) cells/ml). This technique of rosette depletion and enrichment with specific monoclonal antibodies provides a unique method for purifying a homogenous population of myeloid precursor cells with defined surface antigen characteristics.
Enzymatic activities of activated and zymogen forms of human Hageman factor (factor XII)
Authors: Silverberg M , Kaplan AP 
Published: October 2019

Abstract
Pro-Phe-Arg chloromethylketone (PPACMK) at 5.26 microM inactivated the amidolytic activity of native human Hageman factor with an apparent first-order rate constant of 0.75 min-1. The activated forms of Hageman factor, Hfa and HFf, were also inactivated by PPACMK with rate constants 0.82 and 0.72 min-1. These numbers indicate that the activity detectable in native Hageman factor is due to contamination with activated species. Uncleaved Hageman factor reacts slowly with 40 mM diisopropyl fluorophosphate with concomitant loss of its procoagulant activity. Incubation of native Hageman factor with PPACMK does not destroy its procoagulant activity, even in the presence of the activator dextran sulphate, but PPACMK inhibits autoactivation of Hageman factor, suggesting that no active site is formed in uncleaved, surface-bound Hageman factor. The activation of prekallikrein by Hageman factor under initial-rate conditions occurs after a lag and is prevented by an inhibitor of Hageman factor from corn. The kinetics of prekallikrein activation and the effects of inhibitors provide evidence that the amidolytic and proteolytic activities of human Hageman factor reside in the activated forms derived by limited proteolysis of the native molecule.
Abnormal erythroid progenitor cells in human preleukemia
Authors: Chui DH , Clarke BJ 
Published: October 2019

Abstract
Ten patients with preleukemia were studied by the erythroid cell clonal culture technique. In nine of these patients, erythroid colonies derived from peripheral blood BFU-E were not observed, while the other patient had markedly decreased peripheral blood BFU-E-derived erythroid colonies in vitro. In three patients, marrow cells were also cultured and no BFU-E-derived erythroid colonies were detected. These studies indicate that immature erythroid progenitor cells, BFU-E, in patients with preleukemia are either markedly decreased in number or grossly defective in their proliferative or differentiative capacities.
Comparison of 125I-fibrinogen kinetics and fibrinopeptide A in patients with disseminated neoplasias
Authors: Mombelli G , Roux A , Haeberli A , Straub PW 
Published: October 2019

Abstract
To provide more information on the pathways of fibrinogen catabolism in generalized cancer, the effect of heparin on fibrinopeptide A (fpA) and on 125I-fibrinogen kinetics was studied in 15 patients with disseminated neoplasia. Three patients had evidence of venous thrombosis and in 2 additional patients a low fibrinogen level together with increased amounts of FDP/fdp and a positive ethanol test indicated disseminated intravascular coagulation (DIC). The plasma levels of fpA were grossly elevated (4.6--20, mean 11.4 ng/ml, normal values 1.01 +/- 0.45 ng/ml) in patients with thrombosis or DIC, and normal to grossly elevated (0.4--10.4, mean 6.1 ng/ml) in the other patients. Intravenous heparin bolus lowered the fpA level in 11/11 patients, and continuous heparin treatment led to an impressive suppression or complete normalization of the plasma fpA in 5/6 patients. This finding is thought to reflect heparin suppression of thrombin activity on fibrinogen. In some cases, the fpA fall after heparin bolus was slow and/or incomplete, suggesting fpA generation at sites not easily accessible to heparin or insufficient heparin dosage. The 125I- fibrinogen kinetics were characterized by a significantly shorter half- life (t1/2: 2.5 days), increased catabolic rate constant (j: 0.44 days- 1), and increased absolute turnover (68.9 mg fibrinogen/kg/day) as compared to 4 normal subjects (t1/2: 4.2 days; j: 0.26 days-1; turnover 21.7 mg fibrinogen/kg/day). As estimated from the fpA generation rates, intravascular thrombin action on fibrinogen contributed only in minor part to increase the turnover of 125I-fibrinogen. In particular, the turnover was greatly accelerated in heparin-treated patients despite impressive suppression or normalization of the fpA levels in 5/6 cases.
Allogeneic bone marrow transplantation in acute nonlymphocytic leukemia: a pilot study
Authors: Kersey JH , Ramsay NK , Kim T , McGlave P , Krivit W , Levitt S , Filipovich A , Woods W , O'Leary M , Coccia P , Nesbit ME 
Published: October 2019

Abstract
The objective of the current study, initiated in 1976, was to improve upon the high relapse rate and subsequent mortality in children and young adults with acute nonlymphocytic leukemia (ANLL). Seventeen patients, ages 6--28, with ANLL in first bone marrow remission, received cyclophosphamide and total body irradiation using a radiation scheme of 750 rad (7.5 Gy) total dose, delivered at a dose rate of 26 rad (26 cGy) per minute. Allogeneic marrow from HLA-matched sibling donors was followed by prophylactic therapy or graft-versus-host disease (GVHD). Median follow-up of the entire group is 20+ mo; survivors have been followed for a minimum of 14+ mo. Interstitial pneumonitis was observed in 6% of patients, and GVHD was observed in 29%. Seventy percent of patients are alive and in complete continuous remission. Two patients have relapsed (at 7 and 24 mo). Actuarial relapse-free survival is 76% at 1 yr and 64% at 5 yr. Quality of life in this disease-free survivors is excellent; all patients are free of active GVHD, receive no maintenance chemotherapy, and have high Karnofsky performances scores. High dose rate total body irradiation plus cyclophosphamide followed by allogeneic BMT may provide an opportunity for long-term complication-free survival in a substantial proportion of children and young adults with ANLL.
Fibronectin enhances in vitro monocyte-macrophage-mediated tumoricidal activity
Authors: Perri RT , Kay NE , McCarthy J , Vessella RL , Jacob HS , Furcht LT 
Published: October 2019

Abstract
Control of neoplastic proliferation reflects in part monocyte/macrophage destruction of target cells--destruction that evidently requires cell-cell interaction. We herein show it to involve the natural plasma opsonin, fibronectin. With two cultured human tumor lines--Malme melanoma and CAK-I renal carcinoma cells--addition of fibronectin, purified to homogeneity, enhances macrophage-mediated cytotoxicity 2--4-fold (p less than 0.01). Both fresh human monocytes or the U-937-cultured macrophage line become more lethal to tumor cells with added fibronectin. The fibronectin-enhanced monocyte and U-937 tumoricidal activity occurred in a dose-dependent fashion. Specificity of fibronectin's action was validated by use of affinity-purified rabbit antifibronectin antibody, which completely abated its enhancement of tumoricidal activity. Enhancement of tumoricidal activity did not occur when monocytes or U-937 were exposed to fibronectin-coated plates. However, the addition of soluble fibronectin to fibronectin-coated plates was then capable of enhancing cytocidal activity. These studies demonstrate that human fibronectin is capable of increasing both fresh and cultured human monocyte tumor-directed cytotoxicity. Fibronectin appears to be a potentially important circulating molecule that may favorably influence human monocyte tumor cell cytotoxicity.