Showing papers by "St. Jude Children's Research Hospital published in 1979"
TL;DR: Results presented herein suggest that the stimulation of phospholipase A 2 by Ca 2+ is also mediated through calmodulin, adding to the growing list of enzymes whose activities are regulated by cal modulin.
301 citations
TL;DR: It was found that antigenic changes in individual determinants of the haemagglutinin molecule of A/PR/8/34 (H0N1) occurred with an average frequency of 10−6 per infectious dose of virus and that the three determinants described here mutated independently of each other.
Abstract: Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule
209 citations
TL;DR: Three monoclonal hybridoma antibodies were used to select a total of 10 antigenic variants of A/Mem/1/71 (H3N2) virus and a dramatic change in antigenicity appeared to be associated with a single change in the amino acid sequence of the large hemagglutinin polypeptide, HA1.
172 citations
TL;DR: An important role for leukocyte amine components in myeloperoxidase-catalyzed antimicrobial activity in vivo is suggested, due to the ability of NH(2)Cl to penetrate the hydrophobic cell membrane and thus to oxidize intracellular components.
Abstract: Exogenous ammonium ions (NH(4) (+)) and amine compounds had a profound influence on the antibacterial activity of the myeloperoxidase-hydrogen peroxide-chloride system against Escherichia coli. The rate of killing increased in the presence of NH(4) (+) and certain guanidino compounds and decreased in the presence of alpha-amino acids, polylysine, taurine, or tris (hydroxymethyl) aminomethane. Myeloperoxidase catalyzed the oxidation of chloride to hypochlorous acid, which reacted either with bacterial amine or amide components or both or with the exogenous compounds to yield chloramine or chloramide derivatives or both. These nitrogen-chlorine derivatives could oxidize bacterial components. Killing was correlated with oxidation of bacterial components. The rate of oxidation of bacterial sulfhydryls increased in the presence of the compounds that increased the rate of killing and decreased in the presence of the other compounds. The reaction of HOCl with NH(4) (+) yielded monochloramine (NH(2)Cl), which could be extracted into organic solvents. The N-Cl derivatives of bacterial components or of polylysine, taurine, or tris(hydroxymethyl)aminomethane could not be extracted. The effect of NH(4) (+) on killing is attributed to the ability of NH(2)Cl to penetrate the hydrophobic cell membrane and thus to oxidize intracellular components. Polylysine, taurine, and tris(hydroxymethyl)aminomethane formed high-molecular-weight, charged, or polar N-Cl derivatives that would be unable to penetrate the cell membrane. These results suggest an important role for leukocyte amine components in myeloperoxidase-catalyzed antimicrobial activity in vivo.
169 citations
TL;DR: The mode of stimulation of human erythrocyte Ca2+-Mg2--ATPase by calmodulin appears similar to that of Ca2-dependent adenylate cyclase and phosphodiesterase.
112 citations
TL;DR: Patients meeting the criteria described herein are at low risk to develop toxicity with conventional leucovorin rescue and that high-risk patients may be identified early enough to reduce or prevent toxicity.
Abstract: The administration of high-dose methotrexate (HDMTX) with leucovorin rescue carries with it a risk of severe toxicity which may be fatal. In the present study, patients with a 24-h serum concentration of 5 x10- M and an elimination half-life (T1/2) of 3.5 h during the first 24 h after the infusion were considered at low risk for toxicity and received conventional lowdose leucovorin rescue. Patients not meeting these criteria were considered at high risk for toxicity and received an escalated and extended course of leucovorin. The low-risk criteria were met following 109 of 114 HDMTX infusions administered to 30 patients. None of these patients developed toxicity with low-dose leucovorin. The 24-h serum concentration and the t1/2 exceeded the low-risk criteria following five HDMTX infusions administered to three patients. In two of these three patients leucovorin was continued until the MTX concentration was 10-8 M (168–265 h) and no toxicity developed. The third high-risk patient discontinued his leucovorin 11 days prior to a MTX serum concentration 10-8 M and developed moderate toxicity. Clinical features present in the three high-risk patients, which were not present in the low-risk group, included a pleural effusion in one patient and gastrointestinal obstruction in the other two patients. The identification of 3/30 high-risk patients in the present study was consistent with a historical control group in which 6/65 patients developed severe toxicity. These data indicate that patients meeting the criteria described herein are at low risk to develop toxicity with conventional leucovorin rescue and that high-risk patients may be identified early enough to reduce or prevent toxicity.
103 citations
TL;DR: The observation that antigenic differences could be detected between the recent variants with such a small panel of monoclonal antibodies suggests that monoconal antibodies may provide an exquisitely sensitive method for antigenic mapping of influenza viruses.
100 citations
TL;DR: Since the current system of nomenclature was adopted in 1971, it has become apparent that several subtypes can be grouped together and based on new information, consideration is now being given by the World Health Organization to reducing the number of subtypes.
Abstract: Introduction The present system for the nomenclature of influenza viruses is based on recommendations by the participants in a World Health Orgarfization meeting in 1971 (59). The influenza viruses were divided into types A, ]~ and C on the basis of the antigenic character of the internal nucleoprotein (NP) antigen. The other elements of the nomenclature included: the host from which the strain was isolated, the geographical location, the strain number, and the year of isolation. Influenza A viruses were further divided into subtypes on the basis of the character of the hemagglutinin (H) and neuraminidase (N) antigens, e.g., A/Swine/ Wisconsin/I/67 (11sw 1 N 1). A uniform system of nomenclature was recommended for influenza viruses from human and non-human (swine, equine, avian) sources. In this system of nomenclature, inlluenza A viruses are divided into 16 hemagglutinin and 10 neuraminidase subtypes (12, 56, 57, 59). There are four 11 and two N subtypes of influenza A viruses from man (110N1, H1N1 , H 2 N 2 , and 113N2), one I t and N subtype from swine (11swlN1) and two from horses (11eq 1 Neq 1; I teq2Neq2). The largest number of different antigens exists in the avian viruses which include 91t and 6N subtypes, as well as, many of the subtypes present in mammalian viruses. Since the current system of nomenclature was adopted in 1971, it has become apparent that several subtypes can be grouped together and based on new information, consideration is now being given by the World Health Organization to reducing the number of subtypes (60, 42).
75 citations
01 Jan 1979
TL;DR: This chapter defines those viruses that have or may have icosahedral symmetry, appear to replicate in the cytoplasm, and contain DNA, which includes viruses from plants, invertebrates, and vertebrates.
Abstract: Deoxyriboviruses having an apparent icosahedral symmetry and replicating in the cytoplasm have been titled “icosahedral cytoplasmic deoxyriboviruses” (ICDVs) (Kelly and Robertson, 1973; McAuslan and Armentrout, 1974). Members of this group are widely distributed in nature in a variety of hosts and include iridescent viruses from insects, lymphocystis virus from fish, amphibian viruses, African swine fever virus, and cauliflower mosaic and related viruses from plants (Granoff, 1969; Stoltz, 1971; Plowright, 1972; Kelly and Robertson, 1973). In this chapter we have chosen to retain the term “icosahedral cytoplasmic deoxyribovirus,” but because of the diversity of properties of these viruses this term is inadequate for classification and nomenclature pur poses. We might compare this term to grouping papovaviruses, adenoviruses, and herpesviruses under the heading of “icosahedral nuclear deoxyriboviruses.” Our usage of this term merely defines those viruses that have or may have icosahedral symmetry, appear to replicate in the cytoplasm, and contain DNA. It does not imply any taxonomic relationships and includes viruses from plants, invertebrates, and vertebrates. The designation “ICDV” is useful in distinguishing these viruses from the morphologically distinct and structurally complex poxviruses, which also replicate in the cytoplasm (Moss, 1974).
61 citations
TL;DR: F follicular lymphoma in children appears to be different from both its adult counterpart and the diffuse childhood lymphomas, including the absence of tumors of poorly differentiated lymphocytic type, the higher frequency of stage I‐II disease and the better prognosis.
Abstract: Eight cases of follicular lymphoma (FL) were found amount 318 children with non-Hodgkin's lymphoma seen in two decades in four large institutions (overall incidence: 2.5%). The children's ages ranged from 3 to 13 years (median 8). Four patients presented with localized peripheral lymphadenopathy, two with tumors of the digestive tract, two with disseminated disease. Five were tentatively classified as stage I or II and 3 as stage IV. The existence of other diseases responsible for lymphadenopathy could satisfactorily be exclued. All patients are alive after follow-up periods of 1 to 14 years from diagnosis (median 4). Morphologically, 5 lymphomas were mixed and 3 histiocytic. The growth pattern was "expansile" in the younger patients (3 to 9 years), and "infiltrative," as in the adult disease, in the three older children (11 to 13 years). The histiocytic cytology correlated with stage IV disease. FL in children appears to be different from both its adult counterpart and the diffuse childhood lymphomas. Differences with the former include the absence of tumors of poorly differentiated lymphocytic type, the higher frequency of stage I-II disease and the better prognosis. This last feature, as well as the higher frequency of peripheral node involvement and the absence of leukemic conversion or CNS disease, differentiates the follicular from the diffuse childhood lymphomas.
61 citations
TL;DR: Well-defined fragments of the sialoglycoproteins were produced by the freeze-fracture procedure, indicating that selected covalent bonds of these transmembrane proteins were broken.
Abstract: Human erythrocytes have been freeze-fractured, and the polypeptides associated with the separate halves of the membrane bilayer have been analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The transmembrane proteins were differentially separated by the fracture process. Although sialoglycoproteins associated with the outer half of the membrane, the anion transport protein (band 3) mainly remained with the inner half of the membrane. Well-defined fragments of the sialoglycoproteins were produced by the freeze-fracture procedure, indicating that selected covalent bonds of these transmembrane proteins were broken.
TL;DR: Washed human platelets were solubilized and the proteins were separated by preparative gel electrophoresis in the presence of sodium dodecyl sulphate and the effect of the eluted proteins on the clotting of fibrinogen by thrombin was evaluated.
Abstract: Washed human platelets were solubilized and the proteins were separated by preparative gel electrophoresis in the presence of sodium dodecyl sulphate. The gel was cut into slices and the effect of the eluted proteins on the clotting of fibrinogen by thrombin was evaluated. The isolate from only one gel slice strongly inhibited the clotting of fibrinogen. The prolongation of the clotting time was dependent on the concentration of the protein and reached a plateau around 5 microgram. Gel electrophoresis of this isolate showed a prominent glycoprotein with an apparent Mr=150 000. Gel filtration studies with [125I]thrombin showed that the protein isolate bound a significant amount of thrombin which could be displaced with unlabelled thrombin. Another preparation from the same gel or purified gamma-globulin did not bind thrombin or prolong the clotting time of fibrinogen. Glycoprotein I was isolated from human platelets by affinity chromatography on lectin-Sepharose columns. The isolated glycoprotein prolonged the clotting of fibrinogen and bound [125I]thrombin which could be displaced by unlabelled thrombin. It is proposed that the high affinity receptor of thrombin on human platelets is glycoprotein I. In addition, the antithrombin activity of intact platelets is due to binding of thrombin to this glycoprotein.
TL;DR: Macrophage subpopulations derived from PE macrophages placed in tissue culture for 7 days and macrophageSubpopulation cells cultured for 2 days showed differences in acid phosphatase content similar to those seen with freshly obtained subpopulation.
TL;DR: In this paper, the serial cytogenetic findings over a 2-yr period for a patient with juvenile chronic myelogenous leukemia (JCML) were reported, and a large subtelocentric marker chromosome was noted in all metaphases throughout the course of his disease and provided evidence for a clonal etiology of JCML in this patient.
TL;DR: Results are consistent with a unicellular origin for the colonies only when they are cultured at low densities, and there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.
TL;DR: The hypothesis that cyclic GMP is directly involved in stimulus–secretion coupling, but not in a direct causative pathway leading to discharge, is not supported but the requirement for extracellular Ca2+ correlated well with discharge.
Abstract: THE pancreatic acinar cell discharges secretory proteins in response to cholecystokinin–pancreozymin (CCK–PZ) and its analogues, or to cholinergic agonists such as carbamylcholine (carbachol). The mechanisms for stimulus–secretion coupling in the acinar cell are not known, although intracellular and, to some extent, extracellular Ca2+ are required1–4, and a transient 10- to 20-fold increase in intracellular levels of guanosine cyclic 3′5′-monophosphate (cyclic GMP) accompanies onset of induced discharge5,6. It has been proposed5 that cyclic GMP may be a direct mediator of hormone-stimulated discharge, with the Ca2+-dependent event either causing, or being caused by, increases in cyclic GMP7,8. To test this hypothesis, we have monitored the effects of several substances on secretory protein discharge and intracellular cyclic GMP levels in guinea pig pancreatic acini. Our results, reported here, are not consistent with a role for cyclic GMP in a direct causative pathway leading to discharge, as four of the compounds tested (N-methyl-N-nitro-N-nitrosoguanidine (MNNG), sodium nitrite, hydroxyl-amine and sodium nitroprusside) elevated levels of cyclic GMP but did not trigger discharge, although acini treated with these agents remained competent to respond to natural secretagogues. Conversely, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) did not affect cyclic GMP levels, but did elicit discharge. In contrast to observations on cyclic GMP, the requirement for extracellular Ca2+ correlated well with discharge. Our findings therefore do not support the hypothesis that cyclic GMP is directly involved in stimulus–secretion coupling, but are consistent with such a role for Ca2+. A preliminary report of this work has appeared9.
TL;DR: The details of a two-dimensional separation procedure specially designed for the study of erythrocyte membranes are presented and over 90 discrete polypeptides could be detected with this method in the pH range of 5 to 8.
TL;DR: Findings indicate that more specimens are likely to be identified at T-cell luekemias when E-rosette tests of increasing sensitivity and assayss for T- cell antigens are used.
TL;DR: It is indicated that cyclic AMP can enter erythrocytes in sufficient amounts to alter the activity of cyclicAMP-dependent protein kinases, or to altered the rate of turnover of certain phosphorylated membrane peptides.
TL;DR: This lectin stimulates platelets by a mechanism which closely mimics thrombin activation and is independent of intercellular crosslinking.
TL;DR: Inactivated whole-virus vaccine of influenza A/Scotland/74 (H3N2) virus containing 700 or 1,400 chick cell-agglutinating (CCA) units, a purified subunit vaccine of equivalent dosage, or placebo were studied in 186 adult volunteers.
Abstract: Inactivated whole-virus vaccine of influenza A/Scotland/74 (H3N2) virus containing 700 or 1,400 chick cell-agglutinating (CCA) units, a purified subunit vaccine of equivalent dosage, or placebo were studied in 186 adult volunteers. Placebo was least reactogenic, 1,400-CCA unit whole-virus vaccine was most reactogenic, and others were intermediate. Vaccines were equally antigenic, and delineation of antibody specificities revealed antibody cross-reacting with A/Hong Kong/68 (H3N2) virus in all sera. Antibody specific for A/Hong Kong/68 virus was found in 82% of sera and for A/Scotland/74 virus in 46%. When compared with volunteers given placebo, volunteers given 700 CCA units of subunit or whole-virus vaccine exhibited significant protection against infection with live A/Scotland/74 virus. Infections in vaccinees occurred only in those with low titers of antibody to A/Scotland/74 virus, and this antibody was of the cross-reacting type. Persons with moderate and high levels of antibody resisted infection regardless of the absence or presence of antibody specific for A/Scotland/74 virus. Purified subunit vaccines provide an alternative to whole-virus preparations in primed individuals. Efficacy of vaccines may be dependent on the nature of the antibody response.
TL;DR: Data are consistent with the conclusion that inhibition of host cell protein synthesis by ΔFV3 is the result of a selective effect on a step(s) essential for the initiation of translation of cellular mRNAs.
TL;DR: Results emphasize a major form of treatment morbidity resulting from the combined use of multiple radiopotentiating agents and therapeutic irradiation of the gastrointestinal tract.
Abstract: Delayed gastrointestinal complications were reviewed following combined modality therapy in 16 children with non-disseminated rhabdomyosarcoma (RMS) involving the retroperitoneum. Six patients experienced severe life-threatening enteritis or proctitis which was documented histologically and occurred in the absence of recurrent tumor; 3 patients subsequently died of small bowel obstruction and attendant complications. These results emphasize a major form of treatment morbidity resulting from the combined use of multiple radiopotentiating agents and therapeutic irradiation of the gastrointestinal tract.
TL;DR: Since the terminal sialic acid has been implicated in the clearance of platelets from the circulation, wheat germ agglutinin may prove to be a useful tool to explore those clinical conditions in which platelet survival is shortened.
TL;DR: Fathead minnow cells co-infected with purified frog virus 3 DNA and either ultraviolet light-irradiated virus or a temperature-sensitive mutant at a nonpermissive temperature produced infectious progeny with the genotype of the purified DNA.
TL;DR: Previous evidence for the existence of numerous viral regulatory proteins in the control of frog virus 3 gene expression at the transcriptional and post-transcriptional levels is corroborated and extended.
Abstract: Using fluorophenylalanine (FPA) to interfere with functional viral protein synthesis, we have investigated the complex transcriptional and post-transcriptional controls that operate in cells infected with frog virus 3. Our previous data, obtained by polyacrylamide gel electrophoresis of viral RNAs and proteins, showed that the addition of FPA at the beginning of infection completely prevented the synthesis of late viral RNAs and late viral proteins and blocked the normal progressive decline in the rates of synthesis of two quantitatively different classes (class I and class II) of early proteins. These results indicated that the initiation of late RNA and late protein syntheses, as well as the post-transcriptional regulation of early protein synthesis, was under the control of virus-specific proteins (D. B. Willis, R. Goorha, M. Miles, and A. Granoff, J. Virol. 24:326-342, 1977). In this communication, we show that the viral protein required to "turn on" the synthesis of late RNAs and late (class III) proteins was made within 1 to 1.5 h postinfection (p.i.); when we added FPA after this time, we observed the synthesis of all of the late macromolecules. The data also suggest that another viral protein, separate from the "turn-on" protein, controlled the abundance of late RNAs. In addition, at least two separate proteins were involved in the post-transcriptional regulation of two classes of early proteins. When FPA addition was delayed until 2 h p.i., the rate of synthesis of class I proteins (which normally peaked at 2 h p.i.) was reduced by 6 h p.i. just as in a normal infection, but the rate of synthesis of class II proteins (which normally reached a maximum at 4 h p.i. before declining) was reduced only when we waited until 3 or 4 h p.i. to add FPA. These experiments corroborate and extend previous evidence for the existence of numerous viral regulatory proteins in the control of frog virus 3 gene expression at the transcriptional and post-transcriptional levels.
TL;DR: In this article, the clinical courses of 17 patients who had relapsed in the bone marrow after elective cessation of therapy and had been treated again with systemic combination chemotherapy without meningeal prophylaxis were studied.
TL;DR: These studies conclusively demonstrate that (1) a virus-specific protein is required for late transcrip ion and (2) viral DNA synthesis per se is insufficient for the synthesis of late viral mRNAs and proteins.
TL;DR: Results indicate that the predominantly pentacoordinate Fe3+ ion in horseradish peroxidase is accessible to the solvent and that it acquires a water or hydroxyl ligand in the presence of benzohydroxamic acid.