Showing papers by "St. Jude Children's Research Hospital published in 1983"
TL;DR: It is shown that cultivation of influenza B viruses in eggs selects subpopulations which are antigenically distinct from virus from the same source grown in mammalian cell cultures.
Abstract: Extensive antigenic variability and a capricious epidemiology are characteristics of influenza A and B viruses of man. The haemagglutinin (HA) undergoes frequent and progressive antigenic drift as a result of selection, under immunological pressure, of viruses possessing alterations in the amino acid sequences at specific sites in the molecule1. Here we present evidence for an additional selection mechanism for antigenic variants of influenza virus that depends on differing host cell tropisms of virus subpopulations. These studies were initiated after earlier observations of the occurrence of a marked degree of antigenic variation during passage of laboratory strains of influenza virus in eggs and cell cultures (J.C.J., in preparation). We have now shown that cultivation of influenza B viruses in eggs selects subpopulations which are antigenically distinct from virus from the same source grown in mammalian cell cultures. As antigenic characterization of influenza virus strains for epidemiological purposes2 and for the preparation of influenza vaccines3 conventionally relies on the cultivation of virus in eggs, our findings may have important practical implications for vaccine design and efficacy.
303 citations
125 citations
TL;DR: These studies provide the first evidence that the hemagglutinin and neuraminidase are critical for the enterotropism of avian viruses but are not essential for replication in other avian tissues.
102 citations
TL;DR: Monoclonal antibodies specific for the acid-induced conformation of the H3 HA efficiently inhibited hemagglutination of the virus at low pH but were extremely poor inhibitors of virus-induced red blood cell hemolysis at its pH optimum of 5.1.
96 citations
TL;DR: The data indicate that the prognosis for children with neuroblastoma metastatic only to regional lymph nodes is no different from that of patients of similar age with widely disseminated tumor.
86 citations
TL;DR: The substantial interpatient variability in CSF distribution of MTX after intermediate‐dose MTX infusions is established and a significant correlation between steady‐state free concentration ofMTX in serum and CSF MTX concentration is established.
Abstract: Twenty-nine children with acute lymphocytic leukemia were given 24-hr infusions of intermediate-dose methotrexate (MTX, 1000 mg/m2) with and without intrathecal (IT) MTX (12 mg/m2), followed by leucovorin rescue There was substantial interpatient variability in MTX systemic clearance (983 +/- 51 ml/min/m2), inducing total steady-state serum MTX concentrations ranging from 54 to 337 microM The cerebrospinal fluid (CSF) concentration at the end of the infusion was 027 (+/- 01) microM when no IT-MTX was given and correlated with total steady-state (24-hr) serum concentration of MTX By stepwise regression, the CSF MTX concentration correlated better with the nonprotein bound (free) steady-state serum MTX concentration (r = 066, P less than 001) than with total steady-state serum MTX concentration Mean CSF: serum MTX concentration ratio was 0023 (+/- 004) when no IT MTX was given When an IT MTX dose (12 mg/m2) was given at the start of the MTX infusion, the steady-state CSF MTX concentration was 11 (+/- 04) microM, leading to a mean CSF: serum ratio of 0073 (+/- 005) Despite 7-hydroxy-MTX serum concentrations exceeding MTX concentrations immediately after infusion, 7-hydroxy-MTX was not detectable in CSF of most patients (21 of 29), and was less than 50% of the concurrent MTX concentration when detectable These data establish the substantial interpatient variability in CSF distribution of MTX after intermediate-dose MTX infusions and establish a significant correlation between steady-state free concentration of MTX in serum and CSF MTX concentration
79 citations
TL;DR: 13C nuclear magnetic resonance (NMR) of methotrexate, trimethoprim, and pyrimethamine enriched 90% with 13C at C2 has provided a sensitive means of detecting the state of protonation of the heterocyclic rings of these inhibitors.
78 citations
TL;DR: It appears that EBV infections are capable of inducing symptoms similar to those seen in JCML, and changes in patients presenting with symptoms compatible with JCML suggest an underlying defect in the immunoregulatory network controlling EBV infection.
72 citations
TL;DR: In children as well as adults, specific structural abnormalities are correlated with certain morphologic subgroups of ANLL, and statistical analysis of 27 abnormal karyotypes showed preferential structural rearrangement of 8q and 21q.
65 citations
TL;DR: Diminished in vivo and in vitro immunoglobulin synthesis in Evans syndrome is consistent with the decreased T4:T8 ratio in these patients, which may represent an unsuccessful response to an autoimmune process in which the trigger is unknown.
Abstract: Immune function in six patients with Evans syndrome (Coombs-positive hemolytic anemia and immune thrombocytopenia) was compared to that in seven with chronic ITP. The two groups differed in measurements of T-cell subsets and immunoglobulin production. Evans syndrome patients had decreased T4 (T-helper) (P = 0.025), increased T8 (T-suppressor) (P = 0.008), and a decreased ratio of T4:T8 cells (P = 0.0009) when compared to controls. Results in chronic ITP patients were similar to those in controls. Serum IgG, IgM, and IgA levels and in vitro synthesis of IgG and/or IgM were decreased in most Evans syndrome patients. Diminished in vivo and in vitro immunoglobulin synthesis in Evans syndrome is consistent with the decreased T4:T8 ratio in these patients. The altered T4:T8 ratio may represent an unsuccessful response to an autoimmune process in which the trigger is unknown.
65 citations
TL;DR: It is suggested that turkeys as well as pigs are involved in the maintenance of these viruses and their transmission to humans.
Abstract: Influenza A viruses (subtype H1N1), recently isolated from turkeys in different areas of the United States, were determined to be closely related to strains typically associated with pigs. This conclusion was based on comparisons of H1N1 isolates from pigs, humans, ducks, and turkeys with polyclonal and monoclonal antibodies, RNA-RNA competitive hybridization, and replication studies. One of the H1N1 isolates from turkeys caused influenza in a laboratory technician, who displayed fever, respiratory illness, virus shedding, and seroconversion. These results suggest that turkeys as well as pigs are involved in the maintenance of these viruses and their transmission to humans.
TL;DR: It is hypothesized that DCF therapy created a selection pressure, blocking pathways of T‐cell differentiation and proliferation, permitting the emergence of a newly dominant myeloid subclone of a multipotential leukaemic cell progenitor with the innate capacity for both T‐lymphocytic and myeloids differentiation.
Abstract: Summary.
A 6-year-old boy with T-cell acute lymphoblastic leukaemia (ALL) in relapse was treated with the adenosine deaminase inhibitor, 2′-deoxycoformycin (DCF). Remarkably, his residual leukaemia underwent an abrupt phenotypic shift, coincident with a massive anti-leukaemic effect of DCF. Both at diagnosis and prior to therapy with DCF, blast cells had typical lymphoblastic morphology and T-cell characteristics (terminal transferase +, T-antigen +, Ia –, cALLa –, myeloperoxidase –, and high in adenosine deaminase content). After four courses of DCF by constant infusion, the blast cells were myeloid in appearance and reactivity to a variety of tests (terminal transferase –, myeloperoxidase +, Sudan black B +, esterase +, My-1 +). We hypothesize that DCF therapy created a selection pressure, blocking pathways of T-cell differentiation and proliferation, permitting the emergence of a newly dominant myeloid subclone of a multipotential leukaemic cell progenitor with the innate capacity for both T-lymphocytic and myeloid differentiation.
TL;DR: A double-strand DNA copy of the influenza virus A/Seal/Mass/1/80 (H7N7) [seal] hemagglutinin (HA) gene was cloned into the plasmid pAT153/PvuII/8 and sequenced to deduce the primary amino acid sequence.
TL;DR: It is proposed that, in the current system of nomenclature, two serotypes of paramyxoviruses isolated from waterfowl in the U.S.A. and Japan be designated PMV-8 and PMv-9, for which the prototype strain would be PMVs-8/goose/Delaware/1053/76 andPMV-9/domestic duck/New York/22/78.
Abstract: Representatives of paramyxoviruses isolated from waterfowl in the U.S.A., goose/Delaware/1053/76, and Japan, pintail/Wakuya/20/78, were shown to be serologically closely related but distinct from other avian paramyxoviruses. Another isolate, from domestic ducks in the U.S.A., was shown to be representative of a further distinct serotype of avian paramyxoviruses. We propose that, in the current system of nomenclature these serotypes be designated PMV-8, for which the prototype strain would be PMV-8/goose/Delaware/1053/76 and PMV-9, for which the prototype strain would be PMV-9/domestic duck/New York/22/78.
TL;DR: An update on pediatric pharmacokinetics of anticancer drugs in children is warranted due to the increased understanding of the age-related changes that govern drug disposition: absorption, distribution, metabolism, and elimination.
Abstract: Several comprehensive reviews of the disposition of anticancer drugs in children with cancer have been published (1–7). However, recent advances in cellular and molecular biology techniques have led to the design and analysis of clinical pharmacology studies, which have increased our understanding of the age-related changes that govern drug disposition: absorption, distribution, metabolism, and elimination. Moreover, recent studies have characterized the disposition of new anticancer drugs in children, as well as contributed new insights into the use of currently available anticancer drugs. Thus, an update on pediatric pharmacokinetics of anticancer drugs in children is warranted.
TL;DR: It is indicated that antibodies to the hemagglutinin of influenza virus can inhibit virus-induced hemolysis by blocking conformational change in the hemagenetic molecule and blocking later step of fusion than the conformationalchange, in addition to blocking attachment of virus to the receptor of erythrocytes.
Abstract: A/seal/Massachusetts/1/80 (H7N7) influenza virus caused maximal hemolysis at pH 5.9. Monoclonal antibodies to each of the four nonoverlapping antigenic areas on the hemagglutinin molecule of the virus inhibited the hemolysis whereas those belonging to two of the groups did not inhibit hemagglutination of the virus. Hemolysis also occurred when the virus was incubated at pH 5.9 prior to addition of erythrocytes. Such hemolysis caused by acid-treated virus was inhibited with the antibodies as well. At pH 5.9, hemagglutination of neither intact virus nor hemagglutinin rosettes was inhibited with any of the monoclonal antibodies, indicating conformational change in the hemagglutinin molecule, at this pH. On the other hand, hemagglutination-inhibition was observed when the antigens were incubated with the monoclonal antibodies at pH 7.0 and then the pH was later shifted to 5.9, suggesting that antibody-binding interferes with the conformational change in the hemagglutinin molecule at pH 5.9. The present findings indicate that antibodies to the hemagglutinin of influenza virus can inhibit virus-induced hemolysis by blocking conformational change in the hemagglutinin molecule and blocking later step of fusion than the conformational change, in addition to blocking attachment of virus to the receptor of erythrocytes.
TL;DR: Both human lymphoblastoid and murine leukemia cells were found to have a component of uridine transport which is insensitive to the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR), which is inhibited by other nucleosides and by the sulfhydryl reagent p-chloromercuribenzenesulfonate.
TL;DR: Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired.
Abstract: A double-blind, placebo-controlled study was undertaken to determine the efficacy of ketoconazole in the treatment of candidiasis. The drug was administered orally in the dosage of 200 mg/m2 of body surface per day for two weeks to cancer patients with oral candidiasis. Randomization in a 2:1 ratio provided 36 patients treated with ketoconazole and 20 managed with a placebo. Regression of visible lesions was achieved in 26 (72%) of 36 ketoconazole-treated and four (20%) of 20 untreated patients; eradication of culturable organisms occurred in 12 (36%) of 33 ketoconazole-treated and one (7%) of 14 untreated patients; and resolution of lesions plus eradication of Candida albicans occurred in nine (25%) of 36 ketoconazole-treated and one (5%) of 20 untreated patients. Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired.
TL;DR: SJ-9A4 reacted with C-all, B-cell chronic lymphocytic leukemia, platelets and C-ALL neuroblastoma (NB) and the K562 cell lines, and was shown to recognize the same region as two other MoAb to the p24 antigen, BA-2 and DU-ALL-1.
TL;DR: Five additional cases of patients with acute lymphoblastic leukemia with detailed cytologic, immunologic, and cytogenetic studies are reported, with characteristic lymphoblasts contained membrane-bound electron lucent inclusions and immunologic markers showed a common ALL phenotype.
Abstract: Granules in blasts are most typical of acute myeloblastic leukemia. However, there have been scattered reports of patients with acute lymphoblastic leukemia (ALL) that have lymphoblasts with azurophilic cytoplasmic granules. These reports do not describe immunologic markers or cytogenetics. We report five additional cases with detailed cytologic, immunologic, and cytogenetic studies. At diagnosis one of these patients had central nervous system disease, while the others had no unusual features. Four of the five patients attained remission. The blasts of all five patients contained distinct cytoplasmic azurophilic granules. The granules were negative for peroxidase and chloroacetate esterase and positive for PAS, acid phosphatase, alpha-naphthyl acetate esterase incompletely fluoride inhibited, alpha-naphthyl butyrate esterase, and in one case, Sudan black B. In the one patient studied by electron microscopy, characteristic lymphoblasts contained membrane-bound electron lucent inclusions, which stained positively with non-specific esterase. Immunologic markers showed a common ALL phenotype. Different cytogenetic abnormalities were seen in all cases. It is important to recognize the characteristics of this morphologic subtype of ALL in order to avoid a misdiagnosis of acute nonlymphocytic leukemia.
TL;DR: Band 3 of the human erythrocyte is involved in anion transport and binding of the cytoskeleton to the membrane bilayer, and data suggest that a second membrane protein which is trypsin sensitive may be involved with Band 3 in cytoskeletal binding.
TL;DR: Immunoprecipitation studies using infected cell lysates showed that antigenic determinants on A/WSN/33 NS1 are common to NS1 proteins encoded by a wide range of viruses of human, swine, equine, and avian origin.
TL;DR: A cDNA copy of the hemagglutinin (HA) gene of Mem/1/71HA Bel/42NA was cloned into the plasmid pBR322, which contained the coding information for all of the HA except for the hydrophobic membrane insertion sequence of the C-terminus of HA2.
TL;DR: Qualitative and quantitative changes in rat peritoneal macrophage subpopulations, differing in their ultrastructural peroxidatic staining characteristics were followed over the course of a thioglycollate (TG) broth-induced inflammatory response and the implications of these results in regard to the origin(s) of M phi diversity are discussed.
TL;DR: A physical map for the frog virus 3 (FV 3) genome was constructed after digestion with the following restriction endonucleases: EcoRI, HindIII, KpnI, and XbaI, supporting the data that the FV 3 genome is circularly permuted.
TL;DR: The patient with meningoencephalitis should be evaluated carefully for the presence of focal signs referable to involvement of the frontotemporal regions of the brain, and brain biopsy should be done in order to confirm the diagnosis.
Patent•
20 Dec 1983TL;DR: In this paper, a method of producing a live attenuated vaccine useful in humans which comprises producing an influenza A reassortant virus by gene exchange between an avian influenza virus parent and a human influenza vaccine parent and then excluding the internal genes (that code for non-surface viral proteins) of the human vaccine parent from the reassortants by temperature selection and excluding the surface antigen genes of the avian Influenza A virus parent by antibodies.
Abstract: A method of producing a live attenuated vaccine useful in humans which comprises producing an influenza A reassortant virus by gene exchange between an avian influenza virus parent and a human influenza virus parent and then excluding the internal genes (that code for non-surface viral proteins) of the human influenza virus parent from the reassortant by temperature selection and excluding the surface antigen genes of the avian influenza A virus parent by antibodies
TL;DR: Iron‐loaded transferrin exhibited qualitatively and quantitatively equivalent binding reactivity with the transferrin receptor and showed identical electophoretic mobility on SDS gel electrophoresis and evidence that the specific receptor is also endocytosed is provided.
Abstract: Iron-loaded transferrin has been shown to be necessary for the support of cell proliferation in culture. This function depends upon interaction of transferrin with a specific high-affinity cell surface receptor. The present report is directed toward determining the consequences of the interaction of transferrin with this receptor on Concanavalin A-stimulated rat lymphocytes. Three specific questions have been posed: a) Is transferrin endocytosed following binding to its specific receptor in a temperature-dependent fashion? b) Following endocytosis, is the carrier protein released from the cell in a structurally and functionally intact form? and c) Is the cell surface transferrin receptor also endocytosed following ligand binding? The results provide affirmative answers to all questions. Using two independent probes of the cell surface versus intracellular location of transferrin we observed that cell-bound transferrin moved from the cell surface to the inside of the cell and subsequently back to the medium. This process occurred in a temperature-dependent fashion. When cells containing only intracellular transferrin were further incubated at 37 degrees C approximately 80% of cell-bound transferrin was released to the medium. Nearly all of this material retained reactivity with antibody to transferrin. In addition, endocytosed transferrin exhibited qualitatively and quantitatively equivalent binding reactivity with the transferrin receptor and showed identical electrophoretic mobility on SDS gel electrophoresis. Finally, using similar methodology to that employed with transferrin itself, we provide evidence that the specific receptor is also endocytosed.
TL;DR: The sequence of reactions coupling AcAcCoA synthetase and AcAc coenzyme A thiolase in cytoplasm may be an important pathway for generation of AcCoA from KBs for fatty acid synthesis in all regions of the developing brain, and this interpretation is strengthened by evidence of concomitant increases in the activities of fatty acid synthet enzyme and AcCo a carboxylase.
Abstract: Oxidation of ketone bodies (KBs) generates acetyl coenzyme A (AcCoA), which can be further incorporated into fatty acid. We have determined the rates of lipogenesis from ketone bodies in developing rats and their relation to the activities of enzymes involved in the production of cytoplasmic AcCoA via different pathways in brain regions. In the cerebrum (Cbr), rates of fatty acid synthesis from [3-14C]acetoacetate ([3-14C]AcAc) were high during the early postnatal period but decreased rapidly thereafter until weaning. Although similar developmental patterns of synthesis characterized the cerebellum (Cbl), midbrain (Mb), brain stem (Bs), and thalamus (Th), maximal rates were highest in the Cbr and lowest in the Th. In all regions, synthetic rates were higher throughout the entire suckling period than in adulthood. There were no appreciable differences in synthetic rates among brain regions of adult rats. The developmental changes in rates of AcAc incorporation into fatty acids were closely related to AcAcCoA synthetase activity, but not to activities of ATP-citrate lyase or AcCoA synthetase. During the early postnatal stage the enhanced rates of lipogenesis were accompanied by increased activities of AcAcCoA synthetase in all regions, with the highest activity occurring in the Cbr. The sequence of reactions coupling AcAcCoA synthetase and AcAcCoA thiolase in cytoplasm may be an important pathway for generation of AcCoA from KBs for fatty acid synthesis in all regions of the developing brain. This interpretation is strengthened by evidence of concomitant increases in the activities of fatty acid synthetase and AcCoA carboxylase.