Search

The effect of a copper supplement on preventing bone mass loss induced by ovariectomy in rats was investigated.

The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12–18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m² instead of 5 g/m²; in protocol E, citarabine 1 g/m² instead of 2 g/m²; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% ± 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5–9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series. Med. Pediatr. Oncol. 33:88–94, 1999. © 1999 Wiley-Liss, Inc.

Preliminary results on new CCD photometry inV andB bands of approximately 5000 stars in four overlapping fields in the globular cluster M3 are presented. The colour-magnitude diagram shows a very well-defined sequence with a small scatter, going fainter than previously published work on this cluster. The turn-off point found atV=19.1±0.2 mag and (B-V)=0.445±0.01, is slightly redder than those obtained in previous studies.

We present CCD photometry for stars in three fields centered on the old open cluster NGC 188 and in four fields on the intermediate-age cluster NGC 7789, which has been performed with the aim of investigating the HR diagram distribution of the cluster's Main-Sequence (MS) stars. A sufficiently well-defined sequence of subgiant, turn-off (TO), and MS stars have been detected, extending the observed lower MS down to aboutV=20 mag.

New infrared photometry of a sample of 39 stars in the open cluster NGC 752 is presented. These observations confirm the bimodality of the Main Sequence previously reported. We analyze the nature of this behaviour on the basis of the binary hypothesis.

Summary The antiviral action of a new drug, 5-amino-2-(dimethylaminoethyl)-benzo-[de]-isoquinolin-1.3-dione has been studied against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5) grown in Vero cells. The concentration of the drug which gives a 5 log10 reduction in virus titer was 4 µg/ml (maximum tolerated concentration) for HSV-2. The anti-HSV-2 activity of this compound was one log. more powerful than that of iododeoxyuridine (IDU). At this concentration the drug shows virucidal activity against HSV-2. No inhibition was found when the drug was tested against Ad-5. The inhibition of virus production has been studied depending upon the amount of drug or virus, and drug addition-time after infection. Reversibility of inhibition after drug removal, and drug resistance in the presence of the drug have also been determined.

Vaccinia virus mutants were obtained in high frequency from mouse Friend erythroleukemia (FEL) cells persistently infected with this virus, which contains a large (122-MDa) DNA. During long-term cell passages viral particles with deletions of the DNA are generated in FEL cells. These mutants have a major 8-MDa deletion starting between 2.2 and 3.2 MDa from the left terminus of the viral genome. More than half of the left end terminal repetition is deleted. These mutants have reduced infectivity compared to wild-type virus. The ease with which vaccinia virus mutants are obtained in FEL cells should provide a suitable system for generating mutants with other poxvirus and permit study of the genetic basis of virulence for this group of viruses.

In this report we have shown that Friend erythroleukemia cells persistently infected with vaccinia virus maintain the persistent infection even after 1 year of continuous interferon (IFN) treatment. The persistently infected cultures were responsive to IFN as determined by their ability to induce 2-5A synthetase, to increase the intracellular levels of 2-5A, and to cause rRNA cleavage. While large deletions at the left terminus of vaccinia DNA occurred readily in the virus population from untreated cells, IFN completely suppressed the generation of these spontaneous deletions. Removal of IFN from these cultures led to the appearance of similar deletions at the left terminus of the viral genome. The regions deleted contain more than half of the left-end inverted terminal repetition of the vaccinia genome. These findings show that IFN alters specific events associated with the generation of vaccinia DNA deletions.

In this report we used Northern blot hybridization analysis to characterize the fate of several species of viral RNA transcribed from internal and terminal regions of vaccinia DNA in interferon-treated, infected mouse L cells grown in suspension. All species of viral RNAs were expressed but were reduced in amount. Larger-sized RNAs were reduced more than smaller-sized RNAs. This reduction appears to be related to the activation of the interferon-mediated double-stranded RNA-dependent 2-5A synthetase-endoribonuclease system, as the rRNA cleavage pattern characteristic of this system was observed early in infection and in cell extracts in response to exogenous 2-5A. Thus, in interferon-treated, vaccinia-infected mouse L cells in suspension, there is indiscriminate degradation of viral and cellular RNAs, and this RNA breakdown might play a role in the interferon-mediated inhibition of protein synthesis.

To investigate the genetic stability of vaccinia virus DNA, we have tested whether alterations occurred in the polypeptide composition of this complex virus during persistent infections. We found that variants isolated at various passages in Friend erythroleukemia cells persistently infected with vaccinia virus contained, in addition to an 8-megadalton (MDa) deletion on the left terminus of the viral genome, major alterations in the sizes of three structural proteins with molecular masses of about 39, 21, and 14 kDa. Alterations in isoelectric points were also observed in proteins of 48, 27, and 14 kDa. The 14-kDa protein is part of the virus envelope, and the variants increased the size of this protein from 0.5 to 3 kDa with increasing passage number. Alteration in size of the 14-kDa protein is a dominant trait since it appeared in the whole virus population by passage 48. With more passages, some variants were found to increase or decrease the size of a 39-kDa core protein by about 2 kDa and to decrease the size of an envelope protein of 21 kDa by about 2 kDa. These three proteins were immunogenic in mice and elicited a strong host immune response. Major alterations in the sizes of these proteins were prevented by continuous treatment of the persistently infected cultures with interferon. However, after interferon was removed, protein modifications appeared with increasing passage number. Generation of the 8-MDa deletion and alterations in the size of the 14-kDa protein correlated with a marked decrease in virulence of these variants. Our findings suggest that during virus persistence, specific mutations are introduced in the vaccinia virus genome that lead to protein alterations and to highly attenuated viruses.

A monoclonal antibody, MAbC3, that reacts with a 14,000-molecular-weight envelope protein (14K protein) of vaccinia virus completely inhibited virus-induced cell fusion during infection. Immunoblot and immunofluorescence studies revealed that the 14K protein was synthesized at about 6 to 7 h postinfection and transported from the cytoplasm to the cell surface. Synthesis and transport of the 14K protein during infection occurred in the presence of rifampin, an inhibitor of virus maturation. One- and two-dimensional gel electrophoretic analyses demonstrated that the 14K protein forms largely trimers (42K) that are covalently linked by disulfide bonds. The facts that MAbC3 prevents virus uncoating and blocks virus-induced cell fusion but does not prevent virus attachment to cells and the 14K envelope protein forms trimers all suggest that this protein plays major role in virus penetration.

Mo¨ssbauer effect experiments have been done on trans‐ [Fe(diars)2Cl2](BF4) and trans‐[Fe(diars)2Cl2] under variable conditions of temperature and magnetic fields. Paramagnetic hyperfine interactions have been observed in fields up to 60 kOe at temperatures down to 4.2°K. The spectra are characterized by spin Hamiltonians for S=0, (1/2) which in turn have been interpreted in terms of a ligand field of orthorhombic symmetry acting on the t2g5 and t2g6 electronic configurations. A comparison is made with the results for a t2g4 configuration in trans‐[Fe(diars)2Cl2](BF4)2, which is a third member of this series of t2gn complexes.

Human interferon alpha (IFN-α) and interferon gamma (IFN-γ) inhibit African swine fever (ASF) virus replication in Vero cells. IFN-α and IFN-γ exert a synergistic inhibition. Human tumor necrosis factor (TNF) does not inhibit ASF virus replication in this cell line, but in combination with IFNs it has antiviral enhancing activity. Analysis of the mechanism of inhibition suggests that the action of these cytokines blocks a step that comes prior to DNA replication. The 2′-5′ A synthetase activity is induced in Vero cells by treatment with these cytokines and is activated after ASF virus infection. More interesting is the finding that continuous treatment with IFN-α cures Vero cells from lytic and persistent infections with ASF virus. A potential application of IFN for the treatment of animals carrying the virus is suggested.

From a new infrared photometry of the globular cluster M10 its interstellar extinction and distance modulus are discussed. This is done by comparison with the well-studied clusters M3, M13, and M92. Final values ofE(B-V)=0.17±0.05 and (Mv-V)=14.0±0.3 are proposed. The dependence on metallicity of these values is briefly discussed.