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Biomedical subjects

A Battistini

Publications and source records attributed to A Battistini.

At least 55 records · Page 3Linked to original sources

Non-metastatic Ewing's sarcoma: results in 98 patients treated with neoadjuvant chemotherapy.

From June 1983 to December 1987, 98 patients with non-metastatic Ewing's sarcoma of bone were treated by a protocol of neoadjuvant chemotherapy consisting of two months of preoperative chemotherapy with vincristine, adriamycin, and cyclophosphamide followed by local treatment and one year of chemotherapy aimed at preventing recurrence using the same drugs plus dactinomycin. Local treatment consisted of surgery in 39 cases (40%), radiation in 34 (34%), and both surgery and radiation in 25 (26%). After an average follow-up of five years, 51 patients (52%) had remained continuously disease-free (CDF), 46 had developed metastasis, of which 20 with local recurrence, and one had developed a radioinduced sarcoma. The site of the tumor (61% of patients with Ewing's sarcoma of the extremities were CDF vs. 35% with tumor of the pelvis) and the kind of local treatment (61% of patients who underwent surgery with or without radiation therapy were CDF vs. 35% of patients treated with radiation therapy alone) were important prognostic factors. These results are similar to those obtained in 59 patients treated from 1979 to 1982 (average follow-up, 10 years) using the same drugs administered according to adjuvant chemotherapy procedure as well as those reported in the only other large study on this subject in the literature (the multi-institution German study CESS-81). The authors conclude that even though neoadjuvant chemotherapy makes surgery possible and easier in Ewing's sarcoma, it does not significantly increase survival when compared to traditional adjuvant treatment.

Adolescent↗

A full-length murine 2-5A synthetase cDNA transfected in NIH-3T3 cells impairs EMCV but not VSV replication.

Treatment of cells with interferons (IFNs) induces resistance to virus infection. The 2'-5'oligo A (2-5A) synthetase/RNase L is one of the pathways leading to translation inhibition induced by IFN treatment. A murine cDNA encoding the 43-kDa 2-5A synthetase was cloned and sequenced. NIH-3T3 cell clones transfected with this cDNA expressed the enzymatic activity to various extents and exhibited resistance to encephalomyocarditis virus (EMCV) but not to vesicular stomatitis virus replication. The specific resistance to EMCV can be attributed to 2-5A synthetase.

2',5'-Oligoadenylate Synthetase↗

Spectrum of biological activity of interferons.

The interferons comprise a group of proteins first identified by their ability to protect cells against virus infections but also capable of influencing cellular physiology. They are synthesized and secreted by a variety of cell types in response to various inducers. Their effects include antiviral action, inhibition of cell proliferation, modulation of cell differentiation and activation of various cell types in immune system. This review aims to summarize the current state of biology of interferon action with special emphasis on those aspects related to the use of these molecules in antitumoral therapy. The antitumor effects of IFNs results from pleiotropic IFN activity exerted either directly on tumor cells (i.e. antiproliferative effects, effects on oncogene expression, on cell differentiation and enhanced expression of cell surface antigens), or via indirect effects (i.e. activation of effector mechanisms of the host as modulation of the expression of the major histocompatibility antigens, effects on macrophages, NK, T and B cells).

Animals↗

Variation in the relative synthesis of some proteins in mammalian cells exposed to hypertonic medium.

Exposure of a number of quiescent murine and human cell lines to low-graded doses of cycloheximide (CXM) results in a pattern of protein synthesis consisting of enhanced and induced species. This pattern is reminiscent of but not identical to that observed after several stress treatments [V. Sorrentino et al. (1985) J. Cell. Physiol. 125, 313]. A pattern identical to that seen after exposure to CXM is synthesized when cells are exposed to an hypertonic growth medium resulting in a full and reversible block of the initiation of polypeptide chain. This suggests that this kind of response is triggered by a reduction of overall protein synthesis rather than by a slow-down of the elongation step. Analysis of the synthesis of histones and ribosomal proteins during these two nonphysiological treatments (CXM or high salt) shows that these classes of proteins are neither stimulated nor preferentially retained. In contrast, greatly enhanced levels of steady-state histone mRNAs have been observed which have been translated in a reticulocyte lysate system, but are not apparently translated in vivo.

Animals↗

Inhibition of protein synthesis by diphtheria toxin induces a peculiar pattern of synthesized protein species.

The irreversible inhibition of overall protein synthesis induced by diphtheria toxin in mammalian cells is accompanied by a peculiar pattern of synthesized protein species during the early stages of cell intoxication. This pattern closely resembles patterns of synthesized protein species observed in cells treated with reversible inhibitors of protein synthesis acting at different levels. Synthesized proteins are in the Mr range of 70-100 and 20-40 kDa. A 50-kDa protein, the most represented species, exhibits a peptide map identical to that of the 50-kDa species observed in cells treated with cycloheximide and hypertonic medium. The synthesis of these proteins is apparently regulated at both transcriptional and translational levels.

Diphtheria Toxin↗

[Respiratory physio-kinesitherapy in cystic fibrosis: the parents' viewpoint].

The aim of this study was to evaluate the problems found in performing chest physiotherapy (PKT) by patients with Cystic Fibrosis (CF) and by their families. The research has been based upon processing 389 questionnaires (46 items) that were compiled by the families. Thirteen CF centers all over the nation have participated in this study. Patients' mean age was 7.4 years (range 2 months to 14 years). Data about the socio-economic status and illness severity were available for every patient. Many graphs (line connects points with a line = n. 8; bar charts = n. 17; pie charts = n. 13) show the results and their statistical processing. Our purpose was to solve the following problems: 1) What is the extent of the compliance? 2) Who perform, or should perform, PKT in the family environment? 3) What is the kind and extent of the help request? 4) What are the mistakes made in executing PKT? 5) What is the usefulness of precursors and aerosol therapy? 6) What is the link between physical activity and PKT? 7) What are the main difficulties in performing PKT? 8) How effective is PKT? 9) What is the extent of the parents' faith in their capabilities? 10) Are there any prejudices against PKT? Three major findings emerge from this study: 1) the compliance appeared good; 2) the average family understood the meaning of PKT correctly and 3) PKT is usually executed properly. As for negative results are concerned, it is to be noted that the burden of performing PKT is usually up to the mother. This finding is linked both to the socio-economics status of the family and to the severity of the illness. On the other hand, a home PKT service is only asked in very extreme situations such as sudden worsening of the patient's illness. The difficulties met in performing PKT range from the patient's refusal to logistical and organization problems, which are correlated with the socio-economic status of the family. The relationship between PKT and sport is understood well and there is a high percentage of patients doing regular physical activity, even if it is often hindered by the severity of the disease. In conclusion, although there are many problems, there are also many methods to use in order to improve the acceptance and the effectiveness of the PKT.

Adolescent↗

[Therapy of non-metastatic Ewing's sarcoma (pelvis excluded). Results obtained in 48 cases combining local therapy (radiation and/or surgical) and adjuvant chemotherapy with vincristine, adriamycin, dactinomycin and cyclophosphamide].

Combined therapy was used on a consecutive series of 48 patients with extrapelvic Ewing's sarcoma at the Rizzoli Orthopaedic Institute. The adjuvant chemotherapy protocol (VCR, ADM, D-ACT, EDX) was identical in all patients whereas local treatment consisted of amputation, resection and radiation treatment or radiation alone. At a mean follow-up of 58 months (39-78) 30 patients (60%) were free of the disease. This is a significantly higher percentage than that obtained in the same period with adjuvant chemotherapy using only 3 drugs (VCR, ADM, EDX). As far as the type of local treatment is concerned, the percentage of local recurrences and metastases was lower when the primary lesion was treated with surgery or surgery combined with radiotherapy, rather than radiation treatment alone. These suggest that if associated with radiation treatment and chemotherapy, surgery can play an important role that should be considered in the treatment of extrapelvic Ewing's sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

Reduced maturation of Friend virus in adhesive mutants of Friend leukemia cells.

The replication of Friend Leukemia virus (FLV) has been investigated in adhesive clones (FF) of Friend Leukemia cells which were selected via cultivation on top of human fibroblast monolayers. In these adhesive clones a shut-down of FLV production is observed under conditions of culture confluency; this finding is not due either to a reduced number of cell divisions nor to a defective expression of FLV genome as assessed by Northern blot and immunofluorescence studies. Ultrastructural studies showed that virus budding and release into the medium is not detectable under these conditions. Conversely, in confluent FF cell monolayers abundant imperfect type-A enveloped particles were visible, possibly originating from stacks of granular endoplasmic reticulum with thickened membranes. It is postulated that the reduced virus production in adhesive FF monolayers is due to as yet undetermined events taking place during virus maturation at a time coincident with that of cell-cell adhesion under conditions of culture confluency.

Animals↗

L929 cells infected with temperature sensitive mutants of vesicular stomatitis virus: virus replication is necessary for induction of changes in membrane permeability.

Infection of L929 murine cells with vesicular stomatitis virus (VSV) results in inhibition of host protein synthesis and appearance of membrane alterations at a time when cells are still actively engaged in viral protein synthesis. VSV temperature-sensitive (ts) mutants have been used to explore the role(s) played by the virus-coded proteins in the genesis of these effects. Cells were infected with each of five ts mutants representing the known complementation groups of VSV Indiana serotype, and incubated at permissive (32 degrees C) and non-permissive temperatures (39 degrees C). Protein synthesis in the presence and absence of Hygromycin B (Hyg. B) was analyzed during virus infection via incorporation of 35S-methionine in acid-precipitable material and SDS-polyacrylamide gel electrophoresis. Data indicate that mutants belonging to groups I (L protein), II (NS protein) and IV (N protein) do not inhibit host protein synthesis and do not induce any membrane changes when grown at the non-permissive temperature. Mutants of group III (M protein) and V (G protein), instead, do inhibit cell protein synthesis and induce membrane changes also when grown at the non-permissive temperature; this suggests that these effects do not correlate with the biological activity of these proteins and their interaction with the cellular membrane. On the other hand, mutants exhibiting defective steps of nucleocapsid replication are apparently unable to induce these effects once more suggesting that virus replication per se is essential, as also indirectly shown by experiments employing cycloheximide to mimic shut-off.

Animals↗

Friend murine leukemia virus and spleen focus-forming virus expression in highly malignant interferon-sensitive and interferon-resistant Friend leukemia cells.

Analysis of expression of the Friend murine leukemia virus (F-MuLV) and of the spleen focus forming virus (SFFV) has been undertaken in highly malignant interferon (IFN)-sensitive (745) and IFN-resistant (3Cl-8) Friend leukemia cells (FLC), serially passaged intraperitoneally in DBA/2 mice. In vivo passaged 745 cells, as well as the clones derived thereof, did not release Friend virus (FV). Western blot analysis of the plasma membrane fractions of the virus nonproducer 745 cells revealed the lack of gp69/70 glycoprotein expression. At least 10 intraperitoneal passages of virus producer in vitro passaged of virus producer in vitro passaged 745 cells were necessary to obtain the selection of the virus nonproducer phenotype. In contrast in vivo passaged 3Cl-8 cells continued to produce FV even after 100 in vivo passages and expressed gp69/70 antigens to a similar extent as the original in vitro passaged FLC. The expression of F-MuLV and SFFV RNAs in virus producer and virus nonproducer FLC clones has been investigated by means of Northern blot technique using probes specific for either F-MuLV or SFFV. No F-MuLV specific RNA sequences were detected in virus nonproducer 745 clones. SFFV specific RNA transcripts and gp52/55 glycoprotein production could be revealed in all the FLC tested. Southern blot analysis showed the presence of F-MuLV specific sequences in the cellular DNA of virus nonproducer 745 clones. As both in vivo passaged F-MuLV producer 3Cl-8 and F-MuLV nonproducer 745 cells were equally barely immunogenic and highly malignant when injected into syngeneic DBA/2 mice, these results indicate that F-MuLV expression does not result per se in a high immunogenic potential of tumor cells. For the time being, as a specific property of 3Cl-8 versus 745 cells is the interferon-resistant phenotype, it is tempting to speculate that the selection of virus nonproducer cell variants after in vivo passages of interferon-sensitive 745 cells could depend on the presence of low levels of endogenous interferon in normal young mice.

Animals↗

Interferon production in L929 cells under impaired translational conditions: comparison of rates of interferon, actin, Newcastle disease and encephalomyocarditis viruses mRNAs initiation of protein synthesis.

The pattern of Interferon (IFN) production in virus-infected cells has been compared with the rate of bulk cellular protein synthesis, on one hand, and with the synthesis of representative cell and virus proteins such as actin, the gamma and the NP proteins of encephalomyocarditis (EMC) and Newcastle Disease (NDV) viruses, on the other hand. This was investigated under conditions of impaired protein synthesis such as i) high osmolarity media, ii) a virus-induced shut-off, and iii) in cells exposed to relatively low doses of cycloheximide (CXM), which slow elongation of protein chain and thus favour the translation of low-affinity messenger RNAs (mRNAs). In each instance IFN production was compared with 35S-methionine incorporation into TCA-precipitable materials and into SDS-polyacrylamide gel-analysed proteins. Data obtained from each of the experimental approaches all indicate that IFN production and cellular protein synthesis are modified in a closely related fashion suggesting that their mRNAs share a similar degree of affinity for ribosomes. Conversely, two mRNAs coding for representative EMC and NDV virus proteins exhibit, respectively, the highest and the lowest affinity for ribosomes as compared to actin mRNA.

Actins↗

Induction and/or selective retention of proteins in mammalian cells exposed to cycloheximide.

Exposure of a number of murine and human cell lines to low graded doses of cycloheximide (CXM) results in a pattern of protein synthesis consisting of enhanced and induced species. These can be divided into two main classes according to molecular weight (20-40 and 70-120 Kd), similar to what has been described for other agents that modify the physiological conditions of growth. In addition, the pronounced synthesis of a hitherto unreported 50-Kd protein species has been consistently observed in all lines tested. Simultaneous exposure of cells to CXM and actinomycin D results in suppressing synthesis of some but not all protein species observed, indicating that control mechanisms at both transcriptional and posttranscriptional levels may be operative in this system.

Animals↗

Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis.

Taking advantage of the availability of an archive of consanguineous marriages that gives accurate estimates of consanguinity in Italy, it has been possible to calculate the increase of first- and second-cousin marriages among 624 couples of cystic fibrosis (CF) parents over the general population. From these estimates, the incidence of CF in Italy has been found to correspond approximately to 1/2,000. In turn, the same data have been used to test the hypothesis of genetic heterogeneity of CF, recently proposed, which is based on the presence of two distinct genetic disorders having similar frequencies. If such a hypothesis were true, the number of first-cousin marriages among CF parents should be significantly higher than that observed in our present study. Finally, the segregation analysis of 624 CF sibships has yielded under multiple selection a segregation ratio of 0.252, confirming the recessive mode of inheritance.

Consanguinity↗

Interaction of cholera toxin with gangliosides: differential effects of the oligosaccharide of ganglioside GM1 and of micellar gangliosides.

Ultraviolet difference absorption spectra of cholera toxin and its B protomer produced by the oligosaccharide moiety of the monosialoganglioside GM1 were measured as a function of the oligosaccharide concentration. In the presence of oligosaccharide, the spectrum is characterized by three peaks at 282, 288, and 292 nm. A linear increase in difference absorption was observed at these wavelengths vs. oligosaccharide concentration; a saturation effect occurred when the molar ratio of oligosaccharide to cholera toxin was higher than 5. The features of the spectra indicated that the binding with the oligosaccharide affected the environment of tryptophan and tyrosine residues of protomer B. In good agreement with the above results, circular dichroic spectra indicated also a local effect of the binding, mostly restricted to protomer B, while the residues of protomer A remained largely unperturbed. Difference absorption spectra were also measured for cholera toxin in the presence of ganglioside and detergent micelles. The employed gangliosides GD1a and GT1b, unable to bind cholera toxin, interact with the protein by way of contaminating traces of GM1. The preparations of GD1a and GT1b contained 0.8-1.0% (w/w) and 0.4-0.5% (w/w) of GM1, respectively. The results obtained with ganglioside GD1a and GT1b in contrast with the observations made with the oligosaccharide of GM1 indicated a major conformational change of the toxin structure. Upon comparison of the conformational change induced by ganglioside micelles with that induced by sodium dodecyl sulfate it may be suggested that the ganglioside micelle, behaving as a detergent, alters the structure of the toxin such as to induce the penetration of protomer A into the lipid milieu.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholera Toxin↗