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Biomedical subjects

C Chany

Publications and source records attributed to C Chany.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mechanism of homeostatic regulation of tissue growth and reversion of transformed cells to nonmalignancy: a yin-yang problem.

The regulation of coordinated cell growth and the development of malignancy are phenomena that are too complex to be accommodated in a narrow frame. However, on the basis of about 30 years experience with interferon and the analysis of the literature presently available, it can be suggested that: (i) normal growth is discontinuous, promoted by various growth factors; (ii) its development is downregulated by a great variety of alpha/beta interferons, which are easy to detect in rapidly growing tissues during the fetal period. Arrest of the cells in interphase could promote the expression of genetically programmed differentiation; (iii) recycling of growth is obtained by sarcolectins able to downregulate the cellular effects of interferons and to relaunch cell multiplication. To maintain harmonious growth, the synthesis and the effect of these proteins have to be in equilibrium. In transformed cells, after prolonged treatment with IFN (acting as an antioncogene), v-mos, beta interferon, and sarcolectin are continuously expressed and stay in balance. This could explain in part the stable reversion to nonmalignancy, under conditions that are reminiscent of the ancestral "Yin-Yang" principle. The review presented here is restricted to the inteferon system, whose importance in coordinated growth regulation is presently poorly defined. It can be judged, however, probably significant because of the great number of alpha isoforms existing in addition to IFN-beta, which are responsible for the activation of a number of more or less defined secondary proteins; each of these could have a more specific biological role as regards the great number of growth factors and promoters.

Animals↗
PubMed1989

Unusually large interferon-alpha-like mRNAs and high expression of interleukin-6 in human fetal annexes.

Endogenous interferons (IFNs) with antiviral activity have been detected in human fetal annexes, without any apparent induction. Some are of unusually high molecular weight and antigenic properties (Duc-Goiran P., Robert-Galliot, B., Lopez, J., and Chany, C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5010-5014). We study here the expression of IFN genes from the three antigenically distinct groups, in placental tissues taken during third-trimester pregnancies. We show by Northern blot analysis with RNA probes that IFN-alpha-like transcripts correlate with the presence of functionally active protein, purified by immunoaffinity chromatography. We fractionate on a formamide sucrose gradient, identify, and characterize a large 4.3-kb IFN-alpha-like transcript, which may be specifically expressed during fetal development. Despite the absence of IFN-beta transcript, a protein with an antiviral activity which was neutralized with a polyclonal anti-IFN-beta serum was detected in the placenta and could be related to a beta-like IFN. Besides IFNs, various growth factors and cytokines can be found in the placenta. We report here the presence of interleukin-6 expressed at high levels in fetal annexes. The coexpression of Interleukin-6 and endogenous IFNs suggests that they play an important role during development.

Amnion↗
PubMed1989

Pharmacokinetic study of butyric acid administered in vivo as sodium and arginine butyrate salts.

Considering that butyrate-treated malignant cells can recover in a transitory fashion a non-cancerous phenotype, the authors carried out a pharmacokinetics study of butyric acid injected as sodium or arginine salts for possible antitumor therapies. In the case of 1-14C-labelled butyrate, the appearance of radioactivity in the blood of injected mice is rapid and some of it is maintained for relatively long periods in different organs, mainly the liver. However, no precision can be given about the structure of radioactive compounds in blood and tissues. Using gas-liquid chromatography, the authors studied the metabolism of butyrate in both animals and man. In mice and rabbits, the half-life is less than 5 min. In man, the butyric acid elimination curve can be divided into two parts corresponding to two half-lives: for the first (0.5 min), the slope suggests an accelerated excretion, while for the following (13.7 min), a slow plateau is observed. The rapid elimination of butyrate is a limiting factor for practical applications. However, the lack of toxicity supports its use in human therapy.

Adult↗
PubMed1989

Presence of a constitutive paracrine beta-interferon in v-mos-bearing nonmalignant reverted cells.

A stable nonmalignant revertant cell line was derived from Moloney murine sarcoma virus-transformed BALB/c cells after long-term cultivation in the presence of murine type I interferon (IFN). These cells gradually established resistance to exogenous IFN and were also seen to contain IFN-dependent proteins. The presence of an endogenous IFN was confirmed by the results of Northern blot analysis and in situ hybridization with an IFN-beta probe, showing that only mRNA specific for IFN-beta- could be found in the uninduced reverted cells. The latter synthesized only a small amount of IFN-beta protein and exhibited few IFN-specific membrane receptors, which bound recombinant IFN-beta with a high affinity. After treatment with IFN antibody, the overexpression of H-2 major histocompatibility antigen genes was significantly down-regulated. These findings strongly suggest the existence in this reverted cell line of a constitutive IFN which, acting through an autocrine and/or paracrine mechanism, might play a role in maintaining the reverted state.

Animals↗
PubMed1988

Interferon- and sarcolectin-dependent cellular regulatory interactions.

Interferons, via specific membrane-bound receptors, induce various cellular functions of which antiviral protection is the most extensively studied. We have previously reported the existence of interferon antagonists (referred to as sarcolectins) in various tissue extracts from placental blood, cartilage, brain, muscle, or from sarcomas. These sarcolectins have been fully characterized and purified to homogeneity. In interferon-treated cells, they restore virus sensitivity 4-6 h after the establishment of antiviral protection. In the present study we investigate the effect of sarcolectins on the steady state levels of two double-stranded RNA dependent enzymes, 2-5A (p chi (A2'p)nA) synthetase and protein kinase. Several authors have previously emphasized the role of these enzymes in the mechanism of interferon's antiviral action. Interferon promotes a 4-8 fold increase in protein kinase and 2-5A synthetase in cells. Addition of sarcolectin 5 h after interferon results in a dramatic reduction in the steady state levels of both these enzymes, as shown by their decreased activity and yield observed in Western blot assays. The degradation of the antiviral response in sarcolectin-treated cells might therefore be at least partially attributed to a reduced synthesis of protein kinase and 2-5A synthetase. Since there are no direct interactions between sarcolectins and interferon or its receptors, it can be postulated that sarcolectins exert their effect through these interferon-dependent proteins. We postulate that the opposing biological effects of interferon and sarcolectins strike a balance which may, however, be modified in one direction or the other, depending on their respective concentrations.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Detection of vesicular stomatitis virus (VSV) RNA in the central nervous system of infected mice by in situ hybridization.

Using in situ hybridization with a cloned DNA probe specific for the VSV G protein, viral RNA was detected and localized in CNS tissue of mice infected i.c. with either wild or ts G 31 VSV mutant. In both cases, brain and spinal cord neurons were the only cells seen to contain viral RNA. Virus-positive neurons were observed enclosed in spongious areas induced by the ts VSV mutant. These results suggest that the VSV shows a strong tropism for the neuronal cell and indicate that the vacuole formation might be associated with the expression of the VSV G protein gene in infected neurons.

Animals↗
PubMed1987

Cell distribution and antigenic properties of mammalian sarcolectins.

Sarcolectins are present in a great variety of tissues from mammalian origin. Such substances were observed to be secreted from cultures of human embryonic fibroblasts, human osteosarcoma and rat Rous sarcoma transformed cells and could be extracted from TG 180 Crocker Sarcoma or normal human placenta. All sarcolectins tested here, were comparable by their physicochemical properties to those previously reported in hamster or human sarcomas. Indeed, they are proteins or glycoproteins, resistant to pepsin and migrate in SDS-PAGE in the 65 kDa area. They agglutinate cells with an affinity for simple sugars and degrade previously established interferon-induced antiviral resistance. Considering the hamster sarcolectin as reference in this comparative study, both differences and similarities in the antigenic properties of mouse, rat and human sarcolectin variants were demonstrated. An indirect immunofluorescence assay showed that sarcolectins were specifically labelled on the cell surface but not detected in the cytoplasm after methanol or acetone permeabilization of the membrane. By electron microscopy, using immunoperoxidase labelling, sarcolectins can be localized on the surface of normal, transformed, human or rat cells. Only limited segments of normal cell membranes were labelled, while transformed cells were frequently stained on their whole surface. Other known extracellular proteins, such as fibronectin and collagen, did not share common antigenic determinants with sarcolectins.

Animals↗
PubMed1986

Aspartate-assisted immune stimulation: its importance in antitumor and antiviral protection.

Immune stimulators such as Corynebacterium parvum (CP) are useful for antitumoral and antiviral therapy. However, the immune trigger cannot be reactivated without adversely affecting the disease. We have tried to amplify the results yielded by a single injection of CP by using either interleukin-2 (IL2) or aspartate salts (ASP). In the present report, we show that IL2 has no detectable clinical effect. In contrast, the addition of an ASP salt increases the antiviral and antitumoral protection afforded by the CP-induced trigger. Moreover, treatment using only ASP slightly protects against tumor development and significantly increases antiviral resistance during experimental encephalomyocarditis (EMC) infection. This ASP-assisted CP immune stimulation improves antitumoral resistance even when ascitic tumors have already developed. In the latter case, tumor regression can even be detected. Since ASP increases T-cell cytotoxicity in vitro and aggravates spontaneous T-cell lymphomas in AKR mice, the involvement of T-cell-mediated immunity may explain antitumoral and antiviral effects. We propose the use of this therapeutic model for human cancer therapy, and possibly for treating AIDS.

Adjuvants, Immunologic↗
PubMed1986

Role of VSV G antigen in the development of experimental spongiform encephalopathy in mice.

The ts G31 VSV mutant induced spongiform encephalopathy without any inflammatory response when injected i.c. into the mouse. In electron microscopy, no virions could be detected in spongiform lesions. In contrast, with the wild VSV strain inflammatory lesions were seen, which contained viral particles in great abundance. As previously shown in vitro, when using the ts G 31 mutant at the nonpermissive temperature, the G antigen can spread from membrane to membrane to distant sites, fusing a great number of cells even in the absence of virus multiplication. Therefore, we postulate that a comparable mechanism is responsible for extensive brain lesions originating probably from a relatively small number of G antigen-producing cells. Indeed, the spongious regions seen mainly in the grey matter contained vacuoles, whose walls were clearly stained by peroxidase-labelled immune serum to G antigen, without detectable virions or inflammatory lesions. The vacuoles probably represent altered and swollen dendritic cell membranes. The relationship between spongiosis development and antigen diffusion in the absence of significant virus replication is discussed.

Animals↗
PubMed1986

Persistent expression of v-mos oncogene in transformed cells that revert to nonmalignancy after prolonged treatment with interferon.

BALB/c embryonic fibroblasts productively transformed by Moloney sarcoma virus and cultivated for over 600 generations in the presence of mouse alpha/beta interferon reverted to an apparently normal phenotype and were unable to produce tumors in nude mice. Nevertheless, the presence of an integrated Moloney sarcoma virus genome in the nonmalignant Moloney sarcoma virus-transformed interferon-treated cell DNA could be shown by focus formation upon transfection and by hybridization with a v-mos probe. After digestion with various restriction endonucleases, similar hybridization patterns of v-mos sequences were obtained with DNAs from both reverted and transformed cells. However, additional integration sites and at least twice as many copies of the oncogene were found in the nonmalignant Moloney sarcoma virus-transformed interferon-treated cell DNA. Polyadenylylated RNA extracted from reverted and control cells contained two mos-specific transcripts. Interestingly, the nonmalignant Moloney sarcoma virus-transformed interferon-treated cells produced helper virus, but no detectable mos-containing virions, suggesting that a posttranscriptional block in the v-mos gene expression had occurred in these cells. It should be stressed that, after up to 100 additional passages, cells cultured in the absence of interferon maintained their nontumorigenic character in spite of the persistent transcription of the mos oncogene.

Animals↗
PubMed1986

Effects of arginine butyrate on bacterial growth.

The antibacterial activity of arginine butyrate was tested on 15 different strains. Its bacteriostatic action was detected, depending on the organisms, at concentrations between 55 and 250 mM, except for the Streptococcus B. The latter was not only resistant, but its growth was even stimulated at low concentrations (1.95 mM to 31.2 mM). It is possible that this characteristic is related to its persistence in the female genital tract where the anaerobes produce butyrate. It has previously been demonstrated that this cytostatic activity applies not only to the prokaryotes, but also to the eukaryotes, where it is seen in much lower concentrations (6 mM): since the arginine butyrate could be used in antitumor treatment, it is important to investigate its bacterial growth effects.

Arginine↗
PubMed1985

Importance of coordinated immune stimulation in experimental antitumor treatment.

We have proposed an antitumor therapeutic model in mice grafted with Crocker 180TG cells. The treatment strategy involves a coordinated immune stimulation which should always precede treatment of target cells. Potent stimulators mobilizing the majority of immune competent cells can be injected only once since repetition results in adverse effects on the response. Thus, to circumvent this difficulty, we propose the amplification, after a single shot of Corynebacterium parvum extract, of the immune response by cimetidine. Indeed, it has been reported that cimetidine inhibits suppressor T cell functions. The second phase acting on the target employs interferon and arginine butyrate since they reconvert a number of transformed target cells to normal phenotype. Important antitumor effects can be obtained in the present model even if the treatment is initiated relatively late after tumor graft. All the drugs employed are harmless on normal cells and are used at relatively low concentrations.

Adjuvants, Immunologic↗
PubMed1985

Unusual apparently constitutive interferons and antagonists in human placental blood.

We have detected seemingly uninduced interferons (IFNs) in 29/37 human placental samples obtained during caesarian sections at different periods of pregnancy, mostly around the 37th week. The amounts were usually low and did not enable us to correlate our findings with any physiological or pathological conditions. Occasionally the presence of IFN was masked by a lectin-like antagonist. Therefore, in a number of cases, substantially higher amounts of IFN were found after purification by affinity chromatography using concanavalin A, Cibacron blue, or antiserum to IFN-alpha, each coupled to Sepharose. Analysis by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed the presence of IFN-alpha and IFN-beta with molecular masses between 15 and 80 kilodaltons. Some of the high molecular weight components were neutralized either only by monospecific antiserum to IFN-alpha or, to the same extent, by antiserum to IFN-alpha or to IFN-beta, reminiscent of those previously reported after viral induction in the human amniotic membrane. We postulate that both IFNs and antagonist play a physiological role during fetal development.

Amnion↗
PubMed1985

Factors involved in interferon-induced or cholera toxin-induced steroidogenesis in Y-1 mouse adrenal tumour cells.

In addition to its antiviral effect, interferon, at high concentrations, stimulates steroidogenesis and provokes cell rounding in Y-1 mouse adrenal tumour cells. This stimulation was inhibited by cytochalasin B and colchicine. In contrast, dibutyryl cAMP and cholera toxin, also able to induce steroid production and cell rounding, increased steroid production even in the presence of these cytoskeleton-disrupting agents. The initial trigger for interferon or cholera toxin thus probably involves a distinct receptor organization. However, since both inducers increased cAMP synthesis in this differentiated cell line, the further metabolic steps of ketosteroid production could be the same.

Adrenal Gland Neoplasms↗