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Biomedical subjects

C Chany

Publications and source records attributed to C Chany.

At least 55 records · Page 3Linked to original sources

Phosphorylation of recombinant interferon-gamma by kinases released from various cells.

Recombinant interferon-gamma (IFN-gamma) in contact with human embryonic fibroblasts or with a great variety of cells from different animal species was phosphorylated in the presence of [gamma-32P]ATP and magnesium ions by a protein kinase released in the culture medium. Using SDS-polyacrylamide gel electrophoresis, we found that both the monomeric (17 000 to 18 000) and dimeric (34 000 to 35 000) molecular weight forms of IFN-gamma became intensely radioactive. Serine, but not threonine or tyrosine, was phosphorylated. It is of interest that the kinase released from reputedly insensitive cells also phosphorylated IFN-gamma. The process did not noticeably degrade the antiviral functions of the molecule nor did it affect, at least in a detectable manner, its anti-proliferative effect on WISH or Daudi cells. Furthermore, the antigenic structure and its capacity to react with monoclonal antibodies were also unaltered. It is presently not known which biological function is regulated by the phosphorylating process.

Animals↗

Detection of an interferon antagonist, sarcolectin, in human sarcomas and muscles.

In a variety of human sarcomas we detected the presence of a sarcolectin which reversed an established antiviral protection induced by interferon (IFN). For the same protein concentration, this biological activity was significantly increased when compared to that of normal muscles. All the biological characteristics were comparable to those of a sarcolectin found in hamster tissues; namely the capacity to agglutinate cells and its inhibition by specific sugars, migration in sodium dodecyl sulfate gel, and pepsin, heat and sodium dodecyl sulfate stability. Except for its anti-IFN function and cell agglutinating activity, the biological significances of this sarcolectin is presently poorly understood.

Agglutination↗

Human leukocyte interferon administration to patients with symptomatic and suspected rabies.

Body fluids and brain tissue from rabid human patients have demonstrated only low titers of interferon. Therefore, pharmacokinetic studies of systemically administered and locally injected leukocyte interferon were performed in 2 North American patients with suspected rabies who showed no clinically important side effects of this therapy. Similar therapy was given to 5 patients with symptomatic rabies in Europe and America. Although no prolongation of the clinical course was seen in 3 patients given high-dose intraventricular and systemic therapy, treatment was not initiated until between 8 and 14 days after symptoms were seen. The intraventricular dosage regimen produced cerebrospinal fluid levels that appeared to fall progressively over the 24 hours after injection and demonstrated good but somewhat delayed distribution into the lumbar sac. Titers produced by this therapy were 30- to 10,000-fold higher than those normally observed in this infection, however. In the patients treated at the highest dosage, a diminished and delayed antirabies neutralizing antibody titer was observed, probably a result of the administration of the exogenous interferon.

Adolescent↗

Antitumor therapy based on the use of an immune modulator, arginine butyrate and interferon.

The analysis of the likely physiological role of interferon during pregnancy and antitumor protection can be employed in developing a new strategy in antitumor therapy. Indeed, pretreatment of the patients with a potent immune stimulation compensates to some extent interferon's immune repressive effects. Through the modulation of the cytoskeleton, interferon enhances macrophage activity. Moreover, butyrate by its own effect on the malignant phenotype increases interferon sensitivity in a number of malignant cells. All of these substances should be used at the lowest possible concentration delivered as closely as possible to the target area.

Amniotic Fluid↗

Intestinal lesions containing coronavirus-like particles in neonatal necrotizing enterocolitis: an ultrastructural analysis.

Since the outbreaks of neonatal necrotizing enterocolitis occurring in maternity hospitals of Paris and suburbs in 1979-1980, it has been possible to examine by light and electron microscopy gut specimens from ten newborns with this illness. Coronavirus-like particles, enclosed in intracytoplasmic vesicles of damaged epithelial cells of the intestinal mucosa, were observed in the small intestine, appendix, and colon. The ultrastructural study, supported by bacteriologic findings, suggests the role of coronavirus-like particles in the appearance of the lesions. Secondary proliferation of mainly anaerobic bacteria, probably responsible for pneumatosis, may aggravate the disease.

Appendix↗

Sarcolectin: an interferon antagonist extracted from hamster sarcomas and normal muscles. Isolation, characterization, and purification.

In the present work we show that sarcoma and normal hamster tissues contain a protein which agglutinates normal and transformed cells. The inhibition of agglutination by galacturonic acid and occasionally by fucose suggests a resemblance of this protein with vegetal lectins. When added 5 h after interferon, the crude semipurified and electrophoretically homogeneous preparations reduce within 20 h the antiviral state pre-established by interferon. These two biological tests have enabled us to monitor the subsequent purification steps. The isolation of the biologically active protein is greatly facilitated by its resistance to pepsin and nucleases, whereas its sensitivity to trypsin and Pronase suggests its proteinaceous character. Furthermore, the molecule is stable when heated 1-2 min at 100 degrees C in the presence or absence of sodium dodecyl sulfate. After pepsin treatment, Sephacryl G-200 gel filtration, and ion exchange chromatography on DEAE-cellulose, 25-40-fold purification can be obtained. When controlled by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a double band (DEAE-cellulose sample) or single band (octyl-agarose sample) is detected in the 65,000-dalton region and no other contaminator is present. The eluted protein retains full biological activity when assayed by the degradation of the interferon-induced antiviral protection in the cell or titrated by cell agglutination.

Agglutination↗

Effect of coordinated therapeutic assays using C. parvum, interferon and arginine butyrate on spontaneous disease and survival of AKR mice.

AKR mice, known to develop spontaneous leukemia in almost 100% of cases, were studied throughout their life-span. Different treatments combining a potent immune stimulator, Corynebacterium parvum (CP), with interferon (IFN) and arginine butyrate were initiated at the 15th week of life. In a preliminary series of experiments, CP (200 micrograms), IFN (20,000 units) and butyrate 50 mM) were employed in a well-defined chronological order. In controls, the mean survival time (MST) was 35.17 +/- 1.67 weeks and the final survival rates was 0/50 mice for all experiments. Only CP associated with arginine butyrate significantly augmented the MST (42.5 +/- 3.66 weeks) and final survival rate (9/35 mice). In an adjusted set of experiments, reducing the IFN concentration to 10,000 and 5,000 units and that of butyrate to 6 mM greatly improved the results. The MST was substantially increased with the combinations of CP + IFN + butyrate (41.4 +/- 1.86 weeks), CP + IFN (42.73 +/- 3.29 weeks) and butyrate + IFN (41 +/- 2.34 weeks), as well as the final survival rates (8/15, 10/15 and 6/15 mice respectively). An important finding was that when CP and IFN were used separately, they were ineffective.

Animals↗

Unusual human interferons produced by virus-infected amniotic membranes.

Interferon (IFN) induced in the human amniotic membrane contains at least five different molecular species, as shown by analysis in NaDodSO4/polyacrylamide gels after heating and under reducing conditions. Three of the IFN components reported here--migrating at 26, 43, and 80 kilodaltons--are of unusual antigenic structure because they are neutralized to about the same extent by anti-IFN-alpha and anti-IFN-beta antibodies. The 15- to 17-kilodalton species belongs to the IFN-alpha group, while the 21- to 22-kilodalton species, the most frequently detected major peak, is IFN-beta. In addition to their unusual size and antigenic structure, these IFNs could play a role during embryonic development and in the immune tolerance of the mother with regard to the fetus.

Amnion↗

Purification of highly radioactive mouse interferon produced by Ehrlich ascites tumour cells induced by Sendai virus.

Mouse interferon (IFN) was produced to high titres after induction of Ehrlich ascites tumour cells with Sendai virus by using an improved procedure. The IFN molecules were labelled during their synthesis by the incorporation of [3H]leucine and [3H]lysine. Electrophoretically homogeneous labelled IFN with a molecular weight of 34000 was obtained after a two-step purification procedure using poly(I)-agarose and octyl-Sepharose column chromatography followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The specific radioactivity of this IFN was about 10 ct/min/IFN unit.

Animals↗

Coordinated therapeutic effects of immune modulators and interferon.

Immune modulators injected 24 h before encephalomyocarditis virus significantly increase antiviral resistance in mice when interferon is administered 1 h after the virus. These immune modulators can be crude bacterial extracts or synthetic drugs. In some cases, the responses are additive; in others, they are clearly cooperative. To protect the mice against the development of 180 TG Crocker sarcomas, the association of bacterial extracts and interferon is highly effective under the condition that the drug concentrations and chronological order and number of injections are well defined. In contrast, the conjunction of interferon and synthetic immune modulators, in particular cimetidine, result in delayed tumor development with no significant change in the final survival rate in the experimental model described here.

Adjuvants, Immunologic↗

Interferon effect on cytolytic T lymphocytes in a single cycle assay.

In this study we analyse cell-mediated cytotoxicity by the use of 51chromium release and the killer cell enumeration assay. The latter enabled us to estimate cell-mediated cytotoxicity in a single cycle, which confirms the protective effect of interferon (IFN) after target cell treatment. This anti-cytolytic resistance is detected best by microassociation when effector and target cells are separately treated with IFN and associated thereafter. We suggest that, in inflammatory areas, enhanced cytotoxic activity of the IFN-treated effector cells is only operative before the establishment of protection in the targets, which is somewhat slower and appears in about 18 hr. Resistance of the targets could be at least partly attributed to the incapacity of effector cells to bind to them.

Animals↗

Antitumor effect of arginine butyrate in conjunction with Corynebacterium parvum and interferon.

The antitumor effect of arginine butyrate, used alone or in conjunction with interferon (IFN), was studied using randomly selected Swiss mice inoculated i.p. with 10(6) 180 TG Crocker tumor cells. The results of these different therapeutic regimens were estimated by tumor incidence at 10 days, by the time necessary to protect 50% of the animals, and by the final survival rate. Combined treatment by IFN and arginine butyrate was effective; but in order to compensate for IFN's immune repressive effects, a single injection of Corynebacterium parvum was administered in some experiments prior to IFN and/or arginine butyrate. After this immune potentiation, both IFN and arginine butyrate used separately significantly protected the animals. However, optimal results were obtained when a single C. parvum injection was followed by nine daily alternating shots of arginine butyrate and IFN.

Animals↗

The presence of alpha-interferon in human amniotic fluid.

Almost all the samples of amniotic fluid from 62 pregnant women from the 16th week to the end of the pregnancy contained detectable amounts of alpha-type interferon. The presence of this substance in amniotic fluid during pregnancy raises the question of the physiological significance of this finding. It is postulated that the amniotic type of alpha-interferon might be a product of a constitutive gene, rather than induced by latent virus infection.

Amniotic Fluid↗

Association of coronavirus infection with neonatal necrotizing enterocolitis.

From the clustered occurrence of numerous cases of necrotizing enterocolitis in newborns, it was possible to associate this disease significantly with infection due to coronavirus-like agents. Prematurity or low birth weight did not seem to affect the development of the disease, at least during the present epidemic. However, associated gas-producing bacteria could influence its severity and play a role in the appearance of pneumatosis. In many aspects the human disease is reminiscent of experimental necrotizing enterocolitis obtained by infection of germ-free newborn animals, as reported in the literature.

Antibodies, Viral↗