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PubMed1992

IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis.

About 30% of patients suffering from the chronic autoimmune liver disease primary biliary cirrhosis produce autoantibodies against Sp100, a protein migrating in SDS-PAGE at a position corresponding to 100 kDa and located on discrete dot-shaped nuclear structures. The human Sp100 cDNA has recently been cloned and the deduced amino acid sequence was found to contain similarities to several transcriptional regulatory proteins; the biologic function of the Sp100 protein, however, is still unknown. In this study we present data which show that infection of HEp2 cells with influenza A virus, transformation of glial cells with SV40 DNA, and stimulation of PBL with mitogens affect the expression of the Sp100 autoantigen. These observations prompted us to investigate whether expression of the Sp100 protein is modulated by the action of IFN. Immunofluorescence staining of HEp2 and HeLa cells grown in the presence of IFN-alpha, IFN-beta, or IFN-gamma revealed an increase both in size and number of the Sp100 protein-containing nuclear dots, whereas no such effect was observed with cells treated with TNF-alpha. As measured by an immunoblot-based ELISA the amount of Sp100 protein in INF-beta-treated cells (1000 IU/ml, 18 h) was eight to nine times higher than in untreated cells. The enhanced protein expression was accompanied by an accumulation of the Sp100-specific mRNA (13-fold increase of the normal level after 10 h of INF-beta treatment of HEp2 cells). These findings characterize the Sp100 protein as a new member of IFN-modulated proteins and raise the question whether cytokine-mediated increase of Sp100 protein expression plays a role in induction of anti-Sp100 autoantibodies.

Animals↗
PubMed1992

Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper.

Interferons induce a number of different proteins that mediate the antiproliferative, antiviral, and immunomodulatory functions of interferons. At least three different proteins mediate the antiviral response, and one of them, Mx protein, specifically inhibits the replication of influenza virus and (vesicular stomatitis virus). Mouse and rat Mx1 proteins are nuclear, whereas other presently known Mx proteins are cytoplasmic. The cellular functions of Mx proteins are unknown, but all of them contain a consensus GTP binding site. Very little information is available on the structure and characteristics of the mouse Mx1 protein itself. For biochemical characterization, we expressed mouse Mx1 protein in a baculovirus system and purified it to homogeneity. The purified protein as well as the authentic murine cellular Mx1 protein exists in dimers and trimers in the presence of dissociating solvents, whereas in physiological buffers they form aggregates. Cross-linking experiments done on Mx-expressing cells from various species revealed that mouse, rat, and human Mx proteins exist predominantly in trimers. Amino acid sequence analysis shows that all known Mx proteins have conserved leucine repeats typical for a leucine zipper at their COOH-terminal end. In vitro translation of chimeric catechol O-methyltransferase-Mx1 gene constructs revealed that the leucine zipper domain of Mx1 protein is responsible for the oligomerization. The COOH terminus also functions as a nuclear localization signal. Microinjection of purified oligomers into the cell cytoplasm resulted in a fast accumulation of the protein in the resulted in a fast accumulation of the protein in the nucleus. Immunoelectron microscopy revealed that nuclear murine Mx1 protein exists in distinct, electron-dense structures separate from nuclear membrane, and chromatin, or nucleolus. These observations reveal that a COOH-terminal leucine zipper domain is an important structural element of all Mx proteins. Its relevance to the biology and functions of Mx proteins is presently not known.

Animals↗
PubMed1992

Three separate epitopes on human IFN-alpha variants defined by monoclonal antibodies and their role in the binding to receptors.

Two monoclonal antibodies (mAbs) designed 9-1-1 and 2-2-1, produced by murine hybridoma clones, raised to recombinant IFN-alpha 2c and one mAb, designed 3A3-2, raised to recombinant IFN-alpha 88, have been characterized with respect to neutralization of IFN antiviral and antiproliferative activities. The regions of IFN molecule which these antibodies are directed against have been defined by analyzing cross- reactivity with four IFN-alpha subtypes (IFN-alpha 88, IFN-alpha 2a, IFN-alpha 2b, IFN-alpha 2c) and two fragments of IFN-alpha 88. An analysis of cross-reactivity patterns with IFN-alpha 88 and IFN-alpha 2c indicated that 3A3-2 mAb was directed to an epitope on IFN-alpha 88 not overlapping with epitopes of other mAbs, however its localization was not exactly defined. The epitope recognized by 9-1-1 mAb was present on IFN-alpha 88 and IFN-alpha 2c, and also was not overlapping the epitopes of other mAbs. Using another variant IFN-alpha 2a, containing Lys instead of Arg at position 23, for competitive binding study it was shown that Arg 23 was implicated in the epitope recognized by 9-1-1 mAb. The competition study with IFN-alpha 88 fragments allowed to locate the epitope recognized by 2-2-1 mAb between amino acid residues 51 and 166. The epitope blocking test indicated that 2-2-1 mAb was directed to an epitope overlapping that of previously reported for mAb NK-2, located around Glu at position 113.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Can alpha-interferon exacerbate a case of mixed cryoglobulinemia?].

We describe a case of exacerbated mixed cryoglobulinemia in a patient previously treated with alpha-interferon, for chronic active hepatitis. The possible pathogenesis of this exacerbated mixed cryoglobulinemia and the relationship between cytokines, hepatitis viral infections and immune reactions is discussed.

Acute Disease↗
PubMedDate not supplied

alpha-Interferon treatment of chronic hepatitis C in young patients with homozygous beta-thalassemia.

BACKGROUND: Chronic infection with the hepatitis C virus (HCV) and iron overload are the main causes of chronic liver disease in subjects with homozygous beta-thalassemia (HBT). Iron overload can be counteracted by intensive chelation. alpha-interferon reduces viremia and necroinflammation in patients with chronic HCV hepatitis. METHODS: To assess the effectiveness and safety of alpha 2b-Interferon (IFN), we enrolled in an open pilot trial of treatment 12 patients with HBT and biopsy-proven anti-HCV positive chronic hepatitis. IFN was given at a dose of 5 MU/m2 thrice weekly for 8 weeks, then 3 MU/m2 thrice weekly for 18 weeks. Patients were followed up to 24 months after stopping treatment when a second liver biopsy was performed in subjects with sustained response (normal ALT during follow-up). RESULTS: Two patients discontinued IFN at 7 weeks because of haemolytic anemia and one after 8 weeks due to persistent fever. Among 9 subjects completing the protocol, 5 normalized ALT while on treatment and a further 2 within two months after stopping IFN. A sustained response was obtained altogether in 5 patients, since ALT relapsed in 2 responders. None of the 3 subjects who discontinued IFN and of the 2 patients who did not respond to treatment normalized ALT over a 24 months follow-up. Post-treatment liver histology in long-term responders showed a reduction of portal, periportal and lobular necroinflammation, while siderosis was essentially unchanged. CONCLUSIONS: Although the pattern of response to IFN in HCV-infected subjects with HBT might differ from that of non-thalassemics, due to peculiar side effects and delayed response, the drug appears to be effective and deserves further investigation.

Adolescent↗
PubMed1992

Viral hepatitis.

Explore the source record for details and available documents.

Acute Disease↗
PubMedDate not supplied

Ly-6A/E gene is widely expressed among transformed nonhematopoietic cells. Autocrine modulation by interferon.

Expression of the Ly-6A/E gene by transformed cells was investigated in 14 cell cultures of C57BL/6 and BALB/c mouse origin derived from spontaneous or chemically-induced non-hematopoietic tumours and from cells transformed by SV40 virus. Histologic types included carcinomas, sarcomas and a melanoma. Thirteen out of 14 cell cultures expressed membrane Ly-6A/E antigens; only the B16-A melanoma was negative, but it expressed Ly-6A/E after incubation with IFN-gamma. The effect of in vitro permanence was studied on early (< 10) and late (> 20) passages of B16-A melanoma and MN/MCA1 fibrosarcoma. Late passage B16-A cells were Ly-6A/E-negative and refractory to induction of Ly-6A/E (but not of H-2 antigens) by IFN-alpha, IFN-beta, or IFN-gamma; MN/MCA1 maintained a high expression of Ly-6A/E, but no increase was induced by IFNs. It was found that both early and late in vitro passages of MN/MCA1 actively produced IFN-alpha/beta. The analysis of cells of fibroblastic origin revealed a significant correlation between IFN release in the culture medium and Ly-6A/E levels. Culture of fibrosarcoma cells in the presence of an anti-IFN-alpha/beta serum reduced Ly-6A/E expression, thus indicating the existence of an autocrine loop.

Animals↗
PubMedDate not supplied

Highly active effect of alpha interferon in blocking the cutaneous delayed hypersensitivity.

A group of 13 patients with contact dermatitis to various chemical compounds such as potassium dichromate, nickel sulphate, formaldehyde and balsam of Peru, was investigated by patch test and by the agreement between the history of disease and the patch test, the specific allergen involved in each special case could be demonstrated. Two-three days after the first patch test three normal skin areas were chosen. The first area was intradermally infiltrated with alpha-2a Interferon (IFN) (100,000 I.U. in 1 ml), the second area was infiltrated with saline and the third area, considered as control, did not receive any treatment. Once more the corresponding allergen was applied into the skin in a second patch-test. After 48 hours in the IFN infiltrated area, only the delayed contact hypersensitivity become negative thus proving that alpha-2a IFN behaves as an efficient inhibitor of these immune effector reactions. Since the lymphocytes involved in the delayed type hypersensitivity reactions (in our case contact dermatitis) belong to the T helper line, i.e., are CD-4 positive cells we conclude that alpha-2a IFN in vivo is an efficient inhibitor of the activation of these cells. This effect achieved by any CD-4(+) DTH clones does not depend on their antigenic specificity. Some clinical trials are now in progress in our laboratory to turn to account this important biological effect in the clinical practice as an efficient inhibitor in skin contact dermatitis.

Adolescent↗
PubMed1992

[Treatment of chronic hepatitis B with interferon alpha (Wellferon) with and without previous corticosteroid therapy -- results of a multicenter, double blind study].

The present study was aimed to test the efficacy and safety of interferon alpha (Wellferon-Wellcome Foundation Ltd.) either alone, or in combination with short-term corticosteroid pretreatment in the therapy of chronic hepatitis B. 44 patients with documented chronic hepatitis type B (12 women and 32 men; mean age 37.5 years, range 23-59 years) and satisfying the entry criteria were subjects of the study. 30 patients had chronic active hepatitis on liver biopsy, while 14 had chronic persistent hepatitis. Consecutive patients were given either placebo or prednisone in a double-blinded manner for 4 weeks (0.6 mg/kg/day in the first two weeks, 0.45 mg/kg/day in the third week and 0.25 mg/kg/day in the last week), and then, after a 2 week pause, therapy with interferon was instituted for a total of 12 weeks. Interferon was given by intramuscular injection in a single daily dose of 10 x 10(6) IU for 5 days and three times weekly thereafter. However, because of side effects, the dose of interferon was occasionally reduced to 5 x 10(6) IU in most patients. Interferon induced a sustained cessation of HBV replication as judged by loss of DNA-polymerase activity in 26 (59%) patients, 20 (45%) patients seroconverted to anti-HBe. Additionally, 6 (14%) cases lost HBsAg and seroconverted to anti-HBs. Prednisone pretreatment did not seem to improve the efficacy of interferon therapy. The outcome of the treatment was unrelated to gender and pretreatment activity of transaminases, however, patients with low activity of HBV replication were more likely to respond to therapy than patients with high HBV replication.

Adult↗
PubMed1992

[The polychemotherapy of patients with multiple myeloma].

The paper deals with the analysis of the results of chemotherapy of 78 patients with multiple myeloma using various combinations of cytotoxic drugs such as vincristine, cyclophosphamide, sarcolysine (melphalan), rubomycin (adriamycin) and prednisolone (dexamethasone). Reaferon was added in some cases. Response was evaluated according to standard criteria. Survival and response were assessed versus treatment modality and immunochemical type of disease. The most effective chemotherapeutic regimens for multiple myeloma are discussed. It is recommended that remission induction be followed by courses of consolidation treatment and then by maintenance therapy. Reaferon used as a component of complex treatment for multiple myeloma was shown to markedly potentiate the antitumor effect.

Adult↗
PubMed1992

[A rapid method for the determination of the anti-interferon activity of bacteria].

Methods for the rapid and immediate determination of the anti-interferon activity of bacteria have been developed. The use of these methods makes it possible to reduce the time of determination from 48 hours to 24 and 7 hours. The proposed methods require no additional production costs, while their sensitivity and specificity are not inferior to those ensured by the classical method. These methods are recommended for the etiological diagnosis of diseases caused by opportunistic enterobacteria.

Bacteria↗
PubMed1992

[POEMS syndrome and papilledema].

The Crow-Fukase syndrome or POEMS syndrome (Polyneuropathy, Organomegaly, Edema, Monoclonal protein, Skin changes) is an uncommon plasma cell dyscrasia leading to a multisystemic disorder. An optic disc swelling is often related to this syndrome. We report the case of a 51-year-old man with a papilledema. We presume that vasculitis or plasma cell infiltration is the cause of the papilledema.

Adrenal Cortex Hormones↗
PubMed1992

[Treatment of disseminated malignant melanoma. Results are promising, but toxicity is high].

After the promising results achieved with immunotherapy in disseminated malignant melanoma, a disease reported to show little response to chemotherapy, use of combination chemotherapy regimens with interferon or interleukin and interferon has been shown to provide higher response rates and responses of longer duration. A few phase I-II trials on monoclonal antibodies have also been reported. However, toxicity is substantial with these complex combination regimens.

Antibodies, Monoclonal↗