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At least 55 records · Page 3Linked to original sources
PubMed2026

Metabolomics Reveals Metabolic Characteristics of Functional Cure in Chronic Hepatitis B Treated With Entecavir Combined With Pegylated Interferon Alpha.

BACKGROUND: Entecavir (ETV) combined with pegylated interferon alpha (PEG-IFNα) improves chronic hepatitis B (CHB) functional cure rates, but therapeutic heterogeneity and underlying metabolic mechanisms remain unclear. This study used untargeted metabolomics to identify metabolic signatures, mechanisms, and predictive biomarkers of functional cure with ETV-PEG-IFNα. METHODS: Thirty-eight CHB patients were grouped into ETV monotherapy (Group E, n = 12) and ETV-PEG-IFNα combination therapy (Group Z, n = 26); Group Z was subdivided into cured (Group A, n = 13) and noncured (Group B, n = 13). Serum metabolomic profiling, multivariate statistics, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified differential metabolites. A random forest model was built using key metabolites. RESULTS: Three hundred eighty-eight metabolites were identified. Four differential metabolites distinguished Group A and B (upregulated guanidinoacetic acid, uracil 5-carboxylate; downregulated L-methionine S-oxide, oleamide), enriching amino acid metabolism pathways. Nine differential metabolites between Group E and Z implicated amino acid, immune, and fatty acid pathways. The random forest model based on the four Group A/B metabolites showed 88.5% cross-validation accuracy (AUC = 0.920), with L-methionine S-oxide and oleamide as key predictors. CONCLUSIONS: This study reveals metabolic rewiring in CHB functional cure via ETV-PEG-IFNα therapy, involving energy metabolism, oxidative stress, and immunomodulation, based on which we propose a tentative metabolism-immunity synergy model to guide future research. Key metabolites, especially L-methionine S-oxide and oleamide, show exploratory predictive potential for functional cure that warrants further validation in independent cohorts.

Humans↗
PubMed1992

Immunohistochemical detection of double-stranded-RNA-dependent protein kinase (p68) with a novel monoclonal antibody TJ4C4. A case report of an AIDS-associated Kaposi's sarcoma treated with alpha-interferon.

Double-stranded RNA (dsRNA)-dependent protein kinase (p68) has been shown to be induced by alpha-interferon (IFN-alpha) in mammalian cells. It binds to dsRNA, and is believed to be a factor in the control of both cellular and viral protein synthesis. This report describes the use of a new monoclonal antibody (MAb) TJ4C4, to monitor levels of p68 in a patient with AIDS-associated Kaposi's sarcoma. Using a novel immunoperoxidase/iron staining method, we examined formalin-fixed, paraffin-embedded biopsies prior to, and 4 months after the initiation of IFN therapy. Immunostaining showed low levels (1+ staining) of p68 in the pretreatment tissue, whereas a marked increase (4+ staining) was noted during interferon treatment. This staining suggests an increased level of intracellular p68 expression. This patient has subsequently remained on IFN-alpha therapy and is alive with no evidence of Kaposi's sarcoma, 6 1/2 years after diagnosis. The use of MAb TJ4C4 will greatly facilitate the study of p68 kinase in clinical tissues, and may provide a way to monitor the effects of IFN therapy.

AIDS-Related Opportunistic Infections↗
PubMed1992

Comparison of mitogen- and virus-induced interferon production in whole blood cell cultures of patients with various solid carcinomas and controls.

Using a sensitive immunoassay, the mitogen-induced production of interferon-gamma (IFN-gamma) and virus-stimulated IFN-alpha production was investigated in whole blood cell cultures of 115 control subjects and 225 untreated patients with various solid carcinomas. In the cultures of the tumor patients, significantly lower levels of IFN-gamma were found as compared to the controls (p < or = 0.001) and the differences were most evident in those tumor groups containing mostly patients with advanced clinical stages. IFN-alpha values were only slightly lower in the cultures of the carcinoma patients, with p values < or = 0.05. Statistically, there was no correlation between IFN-alpha and IFN-gamma values. Since the IFN-gamma differences between tumor and controls and the correlation to groups with higher tumor stages were much clearer than IFN-alpha differences, we conclude that IFN-gamma measurements after polyclonal induction may be the better parameter for showing a depressed cellular immunological activity in patients with malignancies than virus-induced IFN-alpha secretion.

Adult↗
PubMed1992

A promising interferon plus four-drug chemotherapy regimen for metastatic melanoma.

PURPOSE: The goal of this study was to determine the therapeutic efficacy and toxicity of a four-drug chemotherapy regimen combined with natural leukocyte interferon alfa (IFN-alpha) for metastatic melanoma. PATIENTS AND METHODS: Between December 1988 and December 1991, 48 consecutive unselected patients with metastatic melanoma were entered onto this phase II study. Forty-five of these patients were assessable for response and 46 for toxicity. The four-drug chemotherapy regimen was as follows: dacarbazine (DTIC) 200 mg/m2 days 1 to 5, vincristine 1 mg/m2 days 1 and 4, bleomycin 15 mg days 2 and 5 intravenously (IV), and lomustine (CCNU) 80 mg day 1 orally. IFN-alpha, initiated day 8, was administered 3 x 10(6) IU/d, subcutaneously (SC) for 6 weeks, followed by 6 x 10(6) IU three times per week. A small protocol modification was adopted from the 21st patient onwards whenever there was more than 2 months' stabilization or progression with the original protocol: IFN therapy was split into 2-week treatment periods interrupted by a 2-week rest period. RESULTS: Among the 45 assessable patients, the objective response rate was 62% (95% confidence limit, 48 to 77); six patients (13%) achieved a complete response (CR) and 22 (49%) a partial response (PR). Metastases in such sites as liver also responded favorably (one CR, six PR, one stable disease [SD], two progressive disease [PD]). After splitting IFN therapy for nonresponders, in two patients PD and in another two patients SD changed into regression. Three of the six patients with a CR have suffered a relapse, but the other three have been off treatment for 7, 18, and 31 months without recurrence. Most of the symptomatic patients also experienced rapid relief of symptoms. Overall toxicity of this mainly outpatient regimen seemed to be acceptable. One patient died of a septic fever with grade 4 leukopenia and thrombocytopenia. The most frequent side effects were transient fever, nausea/vomiting, fatigue, and grade I/II hematologic toxicity. CONCLUSION: Results demonstrate a remarkably high response rate in combining IFN-alpha and four chemotherapeutic agents. The apparent schedule-dependency of responses must be further explored in a controlled phase III study.

Adult↗
PubMed1992

Ganoderma tsugae mycelium enhances splenic natural killer cell activity and serum interferon production in mice.

Effects of the water-soluble extract of Ganoderma tsugae mycelium (GT), its alcohol-insoluble subfraction (GTI), and its alcohol-soluble subfraction (GTS) on splenic natural killer (NK) cell activity and serum interferon (IFN) production were assessed in mice. Intraperitoneal administration of GT (4-200 mg/kg) or GTI (1-50 mg/kg), but not GTS, augmented the NK cytotoxic activity in a dose-dependent manner in C3H/HeN mice. This augmentation of splenic NK cytolytic activity was not mouse-strain-dependent. The serum IFN titers of mice were also elevated after i.p.-doses of GTI. The GTI-induced serum IFN was reduced by either IFN-(alpha+beta) antiserum or IFN-gamma monoclonal antibody in vitro. The treatment with antiserum neutralizing IFN-(alpha+beta) resulted in a 70% reduction of GTI-induced IFN, while monoclonal antibody against mouse IFN-gamma, moderately neutralized the GTI-induced IFN (50%). These results demonstrated that both the splenic NK activity and serum IFN [IFN-(alpha+beta) and IFN-gamma] titers are elevated by Ganoderma tsugae mycelium extracts in mice.

Animals↗
PubMedDate not supplied

Some biological properties of the human amniotic membrane interferon.

Human amniotic interferon was investigated to define the species specificity of its antiviral action and to compare its anti-cellular and NK cell stimulating activities with those of other human interferons. The antiviral effect was titrated in bovine (RV-IAL) and monkey (VERO) cells. Amniotic interferon exhibited, in bovine cells, 5% of the activity seen in monkey cells, while alpha interferon displayed 200%. No effect was detected with either beta or gamma interferon in bovine cells. Daudi cells were exposed to different concentrations of various interferons and the cell numbers were determined. The anticellular effect of the amniotic interferon reached its peak on the third day of incubation. Results suggested a higher activity for alpha and gamma interferons and a lower activity for beta when compared to amniotic interferon. Using total mononuclear cells as effector cells and K 562 as target cells in a 51Cr release assay, it was demonstrated that low concentrations of amniotic interferon consistently stimulated NK cell activity in cells derived from several donors, the results indicating a higher level of activity with this interferon than with alpha and beta interferons.

Amniotic Fluid↗
PubMed1992

Effect of interferon (IFN) on refractory idiopathic thrombocytopenic purpura: administration of 6 million units of recombinant IFN alpha-2b.

Five patients (six courses) with refractory idiopathic thrombocytopenic purpura (ITP) were given 6 million units of recombinant interferon (IFN) alpha-2b in 12 doses to achieve an improved response rate compared to previous studies using 3 million units. From the initial IFN administration, the platelet count increased from a pre-treatment level of 20.7 +/- 17.7 x 10(3)/microliters (mean +/- SD) and reached its first peak in weeks 2 or 3 of therapy (p < 0.05). In week 5, the platelet count made its second and maximum peak (66.5 +/- 57.9 x 10(3)/microliters; p < 0.05). A relatively good response of the platelet count (an increase to > 50 x 10(3)/microliters) was observed in three patients (four courses) out of five. These responses were not much faster or more improved than in previous reports, and a dose of 6 million units may be too large to treat some ITP patients. The platelet-associated IgG level showed a tendency to be reduced with IFN therapy. The mechanism for the increase of the platelet count may be the modification of platelet autoantibody production.

Adult↗
PubMed1992

Histological behaviour of chronic hepatitis in patients treated with alpha interferon.

To evaluate the histological effects of alpha Interferon (IFN) therapy, serial liver biopsy specimens from 30 patients with chronic hepatitis were studied. The biopsies were examined using a scoring system. After 12 mths of IFN therapy responders were 8 out of 11 HBV infected patients, 10 out of 12 HCV infected patients and only 1 out of 7 patients with cryptogenetic hepatitis. As spontaneous improvement of hepatic changes is infrequent, our data indicate that in terms of histological patterns interferon therapy is effective in chronic viral hepatitis.

Hepatitis B↗
PubMed1992

Obstructive solitary bronchial non-Hodgkin's lymphoma--a rare presentation of primary extranodal disease.

Endobronchial involvement by non-Hodgkin's lymphoma (NHL) is uncommon and usually occurs in the presence of more generalised disease. Solitary endobronchial lymphoma in the absence of disease elsewhere is extremely rare. In this report we describe a patient with an obstructing endobronchial mass which was the initial manifestation of NHL. The patient was treated initially with radiotherapy followed by cyclic combination chemotherapy with initial complete resolution of the endobronchial disease. However, he subsequently developed widespread lymphoma. This unusual presentation of NHL is discussed and the relevant literature is reviewed.

Aged↗
PubMed1992

Interferon alpha therapy in patients with chronic type C hepatitis: changes of serum ALT, anti-HCV & HCV-RNA.

BACKGROUND: After the discovery of type C hepatitis virus, the studies on this virus are extensively progressing. The treatment of this viral infection is also widely progressing. Among many agents, recombinant interferon alpha therapy is generally accepted as an effective single agent. To evaluate the efficacy of interferon and to observe the changes of serum aminotransferase (ALT), antibody to hepatitis C virus (anti-HCV) and HCV ribonucleic acid (HCV-RNA), we treated 10 patients with chronic type C hepatitis for 6 months. METHODS: Patients were randomly divided into 2 groups: 5 patients in group A received interferon and the other 5 in group B received no therapy. Interferon was administered at a dose of 3 million units (MU) daily for the first month and thrice weekly for the following 5 months, and followed up for 2 years. RESULTS: In group A, serum ALT returned to normal in 4: 3, starting at the first month and one at the 3rd month of therapy and maintained normal throughout the follow-up period. In contrast, serum ALT level persistently fluctuated in 4 patients in group B. In one patient, serum ALT returned to normal one and a half years later. Regardless of therapy, serum anti-HCV titer remained unchanged in all patients. However, HCV-RNA, using polymerized chain reaction (PCR), became undetectable in all responded patients and in one untreated patient whose serum ALT returned to normal spontaneously. CONCLUSION: This study suggested that interferon alpha therapy in patients with chronic type C hepatitis may be clinically effective. Our study also indicated that the detection of HCV-RNA by PCR is useful to predict the prognosis of chronic type C hepatitis.

Adult↗
PubMed1992

[The clinico-laboratory dynamics in the reaferon treatment of glomerulonephritis patients with the nephrotic syndrome].

Overall 40 chronic glomerulonephritis patients with nephrotic syndrome were treated by reaferon. All the patients underwent clinical and laboratory examinations and nephric biopsy. As a result of the treatment, all the patients demonstrated an increase of the level of glomerular filtration, stabilization of protein and lipid metabolism along with the lowering of diurnal proteinuria. Reaferon exerted a beneficial effect on cellular factors of immunity. In some cases, the use of reaferon can be a definite alternative of the conventional treatment methods.

Adolescent↗
PubMed1992

[The use of interferon in the combined therapy of juvenile rheumatoid arthritis].

The efficacy of recombinant gene engineering alpha 2-interferon (reaferon) was studied and compared in 60 patients suffering from verified juvenile rheumatoid arthritis (JRA). Reaferon was shown to possess good tolerance and to produce an adequate therapeutic effect. The combined use of reaferon and methotrexate permits potentiating the therapeutic effect of interferon and avoiding side effects seen with methotrexate used alone. Besides, it makes it possible to reduce the incidence of respiratory infections which are often associated with exacerbation of the underlying disease when treated by conventional methods.

Administration, Rectal↗
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↗