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Gene Ther. 2003 May;10(9):765-73.
Adenovirus-mediated gene transfer of interferon alpha improves dimethylnitrosamine-induced liver cirrhosis in rat model.

Suzuki K, Aoki K, Ohnami S, Yoshida K, Kazui T, Kato N, Inoue K, Kohara M, Yoshida T.

Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.

Several lines of evidence suggest that interferon (IFN)-alpha is effective in suppression of liver cirrhosis (LC) as well as hepatitis C virus (HCV) infection, which is a major cause of LC in Japan. However, IFN-alpha often causes systemic toxicity such as flu-like symptoms, which precludes the IFN-alpha dose escalation required for clinical efficacy. Since IFN-alpha is rapidly degraded in the blood circulation, only a small amount of subcutaneously injected IFN-alpha protein can reach the target organ, the liver. It is expected that on-site IFN-alpha production in the liver overcomes the limitation of the conventional parenteral IFN-alpha administration. An adenovirus vector expressing the rat IFN-alpha gene (AxCA-rIFN) was injected intravenously into rats with dimethylnitrosamine-induced LC. While the subcutaneous IFN-alpha protein injection led to a transient elevation of the cytokine both in the liver and serum, the vector-mediated IFN-alpha gene transduction induced a significant amount of IFN-alpha detected in the liver but not in the serum. The injection of AxCA-rIFN prevented the progression of the rat LC, and improved the survival rate of the treated rats. Although no significant toxicity was noted in the animals, we showed that IFN-alpha gene expression in the liver can be efficiently downregulated by the Cre/loxP-mediated shut-off system, in case the IFN-alpha overdose becomes a problem. The study suggested for the first time the advantage and feasibility of IFN-alpha gene therapy for LC.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12704415&dopt=Abstract

Vaccine. 2001 Feb 8;19(13-14):1827-35.
Humoral and cell-mediated immune responses of foxes (Vulpes vulpes) after experimental primary and secondary oral vaccination using SAG2 and V-RG vaccines.

Lambot M, Blasco E, Barrat J, Cliquet F, Brochier B, Renders C, Krafft N, Bailly J, Munier M, Aubert MF, Pastoret PP.

Department of Immunology-Vaccinology, Faculty of Veterinary Medicine, University of Liege, B43b Sart tilman, 4000, Liege, Belgium.

Humoral and cell-mediated immune responses of 36 captive foxes to two oral vaccines against rabies currently used for foxes in Europe were studied. The Street Alabama Dufferin (SAD) mutant Gif (SAG2) vaccine has been selected by double mutation from the SAD virus. The vaccinia recombinant virus (V-RG) expresses the rabies glycoprotein. Both vaccines induce similar humoral and cell-mediated responses after primary and secondary oral administration. We observed a typical anamnestic response, although of a limited duration, after the booster vaccination. Therefore, our results suggested that two successive oral vaccination campaigns should not significantly improve the immunisation of foxes. Lymphocyte in vitro proliferative response to the SAD antigen highlighted the presence in blood of a T-cell specific memory 6 months after vaccination. The synthesis of several vulpine cytokines was detected in peripheral blood mononuclear cells (PBMC) stimulated by SAD antigen via reverse transcription polymerase chain amplification. The data showed a concomitant expression of interleukin (IL)-4 and interferon-gamma in PBMC of vaccinated foxes. No change was detected in the level of IL-2, IL-10 and IL-12 synthesis, whereas the pro-inflammatory cytokine tumour necrosis factor-alpha seemed involved in the activation of naive T lymphocytes.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11166908&dopt=Abstract

Allergy. 2001 Jan;56(1):69-72.
Molecular features determining lymphocyte reactivity in allergic contact dermatitis to chloramphenicol and azidamphenicol.

Sachs B, Erdmann S, al Masaoudi T, Merk HF.

Department of Dermatology, University Hospitals, Rheinisch-Westfalische Technische Hochschule Aachen, Germany.

BACKGROUND: We report on two cases of allergic contact dermatitis to chloramphenicol and azidamphenicol respectively, with in vivo and in vitro lymphocyte reactivity to both compounds. The molecular features determining lymphocyte reactivity were explored because chloramphenicol, azidamphenicol, and thiamphenicol exhibit almost identical chemical structures. METHODS: With chloramphenicol, azidamphenicol, and the chemically related thiamphenicol, we performed patch tests and lymphocyte transformation tests with both patients. Furthermore, the interleukin-5 and interferon-gamma concentrations in the cultures of peripheral blood mononuclear cells of one patient were determined. RESULTS: Patch tests showed delayed hypersensitivity reactions to chloramphenicol and azidamphenicol, but not to thiamphenicol. These results were confirmed by lymphocyte transformation tests with peripheral blood mononuclear cells of the patients, showing a proliferative T-cell response to azidamphenicol and chloramphenicol. Moreover, lymphocytes from one patient secreted large amounts of interleukin-5, but not of interferon-gamma upon coculture with azidamphenicol. CONCLUSIONS: Since lymphocyte reactivity was observed to chloramphenicol and azidamphenicol, but not to thiamphenicol, the epitope(s) recognized by the allergen-reactive T cells may be formed by the nitro-group of the benzene ring shared by chloramphenicol and azidamphenicol.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11167355&dopt=Abstract

APMIS. 2000 Jul-Aug;108(7-8):531-8.
Effect of IL-12 on T-cell immune responses in patients with chronic HCV infection.

Fan XG, Tang FQ, Yi H, Liu WE, Houghton M, Hu GL.

Department of Infectious Diseases, Xiangya Hospital, Hunan Medical University, Changsha, PR China. xgfaotmail.com

As the host's immune responses may determine the outcome of hepatitis C virus (HCV) infection, and interleukin (IL)-12 plays an essential role in host defense against infectious diseases, we studied the antigen-specific and non-specific cellular immune responses in patients with chronic HCV infection. A proliferative response to phytohemagglutinin (PHA) was found in all 20 patients. Of the 20, 8 (40%) displayed a lymphocyte proliferation in response to HCV antigen c22, 2 (10%) to c33, 6 (30%) to c100-3, and 1 (5%) to NS5. The addition of rhIL-12 to cultures of peripheral blood mononuclear cells (PBMC) stimulated with PHA significantly enhanced the proliferative responses in normal controls as well as in HCV-infected subjects. The increased proliferation was also observed in HCV-infected patients when PBMC were co-cultured with HCV antigens c22 and c100-3 in the presence of rhIL-12. The production of interferon gamma (IFNgamma), IL-2, IL-4 and IL-10 was observed in 7 (58.3%), 5 (41.7%), 3 (25.0%) and 5 (41.7%) HCV-infected individuals stimulated with c22, and in 4 (33.3%), 2 (16.7%), 2 (16.7%) and 2 (16.7%) with c100-3, respectively. All HCV-infected individuals had increased production of cytokines IFNgamma, IL-2, IL-4 and IL-10 in supernatants of PBMC after stimulation with PHA. IL-12 significantly augmented Th1 cytokine production in HCV-infected individuals stimulated with PHA and with HCV antigens. In conclusion, deficient cellular immune responses are present in HCV-infected patients and IL-12 can enhance the immune responses in these patients.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11167550&dopt=Abstract

Artif Organs. 2001 Jan;25(1):36-41.
Systemic effects of hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta.

Tominaga R, Nakano T, Shibata S, Siraishi K, Nagae S, Nakayama J, Yasui H.

Department of Cardiovascular Surgery , Kyushu University Faculty of Medicine, Fukuoka, Japan.

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11167557&dopt=Abstract

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