Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide halflife in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2K b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA 257-268 ). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H-2K b complex-specific CD8 + T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKLspecific CD8 + T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties.Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis.Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma.In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties.Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis.Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma.In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D₃ Induce Antigen-Specific Immune Suppression

The active form of vitamin D3, 1,25-dihydroxyvitamin D₃ (aVD₃), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD₃ remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD₃ within biodegradable nanoparticles (NPs) would enhance the delivery of aVD₃ to antigen presenting cells, while preventing the potential systemic side effects of aVD₃. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD₃ (NP[OVA+aVD₃]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD₃) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD₃) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD₃). These results show that biodegradable NPs encapsulating both antigen and aVD₃ can effectively induce antigen-specific immune suppression.

Avascular Necrosis of the Femoral Head in Patient with Psoriatic Arthritis / 대한류마티스학회지

Psoriatic arthritis and avascular necrosis of the femoral head each are relatively common diseases. However, avascular necrosis of the femoral head in psoriatic arthritisis extremely rare disease and a few cases have been reported to date. It is suggested that the use of steroids or chemotherapeutic agents, hyperuricemia, alcohol abuse, immunologic disorders, coagulopathies are risk factors of the development of avascular necrosis of the femoral head in psoriatic arthritis. This report describes a 58-year-old female patient without any of forementioned risk factors who underwent total hip replacement for femoral head avascular necrosis associated with psoriatic arthritis.

A Case of Overlapping Syndrome of Primary IgA Nephropathy and Membranous Nephropathy / 대한신장학회잡지

We report a rare case of primary glomerular disease with overlapping IgA nephropathy and membranous nephropathy in a 52 year-old man. Clinically, The patient showed microscopic hematuria and proteinuria and had no underlying disorders such as hepatitis B, hepatitis C, drug exposure, SLE or other immunologic diseases. Histologically, glomeruli showed focal cellular proliferartione and electron deposits in the mesangium and concomittant subepithelial deposits. Immunofluorescence revealed IgA depositions in a mesangium and IgG depositions along the glomerular capillary walls, like those of typical membranous nephropathy. These findings suggest the primary glomerular disease overlapping of two different glomerular changes. The patient showed still persistent proteinuria, but have preserved renal function with administrations of ACE inhibitors and diuretics after two years.

A Case of Overlapping Syndrome of Primary IgA Nephropathy and Membranous Nephropathy / 대한신장학회잡지

We report a rare case of primary glomerular disease with overlapping IgA nephropathy and membranous nephropathy in a 52 year-old man. Clinically, The patient showed microscopic hematuria and proteinuria and had no underlying disorders such as hepatitis B, hepatitis C, drug exposure, SLE or other immunologic diseases. Histologically, glomeruli showed focal cellular proliferartione and electron deposits in the mesangium and concomittant subepithelial deposits. Immunofluorescence revealed IgA depositions in a mesangium and IgG depositions along the glomerular capillary walls, like those of typical membranous nephropathy. These findings suggest the primary glomerular disease overlapping of two different glomerular changes. The patient showed still persistent proteinuria, but have preserved renal function with administrations of ACE inhibitors and diuretics after two years.

Predictive value of troponin l and myoglobin in patients with unstable coronary artery disease / 대한내과학회지

BACKGROUND: Patients with unstable angina or non Q wave myocardial infarction still have an elevated risk for subsequent cardiac events. Therefore early assessment of the risk of future cardiac events is important. In this study, prognostic value of troponin l and myoglobin was evaluated and compared with other known early available risk indicators. METHODS: Serum troponin l and myoglobin were measured at presentation and 8 hours, 16 hours, and 24 hours thereafter in 126 patients with unstable angina (n=70) or non Q myocardial infarction (n=56) from Jan 1998, through Feb 2000. Echocardiography was performed with calculation of wall motion score index. The incidence of cardiac death or myocardial infarction was compared between patients with normal troponin l, myoglobin and abnormal ones, respectively. RESULTS: (1) At 6 months, 1 death (2.2%) and 1 myocardial infarction (2.2%) occured in the 45 unstable angina patients with normal troponin l compared with 3 deaths (12.0%) and 8 myocardial infarctions (32.0%) in the 25 unstable angina patients with elevated troponin l. (2) At 6 months, 1 death (1.7%) and 3 myocardial infarctions (5.2%) occured in the 58 unstable angina patients with normal myoglobin compared with 3 deaths (25.0%) and 6 myocardial infarctions (50.0%) in the 12 unstable angina patients with elevated myoglobin.(3) When the analysis was limited to patients with normal baseline troponin l (< or = 0.4 ng/dl: n=45), increased myoglobin level remained significantly associated with increased incidence of cardiac deaths or myocardial infarction compared with normal myoglobin level (16.7% vs 0%). (4) Together with age, diabetes, wall motion score index, troponin I and myoglobin levels were identified as independent prognostic variables for myocardial infarction or cardiac death in a multivariate logistic regression analysis. (5) The maximal troponin l and myoglobin value obtained during the first 24 hours provides independent and important prognostic information regardless of whether the patient is classified as having unstable angina or non Q wave myocardial infarction. CONCLUSION: The maximum troponin l and myoglobin obtained during the first 24 hours provides independent and important prognostic information in patients with unstable angina or non Q wave myocardial infarction.

Giant Intra-articular Osteochondroma of the Knee: A Case Report / 대한정형외과학회잡지

The giant intra-articular osteochondroma of the knee is very rare and is probably result of synovial metaplasia of the fibrous capsule or of the adjacent connencive tissue of a joint, and of the fragment of articular cartilage. The gross findings and histology are consistent with the osteochondroma. The authors experienced a case of giant intra-articular osteochondroma of the right knee in a 19 years old man who had history of knee injury when he was 16 years old. The mass was excised and the symptome was relieved.