Immunization with Small Amyloid-β-derived Cyclopeptide Conjugates Diminishes Amyloid-β-Induced Neurodegeneration in Mice.

Background: Soluble oligomeric (misfolded) species of amyloid-β (Aβ) are the main mediators of toxicity in Alzheimer's disease (AD). These oligomers subsequently form aggregates of insoluble fibrils that precipitate as extracellular and perivascular plaques in the brain. Active immunization against Aβ is a promising disease modifying strategy.

Mass tag-assisted identification of naturally processed HLA class II-presented meningococcal peptides recognized by CD4+ T lymphocytes.

The meningococcal class I outer membrane protein porin A plays an important role in the development of T cell-dependent protective immunity against meningococcal serogroup B infection and is therefore a major component of candidate meningococcal vaccines. T cell epitopes from porin A are poorly characterized because of weak in vitro memory T cell responses against purified Ag and strain variation. We applied a novel strategy to identify relevant naturally processed and MHC class II-presented porin A epitopes, based on stable isotope labeling of Ag.

Identification of formaldehyde-induced modifications in proteins: reactions with model peptides.

Formaldehyde is a well known cross-linking agent that can inactivate, stabilize, or immobilize proteins. The purpose of this study was to map the chemical modifications occurring on each natural amino acid residue caused by formaldehyde. Therefore, model peptides were treated with excess formaldehyde, and the reaction products were analyzed by liquid chromatography-mass spectrometry.

Immunogenicity of peptide-vaccine candidates predicted by molecular dynamics simulations.

We present an in silico, structure-based approach for design and evaluation of conformationally restricted peptide-vaccines. In particular, we designed four cyclic peptides of ten or 11 residues mimicking the crystallographically observed beta-turn conformation of a predicted immunodominant loop of PorA from Neisseria meningitidis. Conformational correctness and stability of the peptide designs, as evaluated by molecular dynamics simulations, correctly predicted the immunogenicity of the peptides.

Identification of immunodominant epitopes derived from the respiratory syncytial virus fusion protein that are recognized by human CD4 T cells.

Memory CD4 T-cell responses against respiratory syncytial virus (RSV) were evaluated in peripheral blood mononuclear cells of healthy blood donors with gamma interferon enzyme-linked immunospot (Elispot) assays. RSV-specific responses were detected in every donor at levels varying between 0.05 and 0.

Intraocular T cells of patients with herpes simplex virus (HSV)-induced acute retinal necrosis recognize HSV tegument proteins VP11/12 and VP13/14.

It has previously been shown that T cells specific for the triggering virus infiltrate the eye of patients with herpes simplex virus type 1 (HSV-1)-induced acute retinal necrosis (ARN). The T cells were mainly directed against 0.67-0.

Solid-phase synthesis and application of double-fluorescent-labeled lipopeptides, containing a CTL-epitope from the measles fusion protein.

The mechanism which enables lipopeptides to induce cytotoxicity is not known. By preparing fluorescent-labeled lipopeptides one might unravel the mechanism of their entry into the cell and their intracellular pathway. A method of preparing double-fluorescent-labeled peptides by solid-phase chemistry is described.

Further evaluation of reproducibility and prognostic value of histologic typing and grading in FIGO stage I ovarian cancer patients without systemic locoregional adjuvant treatment.

In order to analyse the reproducibility and prognostic value of histologic typing and different methods of histologic grading, 102 hematoxylin and eosin stained slides of primary FIGO stage I ovarian cancers of the common epithelial types were evaluated. Patients were treated by surgery only. Histologic typing was done using the FIGO criteria and overall total agreement was 61%.

Role of nucleotide excision repair in processing of O4-alkylthymines in human cells.

O4-Alkylthymines have been implicated as potential carcinogenic DNA lesions. We have studied the effects of O4-methylthymine, O4-ethylthymine, and O4-n-propylthymine in a model system in which a single lesion was located at a defined position on a SV40-based shuttle vector and have found large differences in the effects of these lesions in repair-proficient and nucleotide excision repair-deficient cells. In repair-competent human HeLa cells, normal fibroblasts, and XP-A (2OS) revertant cells, all 3 residues were highly mutagenic; a mutation frequency of approximately 20% was found for both O4-methylthymine and O4-ethylthymine, whereas that of O4-n-propylthymine was approximately 12%.

Quantitative pathologic features as predictors of long-term survival in patients with advanced ovarian cancer treated with cisplatin.

The prognostic value of morphometric and DNA flow cytometric features were studied and compared with FIGO stage, preoperative tumor load, residual disease status, Karnofsky index and classic pathologic features such as Broders' grade and histologic type in 58 FIGO stage III and IV adequately debulked ovarian patients with long-term follow-up. The mitotic activity index, volume percentage of epithelium, and mean and SD of nuclear area were assessed by interactive morphometry, and tumor material was routinely processed for DNA flow cytometric assessment of DNA ploidy and S-phase fraction. Survival analysis (Kaplan-Meier curves, Mantel-Cox test), revealed FIGO stage (P = 0.

Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein.

Starting from the alpha-(2,4-dimethoxybenzyl) ester of N-(9-fluorenylmethoxycarbonyl)aspartic acid [Fmoc-Asp-ODmb], side-chain-protected resin-bound Fmoc-peptides containing an N epsilon-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl lysyl [Lys(Dde)] residue were prepared. The C-terminal dimethoxybenzyl esters of aspartic acid were removed with 1% trifluoroacetic acid and 10% anisole in dichloromethane, followed by Fmoc-cleavage in the usual manner. The resin-bound peptides were then cyclized using 1-benzotriazolyloxy-tris-[N-pyrrolidino]phosphonium hexafluorophosphate (PyBOP) in the presence of N-methylmorpholine.

Human HLA class I- and HLA class II-restricted cloned cytotoxic T lymphocytes identify a cluster of epitopes on the measles virus fusion protein.

The transmembrane fusion (F) glycoprotein of measles virus is an important target antigen of human HLA class I- and class II-restricted cytotoxic T lymphocytes (CTL). Genetically engineered F proteins and nested sets of synthetic peptides spanning the F protein were used to determine sequences of F recognized by a number of F-specific CTL clones. Combined N- and C-terminal deletions of the respective peptides revealed that human HLA class I and HLA class II-restricted CTL efficiently recognize nonapeptides or decapeptides representing epitopes of F.

The Multi-Center Morphometric Mammary Carcinoma Project (MMMCP) in The Netherlands: value of morphometrically assessed proliferation and differentiation.

The Multi-Center Morphometric Mammary Carcinoma Project (MMMCP) was set up to investigate the reproducibility and prognostic value of routine assessments of morphometric parameters [mean nuclear area (MNA), mitotic activity index (MAI), and multivariate prognostic index (MPI)] and cytometric features (DNA ploidy and index, % S-phase cells, as well as other cell cycle data) in comparison with classical prognostic parameters and steroid receptors. Thirty-four hospitals in six geographic regions participated. In 1988-1989, 3427 patients entered the study and morphometric assessments were made.