Retinal vein occlusion (RVO) is one of the most common vascular diseases of the eye and a frequent cause of severe visual loss. It is multifactorial in origin with both local factors and systemic diseases being of etiological importance. Many thrombophilic conditions have recently been identified and studies looking at their potential role in RVO have been undertaken. The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) heterozigosity associated with normal homocysteine level in blood as risk factor for thromboembolic retinal/vitreal manifestations in patients with retinal vasculitis (RV) and RVO where the other risk factors (such as hypertension; atherosclerosis; diabetes; antiphospholipid syndrome) are excluded. Second question was if anticoagulation treatment should be applied together with systemic corticosteroids and/ immunosuppressive therapy? Results obtained from the examined group showed that heterozigosity for MTHFR C677T gene is of statistical significance and correlates with raised values of homocysteine (correlation coefficient = 0.23). At the same time increased levels of homocysteine correlate (correlation coefficient = 0.01) with appearance of RVO. At r = 0.67, if there is no RV present, existence of a single mutated allele for MTHFR C677T gene does not correlate with RVO. There is however significant correlation between the mutation for MTHFR and hemorrhagic type of RV associated with RVO and/ with isolated hemorrhagic vasculitis without RVO (correlation coefficient = 0.33; correlation coefficient = 0.27; respectively).
It is of common knowledge that most leukemic patients succumb to infectious complications beside dysfunction in proliferation/differentiation of hematopoietic cells.Recently, it has been shown by several groups that there is a locus specific HLA class I downregulation in the leukemic cells.However, the HLA status of the phenotypically/morphologically normal granulocytes which can cope up with the infectious complications are not known.Therefore it may be worthwhile to study the HLA status in these cell types.We, therefore, investigated the status of HLA-ABC and HLA-DR in the CD15 + granulocytes and observed a higher expression of HLA-DR in several leukemic samples in comparison to normal volunteers (NV).Our data also suggest that only CD15 + granulocytes of myeloid leukemia, a clonal stem cell disorder, have a tendency of decreased HLA class Ia antigen expression.Moreover CD15 + granulocytes of NV showed an enhanced HLA-DR expression in presence of leukemic cells.Interestingly, CD15 + granulocytes collected from normal volunteers were observed to have phagocytic oxidative burst activity towards HLA class Ia downregulated primary leukemic cells.We therefore suggest that neutrophil transplantation may be used for the treatment of leukemia.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that destroys central nervous system (CNS) myelin. Although, the exact pathophysiology of MS is unknown, it is associated with CNS infiltration of T-cells and monocytes, which subsequently activate phagocytic cells that directly damage myelin. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor (TrkB), have recognized roles in myelin structure formation, maintenance, and repair. We used an experimental autoimmune encephalomyelitis (EAE) model of MS to determine changes in TrkB expression that may contribute to neurological recovery and myelin repair following an early inflammatory immune-mediated attack on CNS myelin. Spinal cord (SC) TrkB gene and protein expression were analyzed at various time intervals post-EAE induction. Analysis of gene and protein expression was conducted in animals with EAE relative to active controls (AC) and naive controls (NC). We showed significant increases in TrkB protein in the SC of EAE rats 12 days post-induction relative to controls. This elevated TrkB expression correlated with the onset of neurological recovery days 12 to 15 post-EAE induction. Furthermore, immunohistochemistry (IHC) analysis revealed up-regulated expression of TrkB in several SC cell types including a specific subset of BDNF responsive neuronal cells. Finally, transmission electron microscopy (TEM) showed the ultrastructural integrity of myelin is already compromised during the early, inflammatory stage of EAE prior to widespread demyelination. Therefore, the molecular signaling of SC BDNF via TrkB represents a key therapeutic target whose manipulation could facilitate myelin repair and neurological recovery following an MS-induced myelin attack.
To study the importance of the bone marrow in the long-term antibody response, IgG and IgA antitoxin antibody-forming cells were evaluated by ELISPOT in Peyer's patches, mesenteric lymph nodes, spleen, lamina propria of the small intestine and bone marrow at several times after oral immunization with cholera toxin. The mesenteric lymph node was the site having the major frequency of IgG antitoxin during the first two weeks after priming, whereas lamina propria was the site with a major number of IgA antitoxin antibody-forming cells. However, from 3 weeks until 10 months after priming, bone marrow became the site with the major frequency of IgG, and especially IgA antitoxin antibody-forming cells (without taking into account the lamina propria). This result indicates that bone marrow was responsible for the long-term antibody response and raises questions concerning the mechanisms involved in the maintenance of antibody production. The importance of bone marrow as a site of antibody production was great when we analysed results as the true contribution of the total number of antitoxin antibody-forming cells, taking into account the number of cells recovered from each organ. When we analysed the anatomical location of memory B and T cells by adoptive transference, we found that cells from mesenteric lymph nodes and spleen were able to transfer a strong antibody response to naive syngeneic recipients, whereas bone marrow cells transferred a weak antibody response.
Most technical problems concerning the production of human macrophages have been resolved by cultures in hydrophobic plastic, gas-permeable bags. This process enables collection of non-adherent macrophages and is well adapted to the safety requirements of cell therapy. Under optimized culture conditions, about one billion macrophages are currently obtained from a single leukapheresis product. In most clinical trials, macrophages have been activated by interferon-gamma (IFN gamma). The injections have little or no toxic effect. The anti-tumour activity of the intravenous (i.v.) administrations is more pronounced in certain protocols than in others. The mechanism remains poorly understood. In vitro, the cytolytic effect of macrophages requires cell-to-cell contact but macrophages injected i.v. show no particular tropism for tumour tissue. This could result from modifications in adhesion molecules occurring during monocyte-macrophage differentiation which might modify recruitment in inflammatory foci. Macrophages can, however, infiltrate tumour cell clusters, which could explain their improved efficacy when injected intratumorally (i.t.). Moreover, several arguments would favour the use of macrophages as human tumour antigen-presenting cells (APCs). In vitro, macrophages are as efficient as monocyte-derived dendritic cells (MDDCs) in stimulating cytotoxic T lymphocyte (CTL) clones or circulating CTL precursors.
Plants offer a cost-effective bioreactor to produce antibodies of diverse types. Recent studies demonstrate that secretory IgA, the predominant antibody isotype of the mucosal immune system, can be made in large quantities in plants. CaroRx, the lead SIgA antibody being developed by Planet Biotechnology Inc., has demonstrated activity in pilot phase II trials versus S. mutans, the major pathogen contributing to development of dental caries. Numerous other SIgA plantibodies are in preclinical development.
The conformation of a synthetic undecapeptide derived from the Escherichia coli tryptophan synthase beta2 subunit was studied by NMR spectroscopy when bound to a monoclonal antibody (mAb 164-2) Fab' fragment directed against the native protein. The peptide 1(H-G-R-V-G-I-Y-F-G-M-K)11, peptide 11, was recognized by the antibody and its corresponding Fab' fragments with high affinity (K(D) = 1.1+/-0.2* 10(-8) M). Peptide 11 was labelled with 15N and its structure at the binding site of the Fab' 164-2 fragment was studied by isotope-editing techniques. 1H-15N heteronuclear spectra indicated the presence of two Fab'-peptide 11 complexes with two different conformations in slow chemical exchange on the chemical shift time scale.
This article reviews the evolution of the development of vaccines against the major fungal pathogens, the state of art of these attempts and future prospects for vaccines for human and veterinary use. The article includes descriptions of the pathogens discussed, the mycoses they cause, their antigenicity, the immune response that they induce in the host and the underlying mechanisms. The final chapters address attempts to develop vaccines in experimental animal models and report on human trials for a selected number of fungi.L'article passe en revue l'évolution du développement des vaccins contre les principaux champignons pathogènes et fait le point de l'état actuel de leurs essais et de leurs perspectives d'avenir en médecine humaine et vétérinaire. Il inclue la description des champignons pathogènes impliqués, des mycoses dont ils sont responsables, de leur antigénicité et de la réponse immunitaire qu'ils induisent chez leur hôte et des mécanismes sous-jacents. Le dernier chapitre rapporte les tentatives pour développer des vaccins sur des modèles animaux expérimentaux et rend compte des essais cliniques pour quelques champignons pathogènes.
Phosphorylated di-, tri- and tetra-saccharides of β-1,2-mannan antigen derived from Candida albicans (C. albicans) cell wall were synthesized and covalently conjugated with keyhole limpet hemocyanin (KLH) and human serum albumin (HSA) via a bifunctional linker under mild conditions. The semi-synthetic β-1,2-mannoside–KLH conjugates were evaluated for the immunization of BALB/c mice. The ELISA results revealed that all three conjugates could elicit high levels of specific IgG antibodies and the acquired antisera could effectively identify the β-1,2-mannan epitope. Furthermore, the immunofluorescence and flow cytometry assays also uncovered that the induced antibodies, especially that obtained from immunization with β-1,2-mannotriose–KLH conjugate (1b), could bind well to fungi cell. Eventually, the structure–immunogenicity relationship analysis of β-mannan showed that the length of oligo-β-mannoses had a big impact on their immunogenicity and β-1,2-mannotriose showed the strongest immunogenicity. The results suggested the great potential of β-1,2-mannotriose–KLH conjugate as an antifungal vaccine candidate.
