Genetic engineering of pollen allergens for hayfever immunotherapy

Type I allergy is an immunoglobulin E-mediated disease, representing a major health problem affecting more than 25% of the world's population. Grass, birch and ragweed pollen are a major source of environmental allergen. Specific immunotherapy is clinically proven to be an effective treatment for allergic conditions that involve the administration of crude extracts prepared from natural sources with potential life-threatening anaphylactic side effects. Recent developments in the molecular biology of pollen allergens have made it possible to design novel therapeutic approaches for improved and safer forms of specific immunotherapy. Hypoallergenic forms of major allergens with reduced immunoglobulin E epitopes have been produced using genetic engineering, whilst preserving other characteristics of the molecule that are able to induce a protective response. These modified forms are expected to make allergen-specific immunotherapy more widely used.     

Genetic markers in glioblastoma: prognostic significance and future therapeutic implications

Glioblastoma multiforme (GBM) is the highest-grade infiltrative astrocytoma and also the most common. It is generally associated with a dismal prognosis (mean survival 11 months), yet individual patient survivals vary. Histologic parameters have had limited value in predicting survival among patients with GBM. The current view of GBM as a histopathologic entity consisting of several genetic subtypes raises the possibility that molecular alterations could be predictive of survival. Common genetic alterations in GBM include gene amplification of epidermal growth factor receptor (EGFR), mutations in the tumor suppressors TP53 and PTEN, and genetic losses on chromosome 10. Less common in GBMs is the combined loss of chromosomes 1p and 19q-a combination that has proven prognostically favorable in oligodendrogliomas. A recent article on prognostic factors in a series of 97 GBMs by Schmidt et al. finds that both TP53 mutations and young patient age at presentation are independent factors associated with a long survival. Loss of heterozygosity (LOH) of chromosome 10q was predictive of a poor outcome. Perhaps most intriguing, the finding of combined LOH of 1p and 19q, which was noted in only five GBMs, was associated with a significantly longer survival. Thus, combined losses of 1p and 19 may be associated with a favorable prognosis in a wider range of infiltrative gliomas that includes GBM. While these findings will be debated and need to be confirmed, it is clear that genotyping of infiltrative gliomas will be an important component of neuro-oncology in the future. Not only will genetic alterations offer prognostication, but they will also serve as targets for directed therapies. Treatments directed against tumors with EGFR amplification, TP53, mutations and PTEN mutations are being developed and tested in clinical trials. It remains to be seen if GBMs with 1p and 19q losses are chemosensitive in the same manner as oligodendrogliomas.     

Cardiac tissue engineering therapeutic products to enhance myocardial contractility

Journal of Muscle Research and Cell Motility - Researchers continue to develop therapeutic products for the repair and replacement of myocardial tissue that demonstrates contractility equivalent to...     

Control of environmental allergens as a therapeutic approach

The first rule of environmental allergen control is that avoidance is appropriate for allergic patients with asthma. Although this rule is obvious to allergists, it frequently is not considered by families and physicians who are not trained in allergy. The next step in environmental avoidance is to determine the specific sensitivity of a patient. Clinically, practitioners have to address reduction of exposure to more than one allergen, and it is likely that the complexity of dealing with several treatment regimes decreases compliance.     

Development of T-cell memory against inhalant allergens: risks for the future

Recent evidence suggests that the development of chronic allergic respiratory disease is a biphasic process. Phase 1 commonly occurs during early childhood and in many instances appears to be initiated in utero . This involves initial priming of the Th-cell system against ubiquitous environmental allergens, and subsequent reshaping of these responses during infancy into Th1- or Th2-polarized immunological memory. The second phase of the process comprises the repeated expression of Th2-polarized allergen-specific immunity at the level of the airway mucosa, producing cumulative damage to local tissue resulting ultimately in phenotypic changes including development of airways hyperreactivity. It is also clear that this second phase occurs in only a relatively small subset of subjects who develop long-term Th2-polarized allergen-specific immunity, given that the majority of skin prick test positive subjects do not develop chronic airways disease. This suggests that an additional set of control mechanisms, which regulate the intensity/duration of local Th-cell responses within airway mucosal tissues, may play an important role in the ultimate expression of chronic immunoinflammatory disease in the airways in 'at risk' atopic subjects.     

Genetic polymorphisms of major house dust mite allergens

BACKGROUND: Polymorphic sequence substitutions in the major mite allergens can markedly affect immunoglobulin E binding and T cell responses, but there are few studies on environmental isolates from Dermatophagoides pteronyssinus and none for D. farinae. OBJECTIVE: To determine the sequence variation of the group 1 and 2 allergens from environmental D. pteronyssinus and D. farinae. METHODS: RNA from each species was isolated from homes in Bangkok and the sequence of Der p 1, Der p 2, Der f 1, and Der f 2 determined from cDNA produced by high fidelity polymerase chain reactions. RESULTS: The enlarged data set revealed preferred amino acid substitutions in residues 19, 81, and 215 of Der p 1 as well as sporadic changes. Der p 2 showed frequent variations with clusters of amino acid substitutions, but the canonical Der p 2.0101 was not found in any of 17 sequences. Der f 2 showed variants with clusters of substitutions similar to Der p 2 but in different amino acid positions and without any structural concordance. Der f 1 in contrast to the other allergens had few amino acid sequence substitutions. CONCLUSIONS: The sequence information on variants provides data important for the optimal design of allergen formulations and useful for the genetic engineering and structure-function analyses of the major allergens.     

Genetic modification and plant food allergens: risks and benefits.

Plant genetic engineering has the potential to both introduce new allergenic proteins into foods and remove established allergens. A number of allergenic plant proteins have been characterized, showing that many are related to proteins which have potentially valuable properties for use in nutritional enhancement, food processing and crop protection. It is therefore important to monitor the allergenic potential of proteins used for plant genetic engineering and major biotechnology companies have established systems for this. Current technology allows gene expression to be down-regulated using antisense or co-suppression and future developments may allow targeted gene mutation or gene replacement. However, the application of this technology may be limited at least in the short term by the presence of multiple allergens and their contribution to food processing or other properties. Furthermore, the long-term stability of these systems needs to be established as reversion could have serious consequences.     

脂肪组织工程的研究现状和未来应用前景展望

软组织缺失是整形外科关注的焦点问题之一,传统软组织重建方法存在供皮区缺损、植入物移动和吸收以及产生异物反应。近年干细胞被认为可能是一种新颖的治疗方法,脂肪干细胞(adipose-derived Stem Cells,ADSCs)是存在于脂肪组织内的一种多能干细胞,具有多向分化潜能,且数量充足、获取方便,它们在临床前试验治疗的研究和临床实验方面已有良好的记录。本文主要从ADSCs获取、ADSCs的分离和扩增、生物材料和ADSCs、生长因子在脂肪组织工程应用以及脂肪组织工程策略等研究进展做一综述,这也是脂肪组织工程研究中不可缺少的重要环节。     

重视抗体工程

目前 ,病理学工作者都能深切体会到抗体与病理学工作关系密切 ,因为 ,抗体已经走进了几乎所有的病理科 ,它在病理学研究 ,特别在日常活检诊断中的普遍应用 ,使之成为病理工作中不可或缺的工具之一。抗体工程就是抗体的人工改造。它与病理学有何关系 ,倒是大家不大清楚的问题 ,好象抗体工程是病理学家身外的事。实际上 ,抗体工程要求全面的病理学的支持。抗体工程参与并推动着病理学技术的重大改革。病理学家是抗体基因工程发展的重要力量。一、抗体化学工程抗体工程可以分为两种 ,一是抗体化学工程 ,二是抗体基因工程。抗体化学工程是从抗体…     

Cartilage tissue engineering: state-of-the-art and future approaches

Lesions of the articular cartilage have a large variety of causes among which traumatic damage, osteoarthritis and osteochondritis dissecans are the most frequent. Returning damaged cartilage in articular joints back to a functionally normal state has been a major challenge for orthopaedic surgeons. This interest results in large part because cartilage defects cannot adequately heal themselves. Current techniques used in orthopaedic practice to repair cartilage give variable and unpredictable results. Bone marrow stimulation techniques such as abrasion arthroplasty, drilling and microfracture produce mostly fibrocartilage. Autologous osteochondral transplant systems (mosaicplasty) have shown encouraging results. Autologous chondrocyte transplantation has led to a hyaline articular cartilage repair but little is known about the predictability and reliability of the procedure. The rapidly emerging field of tissue engineering promises creation of viable substitutes for failing cartilage tissue. Current tissue engineering approaches are mainly focused on the restoration of pathologically altered tissue structure based on the transplantation of cells in combination with supportive matrices and molecules. Among natural and synthetic matrices, collagen and polysaccharidic biomaterials have been extensively used with promising results. Recently, interest has switched to the use of mesenchymal stem cells instead of chondrocytes. Tissue engineering offers the possibility to treat localised cartilage lesions. Genetic engineering techniques using genetically modified chondrocytes offer also the opportunity to treat diffuse cartilage lesions occurring in osteoarthritis or inflammatory joint diseases. Electroporation is specially a reliable and inexpensive technique that shares with electrochemotherapy an ability to target the chondrocytes despite the barrier effect of the extracellular matrix without viral vectors. The authors review recent research achievements and highlight the potential clinical applications of new technologies in the treatment of patients with cartilage injuries.     

In vivo tissue engineering: dreams for the future

Both tissue-engineered organs and hybrid artificial organs are considered to be candidates for the satisfaction of future hopes. The author has been engaged in developing vascular prostheses-neointima formed on vascular prostheses was a product of tissue engineering in vivo. On the basis of the author's experiences, the advantages of in vivo tissue engineering technologies for future artificial organs and dreams for the future are described. The use of primitive young cells is an important point; they proliferate easily and can differentiate along with their environment. They also synthesize various kinds of cytokines and growth factors, which are useful for tissue engineering. Combined use of undifferentiated cells and growth factors can induce organogenesis, so we can aim for the creation of new organs in vivo. The rejuvenation phenomenon of cells, i.e., blastogenesis, is also useful. Extracellular matrix can control cell differentiation, migration, and formation of cell communities, so we must learn to modify extracellular matrices. We humans have an extremely important legacy in our bodies, although we do not know how to use it. We have accumulated many genes during our evolution, and such genes do not become extinct. Therefore we have many genes from our primitive ancestors. These primitive creatures had an extremely strong capability for tissue repair, and we must find a way to make practical application of these dormant traits. In the future human beings will be able to learn how to control and apply them for in vivo tissue engineering technologies.     

Genetic engineering in plants

Until now most research, and its funding, has been focused onanimal and human health care as well as simple microbiologicalmodel systems such as Escherichia coli. and yeast. Molecularplant studies have generally lagged behind, often simply adaptingdiscoveries from the animal field to plants. Clearly, good healthand the efficient tackling of diseases is crucial for the well-beingof humans, and good remedies have a high economic value forthe pharmaceutical industry. However, one should not forgetthat plants are an essential component of the large ecosystemthat is our planet. They are not only the basic food producersbut they are also necessary for a balanced atmosphere (oxygenproduction) and stable and viable elimates. Especially in thisperiod of demographic explosion and growing environmental deterioration,there is a need to rebuild our agricultural systems. Plantsalso have a wide variety of ‘non-food’ uses, forinstance as energy sources, construction materials, or cosmetics.Last, but not least, they produce a lot of chemicals that canbe used as pharmaceuticals. The growing awareness of the importanceof plants has coincided with the development of plant molecularbiology. Specific features make them idealy suited for geneengineering and genetic sudies in general.