Transfusion medicine in the era of proteomics

Blood components (BCs) are highly complex mixtures of plasma proteins and cells. At present, BC and blood derivatives (BDs) quality control is mainly focused on standardized quantitative assessment, providing relatively limited information about products. Unfortunately, during the production, inactivation, and storage processes there is the risk of changes in their integrity, especially at the protein level, which could cause negative effects on transfusion. It is therefore a major challenge to identify significant alterations of these products, and, in this context, proteomics can play a potentially relevant role in transfusion medicine (TM) to assess the protein composition of blood-derived therapeutics, particularly for identifying modified proteins. It can provide comprehensive information about changes occurring during processing and storage of BCs and BDs and can be applied to assess or improve them, therefore potentially enabling a global assessment of processing, inactivation and storage methods, as well as of possible contaminants and neoantigens that may influence the immunogenic capacity of blood-derived therapeutics. Thus, proteomics could become a relevant part of quality-control process to verify the identity, purity, safety, and potency of various blood therapeutics. A more detailed understanding of the proteins found in blood and blood products, and the identification of their interactions, may also yield important information for the design of new small molecule therapeutics and also for future improvements in TM.

Proteomics, together with genomics in the near future, will presumably have an impact on disease diagnosis and prognosis as well as on further advances in the production, pathogen inactivation and storage processes of blood-based therapeutics.     

Multiple effects of kanamycin on translational accuracy

Summary We have studied the effects of kanamycin on the accuracy of translation in vitro by wild-type and mutant ribosomes from Escherichia coli. Kanamycin stimulates the leucine missense error of poly(U) translation by wild-type, Ram, and streptomycin-resistant ribosomes in characteristic ways; in particular, the streptomycin-resistant ribosomes are significantly less error-prone than wild-type or Ram ribosomes at all concentrations of the antibiotic. Kinetic analysis of the effects of kanamycin on the translational accuracy of wild-type ribosomes reveals a different concentration dependence for the perturbation of the initial selectivity and for the proofreading. Furthermore, the initial selectivity of streptomycin-resistant ribosomes is not affected by kanamycin; the drug enhances only the error of proofreading by this mutant ribosome. We suggest that the multiple effects of kanamycin on the errors of translation are due to separate effects at different ribosomal sites.Abbreviations N-AcPhe N-acetylphenylalanine - Km Kanamycin (used in the Figures and Tables only) - Str streptomycin (-'-) - EF elongation factor - TCA trichloroacetic acid - Ram ribosome ambiguity mutant     

Disability and genetics in the era of genomic medicine

Genomic medicine offers a growing number of methods to diagnose, cure or prevent disability. Although many disabled people welcome these advances, others have reservations about the impact of genetic knowledge on disabled people's lives, arguing that genetic science might exacerbate the deep ambivalence that society as a whole has towards physical difference and anomaly. It is also possible, however, that being able to specify the genetic bases of disability, and distinguish them from other causative factors, will contribute to a fuller understanding of disability and a better response to disabled people.     

Multiple endocrine neoplasia associated with von Recklinghausen's disease.

Details were studied of three patients with duodenal carcinoid tumour in association with neurofibromatosis and phaeochromocytoma, and of four patients with duodenal carcinoid and either von Recklinghausen''s disease or phaeochromocytoma. The rarity of these endocrine tumours, together with the unusual morphological features and somatostatin content of the two duodenal carcinoids examined, suggest that this combination of tumours is not a chance association. It is suggested that this linkage of neurofibromatosis, phaeochromocytoma, and duodenal carcinoid is a specific multiple endocrine neoplasia syndrome.     

关于转化医学在生化教学中的几点对策与思考

转化医学(translational medicine),其核心是要将生物医学基础研究成果迅速有效的转化为可在临床医学实际应用的理论、技术、方法和药物。作者作为生物化学与分子生物学教师,在转化医学大背景下在生化教学改革方面进行了一些尝试,提出了转化医学在生化教学中的几点对策与思考,以供大家探讨。     

Liu Shih-Hao: Pioneer of translational medicine in China

Editorial comment Translational medicine is a new discipline which aims to eliminate the barrier between preclinical and clinical medicine. Here, Dr. Li discusses the application of translational medicine in the research, teaching and clinical work of Prof. Liu Shih-Hao, the founder of endocrinology in China, who was particularly renowned for his early work in calcium and phosphorus metabolism. This well-known success story can be traced back to an early appreciation of translational medicine by Prof. Liu Shih-Hao, and serves as an important and revelatory lesson for us all.     

Multiple translational products from a Mycoplasma hyorhinis gene expressed in Escherichia coli.

We analyzed protein expression from a cloned Mycoplasma hyorhinis genomic fragment that produces in Escherichia coli a set of related polypeptides of 110, 100, 65, and 55 kilodaltons from a coding region of just over 3.0 kilobases. Expression of these multiple products resulted from a mechanism operating at the translational level but not from truncation at UGA termination codons, which are known to encode tryptophan in several mycoplasma species. The structural relatedness of the proteins was demonstrated by two-dimensional tryptic peptic mapping, but their generation by posttranslational processing was ruled out by pulse-chase labeling analysis. Examination of proteins expressed from plasmid constructs and tryptic peptide analysis of these polypeptides and the original set of proteins revealed that they share carboxy-terminal regions, an observation inconsistent with truncation at UGA codons. Expression of proteins from this cloned fragment was not dependent on vector sequences and was observed when the coding region was placed under control of a T7 promoter, suggesting that all products were translated from a single message. Expression of related products in mycoplasmas was examined by immunoblot analysis of M. hyorhinis proteins with antiserum against overexpressed recombinant proteins. A single 115-kilodalton mycoplasma protein was detected, which is larger than any of the related proteins expressed in E. coli. Our analysis indicated that translation initiation sites are used in E. coli that are not active in mycoplasmas, thereby defining differences between the translational regulatory signals of mycoplasmas and eubacteria.     

Stereotactic radiation therapy in the era of precision medicine for cancer

Unlike conventional radiation therapy, stereotactic radiation therapy(SRT) is an emerging tumor-ablative radiation technology with a high-dose delivery to targets while dramatically sparing adjacent normal tissues. The strengths of SRT involve noninvasive and short-course treatment, high rates of tumor local control with a low risk of side effects. Although the scientific concepts of radiobiology fail to be totally understood currently, SRT has shown its potential and advantages against various tumors, especially for those adjacent to less tolerable normal organs(spinal cord, optic nerve, bowels, etc.). Nowadays, the clinical efficacy of SRT has been widely confirmed in certain patients, especially for those medically inoperable, unwilling to undergo surgery, medicine ineffective with tumor progression. Moreover, SRT could be properly used as palliative treatment aiming at relieving local symptoms and pain, and eventually achieving a potential survival benefit of several months. However, the weaknesses of SRT relate to inevitable radiation-induced toxicities as well as the inaccessibility of prophylactic irradiation. In general, one flaw cannot obscure the splendor of the jade. The emergence and development of SRT has opened the new era of precision radiation therapy, and SRT will probably step gloriously onto the remarkable stage for precision medicine.