Systems biology: integrating technology,biology, and computation

The Human Genome Project has changed the worlds of biology and medicine-helping to catalyze two major paradigm changes: systems biology and predictive, preventive and personalized medicine. These two themes will dominate 21st century biology and medicine. I will discuss these changes and indicate how they may interface with with the process of aging.     

CIRCADIAN RHYTHMS: A MODEL FOR THE INTERPRETATION OF MULTIMODAL CIRCADIAN SPECTRA

A nonlinear circadian model is postulated as the underlying process in the generation of biological data containing several significant non-24-hour rhythms. The model (a) attributes observed multimodal dispersion to the nonlinear influence of processes which modulate the circadian rhythm, but which are very slow compared to 24-hour processes, and (b) provides quantitative estimates of the period of this slow modulation, as well as the period of the basic circadian rhythm. Under this model, circadian data previously presumed to be anomalous gives a consistent derived basic rhythm of about 24 hours.     

Biolistic transformation of Trichoderma harzianum and Gliocladium virens using plasmid and genomic DNA

Biolistic (biological ballistic) and protoplast-mediated procedures were compared as methods for transforming strains of Gliocladium virens and Trichoderma harzianum. For biolistic transformation, conidia were bombarded using a helium-driven biolistic device to accelerate M5 tungsten particles coated with plasmid or genomic DNA. DNA from either source contained a bacterial hygromycin B resistance gene (hygB) as a dominant selectable marker. The same sources of DNA were also used to transform protoplasts using a standard polyethylene glycol-CaCl₂ protoplast fusion protocol. Hygromycin B-resistant (HygB^R) transformants were recovered from all strains, methods, and DNA sources except for genomic DNA used with the protoplast method. The biolistic procedure was technically simpler, and increased transformation frequency and genetic stability in the progeny as compared with the protoplast-mediated transformation. Southern analysis of homokaryotic HygB^R progenies showed that the transforming sequences were integrated into the genome of the recipient strains, and apparently were methylated. This is the first study presenting detailed results on biolistic transformation of a filamentous fungus.     

Artificial Liver: Present and Future

Early in 1956, the first model of a biological artificial liver, using a live dog's liver incorporated in a cross-hemodialyzer, was placed in an experimental animal with portocaval encephalopathy. This "biological artificial liver," a hybrid artificial liver in the present terminology, was the first in the world. In October 1958, the first human patient, a young male patient in hepatic coma due to liver cirrhosis, was placed on the laboratory-made biological artificial liver composed of four parabiotic cross-hemodialyzers connected with four live dogs' livers to which the "hepatic reactors" for ammonium adsorption and acid-base balance were additionally equipped. This first case was very successful, resulting in the patient's recovery from coma. This article introduces the past history of the artificial liver, research of which has mainly been conducted in Japan since the early 1950s by the author, M. Mito, and Y. Nosé. Until recently, little progress has been made in this field through the application of blood purification principles such as hemoadsorption, plasmapheresis, and other modifications and combinations. Accumulation of clinical experiences with such conventional methods has stimulated the third generation of the artificial liver to a return to a hybrid organ applying modern science and technology. A concept of hybrid organs in comparison with organ transplants is introduced. The Japanese national project of developing a new artificial liver system, as conducted by the author as the chairman and his associates, is introduced.     

n-Hexane urine elimination and weighted exposure concentration

Summary The concentration of n-hexane in urine was determined in 30 subjects occupationally exposed to n-hexane (median value 59.6 mg/m³) in a shoe factory. The measurement of the substance was performed by means of a Hewlett-Packard 5880 gas chromatograph supplied with a Hewlett-Packard 5970 Mass Selective Detector. The analyses were performed by the head space method (constant volume method, after determination of the urine partition coefficient by the multiple phase equilibration method). The authors found a significant correlation between the n-hexane urine concentrations (g/1, Cu) and the n-hexane environmental concentrations (mg/m³, Ci) (r = 0.84; Cu = 0.0669 x Ci + 0.8396).This work was supported by the research funds given to Fondazione Clinica del Lavoro, Pavia by the Health Council     

富血小板血浆在妇科疾病治疗中应用及其研究现状

富血小板血浆(PRP)是人自体全血经离心后获得的血小板浓缩物,含有大量生长因子及蛋白质。PRP因其有助于组织再生、伤口愈合、瘢痕修复等作用,在骨科、皮肤科、口腔颌面外科、整形美容科等领域应用广泛,而在妇科领域应用迄今相对较少。最新研究结果显示,PRP具有促进子宫内膜和卵泡生长作用,在治疗薄型子宫内膜(TE)、改善子宫内膜容受性(ER)、恢复卵巢功能等方面取得较大进展,并为多种妇科疾病治疗提供新的研究方向和手段。笔者拟就PRP的制备及分类、在妇科疾病治疗中的应用及其前景展望等最新研究现状进行阐述。     

复合生长因子材料在组织工程中的应用

组织工程就是应用细胞,在体内或体外重建组织,或缺损组织,器官的生物活性替代物,除了细胞和支架,生长因子在组织的再生中是重要的,复合生长因子或生长因子质粒DNA的材料在组织工程的应用中有广阔的前景。     

Elbow reconstruction after excision of proximal ulna tumors: Challenges and solutions

Most malignant bone tumors are treated with surgical excision, adhering to oncologic principles, followed by reconstruction to preserve form and function whenever feasible. Primary bone tumors around the elbow are rare accounting for <1% of all skeletal tumors. They pose a reconstructive challenge, due to the complex interplay between the osseous & capsulo-ligamentous structures which is essential for elbow stability and function. Tumors affecting the proximal ulna are rare and reconstruction of the defects following these tumors is extremely challenging. Various reconstruction options like arthrodesis, autogenous bone grafts, allografts, re-implantation of sterilized tumor bone, pseudoarthrosis, and endoprosthesis have been tried with variable success. However, due to lack of standardization and the rarity of the site, surgeons are often in a dilemma to choose the correct option. This can lead to suboptimal functional outcomes and long-term failures. In this article, we reviewed the published literature on proximal ulnar tumors and noted the pros and cons of various reconstructive procedures. We have also attempted to formulate reconstruction recommendations based on the level of resection of proximal ulna.     

Use of biologics in rotator cuff disorders: Current concept review

Poor tendon to bone healing following rotator cuff repair has led to the continued interest and investigation into biological augmentation. The biology of tendinopathy is not fully understood and consequently the availability of disease modifying therapeutic targets is limited. A ceiling of benefit has been reached by mechanical optimisation of rotator cuff repair and thus, in order to improve healing rates, a biological solution is required. This review focuses on the strategies to biologically augment rotator cuff disorders with an emphasis on rotator cuff repair. Leucocyte rich platelet rich plasma has been shown to improve healing rates without clinically relevant improvements in outcome scores. Similarly, improved healing rates have also been reported with bone marrow stimulation and in long-term follow-up with bone marrow concentrate. Extracellular matrix (ECM) and synthetic scaffolds can increase healing through mechanical and or biological augmentation. A potential third category of scaffold is bio-inductive and has no mechanical support. Studies involving various scaffolds have shown promising results for augmentation of large to massive tears and is likely to be most beneficial when tendon quality is poor, however level I evidence is limited.     

Effect of administration of diethylcarbamazine with and without fluconazole on experimental fungal infections in mice

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In our current experiments, DEC treatment was associated with lower brain fungal burden in fluconazole-treated mice following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans. Further investigation of combined DEC and fluconazole treatment of fungal infections is warranted.