Solid-Supported Oligonucleotide Systems for Special Biomedical Applications

Abstract

The use of composite beads consisting of a 6 μm polystyrene core with 30 nm surface-bound silica particles to routine automatic oligodeoxynucleotide (ODN) synthesis is described.     

Murine gamma interferon inhibits v-mos-induced fibroblast transformation via down regulation of retroviral gene expression.

Expression of the retroviral vector Neor myeloproliferative sarcoma virus (MPSV), which contains the v-mos oncogene and the neomycin resistance gene, leads to neoplastic transformation of mouse fibroblasts. Murine recombinant gamma interferon (IFN-gamma) could revert the neoplastic properties of established Neor MPSV-transformed cell lines to an apparently untransformed phenotype. In the presence of IFN-gamma, the Neor MPSV transformants showed a greater than 97% reduction of cloning efficiency in soft agar, strongly reduced proliferative capacity, and morphological changes. The IFN-gamma-induced phenotypic reversion was preceded by a rapid and selective reduction of all retroviral RNA species, apparently due to IFN-gamma action on the long terminal repeat of Neor MPSV. The mRNA levels of cellular genes either remained unaffected (beta-actin) or were even enhanced (H-2) in IFN-gamma-treated Neor MPSV-transformed cells. Upon removal of IFN-gamma, retroviral gene expression was fully recovered and a gradual reappearance of the transformed phenotype of these cells within 3 weeks was noted. These data show that IFN-gamma can cause a virtually complete, but reversible, inhibition of v-mos-induced neoplastic properties in transformed fibroblasts by selective down regulation of retroviral RNA levels.     

Detection of renal cell carcinoma-associated markers via proteome- and other 'ome'-based analyses.

Proteome analysis has rapidly developed in the post-genome era and is now widely accepted as the complementary technology for genetic profiling. It has been shown to be a powerful tool for studying human diseases and for identifying novel prognostic, diagnostic and therapeutic markers. This review focuses on the identification of new biomarkers and therapeutic targets for renal cell carcinoma using different 'ome'-based technologies.     

A chemiluminescent probe specific for singlet oxygen

We have synthesized a methoxyvinylpyrene (MVP) in order to model the mechanism for the observed microsomal chemiluminescence of benzo[a]pyrene 7,8-dihydrodiol, the proximate carcinogenic metabolite of benzo[a]pyrene. This MVP analog has been found to be a highly efficient and specific chemiluminescent probe for picomole quantities of singlet oxygen and singlet oxygen equivalents, and it produces significant chemiluminescence when reacted with cytochrome P-450 enzymes.     

The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains

Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system.     

Activity pattern, smoking habits, and somatometric variables of the Czechoslovakian population

A total of 3762 subjects of both sexes, natives of Czechoslovakia, ranging in age from 12--55 years, were examined. Both anamnestic data and selected anthropometric variables were evaluated. The proportion of non-smokers for adult males was 47--56%, and for adult females was 54--74% of the population. The proportion of subjects not engaged in any type of physical activity decreases in boys between 12 and 18 years from 28 to 16%, in girls between 12 and 15 years from 25 to 22%; from then on the trend reverses and the percentages rises up to 42% in men and 65% in women. The number of subjects participating in competitive sporting activity reaches its peak at 18 years, when 46% of boys annd 43% of girls compete, but then decreases quickly. 12 year old girls are taller and heavier than boys but at 15 years the relationship is reversed. The LBM at the age of 12 is equal in boys and girls, but from then till 18 years the increase is larger in boys. The LBM weight in adults remains steady, women attaining 77% of the value found in men. The skinfold increases with age similarly in both sexes, except for an interval between 12 and 18 years, when girls show a steeper increase. Adult women attain 121--160% of the values characteristic for men. The grip strength of the right hand equals about 50 kp in adult men and 30 kp in adult women. Within the age range followed, it remains unaffected by age.