Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA

Neurons can communicate with each other either via exchange of specific molecules at synapses or by direct electrical connections between the cytoplasm of either cell [for review see Bruzzone et al. (1996) Eur. J. Biochem., 238, 1-27]. Although electrical connections are abundant in many nervous systems, little is known about the mechanisms which govern the specificity of their formation. Recent cloning of the innexins--gap junction proteins responsible for electrical coupling in invertebrates (Phelan et al. (1998) Trends Genet., 14, 348-349], has made it possible to study the molecular mechanisms of patterning of the electrical connections between individual neurons in model systems. Here we demonstrate that intracellular injection of mRNA encoding the molluscan innexin Panx1 (Panchin et al. 2000 Curr. Biol., 10, R473-R474) drastically alters the specificity of electrical coupling between identified neurons of the pteropod mollusc Clione limacina.     

Evolutionarily new sequences expressed in tumors

Background  

Earlier we suggested the concept of the positive evolutionary role of tumors. According to this concept, tumors provide conditions for the expression of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are considered as evolutionary proving ground or reservoir of expression. To support this concept we have previously characterized in silico and experimentally a new class of human tumor-related transcribed sequences.     

Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion

Background  

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells.     

Second-look arthroscopic observations after radiofrequency treatment of partial thickness articular cartilage defects in human knees: report of four cases

Partial thickness articular cartilage defects in the knee are commonly encountered clinical problems. Recently, use of radiofrequency-based devices for performing arthroscopic chondroplasty has gained popularity. However, published experimental studies using different methods for evaluating the histologic effects of radiofrequency-chondroplasty on surrounding cartilage offer contradictory results. To date, few clinical findings after radiofrequency-based chondroplasty have been reported. We present four patients where follow-up arthroscopy documented partial thickness articular defects treated previously with radiofrequency-based chondroplasty to be completely filled with stable repair tissue. No attempt was made to stimulate cartilage regeneration (ie, abrasion or microfracture) in any of these cases.     

Lis1 is necessary for normal non-radial migration of inhibitory interneurons

Type I lissencephaly is a central nervous system (CNS) malformation characterized by mental retardation and epilepsy. These clinical features suggest a deficit in inhibitory neurons may, in part, underlie the pathogenesis of this disorder. Mutations in, or deletions of, LIS1 are the most commonly recognized genetic anomaly associated with type I lissencephaly. The pathogenesis of type I lissencephaly is believed to be a defect in radial neuronal migration, a process requiring LIS1. In contrast the inhibitory neurons migrate non-radially from the basal forebrain to the neocortex and hippocampus. Given that Lis1 is expressed in all neurons, we hypothesized that Lis1 also functions in non-radial migrating inhibitory neurons. To test this hypothesis we used a combination of in vivo and in vitro studies with Lis1 mutant mice and found non-radial cell migration is also affected. Our data indicate Lis1 is required for normal non-radial neural migration and that the Lis1 requirement is primarily cell autonomous, although a small cell non-autonomous effect could not be excluded. These data indicate inhibitory neuron migration is slowed but not absent, similar to that found for radial cell migration. We propose that the defect in non-radial cell migration is likely to contribute to the clinical phenotype observed in individuals with a LIS1 mutation.     

Preserving the left arm vein in cases of hemodialysis access generating left internal mammary artery steal syndrome

In patients undergoing chronic hemodialysis (HD) through an arm arteriovenous fistula (AVF), coronary insufficiency can occur if the patient undergoes a coronary artery bypass graft (CABG) using the ipsilateral internal mammary artery (1-4). Therefore, the creation of a new AVF after CABG should avoid using the arm ipsilateral to the side where the internal thoracic artery was used. In cases where coronary syndrome appears when this advice is not followed, treatment should be offered aimed at overcoming the hemodynamic interference between the diminished coronary supply through the left or right internal mammary artery by closure of the existing fistula, with or without temporary central venous line insertion until the maturation of a new fistula. We suggest a different approach by moving only the arterial inflow site of the AVF to the controlateral subclavian artery, but in addition, leaving the well functioning venous outflow tract intact. In cases of left internal mammary steal it is achieved by creating a conduit running from the right subclavian artery to the left cephalic vein; therefore, creating a new arterial inflow source, connected to the existing functioning old venous outflow tract to maintain an immediately functioning new fistula without a coronary steal.     

Can an apple a day keep the doctor away?

The modern pharmaceutical industry based on synthetic chemistry severed the historical connection between plants, food and medicines. The growing costs of discovering new chemical entity-based drugs through high throughput screening methods may yet again reconnect plants and human health at a new level of technological sophistication. Multi-component botanical therapeutics that comprise functional foods, dietary supplements and botanical drugs hold several advantages over conventional drugs that may earn them a more prominent place in the medicine of the future. They can deliver mixtures of multi-functional molecules with potentiating and synergistic effects and pleiotropic targeting at a reasonable cost and with fewer regulatory constraints. They are well suited for long-term disease prevention in an era of genetic testing and increased life expectancy. They also provide additional vehicles for delivering health and wellness. Technologies that address the needs of discovery, development and manufacturing of multi-component botanical therapeutics are emerging. They include computational and bioinformatics approaches, cell based gene expression and high-content screening systems, and phytochemical elicitation and unique plant cultivation / extraction methods designed to optimize the production of bioactives, standardize overall extract composition and assure batch-to-batch product consistency. Nevertheless, multi-component botanical therapeutics carry risks associated with potential interactions with conventional drugs and adverse reactions, which are difficult to detect and diagnose. They face problems of acceptance by the medical community and pharmaceutical industry, safety and efficacy validation, poor standardization and quality control, and difficulties in identifying active ingredients and determining their complex mode(s) of action. Solving these problems will accelerate the merger of grocery stores with pharmacies and agriculture with chemical manufacturing and provide physicians and patients with broader and more individualized choices for disease prevention and treatment.