Carbohydrate based vaccines

In the past decades, a gradual increase in the resistance to antibiotics has been observed, leading to a serious thread for successful treatment of bacterial infections. This feature in addition to difficulties in developing adequate drugs against (tropical) diseases caused by parasites has stimulated the interest in vaccines to prevent infections. In principle, various types of cell surface epitopes, characteristic for the invading organism or related to aberrant growth of cells, can be applied to develop vaccines. The progress in establishing the structure of carbohydrate immuno-determinants in conjunction with improvements in carbohydrate synthesis has rendered it feasible to develop new generations of carbohydrate-based vaccines.     

HIV vaccines in infants and children: past trials,present plans and future perspectives

This review will address the recent history in HIV vaccine trials in the pediatric population while giving due respect to the pediatric vaccine successes achieved over the past decades. Success and failure seen when utilizing the neonatal macaque model of SIV infection and the ramifications of these studies will be discussed. The short list of pediatric HIV vaccine trials currently in progress and those in early planning stages will be reviewed. Finally, future perspectives on the impact of a vaccine that could be used to potentially avert mother-to-child transmission of HIV and lead ultimately to the establishment of immunity throughout adolescence and beyond will be presented.     

Control of meningococcal meningitis with meningococcal vaccines.

The development of effective meinigococcal vaccines was based upon the finding that immunity to the meningococcus was directly correlated with serum bactericidal antibodies. Purified high molecular weight capsular polysaccharides of serogroups A and C meningococci stimulated the production of humoral antibodies which had group specific bactericidal activity. In controlled field trials in Army recruits, group C polysaccharide vaccines were highly effective in preventing group C disease. Following its use as a routine immunization in recruits in October 1971 group C meningococcal disease has been almost completely eliminated from Army training centers. Group A vaccine has been field tested in Egyptian school children with great success. Group B polysaccharide has failed to induce bactericidal antibodies in humans and, therefore, new research is underway to attempt to develop a cell wall protein antigen as a vaccine against group B disease.     

Anti-idiotype cancer vaccines: past and future

 Anti-idiotypic antibodies (Ab2) binding to the antigen-combining site of antitumor antibodies (Ab1) can induce anti-anti-idiotypic antibodies (Ab3) that specifically bind to the tumor antigen recognized by Ab1. Furthermore, Ab2, mimicking tumor antigens, have been shown to induce anti-anti-idiotypic proliferative T lymphocytes of the helper and suppressor type, as well as cytotoxic lymphocytes. The immunomodulatory activities of Ab2 have been demonstrated both in animals and in patients. The demonstration of tumor growth inhibition by anti-idiotypes in preclinical and phase I clinical studies emphasizes that randomized control trials should be performed to demonstrate clinical efficacy of Ab2 vaccines. Received: 25 July 1996 / Accepted: 22 August 1996     

Polymorphisms past and present

Polymorphisms, particularly genetic variants of the red blood cell, have served as a major focus for the research of Frank B. Livingstone over the course of a long and productive career. Recent investigations confirm the value of key insights that he contributed to this area more than four decades ago. As Livingstone recognized, the same underlying evolutionary model that guides genetic studies in present populations also provides a productive framework for interpreting patterns of variation in the skeleton and dentition throughout past human evolution. Examples explored in detail here include polymorphisms in hominoid nasal bone shapes and fourth lower premolar roots. This work provides both empirical and theoretical contexts for investigating patterns of human variation over the last 6 to 8 million years.     

Plant microtubule studies: past and present

Here, I briefly review historical and morphological aspects of plant microtubule studies in land plants. Microtubules are formed from tubulins, and the polymeric configurations appear as singlet, doublet, and triplet microtubules. Doublet microtubules occur in the axoneme of cilia and flagella, and triplet microtubules occur in the basal bodies and centrosomes. Doublet and triplet microtubules are lost in all angiosperms and some gymnosperms that do not possess flagellated sperm. In land plants with flagellated sperm, centriolar centrosomes transform into basal bodies during spermatogenesis. In flowering plants, however, most male gametes (sperm) are conveyed to eggs without the benefit of cilia or flagella; thus, higher plants lack centriolar centrosome and doublet and triplet microtubules. The loss of centriolar centrosomes from the life cycle of flowering plants may have influenced the evolution of the plant microtubule system. Comparison of mitotic apparatuses in basal land plants and flowering plants illuminates the evolutionary transition from the centriolar microtubule system to the acentriolar microtubule system.     

Schistosomiasis in Indonesia: past and present

Schistosomiasis is endemic in Indonesia in two isolated areas, Lindu valley and Napu valley, both located in the Province of Central Sulawesi. In 1940, a prevalence survey was initiated in Lake Lindu, which indicated a Schistosoma japonicum infection prevalence of 56% among the population of Anca, Tomado and Langko villages. Another survey was conducted in 1973 in Napu valley and very high infection prevalences of up to 72% were found among the population in Winowanga village. Since then, comprehensive studies on the epidemiology and the effects of control have been carried out in 24 endemic villages in both areas. Over the past six decades, schistosomiasis control has been implemented and the average prevalence is now much lower than before the control programme was launched. In 2006, it was 0.49% in 7 villages in Lindu valley. In Napu valley, the average infection prevalence among the population of 17 villages was 1.08% in the same year. Again in 2006, the prevalence of infection in snails ranged from 0 to 13.4% and from 0 to 9.1% in Napu and Lindu valleys, respectively. The highest prevalence among snails was found in Dodolo village. The prevalence of S. japonicum in the reservoir host Rattus spp. ranged from 0 to 20% and the highest prevalence was again found in Dodolo village. Contemporary data suggest that transmission of schistosomiasis is still ongoing in Indonesia despite regular surveillance and control activities covering the whole endemic area.     

Chitosomes: past, present and future

José Ruiz-Herrera's discovery that chitin microfibrils could be made by a fungal extract paved the way for elucidating the intracellular location of chitin synthetase. In collaboration with Charles Bracker, chitosomes were identified as the major reservoir of chitin synthetase in fungi. Unique in size, buoyant density, and membrane thickness, chitosomes were found in a wide range of fungi. Their reversible dissociation into 16S subunits is another unique property of chitosomes. These 16S subunits are the smallest molecular entities known to retain chitin synthetase activity. Further dissociation leads to complete loss of activity. From studies with secretory mutants, yeast researchers concluded that chitosomes were components of the endocytosis pathway. However, key structural and enzymatic characteristics argue in favor of the chitosome being poised for exocytotic delivery rather than endocytotic recycling. The chitosome represents the main vehicle for delivering chitin synthetase to the cell surface. An immediate challenge is to elucidate chitosome ontogeny and the role of proteins encoded by the reported chitin synthetase genes in the structure or function of chitosomes. The ultimate challenge would be to understand how the chitosome integrates with the cell surface to construct the organized microfibrillar skeleton of the fungal cell wall.     

Life: past, present and future

Molecular methods of taxonomy and phylogeny have changed the way in which life on earth is viewed; they have allowed us to transition from a eukaryote-centric (five-kingdoms) view of the planet to one that is peculiarly prokarote-centric, containing three kingdoms, two of which are prokaryotic unicells. These prokaryotes are distinguished from their eukaryotic counterparts by their toughness, tenacity and metabolic diversity. Realization of these features has, in many ways, changed the way we feel about life on earth, about the nature of life past and about the possibility of finding life elsewhere. In essence, the limits of life on this planet have expanded to such a degree that our thoughts of both past and future life have been altered. The abilities of prokaryotes to withstand many extreme conditions has led to the term extremophiles, used to describe the organisms that thrive under conditions thought just a few years ago, to be inconsistent with life. Perhaps the most extensive adaptation to extreme conditions, however, is represented by the ability of many bacteria to survive nutrient conditions not compatible with eukaryotic life. Prokaryotes have evolved to use nearly every redox couple that is in abundance on earth, filling the metabolic niches left behind by the oxygen-using, carbon-eating eukaryotes. This metabolic plasticity leads to a common feature in physically stratified environments of layered microbial communities, chemical indicators of the metabolic diversity of the prokaryotes. Such 'metabolic extremophily' forms a backdrop by which we can view the energy flow of life on this planet, think about what the evolutionary past of the planet might have been, and plan ways to look for life elsewhere, using the knowledge of energy flow on earth.     

Growth hormone-releasing hormone: past and present

The discovery of hypothalamic hypophysiotropic factors confirmed the hypothesis of Green and Harris in the late 1940s. These hormones were isolated from their eutopic site of production (the hypothalamus) with the exception of growth hormone (GH)-releasing hormone (GHRH), which was isolated from an ectopic, tumoral site of production and found to be responsible for acromegaly. Following the isolation, characterization and synthesis of human GHRH, clinical studies were performed and are described below. Circulating levels of GHRH can be measured and provide the basis for the diagnosis of acromegaly related to the ectopic, tumoral production of GHRH. At present, GHRH is used as a test of GH secretion mainly as an adjunct to other agents which modify somatostatin status, or to GH-releasing peptides. Its therapeutic potential in children and the elderly is still under investigation. The role of GHRH in the pulsatile secretion of GH is described.