Prestin and the cochlear amplifier

In non-mammalian, hair cell-bearing sense organs amplification is associated with mechano-electric transducer channels in the stereovilli (commonly called stereocilia). Because mammals possess differentiated outer hair cells (OHC), they also benefit from a novel electromotile process, powered by the motor protein, prestin. Here we consider new work pertaining to this protein and its potential role as the mammalian cochlear amplifier.     

Parasites and the hygiene hypothesis

The hygiene hypothesis proposes that the stimulation of the immune system by microbes or microbial products protects from the development of inflammatory diseases; therefore a reduced exposure to infectious agents may explain the rise in allergic and autoimmune diseases in industrialized countries. The contribution of studies on parasites and allergy to our understanding of the hygiene hypothesis has been two-fold. First, several studies have shown an inverse association between exposure to (Toxplasma gondii) or harbouring of parasites (Schistosoma or Intestinal helminths) and allergy. Second, the mechanisms behind such protective effects have provided new insights and theories on the ability of parasite derived molecules to down-regulate immune responses and thereby to control inflammatory diseases such as allergies. In this review, recent findings and new concepts relating to the associations between parasites and allergies at the epidemiological, cellular and molecular level are discussed.     

Alzheimer dementia and the aluminum hypothesis

The possible involvement of environmental aluminum in the etiology of Alzheimer disease and of senile dementia of the Alzheimer type is supported by both direct and indirect relationships between some encephalopathies and the abnormal presence of aluminum(III) in human and animal brain tissues. Proposals for further biochemical, toxicological and analytical work are illustrated.     

Chagas' disease and the autoimmunity hypothesis

The notion that the pathology of Chagas' disease has an autoimmune component was initially based on the finding of circulating antibodies binding heart tissue antigens in patients and mice chronically infected with Trypanosoma cruzi. Later, T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic mice and patients, extending the concept to include cell-mediated immunity. However, there is disagreement about whether the observed immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host tissue antigens by virtue of molecular mimicry or are elicited by host antigens exposed to lymphocytes after tissue damage caused by the parasite. There is also disagreement about the relevance of immunologic autoreactivities to the pathogenesis of Chagas' disease because of the lack of reproducibility of some key reports supporting the autoimmunity hypothesis, conflicting data from independent laboratories, conclusions invalidated by advances in our understanding of the immunologic mechanisms underlying cell lysis, and, last but not least, a lack of direct, incontrovertible evidence that cross-reacting antibodies or autoreactive cells mediate the typical pathologic changes associated with human Chagas' disease. The data and views backing and questioning the autoimmunity hypothesis for Chagas' disease are summarized in this review.     

Diabetes and the menopause

Diabetes mellitus is the commonest chronic disease in post-menopausal women and is a predisposing factor for cardiovascular disease, which is the leading cause of death in this cohort in Western societies. Diabetes and the menopause are two independent risk factors for development of cardiovascular disease. Risk factor modification in terms of diabetes appears straightforward; however, correction of oestrogen deficiency which hallmarks the menopause appears complex. Our aim is to discuss this question based on the evidence available. Co-morbid diseases are common in post-menopausal diabetics. Hence, it not easy to either conduct or establish clear causal relationships in randomised controlled trials. Consequently, making decisions about treatment becomes difficult. However, it is important adopt strategies to help post-menopausal diabetic women alleviate their menopausal symptoms and to minimise the adverse consequences of their condition. We conclude that the low-risk diabetic post-menopausal women should be offered appropriate hormone replacement therapy, whereas non-oestrogen-based treatments should be the treatment of choice for high-risk women.     

Sex determination and the maternal dominance hypothesis

The maternal dominance hypothesis has been derived from workwith humans which shows that women who are more dominant thanother women are more likely to conceive sons. In both animalsand humans dominance is a characteristic or personality trait,underpinned by testosterone and responsive to a range of environmentalchanges: physical, social and psychological. Studies of thesex ratio in the social sciences and animal behaviour eithersupport or are compatible with the idea that the sex-determiningrole of X- and Y-chromosome bearing spermatozoa may be precededby factors under maternal control which provide for differentialaccess of spermatozoa. Findings in reproductive physiology andphysiological psychology suggest that folh'cular testosteroneor a related hormone may play a critical role. Reproductivephysiologists have already identified maternal mechanisms whichcould provide the context for such a model.     

Analysis of the oncogene hypothesis

Cancer may be a natural biological event commencing at birth. Its activity is dependent upon the absence of an anti cancer gene agent or agents which are also present from birth.     

Analysis of the protovirus hypothesis

Cancer may be endogenous to all mankind. Its activity is dependent upon the absence of anti cancer gene agent or agents.     

Evidence for the vesicle hypothesis

1. The relationship of synaptic vesicles to the synaptic cleft was examined with the electron microscope at neuromuscular junctions in the rat diaphragm before and after bathing the preparation in a physiological salt solution for 2 hr.2. A population of vesicles was defined which appeared to ;touch' the axoplasmic membrane. These vesicles were found to be aggregated adjacent to axoplasmic densities which lay opposite the mouths of post-synaptic junctional folds.3. Soaking in the salt solution and modifications of this solution increased the proportion of folds opposed by presynaptic densities with associated vesicles.4. Soaking in solutions with 20 mM-KCl depleted both the specific vesicle population and the whole population of terminal vesicles. The effect was shown in paired experiments to be a specific effect of the 20 mM-KCl, and it was prevented by a concomitant increase of the bathing MgCl(2) concentration.5. Soaking in solutions with a raised osmotic pressure reduced the specific but not the general vesicle population.6. It is suggested that these observations support the vesicle hypothesis and that the specific vesicle population forms part of a feed-back mechanism adjusting transmitter synthesis and mobilization to the rate of release of transmitter.