Wilson's disease: a common liver disorder?

In two sibships 7 of 24 siblings were homozygous for Wilson''s disease. In family A, the largest kindred of this recessively inherited disease thus far reported, the proband presented with chronic active hepatitis, one sibling died of cirrhosis, a second had clinical evidence of chronic liver disease and two others had biochemical and histologic changes in liver biopsy specimens. In family B the proband had cirrhosis and portal hypertension and one sibling had biochemical and histologic evidence of liver disease. All six living patients had low serum concentrations of ceruloplasmin and copper and a high 24-hour urinary excretion of copper, which was greatly increased by administration of D-penicillamine. None showed neurologic abnormalities and only one had Kayser-Fleischer rings (detectable only by slit-lamp examination). Each patient had an erythrocyte sedimentation rate (ESR) of 8 mm/h or less. After 3 and 2 years, respectively, of D-penicillamine therapy the conditions of the two probands had improved. Liver function became normal in three siblings, and no abnormalities developed in the remaining one. Thus, since Wilson''s disease may present with chronic active hepatitis or cirrhosis with a normal ESR and without ocular or neurologic signs, it may be a more common cause of liver disease in young people than has been appreciated.     

Prion: disease or relief?

The self-perpetuating amyloid isoform, or prion, of the yeast translation termination factor eRF3 modulates programmed translational frameshifting that controls a regulatory circuit determining the polyamine levels in a yeast cell. But it is still unclear whether this effect is adaptive or pathological.     

A cost of disease resistance: paradigm or peculiarity?

Disease is one of the main driving forces of biological evolution. Parasites cause natural selection for disease resistance in populations of their hosts. Why then are all organisms susceptible to some parasites? One explanation is that resistance to disease is costly, reducing the fitness of the host in the absence of disease. A recent article shows that such costs might have helped to maintain polymorphism at a resistance locus. Other work, however, has questioned whether the costs of resistance are indeed necessary to account for polymorphism in host–parasite interactions.     

British weather: Conversation topic or serious health risk?

Britain is renowned for low indoor winter temperatures and a high rate of excess winter deaths and a causal association has been drawn between the two. A lack of priority given to energy efficiency here is often justified in terms of the mild climate. However, it can be shown that British climatic features may be related to poor health as long as poor standards of construction and insulation prevail. Legislation should therefore be implemented to improve standards both for new housing and refurbishment of much existing housing stock, not only for reasons of energy conservation but also for community health.This paper is based on a dissertation accepted for the MSc in Architecture (Advanced Environmental and Energy Studies) at the University of East London, September, 1994     

The use of fetal bovine serum: ethical or scientific problem?

Fetal bovine serum (FBS) is a common component of animal cell culture media. It is harvested from bovine fetuses taken from pregnant cows during slaughter. FBS is commonly harvested by means of a cardiac puncture without any form of anaesthesia. Fetuses are probably exposed to pain and/or discomfort, so the current practice of fetal blood harvesting is inhumane. Apart from moral concerns, several scientific and technical problems exist with regard to the use of FBS in cell culture. Efforts should be made to reduce the use of FBS or, preferably, to replace it with synthetic alternatives.     

Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity.     

Mastalgia: psychoneurosis or organic disease?

To test the traditional surgical view that pain in the breast is largely an expression of psychoneurosis, the Middelesex Hospital Questionnaire was given to 317 women with mastalgia and 170 controls with varicose veins. Their scores were compared with those of 173 women psychiatric outpatients tested by the designers of the questionnaire. The results were broadly similar in the mastalgia and varicose veins groups, and where there were significant differences women with varicose veins had a higher psychoneurotic score in each case. Within the mastalgia group no difference in scores was observed between patients with cyclical mastalgia and those with mastalgia due to periductal mastitis. Both groups of surgical outpatients had significantly lower scores in major traits than the psychiatric group, except for a small group of patients with breast pain who persistently failed to respond to treatment. Patients with mastalgia are therefore no more "neurotic" than those with varicose veins, and differ greatly from patients with recognized psychoneurosis. Most patients have a physiological or pathological basis for their breast pain, and they deserve an appropriate diagnostic and therapeutic approach.     

Cardiac parasympathetic abnormalities: Cause or consequence of chagas heart disease?

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy are unknown but are the subject o f several hypotheses. In this paper, Diego Davila, Osman Rossell and Jose Donis discuss the aetiology of cardiac failure in Chagas disease and suggest that parasympathetic abnormalities are a consequence of, rather than the cause of, the progressive cardiac enlargement seen in these patients.     

Epigenetics in disease: Leader or follower?

Epigenetic silencing is a pervasive mode of gene regulation in multicellular eukaryotes: stable differentiation of somatic cell types requires the maintenance of subsets of genes in an active or silent state. The variety of molecules involved, and the requirement for active maintenance of epigenetic states, creates the potential for errors on a large scale. When epigenetic errors - or epimutations - activate or inactivate a critical gene, they may cause disease. An epimutation that occurs in the germline or early embryo can affect all, or most, of the soma and phenocopy genetic disease. But the stochastic and reversible nature of epigenetic phenomena predicts that epimutations are likely to be mosaic and inherited in a nonmendelian manner; epigenetic diseases will thus rarely behave in the comfortably predictable manner of genetic diseases but will display variable expressivity and complex patterns of inheritance. Much phenotypic variation and common disease might be explained by epigenetic variation and aberration. The known examples of true epigenetic disease are at present limited, but this may reflect only the difficulty in distinguishing causal epigenetic aberrations from those that are merely consequences of disease, a challenge further extended by the impact of environmental agents on epigenetic mechanisms. The rapidly developing molecular characterization of epigenomes, and the new ability to survey epigenetic marks on whole genomes, may answer many questions about the causal role of epigenetics in disease; these answers have the potential to transform our understanding of human disease.     

Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?

The reactive oxygen species that are generated by mitochondrial respiration, including hydrogen peroxide (H2O2), are potent inducers of oxidative damage and mediators of ageing. It is not clear, however, whether oxidative stress is the result of a genetic programme or the by-product of physiological processes. Recent findings demonstrate that a fraction of mitochondrial H2O2, produced by a specialized enzyme as a signalling molecule in the pathway of apoptosis, induces intracellular oxidative stress and accelerates ageing. We propose that genes that control H2O2 production are selected determinants of lifespan.     

An ideal biological marker of Alzheimer's disease: dream or reality?

Senile dementia of Alzheimer's type (AD) is commonly characterized as a neurodegenerative disorder, which exhibits gradual changes of consciousness, loss of memory, perception and orientation as well as loss of personality and intellect. AD prevalence increases dramatically with age and is the fourth cause of death in Europe and in the USA. Currently, there are no available biological markers, which gives clinicians no other alternative than to rely upon clinical diagnosis by exclusion. There is no assay of objective ante mortem biochemical phenomena that relate to the pathophysiology of this disease. The pathophysiology of AD is connected with alterations in neurotransmission, plaque formation, cytoskeletal abnormalities and disturbances of calcium homeostasis. The search for a test, which is non-invasive, simple, cheap and user-friendly, should be directed at accessible body fluids. Only abnormalities replicated in large series across different laboratories fulfilling the criteria for a biological marker are likely to be of relevance in diagnosing AD. To date, only the combination of cerebrospinal fluid tau and Abeta42 most closely approximate an ideal biomarker of Alzheimer's disease. A short review on the role of biological markers in AD on the basis of the literature, contemporary knowledge and our own recent findings are presented.