Review Article

Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread enzymes, present in mammals in at least 14 different isoforms. Some of these isozymes are cytosolic (CA I, CA II, CA III, CA VII, CA XIII), others are membrane-bound (CA IV, CA IX, CA XII and CA XIV), CA V is mitochondrial and CA VI is secreted in the saliva and milk. Three cytosolic acatalytic forms are also known (CARP VIII, CARP X and CARP XI). The catalytically active isoforms, which play important physiological and patho-physiological functions, are strongly inhibited by aromatic and heterocyclic sulfonamides. The catalytic and inhibition mechanisms of these enzymes are understood in great detail, and this greatly helped the design of potent inhibitors, some of which possess important clinical applications. The use of such CA inhibitors (CAIs) as antiglaucoma drugs are discussed in detail, together with the recent developments that led to isozyme-specific and organ-selective inhibitors. A recent discovery is connected with the involvement of CAs and their sulfonamide inhibitors in cancer: many potent CAIs were shown to inhibit the growth of several tumor cell lines in vitro and in vivo, thus constituting interesting leads for developing novel antitumor therapies. Future prospects for drug design of inhibitors of these ubiquitous enzymes are dealt with. Although activation of CAs has been a controversial issue for some time, recent kinetic, spectroscopic and X-ray crystallographic experiments offered an explanation of this phenomenon, based on the catalytic mechanism. It has been demonstrated recently, that molecules that act as carbonic anhydrase activators (CAAs) bind at the entrance of the enzyme active site participating in facilitated proton transfer processes between the active site and the reaction medium. In addition to CA II-activator adducts, X-ray crystallographic studies have been also reported for ternary complexes of this isozyme with activators and anion (azide) inhibitors. Structure-activity correlations for diverse classes of activators is discussed for the isozymes for which the phenomenon has been studied, i.e, CA I, II, III and IV. The possible physiological relevance of CA activation/inhibition is also addressed, together with recent pharmacological/biomedical applications of such compounds in different fields of life sciences.     

The Law of the Land: A Review Article

This is a review article of the book Native Title Corporations: A Legal and Anthropological Analysis from the point of view of anthropology. I begin by highlighting the development of Anglo‐Australian social anthropology from such figures as Radcliffe‐Brown and Fortes, who were heavily influenced by regulatory and normative models from the domain of legal and judicial scholarship and speculate on the contemporary conditions by which this original social anthropological metaphor has apparently achieved a new literalisation. I criticise the legalistic appropriation of anthropological and ethnographic methodology that this book makes explicit, and finally, I express scepticism for the future success of the prescribed body corporate, as described in the Native Title Act (1993), as a model for the possession, transmission and elaboration of indigenous rights to country.     

Review Article Number 138: Constituents of the yew trees

Yew trees, taxonomically classified under the genus Taxus, are sources of a number of physiologically active compounds of different classes. Taxane derivatives with various carbon skeletons, lignans, flavonoids, steroids and sugar derivatives have been isolated from different Taxus species. Compounds isolated from the genus Taxus between 1908 and December 1997 have been comprehensively reviewed.     

Assessing Social Networks in Patients with Psychotic Disorders: A Systematic Review of Instruments

Background

Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used.

Aims

To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties.

Method

A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders.

Results

Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability.

Conclusions

The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies.     

Drug Addiction,Psychotic Illness and Brain Self-Stimulation: Effective Treatment and Explanatory Hypothesis

Similarities between drug addiction and psychotic illness suggested that drug addicts could be treated with intensive ECT and phenothiazine drugs, a therapeutic approach effective in more serious psychotic illnesses.The use of this intensive treatment method is described in six drug addicts. Successful results were achieved in four patients who have been followed up for two to five years. The treatment program, the preliminary investigations and the follow-up procedures are described.Particular reference is made to the brain self-stimulation studies of Olds and others in animals, and those of Heath in man. A hypothesis is advanced to explain the various aspects of the clinical picture in both psychotic illness and drug addiction.The intensive method of treatment should be considered for drug addicts whose prognosis is otherwise poor. Further investigations along the lines of the proposed hypothesis might be profitable in other types of abnormal and maladaptive behaviour.     

The Crisis Treatment of Suicide

Almost all suicidal persons who consult physicians wish to live. Generally they fall into one of two groups. Interpersonal suiciders manifest frequent threats and attempts, are emotionally labile, have ill-defined suicide plans, and clear ideas as to how their crises might be resolved. Intrapersonal suiciders are less open in manifestations of suicidal drive, withdrawn rather than emotional, often have clearly-formulated suicide plans and do not have ideas (other than suicide) as to how their crises might end. The suicidal situation results from two factors: (1) the loss of some valuable person or commodity, and (2) the loss of self-esteem. What ensues is temporary character disorganization—crisis. Treatment is based on restoration or replacement of lost objects and building up of self-esteem.     

Review Article Coenzyme-B(12)-Dependent Glutamate Mutase

Adenosylcobalamin (coenzyme B12)-dependent glutamate mutase catalyzes a most unusual carbon skeleton rearrangement involving the isomerization of l-glutamate to L-threo-methylaspartate, a reaction that is without precedent in organic chemistry. This reaction proceeds through a mechanism involving free radical intermediates that are initiated by homolysis of the cobalt-carbon bond of the coenzyme. The enzyme serves as a paradigm for adenosylcobalamin-dependent catalysis and, more generally, provides insights into how enzymes generate and control reactive free radical species. This review describes how recent studies on the mechanism and structure of glutamate mutase have contributed to our understanding of adenosylcobalamin-mediated catalysis. Copyright 2000 Academic Press.