Mapping the active-site tyrosine of vaccinia virus DNA topoisomerase I.

Site-directed mutagenesis of the vaccinia virus gene encoding a type I DNA topoisomerase implicates Tyr-274 as the active-site residue that forms a covalent adduct with DNA during cycles of DNA-strand breakage and reunion. Replacement of Tyr-274 by phenylalanine results in loss of the ability of the enzyme to relax negatively supercoiled DNA as well as to form the covalent DNA-protein intermediate. Substitution of phenylalanine for tyrosine at nine other sites in the protein has no apparent effect on enzyme activity. Amino acid sequence alignment reveals Tyr-274 to be homologous to Tyr-727 and Tyr-771, respectively, of the type I topoisomerases from Saccharomyces cerevisiae and Saccharomyces pombe; Tyr-727 and Tyr-771 have been shown to represent the active-site tyrosines of those enzymes. Sequence comparison of the active-site regions defines a motif Ser-Lys-Xaa-Xaa-Tyr common to the viral and cellular type I topoisomerases, including the human enzyme.     

A proposed classification of swollen legs

The subject of enlarged legs is vast and complex. Up to now there has been no organic classification of the clinical picture involved. The basic problem is that of the criterion on which to base the classification. Literature on this subject has opted for the pathogenic criterion because it seems to facilitate the formulation of a classification which is of use to the doctor. One possibility would be to divide the syndrome into vascular and non-vascular swollen legs. The first group could in turn be separated into macro-circulating and micro-circulatory. The micro-circulatory forms can be primitive or secondary. Amongst the secondary micro-circulatory forms, two other groups can be singled out: secondary forms with local cause and secondary forms caused by organic pathology. However, there are clinical forms which are on the periphery of these different groups and these forms are subject to discussion regarding nosographic localization.     

Bonnet syndrome and posterior parasagittal tumor: clues to neural mechanisms

A case of Bonnet syndrome associated with blindness due to bilateral eye disease and a posterior parasagittal meningioma is reported. It is assumed that visual afferent deprivation alone is not enough to produce the syndrome and that, in most instances, a 'cerebral factor' must be operative if hallucinoses are to occur. The distinction between hallucinosis and hallucinations is favored and a common neural circuit for the mediation of hallucinotic imageries in general is suggested. One should not immediately put the blame on obvious eye or visual pathways affections when facing cases of Bonnet syndrome, as they are not likely to explain the complex array of images perceived by any given patient. On the contrary, the possibility of a clinically covert intracranial disease should be always raised and intensively looked for.     

Heart size and function of soldiers, athletes, and sedentary men

This study compares the heart sizes and left ventricular masses of soldiers (n = 11) with age- and body size-matched groups of sedentary men (n = 10) and accomplished athletes (n = 11). Echocardiography revealed that active duty soldiers (A) who met minimal fitness standards and pentathletes (P) had greater average left ventricular (LV) end-diastolic volumes (A = 10%, NS; P = 28%, p less than 0.05), stroke volumes (A = 29%, NS; P = 44%, p less than 0.01), and LV masses (A = 22%, NS; P = 76%, p less than 0.01) than sedentary subjects. Athletes had an average LV wall thickness which was 23% (p less than 0.05) greater than that of soldiers and 32% (p less than 0.01) greater than that of sedentary men. The LV wall thickness to radius ratio (h/r) was similar between soldiers and sedentary men, but in athletes the h/r was greater (p less than 0.01) than in the less conditioned subjects. These data suggest that soldiers who meet minimal standards of fitness exhibit cardiac morphometric features consistent with endurance conditioning. However, the soldiers studied were significantly less (p less than 0.001) conditioned than the competitive athletes. These data suggest that improvements in aerobic and cardiac conditioning could be achieved through a greater emphasis on physical training.