The fragile (X) syndrome: the mutation problem

In an attempt to understand the nature of the mutational event leading to the fra(X) syndrome, we have searched for sporadic cases in 3 populations: affected males, affected females, and non-affected transmitting females. In all 3 populations there was a dearth of isolated cases, and the reasons for this are discussed.     

A cytogenetic survey of an institution for the mentally retarded: I. Chromosome abnormalities

A cytogenetic survey of 475 patients in an institution for the mentally retarded is reported. The chromosomes of all patients were studied using both a non-banding and a G-banding technique in order to estimate the relative efficiency of the two technique in detecting structural rearrangements of the chromosomes. A total of 57 patients was found to have a chromosome abnormality, including five with a balanced structural rearrangement. The contribution of chromosome aberrations to the etiology of mental retardation is discussed with special emphasis on the contribution of balanced structural rearrangements.     

Yersinia enterocolitica associated diarrhoea in a neonate

European Journal of Clinical Microbiology &; Infectious Diseases -     

Development of a larval bioassay for susceptibility of cat fleas (Siphonaptera: Pulicidae) to imidacloprid

Strategies for controlling cat fleas, Ctenocephalidesfelisfelis (Bouché), have undergone dramatic changes in the past 5 yr. With the advent of on-animal treatments with residual activity the potential for the development of insecticide resistance increases. A larval bioassay was developed to determine the baseline susceptibility of field-collected strains of cat fleas to imidacloprid. All four laboratory strains tested showed a similar level of susceptibility to imidacloprid. Advantages of this bioassay are that smaller numbers of fleas are required because flea eggs are collected for the test. Insect growth regulators and other novel insecticides can also be evaluated. Using a discriminating dose, the detection of reduced susceptibility in field strains can be determined with as few as 40 eggs.     

Role of the Phagocyte in Host-Parasite Interactions XXIV. Aldehyde Generation by the Myeloperoxidase-H(2)O(2)-Chloride Antimicrobial System: a Possible In Vivo Mechanism of Action

Myeloperoxidase (MPO), H₂O₂, and chloride ions in the presence of bacteria form aldehydes and are bactericidal. The use of heat-inactivated MPO prevented both killing and aldehyde generation. Decarboxylation and deamination of carboxyl and amino group substrates arising from the bacterial surface may participate in the reaction which yields aldehydes. Bacterial contact was essential for killing. Decarboxylation and bactericidal activities were noted when physiological concentrations of chloride were used. When MPO was replaced with horseradish peroxidase (HPO) in the chloride medium, decarboxylation and bactericidal activities were no longer noted. In contrast, iodide functioned in the antimicrobial system with either MPO or HPO. The iodide concentrations required were at least sixfold greater than circulating blood iodide levels. Moreover, decarboxylation did not occur in the presence of iodide with either enzyme. Thus, both halides function in the MPO-H₂O₂ system but by different mechanisms. It is likely that in vivo under most conditions chloride is the functional halide and that generation of aldehydes is the mechanism responsible for the antimicrobial activity of the MPO-H₂O₂-chloride system.     

Interleukin-1 beta regulation of islet and thyroid autoimmunity in the BB rat.

Daily injections of high dose human recombinant interleukin-1 beta (IL-1 beta) accelerated the onset of both insulin-dependent diabetes mellitus and lymphocytic thyroiditis in genetically prone BB rats. In diabetes-resistant BB rats, high dose IL-1 beta failed to induce diabetes. Additionally, the presence of neutralizing IL-1 beta antibodies in these rats strongly correlated with inhibition of lymphocytic thyroiditis. Since low dose IL-1 beta protects diabetes-prone rats from IDDM, we conclude that IL-1 beta is a potent modulator of autoimmune diabetes and thyroid disease in genetically susceptible rats.     

Human mtDNA sublimons resemble rearranged mitochondrial genoms found in pathological states

Sublimons, originally identified in plant mitochondria, are defined as rearranged mtDNA molecules present at very low levels. We have analysed the primary structures of sublimons found in human cells and tissues and estimated their abundance. Each tissue of a given individual contains a wide range of different sublimons and the most abundant species differ between tissues in a substantially systematic manner. Sublimons are undetectable in rho(0) cells, indicating that they are bona fide derivatives of mtDNA. They are most prominent in post-mitotic tissue subject to oxidative stress. Rearrangement break-points, often defined by short direct repeats, are scattered, but hotspot regions are clearly identifiable, notably near the end of the D-loop. The region between the replication origins is therefore frequently eliminated. One other hotspot region is located adjacent to a known site of protein binding, suggesting that recombination may be facilitated by protein-protein interactions. For a given primary rearrangement, both deleted and partially duplicated species can be detected. Although each sublimon is typically present at a low level, at most a few copies per cell, sublimon abundance in a given tissue can vary over three orders of magnitude between healthy individuals. Collectively, therefore, they can represent a non-negligible fraction of total mtDNA. Their structures are very similar to those of the rearranged molecules found in pathological states, such as adPEO and MNGIE; therefore, we propose that, as in plants, human mtDNA sublimons represent a pool of variant molecules that can become amplified under pathological conditions, thus contributing to cellular dysfunction.