A polymorphic region was discovered in the genetically uncharacterized opportunistic pathogen Mycobacterium abscessus. The region contains a novel 17 kb insertion sequence (IS) named ISMab1. ISMab1 contains two complete ORFs and one partial ORF located in segments with over 80 % nucleotide identity to Mycobacterium avium IS1601 and IS999 and to previously unreported IS-like elements from Mycobacterium smegmatis. The marked similarity within this family of elements is supportive of horizontal transfer between environmental mycobacterial species. In clinical isolates, ISMab1 was either present as a single copy or absent. The polymorphic region containing ISMab1 was identified by genomic subtraction between a parental strain and phenotypic variant. The variant has a 142 kb genomic deletion and this is flanked in the parental strain by complex arrays of inverted and direct repeats. Clinical isolates of M. abscessus were probed for the deletion and flanking sequences and two were found to be missing more than 20 kb. No regional deletions were found in the type strain, ATCC 19977. Although M. abscessus is a rapidly growing species, comparative sequence analysis of 23 kb from the polymorphic region showed that most local ORFs have greater amino acid identity to proteins encoded by genes from the slowly growing mycobacteria, M. avium and Mycobacterium tuberculosis, than to the rapid-grower M. smegmatis. Several ORFs also have strong similarity to Pseudomonas aeruginosa genes with a potential role in β-oxidation.Keywords : rapidly growing mycobacteria, insertion element, horizontal transfer, genetic variation INTRODUCTIONThe genus Mycobacterium has been divided into two groups on the basis of growth rate and, in general, this division is supported by phylogenetic analyses of the 16S rRNA gene (Pitulle et al., 1992). The major pathogens Mycobacterium leprae, the Mycobacterium tuberculosis complex and Mycobacterium avium complex, are members of the slowly growing mycobacteria. The second group, the rapidly growing mycobacteria (RGM), in- Abbreviations : DR, direct repeat ; IR, inverted repeat ; IS, insertion sequence ; RGM, rapidly growing mycobacteria.The GenBank accession number for the sequence reported in this paper is AF513500.cludes saprophytic species found in soil and water systems (Falkinham, 1996 ;Howard & Byrd, 2000). Comparative analysis of 16S rRNA gene sequences indicates that the RGM may be the phylogenetically older group (Pitulle et al., 1992).Several species of RGM, particularly Mycobacterium abscessus, Mycobacterium chelonae and Mycobacterium fortuitum, are opportunistic pathogens and can cause infections ranging from localized abscesses to pulmonary and disseminated disease (Griffith et al., 1993 ;Howard & Byrd, 2000 ;Wright & Wallace, 1995). RGM-associated disease tends to be sporadic and usually associated with injury or surgical procedures (Wright & Wallace, 1995). However, large outbreaks of post-operative wound infections (Chadha et al., 1998) and post-injection abscesses (Galil et al., 1999 ; Vill...

The 5-HT3 receptor is thought to play a role in the reward pathway and the phenomena of drug abuse by modulating dopamine release in the mesolimbic pathway. Studies involving this receptor have been hampered due to the low level of 5-HT3 receptors in the CNS. A 5-HT3 receptor over-expressing mouse was produced to study the role of this receptor in the rewarding properties of drugs of abuse. Over-expression was restricted to the forebrain by controlling gene expression with the Ca2+ calmodulin (CAM) kinase IIalpha promoter. No over-expression was detected in other body organs nor the cerebellum, as measured by ligand binding and Northern analysis. 5-HT3 receptor over-expressing mice drank less alcohol than non-transgenic mice in a two-bottle free choice test. Over-expression of the 5-HT3 receptor in these mice resulted in a decrease in ethanol consumption. These mice should prove useful in testing hypothesis regarding a common reward pathway for drugs of abuse and the role 5-HT3 receptors play in this pathway.

We used a deer mouse (Peromyscus

It could be said with little fear of contradiction that the hemolytic streptococcus presents a more hazy picture to bacteriologists and immunologists than does an organism like the pneumococcus. Its study presents many difficulties. In the first place, many strains which are pathogenic for man may show little or no primary virulence for animals. In the second place, antisera cannot be produced readily and consistently against all pathogenic strains. In the third place, although it is certain that many different types exist, typing by agglutination is full of pitfalls, both in technique and in the interpretation of results.It seemed to us that the foundation for any work on the hemolytic streptococcus was a careful study of the characteristics of the organism on first isolation from the body, and the ways in which it changed on mouse passage or culture passage; and the results of this part of the work are recorded in this first paper. We were aided in this investigation by the studies of several workers in this field, although it was sometimes difficult to correlate their descriptions of the variants of the hemolytic streptococcus with our own observations. Cowan (1) was the first to correlate cultural characteristics with virulence. She described a virulent S colony and an avirulent R colony. These variants were apparently found in stock laboratory cultures.

We have developed a model of cutaneous herpes simplex virus‐1 (HSV‐1) reactivation in SKH‐1 hairless mice which closely mimics the condition in humans. Sixty plaque‐forming units of HSV‐1 strain 17 syn+ were applied to a superficially abraded area on the lateral body wall. More than 85% of mice developed primary HSV‐1 infection characterized by a zosteriform pattern of cutaneous vesiculation and ulceration. Approximately one‐third of mice with primary skin lesions succumbed to neurologic disease and in the remaining mice cutaneous lesions healed completely. Subsequent exposure of healed areas to two minimal inflammatory doses of UV resulted in recrudescence of skin lesions in the irradiated areas in almost 60% of mice. Lesions appeared approximately 4 days after irradiation, persisted for 3–5 days and then resolved completely. Reactivation rarely resulted in death due to neurologic disease. Primary lesions had a histologic appearance typical of cutaneous HSV‐1 infection with vesicles and focal epithelial necrosis accompanied by the formation of epithelial syncytial cells and the presence of herpetic intranuclear inclusion bodies. In primary lesions HSV‐1 was demonstrated by immunohistochemistry, polymerase chain reaction and culture. In reactivated lesions epithelial syncytia and inclusion bodies were not seen; however, virus was demonstrable by polymerase chain reaction and culture. Exposure of the uninfected side to UV did not stimulate disease recurrence suggesting that local effects of UV rather than systemic immunosuppression were responsible for reactivation. Reactivation could also be obtained with two minimal inflammatory doses of UV from a UV‐340 light source which emits light approximating the solar spectrum.