Physical map of the region surrounding the ataxia-telangiectasia gene on human chromosome 11q22-23.

Ataxia telangiectasia (A-T) is an autosomal recessive disease affecting multiple systems, including the development of the cerebellum and thymus. This results in a progressive cerebellar ataxia with onset between 1-3 years, telangiectasia occurs within the subsequent 3-5 years. We localized the A-T gene by linkage analysis to chromosome 11q22-23, between the markers D11S384, and D11S535, and constructed a series of contigs using three BACs and twelve cosmids, spanning a region of approximately 400 kb. We developed a set of sequence-tagged site (STS) markers from the ends of the BACs and cosmids. The A-T gene was isolated from within this region. It is now possible to precisely orient specific BACs, cosmids, and STSs with respect to the exons of the A-T gene (ATM). We anticipate that this information will be useful for further studies of functional domains and regulatory elements within the ATM gene, as well as for other genes in this region. In addition, these clones can be used for FISH studies of deletions, translocations and for loss of heterozygosity in various tumors.

Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death.

BACKGROUND: Coronary thrombosis has been reported to occur most frequently in lipid-rich plaques with rupture of a thin fibrous cap and contact of the thrombus with a pool of extracellular lipid. However, the frequency of coronary artery thrombosis with or without fibrous cap rupture in sudden coronary death is unknown. In this study, we compared the incidence and morphological characteristics of coronary thrombosis associated with plaque rupture versus thrombosis in eroded plaques without rupture. METHODS AND RESULTS: Fifty consecutive cases of sudden death due to coronary artery thrombosis were studied by histology and immunohistochemistry. Plaque rupture of a fibrous cap with communication of the thrombus with a lipid pool was identified in 28 cases. Thrombi without rupture were present in 22 cases, all of which had superficial erosion of a proteoglycan-rich plaque. The mean age at death was 53 +/- 10 years in plaque rupture cases versus 44 +/- 7 years in eroded plaques without rupture (P < .02). In the plaque-rupture group, 5 of 28 (18%) were women versus 11 of 22 (50%) with eroded plaques (P = .03). The mean percent luminal area stenosis was 78 +/- 12% in plaque rupture and 70 +/- 11% in superficial erosion (P < .03). Plaque calcification was present in 69% of ruptures versus 23% of erosions (P < .002). In plaque ruptures, the fibrous cap was infiltrated by macrophages in 100% and T cells in 75% of cases compared with 50% (P < .0001) and 32% (P < .004), respectively, in superficial erosions. Clusters of smooth muscle cells adjacent to the thrombi were present in 95% of erosions versus 33% of ruptures (P < .0001). HLA-DR expression was more often seen in macrophages and T cells in ruptures (25 of 28 cases) compared with expression in macrophages in superficial erosion arteries (8 of 22 cases, P = .0002). CONCLUSIONS: Erosion of proteoglycan-rich and smooth muscle cell-rich plaques lacking a superficial lipid core or plaque rupture is a frequent finding in sudden death due to coronary thrombosis, comprising 44% of cases in the present study. These lesions are more often seen in younger individuals and women, have less luminal narrowing and less calcification, and less often have foci of macrophages and T cells compared with plaque ruptures.

Stimulation of precise excision and recombination by conjugal proficient F'plasmids.

Large F plasmids such as F'128 stimulate precise excision of the transposons Tn5 and Tn10 in E. coli K12. This stimulation occurs when the transposons are either on the F'128 plasmid or the bacterial chromosome. Stimulation of precise excision is dependent upon conjugal transfer proficient F'plasmids. Tra- mutations which are defective in conjugal transfer negate this F'128 plasmid stimulation effect. F'128 traS mutations, which are surface exclusion defective and thus permit matings between male cells, thereby increasing conjugal transfer, increase the F plasmid stimulation effect. When the F' plasmid is present in a cell with the small plasmid, pRS31, carrying the traS to traZ region of F, stimulation of precise excision is no longer observed. This complementation-like activity by pRS31 is abolished by a Tn5 insertion in the traS gene. Data are presented supporting the notion that F' plasmid stimulation of precise excision occurs in the recipient during conjugal transfer. F'128 traS also stimulates recA-dependent recombination between DNA sequences on the small, nontransferrable plasmid pRDK41, DNA sequences that are unrelated to those of the F plasmid. The F'plasmid stimulation of precise excision of Tn5 is not seen with F+ but only with certain F's with large insertions of chromosomal DNA.

Recombination genes on the Escherichia coli sex factor specific for transposable elements.

The Escherichia coli sex factor stimulates precise excision of transposons Tn5 and Tn10 from sites either within the bacterial chromosome or within the factor itself. We have isolated two kinds of mutations that affect this activity. The ferA mutations eliminate the stimulation; the ferB mutations enhance it in the presence of FerA+. We conclude that ferA defines a sex factor gene that stimulates precise excision. The ferB mutations also specifically increase the rate of recombination between two IS3 elements on F' lac-pro (F'128) in a reaction that requires the product of recA. The stimulation of this recombination by ferB also requires an active ferA gene, which implies that the ferA gene stimulates this reaction as well as precise excision. A ferA mutation was mapped at 84.2 kilobases on the F factor, and a ferB mutation was mapped at 82.5 kilobases. The fer mutants were obtained by an approach that permits the isolation of mutants affecting precise excision.