f Two Southeast Asian students attending the same school in the United Kingdom presented with pulmonary tuberculosis. An epidemiological investigation failed to link the two cases, and drug resistance profiles of the Mycobacterium tuberculosis isolates were discrepant. Whole-genome sequencing of the isolates found them to be genetically identical, suggesting a missed transmission event.T uberculosis is a major global public health challenge, with an incidence of 8.8 million new cases and 1.4 million deaths in 2010 (1). The United Kingdom is a low-prevalence country, with 8,963 new cases reported in 2011, giving an overall incidence of 14.4 cases per 100,000 population per year (2). The majority of cases (74%) occur in persons born outside the United Kingdom, and the rate of tuberculosis is almost 21 times higher in nonUnited Kingdom-born than United Kingdom-born individuals. The United Kingdom Health Protection Agency collects clinical and epidemiological information about all tuberculosis cases through the National Enhanced Tuberculosis Surveillance system. In 2010, a national strain typing service was introduced in order to aid in the investigation of outbreaks. This uses the 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTRs) to type all Mycobacterium tuberculosis isolates that are submitted to the reference laboratory (2). M. tuberculosis is a clonal organism, and accumulating evidence suggests that conventional typing may be insufficient to discriminate between closely related strains within a given lineage. Whole-genome sequencing provides the ultimate resolution of genomic data and has been shown to be superior to MIRU-VNTR typing in the investigation of a large outbreak in Canada (3). Here, we describe the use of whole-genome sequencing to investigate a suspected tuberculosis outbreak in a language school in Cambridge, United Kingdom.Case histories. On 5 November 2010, a 22-year-old South Korean man presented to our hospital with smear-positive pulmonary tuberculosis. He had no medical history and no known contact with tuberculosis and was studying at a local English language school. Treatment was commenced with standard antituberculosis therapy (rifampin, isoniazid, pyrazinamide, and ethambutol), and he was discharged from the hospital on 17 November 2010. Antibiotic susceptibility results subsequently revealed resistance to isoniazid, prothionamide, and streptomycin, and moxifloxacin was substituted for isoniazid.On 22 November 2010, a 24-year-old Japanese man presented to our hospital with smear-positive pulmonary tuberculosis. He had no medical history and no known contact with tuberculosis and was also studying at the same language school. Treatment was commenced with standard antituberculosis therapy. Progress was complicated by hepatitis (which necessitated temporary interruption of rifampin, isoniazid, and pyrazinamide and the addition of streptomycin to ethambutol), a spontaneous pneumothorax (which resolved), and prolonged fever. Antimicrobial suscept...

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We have examined immunocytochemically the subcellular distribution of the cell adhesion molecule uvomorulin in cleavage stage mouse embryos using conventional and confocal microscopy, under a range of detergent extraction and fixation regimes. Only traces of uvomorulin were detectable on the surface of unfertilised oocytes, whereas between 6 and 11 h after activation detergent-resistant surface expression was evident. This shift correlates with previously demonstrated changes in the pattern of synthesis and accumulation of uvomorulin from precursor state in unfertilised oocytes to mature protein after fertilisation. Embryos at subsequent stages up to the 8-cell stage exhibited a uniform distribution of uvomorulin on free surfaces and its concentration in regions of contact between blastomeres. At the 8-cell stage, during compaction, there was increased intercellular adhesion with concomitant accumulation of uvomorulin at intercellular contacts, whilst free surface uvomorulin was reduced and became relatively more susceptible to detergent extraction. When compact 8-cell embryos were decompacted in calcium-free medium, uvomorulin at contacts decreased while free surface and cytoplasmic staining increased. Blastomeres disaggregated from 4-and 8-cell embryos showed traces or 'footprints' of anti-uvomorulin staining in regions previously in apposition. These footprints disappeared over 45-60 min, during which time uvomorulin distribution became uniform. Possible mechanisms underlying the rearrangements which take place both at fertilisation and during compaction and experimental decompaction are discussed.

In emphysema, the lung cannot spontaneously regenerate lost alveolar tissue. Treatment with retinoic acid (RA) in rodent models of emphysema induces alveolar regeneration. However, some animal studies have failed to show regeneration when using different species and strains. We have previously shown that dexamethasone (Dex) treatment of newborn TO outbred strain mice permanently disrupts alveolar development. Later RA treatment restores alveolar architecture to normal. To determine whether this model of alveolar regeneration is strain specific, our protocol was repeated with two new outbred mouse strains. ICR and NIHS mice received Dex from Postnatal Days 4 to P15 (P4- P15). From P46 to P57, mice received RA (2 mg/kg) or vehicle. An additional ICR group received 5x RA (10 mg/kg) from P46 to P57. Control groups received vehicle at both treatment points. All mice were killed at P90 and lung morphology analyzed. Dex-treated ICR and NIHS mice showed increased mean alveolar chord length (Lm) and reduced alveolar surface area (SA) and SA/lung volume (SA/LV) compared with controls. RA-treated NIHS mice showed return of Lm, SA, and SA/LV toward control values, indicating alveolar regeneration. ICR RA group mice did not regenerate, but 5x RA mice showed Lm, SA, and SA/LV values consistent with alveolar regeneration. In conclusion, the Dex-treated mouse model of emphysema is robust and repeatable in different strains. RA-induced alveolar regeneration is not a strain-specific phenomenon. RA dose threshold for inducing alveolar regeneration is higher in ICR mice, suggesting a difference in retinoid pharmacokinetics between strains. These results provide a possible explanation for previous failed studies of RA-induced alveolar regeneration.

We describe two cases of patients with emphysema who, in the lead up to hyperinflation intervention, developed pneumonia with significant physiological, anatomical, functional and quality of life improvement observed following. This directly goes against the natural history of both disease processes, demonstrating the benefit resulting from infective autobullectomy.