Summary Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum sensing -regulated low-molecular-weight excreted molecule, and triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data both identify a new programmed cell death system, and a novel role for HQNO as a critical-inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.

No abstract

Pulmonary function was measured before and at intervals after treatment in 44 patients who received a bone marrow transplant for chronic myeloid leukaemia in the chronic phase. All patients were treated with cytotoxic drugs, total body irradiation, and post-graft immunosuppression. Thirty four patients surviving for 12 months were followed at three monthly intervals and 16 patients for 24 months. Fifteen patients received unmanipulated donor marrow cells and 29 patients received donor marrow cells depleted of lymphocytes ex vivo with the -monoclonal antibody Campath-1. The 21 patients treated early in this study received 10 Gy of total body irradiation whereas the 23 patients treated more recently, who were all T lymphocyte depleted, received 12 Gy. Pretransplant lung function for the group was normal and was similar in survivors (n = 34) and nonsurvivors (n = 10), and in smokers (n -= 8) and non-smokers (n = 36). (Carbon monoxide transfer factor-TLCO) was under 75% of predicted normal in nine patients before transplantation. TLCO, carbon monoxide transfer coefficient (Kco), FEV,, and vital capacity (VC) values were lower 6 and 12 months after bone marrow transplant than initially. The greatest decline was in TLCO, from an initial value of 89% to 66% at 6 and 70% at 12 months. The 16 longer term survivors showed significant recovery of function between 6 and 24 months after bone marrow transplant for TLCO, Kco, and VC, the increase ranging from 6 3% to 7-3% predicted. Airflow obstruction (FEV,/VC ratio <70%) developed in one patient. The major factors associated with deterioration in pulmonary function at 6 and 12 months after transplantation in the 34 survivors (stepwise multiple regression analysis) were (a) transplantation with T cell depleted donor marrow (p < 0 005) and higher total body irradiation dose (p < 0-02) with a fall in Kco and an increase in the FEV,/VC ratio; (b) chronic graft versus host disease with a fall in VC (p < 0 01); and less fall in Kco (p < 0'01); and (c) acute graft versus host disease-with a fall in FEV, (p < 0 01). It is considered that most patients who survive the short term risks of bone marrow transplant have only minor long term impairment of pulmonary function.Since the introduction of allogeneic bone marrow transplantation for the treatment of haematological diseases, pulmonary complications, especially opportunistic infections, are recognised as a common cause of morbidity and mortality.' Even in the absence of infection, pulmonary function tends to deteriorate over the months after transplantation. The relative contributions of chemotherapy, total body irradia-

This study demonstrated that MRI should be the investigation of choice for retrorectal lesions. Biopsy of solid lesions is safe and useful for guiding neoadjuvant and surgical therapy. Cystic lesions without suspicious radiological features can be followed by serial imaging without resection.

Transobturator tape procedures are associated with a good (73.8%) patient reported success rate at a minimum of 3 years of followup in the surgical management of mixed urinary incontinence in women with predominant stress urinary incontinence symptoms. Nearly half of the women reported cure of urgency/urgency incontinence.