Transmission of an extended-spectrum-beta-lactamase-producing Escherichia coli (sequence type ST131) strain between a father and daughter resulting in septic shock and Emphysematous pyelonephritis.

Probable transmission of an extended-spectrum-beta-lactamase-producing Escherichia coli strain (sequence type ST131) between a father and daughter was documented. The father developed severe, recurrent pyelonephritis with multiple small abscesses; the daughter later developed septic shock, bacteremia, and extensive emphysematous pyelonephritis. This multidrug-resistant E. coli clone appears to be highly pathogenic and transmissible.

Pacemaker activity in the upper urinary tract.

Ureteral peristaltic activity begins with the origin of electrical activity at pacemaker sites. These sites are located in the proximal portion of the urinary collecting system. The 'atypical' smooth muscle cells at these sites fire 'pacemaker' potentials at a frequency higher than the 'driven' action potentials recorded from typical smooth muscle cells. In contrast to typical smooth muscle cells, these atypical pacemaker cells have less than 40% of their cellular area occupied by contractile filaments and demonstrate a sparse immunoreactivity for alpha-smooth muscle actin. Expression of c-Kit, a tyrosine kinase receptor, correlates with the onset of organized ureteral peristalsis in the embryo. Capsaicin-sensitive sensory afferents and the endogenous release of tachykinins and prostaglandins are involved in the maintenance of normal ureteral peristalsis.

A role for Akt in the rapid regulation of inflammatory and apoptotic pathways in mouse bladder.

Akt is linked to both inflammatory and neoplastic pathways. Akt activation is dependent on the phosphatidylinositol-3 kinase (PI3K) signaling pathways. Upon phosphorylation by PI3K, Akt can phosphorylate nuclear factor kappa B (NF-kappaB) and members of the forkhead family of transcription factors, which includes AFX. Our goal is to examine the effect of Escherichia coli lipopolysaccharide (LPS) on early cellular signaling in inflammatory (NF-kappaB) and apoptotic pathways (AFX) in a mouse-bladder model and in T-24 urothelial cancer cells. Female C57BL/6 mice were given an intraperitoneal (IP) injection of LPS or LPS free water and sacrificed 0-120 minutes later. Bladders were harvested, and immunohistochemistry (IHC) and/or immunoblotting performed using antibodies to PI3K, inhibitor kappa B-alpha (IkappaB-alpha), and total and phosphorylated Akt, NF-kappaB and AFX. Levels of IkappaB-alpha and total and phosphorylated Akt and NF-kappaB were determined in T-24 cells treated with LPS for 0-120 minutes. Bladders and T-24 cells were treated with PI3K inhibitors in some experiments. Protein amounts in different samples were normalized to immunoreactive actin. Phosphorylated and non-phosphorylated species of Akt, NF-kappaB, and AFX were localized to the urothelium. IP LPS injection rapidly (within 30 minutes) increased Akt phosphorylation. IP LPS injection decreased IkappaB-alpha levels, and increased NF-kappaB and AFX phosphorylation. Wortmannin effectively blocked phosphorylation of Akt in LPS-treated mice, and also reduced phosphorylation of AFX and, to a lesser extent, NF-kappaB. After treatment with LPS, Akt and NF-kappaB phosphorylation was rapidly increased in T-24 cells. Akt phosphorylation, and to a lesser extent NF-kappaB phosphorylation, were blocked by LY-294,002. LPS/PI3K/Akt is a cellular signaling pathway which rapidly activates downstream pathways of inflammation and neoplasia in bladder urothelium.

Rapid up-regulation of endothelial nitric-oxide synthase in a mouse model of Escherichia coli lipopolysaccharide-induced bladder inflammation.

Increases in the signaling molecule nitric oxide (NO) during inflammation may be linked not only to inducible nitric-oxide synthase (iNOS) but also to endothelial (e)NOS. Escherichia coli lipopolysaccharide (LPS) induces an inflammatory response in the bladder and rapidly increases phosphorylation of Akt/protein kinase B (Akt), a key enzyme regulating proliferation, apoptosis, and inflammation. Activated Akt phosphorylates human eNOS at serine 1177 and subsequently increases NOS activity. Because Akt and eNOS are both localized in the bladder urothelium, phosphorylation of eNOS by Akt provides an attractive mechanism for rapid increases in urinary NO production. Female mice were intraperitoneally injected with LPS (25 mg/kg) or pyrogen-free water (control). Four hours before LPS injection, some mice were injected with wortmannin, which inhibits Akt phosphorylation. Levels of urinary cyclic GMP, a downstream product of NO, increase 75% within 1 h after intraperitoneal injection of LPS, and this increase is blocked by wortmannin. Bladder eNOS and phosphorylated eNOS protein increase 94 and 151%, respectively, 1 h after LPS treatment, whereas iNOS was not detected. Wortmannin decreases eNOS phosphorylation by 60%. Furthermore, bladder Ca(2+)-dependent NOS activity (eNOS, neuronal NOS) is increased 79 +/- 20% 1 h after LPS treatment, whereas there is no increase in Ca(2+)-independent (iNOS) activity (n = 4). Increases in urinary cyclic GMP, NOS activity, and eNOS protein and phosphorylation 1 h after induction of inflammation with LPS, indicate that eNOS plays a role in the early response to bladder inflammation.