Author Correction: The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding.

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The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding.

Voltage-sensing (VSD) and cyclic nucleotide-binding domains (CNBD) gate ion channels for rapid electrical signaling. By contrast, solute carriers (SLCs) that passively redistribute substrates are gated by their substrates themselves. Here, we study the orphan sperm-specific solute carriers SLC9C1 that feature a unique tripartite structure: an exchanger domain, a VSD, and a CNBD. Voltage-clamp fluorimetry shows that SLC9C1 is a genuine Na+/H+ exchanger gated by voltage. The cellular messenger cAMP shifts the voltage range of activation. Mutations in the transport domain, the VSD, or the CNBD strongly affect Na+/H+ exchange, voltage gating, or cAMP sensitivity, respectively. Our results establish SLC9C1 as a phylogenetic chimaera that combines the ion-exchange mechanism of solute carriers with the gating mechanism of ion channels. Classic SLCs slowly readjust changes in the intra- and extracellular milieu, whereas voltage gating endows the Na+/H+ exchanger with the ability to produce a rapid pH response that enables downstream signaling events.

Sensorimotor gating, cannabis use and the risk of psychosis.

Sensorimotor gating, measured as the modification of eye blink startle reflexes to loud acoustic stimuli by quieter preceding stimuli, is altered in those with psychosis, their relatives and those at high clinical risk for psychosis. Alterations have also been shown in cannabis users, albeit to a lesser extent, and cannabis is a known risk factor for the onset of psychosis in clinically and genetically susceptible individuals. We examined the interaction between clinical risk for psychosis and cannabis use on sensorimotor gating, both Prepulse Inhibition (PPI) and Prepulse Facilitation (PPF). We tested PPI and PPF in participants with an At Risk Mental State (ARMS) for psychosis and a matched control group. Both groups included a proportion of subjects who had recently used cannabis, as confirmed by urinary drug screening (UDS) on the day of testing. We found that ARMS participants showed reduced PPF and PPI relative to controls, the latter driven by a group by cannabis use interaction, with recent use reducing PPI in ARMS participants but not in controls. When the analysis was limited to UDS-negative participants there was significantly reduced PPF in ARMS subjects relative to controls, but no differences in PPI. Within the ARMS group reduced sensorimotor gating, measured by both PPI and PPF, related to reduced overall level of function. Cannabis use in clinical high risk individuals may increase the risk of psychosis in part through worsening PPI, while PPF is altered in ARMS individuals irrespective of cannabis use. This develops our understanding of cognitive mechanisms leading to the experience of aberrant perceptual phenomena and the subsequent development of psychotic symptoms.

Hemolytic-uremic syndrome associated with an infection by verotoxin producing Escherichia coli 0111 in a woman on oral contraceptives.

A case of hemolytic-uremic syndrome (HUS) associated with an infection by a verotoxin-producing Escherichia coli (VTEC), serotype 0111:NM, in a 22-year-old woman who had been on oral contraceptives is presented. VTEC-associated cases of HUS infected by E. coli 0111 have been reported before, but never in adults. The kinetics of the humoral immune response to verotoxin in the patient is observed over three months and described for the first time. The possible role of contraceptives that have been incriminated in the etiology of HUS before is discussed as well. Possible benefits of therapeutical interventions such as hemodialysis, therapeutic plasma exchange, converting enzyme inhibitors, or antibiotics still need clarification. However, it is strongly suggested to include tests for VTEC in the work-up of patients suffering from HUS.

PIP: Confirmation of a causal relationship between hemolytic-uremic syndrome (HUS) and verotoxin-producing Escherichia coli (VTEC) infection is provided by the case of a 22-year-old West German woman. The patient presented with fatigue, nausea, and headache. Ultrasonography revealed enlarged kidneys, and laboratory investigations showed uremia, hemolytic anemia, lactate dehydrogenase, haptoglobin below the detection limit, and thrombocytopenia. She received hemodialysis and drug treatment (heparin, dopamine, and furosemide). To investigate the kinetics of the humoral response to verotoxin, the patient was followed for 3 months. Fecal specimens on day 23 yielded E coli serotype 0111:NM, and stool filtrates on days 16 and 23 showed highly cytotoxic activity for HeLa cells. While the patient's initial serum showed a high IgM immune response against purified Shiga toxin, there was a steady decline in IgM and steady increase in IgG antibodies over the ensuing 3 months. These findings are suggestive of a recent infection by a verotoxin-producing organism. This is the 1st reported case of VTEC-associated HUS with e coli 0111 infection in an adult, and the patient's 4-year history of oral contraceptives (OCs)--ethinyl estradiol and chlormadinoneacetate--is considered to be of etiologic significance. The diminished antibody coating of bacteria in the urinary tract of OC users may have facilitated invasion of verotoxin across the mucosal barrier in this patient. Severe hypertension has been reported previously in OC users with HUS. It is speculated that verotoxin may trigger HUS in longterm OC users, initiating vasoconstriction and microangiopathic hemolysis.

[Abdominal pseudotumor as the clinical manifestation of Whipple's disease. T-cell index as an indicator of disease activity and a parameter of the duration of therapy?]. / Abdominaler Pseudotumor als klinische Manifestation eines Morbus Whipple. T-Zell-Index als Indikator der Krankheitsaktivität und Parameter der Therapiedauer?

A large nonresectable upper-abdominal tumor in a 61-year-old woman was found to have been caused by inflammatory infiltration and mechanical obstruction of the mesenteric lymph nodes resulting in obstruction to lymphatic flow. Biopsy at the root of the mesentery and of abdominal lymph nodes raised the suspicion of Whipple's disease, a diagnosis confirmed by a small-intestine biopsy. Long-term antibiotic treatment was successful. Quantitative changes in the composition of the T-cell subpopulations at the time of the diagnosis reverted to normal in the course of treatment.