Cytoskeletal integration in a highly ordered sensory epithelium in the organ of Corti: reponse to loss of cell partners in the Bronx waltzer mouse

This report is concerned with control of cell shaping, positioning, and cytoskeletal integration in a highly ordered cochlear neuroepithelium. It is largely based on investigations of events that occur during abnormal morphogenesis of the organ of Corti in the Bronx waltzer (bv/bv) mutant mouse. The organ's sensory hair cells and adjacent supporting cells ordinarily construct a spatially elaborate and supracellularly integrated cytoskeletal framework. Large microtubule bundles are connected to cytoskeletal components in neighbouring cells by actin-containing meshworks that link them to substantial arrays of adherens junctions. In bv/bv mice, degeneration and loss of most inner hair cells and outer pillar cells occurs during organ development. These cells flank each side of a row of inner pillar cells that respond by upregulating assembly of their actin-containing meshworks. This only occurs in surface regions where they no longer contact cell types involved in construction of the cytoskeletal framework. The meshworks are larger and exhibit a more extensive sub-surface deployment than is normally the case. Hence, assembly of intercellular cytoskeletal connecting components can proceed without contact with appropriate cell neighbours but termination of assembly is apparently subject to a negative feedback control triggered by successful completion of intercellular connection with the correct cell neighbours. In addition, inner pillar cells compensate for loss of cell neighbours by interdigitating and overlapping each other more extensively than is usually the case to increase opportunities for generating adherens junctions. Certain adherens junctions in the organs of +/+ and bv/bv mice exhibit features that distinguish them from all previously described cell junctions. The dense plaques on their cytoplasmic faces are composed of aligned ridges. We suggest that they are called ribbed adherens junctions. Perturbations of cell shaping and positioning indicate that loss of inner hair cells is the primary consequence of the bv mutation. Most of the other abnormalities can be understood in terms of a secondary sequence of morphogenetic aberrations (precipitated by loss of inner hair cells). These aberrations provide new information about the ways in which supporting cells help to control hair cell positioning.     

Hypothermia does not result in more complications after colon surgery

Our objective was to determine the incidence of complications in postoperative patients who were either normothermic or hypothermic. A recent, widely publicized paper concluded that the maintenance of normothermia could reduce the incidence of infectious complications and shorten hospitalization in patients undergoing colorectal surgery. However, some controversy arose regarding the methods of this paper. Patients were deliberately rendered hypothermic, were given more than 3.5 days of prophylactic antibiotics and were transfused significantly more units of blood. We reviewed the charts of 150 consecutive patients who underwent elective partial or subtotal colectomy with primary anastomosis. Among the key items analyzed were intraoperative and postoperative temperature, use of warming devices, duration of surgery, transfusions, interval to oral intake and bowel function, length of stay, complications, infections, and laboratory values. Hypothermia was defined as intraoperative temperature <95.5 degrees F. There were 101 normothermic patients and 49 hypothermic patients. Hypothermic patients had a mean age of 68.7 years versus 66.8 for the normothermic patients (P = 0.472). Comorbidities were similar in both groups. Warming devices were used in >90 per cent of the patients in both groups. The rates of postoperative infections and complications were similar in both groups. Postoperative lengths of stay were also not different. Despite finding that one-third of our patients were hypothermic during elective colon resection, hypothermia had no effect on outcome variables. In contrast to the previous study, the incidence of infectious complications was identical in our patients. Before ascribing postoperative complications and increased resource utilization as adverse effects of hypothermia, further studies are indicated.     

First principles investigation of singly reduced cytochrome P450.

1. The application of novel ab initio quantum mechanical methods to the states in the catalytic cycle of cytochrome P450 following the first reduction step is described. 2. A good correlation was found between the calculated energy of reduction and the experimentally determined redox potential for a range of substrate- and substrate analogue-bound systems. 3. On reduction of the haem system, the ground state of Fe remains Fe3+. On binding of a CO molecule, Fe adopts a low-spin Fe2+ state, in agreement with experiment. However, on binding of an O2 molecule, calculations indicate that the system adopts a ferric superoxide ground state, in which the Fe is in a low-spin Fe3+ state.