Oscillations in NF-kappaB signaling control the dynamics of gene expression.

Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus. NF-kappaB regulation of IkappaBalpha transcription represents a delayed negative feedback loop that drives oscillations in NF-kappaB translocation. Single-cell time-lapse imaging and computational modeling of NF-kappaB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IkappaBalpha transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations.

Persistent bronchopleural air leak during mechanical ventilation. A review of 39 cases.

Bronchopleural fistula (BPF), or bronchopleural air leak, is regarded as an ominous complication of ventilator management in acute respiratory failure, but data on its natural course and prognosis are lacking. We reviewed all instances of mechanical ventilation at a major trauma center during a four-year period, and found that 39 of the 1,700 mechanically-ventilated patients developed BPF lasting at least 24 hrs. Overall mortality in these 39 patients was 67 percent, and this was higher when BPF developed late in the illness (16 of 17, or 94 percent, when mean onset was hospital day 13), than when it occurred within 24 hours of admission (ten of 22, or 45 percent, p = 0.002). Survival in patients with chest trauma (12 of 27, 44 percent), most of whom had air leaks on or just after admission, was better than in those with other primary diagnoses (one of 12, 8 percent, p less than 0.005). All eight patients whose maximum air leak exceeded 500 ml per breath died, whereas 13 of 30 with smaller maximum leaks survived (p less than 0.05). Despite leaks as large as 900 ml per breath, however, conventional ventilator adjustments permitted avoidance of severe respiratory acidosis (pH less than 7.30) in all but two patients. We conclude that the occurrence of BPF during mechanical ventilation identifies patients with high mortality, but that unmanageable respiratory acidosis from this complication is rare.

Microbiologic evaluation of cutaneous cellulitis in adults.

Fifty patients with cellulitis were evaluated prospectively using cultures of aspirates from the advancing edge of cellulitis, skin biopsy specimens, and blood. Potential microbial pathogens were isolated in 13 patients. Biopsy specimen cultures were positive in ten patients, while aspirate and blood cultures were positive in five and two, respectively. Aspirate, biopsy, or blood cultures were more often positive in patients with apparent primary lesions than in patients without such lesions. Apparent primary sites of infection were identified and cultured in 24 patients. beta-Hemolytic streptococci were isolated from 17 primary lesions, and coagulase-positive staphylococci were present in 13. Both organisms were isolated from ten primary lesions. Among patients with positive aspirate, biopsy, and/or blood cultures, the same pathogens were also isolated from primary sites in ten of ten patients. Clinical features, including temperature, white blood cell count, and erythrocyte sedimentation rate, were not predictive of positive aspirate, biopsy, or blood cultures. These cultures provided no microbiologic information that was not obtainable from culture of primary lesions.

An X-autosome fusion chromosome of Caenorhabditis elegans.

The translocation mnT12(IV;X) is a fusion of holocentric chromosomes IV and X, the breakpoints occurring near the left end of IV and the right end of X. Animals homozygous for mnT12 are viable and fertile; they contain five pairs of chromosomes rather than the normal set of six pairs. The mnT12 chromosome is larger than all wild-type chromosomes and thus identifies linkage groups IV and X cytologically. Hermaphrodites heterozygous for mnT12 show high frequency meiotic nondisjunction both between mnT12 and the X chromosome, which results in a high incidence of male self progeny (27% compared to the wild-type incidence of 0.2%), and between mnT12 and chromosome IV, which results in a high incidence of self progeny essentially trisomic for chromosome IV (karyotype IV/mnT12/mnT12). The viability of chromosome IV trisomics has been confirmed by constructing animals trisomic for only normal copies of chromosome IV; these animals are morphologically wild type. Meiotic chromosome disjunction in mnT12 homozygotes appears to be normal, although the frequency of recombination between markers that are normally X-linked is significantly reduced. Males of genotype IV/mnT12/0 are fertile. They can be thought of as having a neo-X(mnT12) neo-Y(normal IV) karyotype since it is possible to maintain a male-hermaphrodite stock of C. elegans consisting of such males and hermaphrodites carrying two neo-X chromosomes and no neo-Y; the organism is thus converted from an XO:XX type of sex determination to an XY:XX system.

Failure of intensive care unit support to influence mortality from pneumococcal bacteremia.

One hundred thirty-four consecutive cases of pneumococcal bacteremia observed during a six-year period were evaluated. One hundred nineteen (89%) were associated with pneumonia. Factors associated with increased mortality were advanced age, a leukocyte count at admission of less than 5,000/cu mm, neoplastic disease, and involvement of two or more pulmonary lobes in patients with pneumonia. Mortality was 30.5% overall, and 76% in patients admitted to the intensive care unit with pneumococcal bacteremia. Pneumococcal infection continues to be an important cause of morbidity and mortality despite modern supportive care and antimicrobial therapy.