Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959

A human immunodeficiency virus type 1 (HIV-1) variant with highly reduced susceptibility to Ro 31-8959, an inhibitor of the viral proteinase, has been selected by repeated passage of wild-type virus in CEM cells in the presence of increasing concentrations of the inhibitor. Peptide sequences of the proteinase of selected virus were obtained from proviral DNA. Sequence comparison to wild-type (wt) proteinase demonstrated two amino acid substitutions in the resistant virus, a Gly to Val exchange at position 48 and a Leu to Met exchange at position 90. Furthermore, sequences of intermediate passage virus suggest contributions from positions 12, 36, 57, and 63 in early steps of resistance development. The selected virus showed a ca. 40-fold increase in 50% inhibitory concentration of Ro 31-8959. Growth kinetics of resistant virus were comparable to wild-type virus and the resistant genotype proved to be stable in the absence of inhibitor. Directed mutagenesis of the HIV-1 HXB2 proteinase at positions 48 and 90 suggested that each mutation alone led to a moderate decrease in sensitivity of the recombinant virus to proteinase inhibitor. However, a recombinant virus carrying both mutations in the proteinase gene showed a significant reduction in its sensitivity to Ro 31-8959 thus proving the importance of these exchanges for the resistance phenotype.     

Laser Doppler flowmetry during open reduction for developmental dysplasia of the hip

Laser Doppler flowmetry was used intraoperatively to monitor femoral head perfusion during open reduction of 13 congenital hip dislocations in 11 patients. Laser Doppler determinations ranged from 12 to 400 mV before reduction and 30 to 300 mV after reduction. Three patients had magnitude changes in excess of 50%. One had increased perfusion, and two had decreased blood flow. Avascular necrosis of the hip occurred in one patient that was not predicted by laser Doppler flowmetry. Femoral head perfusion measured 175 mV for the dislocated hip and 180 mV after reduction of the femoral head and completion of the pelvic osteotomy. The authors conclude that laser Doppler flowmetry is not a reliable method for monitoring femoral head perfusion during open reduction of the hip for developmental hip dysplasia.     

Cellular depletion of p56lck during thymocyte apoptosis

The src-related protein tyrosine kinase p56lck is thought to be important in regulating maturation and functional responsiveness of T cells and thymocytes. In the present studies we report that expression of p56lck is suppressed during apoptosis. Using primary cultures of rat thymocytes, we found that agents that are effective in inducing apoptosis, including okadaic acid, dexamethasone, and antibodies to the CD3 receptor, also deplete cells of p56lck. This process is rapid, occurring within 24 h, and is not due to cytotoxicity. Inhibition of DNA fragmentation in apoptotic cells with the endonuclease inhibitor ZnCl2 failed to prevent depletion of p56lck, suggesting that it was not a consequence of the DNA degradation process. Using the thymic lymphoma cell line LSTRA, apoptosis was also associated with cellular depletion of p56lck. In contrast to thymocytes, this process required 48-72 h possibly because these cells overexpress p56lck. Although at this time we are uncertain as to the precise role of p56lck in the process of apoptosis, our results indicate that changes in the expression of this protein in thymocytes is an important marker of programmed cell death.     

Supracondylar humerus fractures in children

Supracondylar fractures of the humerus are the most common fractures in children that require surgery. A significant advancement in the field of pediatric orthopedics has been closed reduction and percutaneous pinning of these fractures. This technique, using high quality fluoroscopic imaging, allows for a near anatomical reduction of fractures without the need for an open surgical procedure or prolonged traction. Supracondylar fractures in children are often associated with neurologic and vascular damage that must be recognized before fracture reduction. Nursing staff members' skill with pediatric patients can greatly aid the surgeon in the timely and safe treatment of these fractures.     

Translumbar placement of inferior vena caval catheters: a solution for challenging hemodialysis access

Access to the central venous circulation for hemodialysis has traditionally been achieved via the subclavian or jugular venous routes. With ongoing improvements in medical management, many hemodialysis recipients develop exhaustion of these routes and require alternative means of central venous access. Inferior vena caval (IVC) catheters have been placed with a percutaneous translumbar approach to allow central venous access for chemotherapy, harvesting of stem cells, and total parenteral nutrition. Translumbar placement of IVC catheters has become accepted by some as a useful and reliable alternative in patients who require long-term hemodialysis but have exhausted traditional access sites. IVC catheters have been placed in patients with IVC filters, and IVC filters have been placed in patients with IVC catheters. Complications include those associated with central venous catheters, for example, sepsis, fibrin sheaths, and thrombosis. A complication specific to placement of IVC hemodialysis catheters is migration of the catheter into the subcutaneous soft tissues, retroperitoneum, or iliac veins. Translumbar placement of IVC catheters is performed only in patients considered to have few or no other medical options and is not intended as a primary means of central venous access.     

Genetic variation and prediction of additive and nonadditive genetic effects for six carcass traits in an Angus-Brahman multibreed herd

Estimates of covariances and sire expected progeny differences of additive and nonadditive genetic effects for six carcass traits were obtained using records from 486 straightbred and crossbred steers from 121 sires born between 1989 and 1995 in the Angus-Brahman multibreed herd of the University of Florida. Steers were slaughtered at a similar carcass composition end point. Covariances were estimated by REML procedures, using a generalized expectation-maximization algorithm applied to multibreed populations. Straightbred and crossbred estimates of heritabilities and additive genetic correlations were within ranges found in the literature for steers slaughtered on an age- or weight-constant basis for hot carcass weight, longissimus muscle area, and shear force but equal to or less than the lower bound of these ranges for fat-related traits. Maximum values of interactibilities (i.e., ratios of nonadditive variances to phenotypic variances in the F1) and nonadditive genetic correlations were smaller than heritabilities and additive genetic correlations in straightbreds and crossbred groups. Sire additive and total direct genetic predictions for longissimus muscle area, marbling, and shear force tended to decrease with the fraction of Brahman alleles, whereas those for hot carcass weight and fat thickness over the longissimus were higher, and those for kidney fat were lower in straightbreds and F1 than in other crossbred groups. Nonadditive genetic predictions were similar across sire groups of all Angus and Brahman fractions. These results suggest that slaughtering steers on a similar carcass composition basis reduces variability of fat-related traits while retaining variability for non-fat-related traits comparable to slaughtering steers on a similar age or weight basis. Selection for carcass traits within desirable (narrow) ranges and slaughter of steers at similar compositional end point seems to be a good combination to help produce meat products of consistent quality.