The Nicolas Andry Award-1995. Fracture healing. Radiation induced alterations

This study investigated the effects of radiation on fractures in a rat femur model. Two different radiation dosage fractionation schemes (1100 rads given in one dose and 2500 rads given in 10 divided doses over 12 days) and three different times of initiation of radiation (1 day before fracture, 3 or 10 days after fracture) were studied. Fractures exposed to these levels of radiation all appeared to heal during the course of this experiment, although with varying degrees of delay, with the exception of those exposed to a single dose of 1100 rads 3 days after fracture. These animals remained at a more immature level of repair histologically compared with the control group, throughout the entire time evaluated. The strength of the final repair remained less than the control for all the groups receiving treatment. These results may offer some explanation for the clinical observations of an increased incidence of delayed union and nonunion of fractures, an increased incidence of fracture and refracture in irradiated bone, and an increased incidence of fracture and nonunion in constructs using radiation in conjunction with allogeneic bone. Furthermore, the observed effects were generally no different in the animals treated with the two clinically relevant dose fractionation schemes chosen for this study.     

Pregnancy loss and autoantibodies against phospholipid-binding proteins

We investigated the utility of two approaches for exploiting pleiotropy to search for genes influencing related traits. To do this we first assessed the genetic correlations among a set of five closely related quantitative traits (Q1, Q2, Q3, Q4, Q5). We then used the genetic correlations among these five traits both to remove the common genetic effects of the four remaining traits, thereby identifying the unique genetic contribution to each trait, and to extract a synthetic phenotype which exploits the shared genetic information (pleiotropy) among these five traits. After obtaining these conditional traits, we then searched for evidence of quantitative trait loci (QTLs) (using variance component linkage) influencing the unique residual genetic component for each trait as well as those influencing the expression of the synthetic traits. From this work, we conclude that the removal of the common genetic effects of other traits in a group may be of greater utility when the majority of the pleiotropy initially detected between traits is attributable to the shared additive effects of polygenes, rather than to those of major loci. By contrast, decomposition of the genetic covariance matrix to its principal components is a greater utility when the majority of pleiotropy is attributable to major loci.     

Alanine and glutamine kinetics at rest and during exercise in humans

PURPOSE: The purpose of this study was to quantify both alanine and glutamine kinetics during exercise of moderate intensity to determine the sum total of alanine and glutamine flux. METHODS: Tracer methods were used to quantify alanine and glutamine rates of appearance (Ra) in plasma at rest and during 180 min of approximately 45% VO2max treadmill exercise in six normal volunteers (25 +/- 2 yr, 68 +/- 2.5 kg, VO2max 43 +/- 2.4 mL.min-1.kg-1; means +/- SE). Bolus injections (N = 3) or primed-constant infusions (N = 3) of 2H5-glutamine and 3-13C-alanine were given at rest on 1 d and 10-15 min after the onset of exercise on a separate day less than 2 wk later. Plasma enrichment decay curves and plateau enrichments were used to estimate alanine and glutamine kinetics. RESULTS: Whereas alanine Ra increased significantly from rest to exercise (5.72 +/- 0.31 vs 13.5 +/- 1.9 mumol.min-1.kg-1, respectively; P < 0.01), glutamine Ra was not significantly altered by exercise (6.11 +/- 0.44 and 6.40 +/- 0.69 mumol.min-1.kg-1 at rest and during exercise, respectively). The total of alanine and glutamine flux increased from 17.93 +/- 0.88 to 25.98 +/- 3.04 (P < 0.05). CONCLUSIONS: Since most muscle amino-N is released as alanine and glutamine, these findings provide strong evidence that amino-N delivery from muscle to the liver is increased during exercise. In addition, it appears that alanine, rather than glutamine, is the predominant N carrier involved in the transfer of N from muscle to the liver during moderate intensity exercise.     

Pheromone regulated production of inositol-(1, 4, 5)-trisphosphate in the mammalian vomeronasal organ

Social behaviors of most mammals are profoundly affected by chemical signals, pheromones, exchanged between conspecifics. Pheromones interact with dendritic microvilli of bipolar neurons in the vomeronasal organ (VNO). To investigate vomeronasal signal transduction pathways, microvillar membranes from porcine VNO were prepared. Incubation of such membranes from prepubertal females with boar seminal fluid or urine results in an increase in production of inositol-(1, 4, 5)-trisphosphate (IP3). The dose response for IP3 production is biphasic with a GTP-dependent component at low stimulus concentrations and a nonspecific increase in IP3 at higher stimulus concentrations. The GTP-dependent stimulation is mimicked by GTPgammaS and blocked by GDPbetaS. Furthermore, the GTP-dependent component of the stimulation of IP3 production is sex specific and tissue dependent. Studies with monospecific antibodies reveal a G alpha(q/11)-related protein in vomeronasal neurons, concentrated at their microvilli. Our observations indicate that pheromones in boar secretions act on vomeronasal neurons in the female VNO via a receptor mediated, G protein-dependent increase in IP3. These observations set the stage for further investigations on the regulation of stimulus-excitation coupling in vomeronasal neurons. The pheromone-induced IP3 response also provides an assay for future purification of mammalian reproductive pheromones.     

Preliminary observations on an intervention program for heavy smokers

Each of 571 smokers selected one of three methods of smoking cessation: group therapy, individual counseling, and hypnosis. One-year results suggest little difference between the three methods in producing ex-smokers. All methods produced an average success rate of approximately 20%. It should be noted, however, that with all types of verbal or verbally related therapy it is not known precisely how these techniques work or whether the outcomes are really a function of what is put into the therapy by the treatment agent and/or the recipient. It was generally found that younger, more educated smokers chose hypnosis; older, more educated smokers chose group therapy; and older, less-formally educated smokers chose individual counseling while the youngest and generally less educated smokers chose to become nonattenders and not take part in therapy. These results have important implications for designing optimal treatment programs which will be acceptable and effective for the greatest number of smokers.     

On the Capacity of Radio Communication Systems with Diversity in a Rayleigh Fading Environment

In this paper, we study the fundamental limits on the data rate of multiple antenna systems in a Rayleigh fading environment. WithMtransmit andMreceive antennas, up toMindependent channels can be established in the same bandwidth. We study the distribution of the maximum data rate at a given error rate in the channels between up toMtransmit antennas andMreceive antennas and determine the outage probability for systems that use various signal processing techniques. We analyze the performance of the optimum linear and nonlinear receiver processor and the optimum linear transmitter/receiver processor pair, and the capacity of these channels. Results show that with optimum linear processing at the receiver, up toM/2channels can be established with approximately the same maximum data rate as a single channel. With either nonlinear processing at the receiver or optimum linear transmitter/receiver processing, up toMchannels can be established with approximately the same maximum data rate as a single channel. Results show the potential for large capacity in systems with limited bandwidth.     

Reducing the effects of transmission impairments in digital fiberoptic systems

The major impairments in lightwave systems and the signal-processing techniques that can be used to reduce these impairments are discussed. Guidelines for the use of these techniques are presented. These guidelines are used to determine the techniques with the most potential for providing improved performance in long-haul systems, local-area networks, and local loop systems. Although many of the techniques have been previously considered for these applications, few have been implemented in commercial products. Some of the most promising techniques include dispersion-compensating fibers, polarization control, nonlinear cancellation (NLC), and coding for reducing the effect of distortion in long-haul single-frequency-laser direct-detection systems