Hindshaker, a novel myelin mutant showing hypomyelination preferentially affecting the spinal cord

Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.     

Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

OBJECTIVE: The initially well-fixed implants of total hip replacement (THR) are in the long-term subject to aseptic loosening. Many cytokines can contribute to osteolysis due to osteoclast recruitment and/or activation. However, in this respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating factor. The aim of this study was to assess the eventual presence, cellular localization and extent of expression of TNF-alpha in the synovial-like membrane at the implant or at the cement to bone interface compared to control synovial membrane. METHODS: Twenty samples from the synovial-like membrane of the periprosthetic tissues were compared to control samples. TNF-alpha containing cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and analyzed by light microscopy, double labelling and image analysis. RESULTS: TNF-alpha was found in the periprosthetic tissues in fibroblasts and vascular endothelial cells, but mainly in the macrophages was it found to coincide with areas containing implant-derived debris. TNF-alpha containing cells were more numerous in the synovial-like membrane in the interface tissue from the proximal stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93 cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/- 582 cells) was also seen in the synovial-like membrane of the pseudocapsule. CONCLUSION: These findings suggest that the foreign body-type host reaction caused by THR is characterized by the high expression of TNF-alpha. Because such expression occurred in the interface tissue between the implant and surrounding bone, TNF-alpha, due to its pivotal direct and indirect role in the activation and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and to the loosening of THR.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Information technology and the accountant: a case study

The factors leading to the success or failure of IT implementations by accountants are investigated in a health service situation. Tbe case study adopts the participant observation methodology and the factors observed are classified as motivators and demotivators. Using a project dependent definition of success, a catastrophe theory framework is used to describe the outcome of the combined influence of these factors. Four particular IT projects are discussed and the factors observed include: the influence of higher levels in the organizational hierarchy, some systems characteristics, the seduction of technology, external pressures, the 'rate of change', skills shortage and reliability. By comparing the examples described with features mentioned by other authors, it is noted that some factors appear to be generally applicable, whereas others may be context dependent.     

EEG monitoring during carotid surgery: who should do the monitoring?

Recently, a new hematopoietic growth factor, stem cell factor, the ligand for the c-kit-proto-oncogene, has been cloned. The gene for this factor or for its receptor are deleted in two well known series of mice mutants which display pleiotropic stem cell defects. Therefore, this factor supposedly plays an important role in stem cell biology. This paper reviews some of the elegant genetic work which led to the discovery of the factor and of its receptor, the biological effects that this factor exerts in the hematopoietic system in normal individuals and in patients with Diamond-Blackfan anemia and speculates on some of its potential clinical applications.     

Changes in torque and electromyographic activity of the quadriceps femoris muscles following isometric training

BACKGROUND AND PURPOSE: The purpose of this study was to examine the effect of isometric training of the quadriceps femoris muscles, at different joint angles, on torque production and electromyographic (EMG) activity. SUBJECTS: One hundred seven women were randomly assigned to one of four groups. Three groups trained with isometric contractions three times per week at a knee flexion angle of 30, 60, or 90 degrees. The fourth group, which served as a control, did not exercise. METHODS: Isometric torque was measured using a dynamometer, and EMG activity was measured using a multichannel EMG system. Measurements were obtained during maximal isometric contraction of the quadriceps femoris muscles at 15-degree increments from 15 to 105 degrees of knee flexion. Measurements were taken before and after 8 weeks of training. RESULTS: Following isometric exercise, increased torque and EMG activity occurred not only at the angle at which subjects exercised, but also at angles in the range of motion at which exercise did occur. Further analyses indicated that exercising in the lengthened position for the quadriceps femoris muscles (90 degrees of knee flexion) produced increased torque across all angles measured and appeared to be the more effective position for transferring strength and EMG activity to adjacent angles following isometric training as compared with the shorter positions of the muscle (30 degrees and 60 degrees of knee flexion). CONCLUSION AND DISCUSSION: These findings suggest that an efficient method for increasing isometric knee extension torque and EMG activity throughout the entire range of motion is to exercise with the quadriceps femoris muscles in the lengthened position.     

Ti3+ ion concentration and Ti:sapphire laser performance

The pulsed and CW laser performance of a range of titanium sapphire laser crystals is reported. Titanium ion concentration in the crystals ranged from 0.07 at.% to 0.25 and 0.41 at.% for some recently developed heavily doped crystals. Values of the crystal figure of merit lay between 30 and 220. Threshold, slope efficiency, tunability, and temporal response are assessed. Comparisons are made with the predictions of a simple rate equation model