Wear properties of alumina/zirconia composite ceramics for joint prostheses measured with an end-face apparatus

While only alumina is applied to all-ceramic joint prostheses at present, a stronger ceramic is required to prevent fracture and chipping due to impingement and stress concentration. Zirconia could be a potential substitute for alumina because it has high strength and fracture toughness. However, the wear of zirconia/zirconia combination is too high for clinical use. Although some investigations on composite ceramics revealed that mixing of different ceramics was able to improve the mechanical properties of ceramics, there are few reports about wear properties of composite ceramics for joint prosthesis. Since acetabular cup and femoral head of artificial hip joint are finished precisely, they indicate high geometric conformity. Therefore, wear test under flat contact was carried out with an end-face wear testing apparatus for four kinds of ceramics: alumina monolith, zirconia monolith, alumina-based composite ceramic, and zirconia based composite ceramic. Mean contact pressure was 10 MPa and sliding velocity was 40 mm/s. The wear test continued for 72 hours and total sliding distance was 10 km. After the test, the wear factor was calculated. Worn surfaces were observed with a scanning electron micrograph (SEM). The results of this wear test show that the wear factors of the both composite ceramics are similarly low and their mechanical properties are much better than those of the alumina monolith and the zirconia monolith. According to these results, it is predicted that joint prostheses of the composite ceramics are safer against break down and have longer lifetime compared with alumina/alumina joint prostheses.     

Developmental changes in concentrations and distributions of neurotrophins in the monkey cerebellar cortex

Neurotrophins are involved in the survival, differentiation, migration and neurite outgrowth of various neuronal populations. Neurotrophins and their receptors are widely expressed in the developing cerebellum of various experimental animals. To gain some insight into the possible roles played by these molecules in monkey cerebellum, we examined the protein levels of BDNF, NT-4/5 and NT-3 and distributions of those neurotrophins and TrkC, a high affinity receptor for NT-3, in the cerebellum of developing macaque monkeys using ELISAs and immunohistochemical methods. We found that the level of BDNF increased during development, while the level of NT-3 was higher during embryonic stages and decreased toward adulthood. The level of NT-4/5 increased from embryonic stages to infant stages and gradually declined with age. Among the three neurotrophins, BDNF immunoreactivity was found in all kinds of cerebellar neurons, including all inhibitory interneurons, throughout the postnatal periods examined, indicating that BDNF may be an essential factor for the maintenance of cerebellar neural functions. The Bergmann glial fibers and the internal part of the external granule cell layer were strongly NT-3 immunopositive at the early postnatal stages, and more weakly immunoreactive toward adulthood. In addition, we found that the premigratory precursors of the granule cells were TrkC immunopositive at early postnatal stages. These findings suggest that NT-3 in Bergmann glial fibers may be involved in the migration of the premigratory granule cells.     

Inhibition of endoplasmic reticulum-associated degradation in CHO cells resistant to cholera toxin,Pseudomonas aeruginosa exotoxin A,and ricin

Many plant and bacterial toxins act upon cytosolic targets and must therefore penetrate a membrane barrier to function. One such class of toxins enters the cytosol after delivery to the endoplasmic reticulum (ER). These proteins, which include cholera toxin (CT), Pseudomonas aeruginosa exotoxin A (ETA), and ricin, move from the plasma membrane to the endosomes, pass through the Golgi apparatus, and travel to the ER. Translocation from the ER to the cytosol is hypothesized to involve the ER-associated degradation (ERAD) pathway. We developed a genetic strategy to assess the role of mammalian ERAD in toxin translocation. Populations of CHO cells were mutagenized and grown in the presence of two lethal toxins, ETA and ricin. Since these toxins bind to different surface receptors and attack distinct cytoplasmic targets, simultaneous acquisition of resistance to both would likely result from the disruption of a shared trafficking or translocation mechanism. Ten ETA- and ricin-resistant cell lines that displayed unselected resistance to CT and continued sensitivity to diphtheria toxin, which enters the cytosol directly from acidified endosomes, were screened for abnormalities in the processing of a known ERAD substrate, the Z form of alpha1-antitrypsin (alpha1AT-Z). Compared to the parental CHO cells, the rate of alpha1AT-Z degradation was decreased in two independent mutant cell lines. Both of these cell lines also exhibited, in comparison to the parental cells, decreased translocation and degradation of a recombinant CTA1 polypeptide. These findings demonstrated that decreased ERAD function was associated with increased cellular resistance to ER-translocating protein toxins in two independently derived mutant CHO cell lines.     

Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid.

Vaccination of normal adults with tetanus toxoid induced a two-three-fold rise in the frequency of IgM anti-IgG (rheumatoid factor, RF) B lymphocytes inducible by the polyclonal B cell activator, Epstein-Barr virus. The increase in IgM-RF precursors occurred earlier, was greater in magnitude, and was more sustained than the change in plasma IgM-RF. It was associated with a rise in total IgM levels, and correlated positively with the magnitude of the IgG anti-tetanus antibody response, but not with levels of circulating immune complexes. The ability of apparently innocuous infections and immunizations to increase the frequency of IgM-RF precursor B lymphocytes may be the reason for the previously noted expansion in this autoreactive B cell pool between birth and adulthood.     

Recognition of Staphylococcus saprophyticus in urine cultures by screening colonies for production of phosphatase.

Phenolphthalein diphosphate was incorporated into a primary blood agar medium for use in performing quantitative urine cultures. Phosphatase-negative staphylococci, such as Staphylococcus saprophyticus, were differentiated from phosphatase-positive species, such as Staphylococcus epidermidis, by spot testing colonies on filter paper saturated with 1 N NaOH. Phosphatase-positive colonies turned pink within seconds, and phosphatase-negative colonies showed no color. None of 55 S. saprophyticus isolates showed production of phosphatase on this medium. Of 193 consecutive coagulase-negative staphylococci isolated from the urine of 190 adolescent female patients, 84% were phosphatase positive, non-S. saprophyticus species; 16% were phosphatase-negative and indicated S. saprophyticus (22), Staphylococcus haemolyticus (4), Staphylococcus simulans (2), Staphylococcus warneri (1), and Staphylococcus hominis (1). Phosphatase activity was variable in the other flora encountered in the urine cultures. Mixtures of phosphatase-positive and -negative organisms did not cause false-positive reactions.     

Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.     

Role of oxidative stress,angiogenesis and chemo-attractant cytokines in the pathogenesis of ischaemic protection induced by remote ischaemic conditioning: Study of a human model of ischaemia-reperfusion induced vascular injury

Aims

We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.

Laser ablation of discs of agar gel

Discs of agar gel mixed with ink were used to study ablation effects with an argon laser as a light source. Varying amounts of ink were added resulting in a variation of the attenuation coefficient between 0.45 and 6.3 mm-1. For laser beam irradiation horizontally incident on a vertical sample, the average velocity of ablation was found to be approximately constant for thicknesses up to 1.7 mm. When the laser beam was directed vertically on a sample held horizontally, the vaporized debris present in the beam attenuated the incident laser energy to such a degree that the average ablation velocity decreased by a factor of approximately five. Horizontal beam experiments for various attenuation coefficients showed that an attenuation coefficient of about 1.7 mm-1 is optimal for fast penetration of discs thicker than 4 mm. Thus, based upon the optical properties of a given tissue, there may exist an optimum laser wavelength to maximise ablation velocity.     

Effects of temperature, time, and toxin concentration on lesion formation by the Escherichia coli hemolysin.

We performed osmotic protection experiments to test the hypothesis that the Escherichia coli hemolysin forms a discrete-size pore in erythrocyte membranes. The effects of toxin concentration, assay time, temperature, and protectant concentrations were examined. The results we present here raise doubts about the existing model of pore formation by hemolysin. We demonstrate that osmotic protection by various sugars of different sizes is a function of hemolysin concentration and assay time. The data indicate that under various conditions, lesion sizes with a diameter ranging from < 0.6 to > 1.2 nm can be inferred. Quantification of hemolysin permitted the estimation of the number of HlyA structural protein molecules required per erythrocyte for lysis in the presence of each protectant. It appears that hemolysin induces heterogeneous erythrocyte lesions which increase in size over time. Influx experiments utilizing radioactive sugar markers indicated that time-dependent osmotic protection patterns are independent of the diffusion rates of individual protectants. We demonstrate that the rate of the putative growth in the size of hemolysin-mediated lesions is temperature dependent. The erythrocyte membrane lesions formed at 37 degrees C can be stabilized in size when shifted to 4 degrees C. On the basis of these data, new models for the nature of the hemolysin-mediated erythrocyte membrane lesions are presented.