Quantitative peripheral computed tomodensitometric study of cortical and trabecular bone mass in relation with menopause

Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2), monocytes/macrophages (Leu M5), and HLA-DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4-positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1.35/l), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1.75/l). Aberrant HLA-DR expression was found in 21.05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation of the percentage of positive cells with CD4- and CD8-positive lymphocyte populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4-positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA-DR antigen. There were no statistically significant differences in the population densities of B cells, CD8- or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA-DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA-DR expression by tumour cells reflect the existence of separate HLA-DR-positive or HLA-DR-negative tumour clones.     

Pretreatment with pertussis toxin blocks morphine- but not beta-endorphin-induced antinociception in the mouse

We have previously demonstrated that the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) is mediated by the stimulation of respective mu- and epsilon-opioid receptors. The effects of i.c.v. pretreatment with pertussis toxin on the antinociception induced by morphine and beta-endorphin given i.c.v. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. Pretreatment with pertussis toxin (0.5 microgram) given i.c.v. 96 h earlier blocks the antinociception induced by i.c.v. administered morphine in both tail-flick and hot-plate tests. The same pretreatment did not affect the antinociception induced by i.c.v. administered beta-endorphin. Our results indicate that morphine-, but not beta-endorphin-induced antinociception is mediated by pertussis toxin sensitive G-proteins.     

Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling

trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In vivo, three isoforms of the receptor are generated by differential splicing--gp145trkB or the full-length trkB receptor, and trkB.T1 and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.T1, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145trkB, but not trkB.T1 or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-gamma-mediated mechanism) after stimulation by BDNF. When trkB.T1 and trkB.T2 were coexpressed with gp145trkB, they acted as dominant negative receptors, inhibiting the BDNF signal by forming nonfunctional heterodimers with the full-length receptors. An ATP-binding mutant of gp145trkB had similar dominant inhibitory effects. Our data suggest that naturally occurring truncated trkB receptors function as inhibitory modulators of neurotrophin responsiveness. Furthermore, the homodimerization of gp145trkB appears to be an essential step in activation of the BDNF signaling cascade.     

Determinants of midterm outcome of partial left ventriculectomy in dilated cardiomyopathy

The objective of this study was to test the hypothesis that maternal CRH concentrations are elevated in women experiencing threatened preterm labor who subsequently give birth within 24 h compared to those in women who do not. We also characterized the changes in maternal plasma cortisol, ACTH, corticosteroid binding capacity (CBC), and CRH concentrations in 28 healthy pregnant women between 20-38 weeks gestation. Overall, maternal plasma CRH concentrations were significantly greater (P < 0.05) in those women giving birth within 24 h (1343.3 +/- 143.9 pg/mL; n = 81) compared to those in women who did not (714.5 +/- 64.8 pg/mL; n = 144) or those in normal subjects. This difference was present between 28-36 weeks, but not 24-28 weeks gestation. The ratio of maternal cortisol to CBC was also significantly greater (P < 0.05; 0.65 +/- 0.04; n = 82) in women giving birth within 24 h than in those who did not (0.55 +/- 0.02; n = 136). This difference was significant at all gestational ages studied. Elevated CRH concentrations and bioavailability of free cortisol may both be implicated in the pathogenesis of preterm labor in some women. Further prospective clinical trials are warranted to determine the positive and negative predictive values of maternal CRH concentrations and/or the ratio of cortisol/CBC for identifying women with threatened preterm labor destined to give birth within 24 h.     

A NEW METHOD FOR PREDICTING FATIGUE LIFE IN NOTCHED GEOMETRIES

The objective of this paper is to develop a notch crack closure model, called NCCM, based on plasticity-induced effects and short fatigue crack growth in the vicinity of the notch, and to predict the fatigue failure life of notched geometries. By using this model the regime for non-propagating cracks (n.p.c.) and the relationship between the fatigue strength reduction factor, Kf , and the elastic stress concentration factor, Kt , under mean stress conditions, can be determined quantitatively. A crack closure model is assumed to apply in the notch regime based on an approach developed to explain the crack growth retardation behavior observed in smooth specimen geometries after an overload. Notch plasticity effects are also applied in the NCCM model. Fatigue failure life is calculated from both short fatigue crack growth in the notch region where elastic–plastic fracture mechanics (EPFM) is applied and from long fatigue crack growth remote from the notch where linear elastic fracture mechanics (LEFM) occurs. This prediction is obtained using a quantity called the effective plasticity-corrected pseudo-stress. The NCCM can be used to account quantitatively for various observed notch phenomena, including both the relationship between Kf and Kt and n.p.c. The effects of the tensile mean stress on the Kf versus Kt relationship is investigated and leads to the little recognized but technologically important observation that mean stress conditions exist where Kf can be greater than Kt . The role of notch radius and tensile mean stress on n.p.c. behavior is also explored. The model is verified using experimental data for notch geometries of aluminum alloy 2024-T3, alloy steel SAE 4130 and mild steel specimens tested at zero and tensile mean stress.     

Effect of bacterial association on the phenotype and genotype of an Entamoeba histolytica clonal population

A several-times-cloned population of Entamoeba histolytica trophozoites (clone MAVIII) was cultured under axenic (MAVIIIax), monoxenic (MAVIIImx) and polyxenic (MAVIIIpx) conditions. Clones MAVIIIax and MAVIIImx presented similar virulence in vitro, but differed in their virulence in vivo, whereas MAVIIIpx trophozoites were neither virulent in vitro or in vivo. The MAVIII clones maintained their zymodeme and exhibited three unusual glucose phosphate isomerase bands, absent in other E. histolytica strains studied. Similar patterns were shown by the three MAVIII clones in the signature of a 482-bp DNA fragment from the M17 gene (which encodes for a variable immunodominant antigen), obtained by low stringency single specific primer PCR technique. However, MAVIII clones displayed genotypic variability in the patterns obtained by the random amplified polymorphic DNA technique using total DNA as template. Results suggest that monomorphism is kept in certain regions of the genome, mainly in those carrying protein encoding genes, but a high polymorphism is present in total DNA of cloned trophozoites cultured under different conditions, confirming the plasticity of the E. histolytica genome.