Expansions of T-cell subsets expressing particular T-cell receptor variable regions in chronic beryllium disease

Bisphosphonates are currently the most important class of antiresorptive drugs used for the treatment of metabolic bone diseases. Although the molecular targets of bisphosphonates have not been identified, these compounds inhibit bone resorption by mechanisms that can lead to osteoclast apoptosis. Bisphosphonates also induce apoptosis in mouse J774 macrophages in vitro, probably by the same mechanisms that lead to osteoclast apoptosis. We have found that, in J774 macrophages, nitrogen-containing bisphosphonates (such as alendronate, ibandronate, and risedronate) inhibit post-translational modification (prenylation) of proteins, including the GTP-binding protein Ras, with farnesyl or geranylgeranyl isoprenoid groups. Clodronate did not inhibit protein prenylation. Mevastatin, an inhibitor of 3-hydroxy-3-methylglutatyl (HMG)-CoA reductase and hence the biosynthetic pathway required for the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, also caused apoptosis in J774 macrophages and murine osteoclasts in vitro. Furthermore, alendronate-induced apoptosis, like mevastatin-induced apoptosis, could be suppressed in J774 cells by the addition of farnesyl pyrophosphate or geranylgeranyl pyrophosphate, while the effect of alendronate on osteoclast number and bone resorption in murine calvariae in vitro could be overcome by the addition of mevalonic acid. These observations suggest that nitrogen-containing bisphosphonate drugs cause apoptosis following inhibition of post-translational prenylation of proteins such as Ras. It is likely that these potent antiresorptive bisphosphonates also inhibit bone resorption by preventing protein prenylation in osteoclasts and that enzymes of the mevalonate pathway or prenyl protein transferases are the molecular targets of the nitrogen-containing bisphosphonates. Furthermore, the data support the view that clodronate acts by a different mechanism.     

Mating-related stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in progestin receptor-containing areas in the female rat brain

Vaginal-cervical stimulation induces a number of physiological and behavioral events, including the facilitation of mating behavior. Although the facilitation of one component of mating behavior, lordosis, by vaginal-cervical stimulation does not require the presence of progesterone, it appears to be mediated by neural progestin receptors. Abundant evidence suggests that dopamine may play a role in the neural circuitry activated by vaginal-cervical stimulation, including the mating-induced release of dopamine in progestin receptor-containing areas of the brain, changes in the activational state of progestin receptors because of dopamine D1 receptor stimulation, facilitation of lordosis by D1 receptor stimulation in estradiol-primed rats via progesterone-independent events, and D1 agonist-induced neuronal responses in progestin receptor-containing areas and cells. We tested the hypothesis that vaginal-cervical stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32; Mr = 32,000), a protein phosphorylated predominantly in response to the stimulation of D1 receptors. At 9 d after ovariectomy, female rats were injected subcutaneously with a behaviorally effective dose of estradiol benzoate. At 48 hr later they received vaginal-cervical or control (perineal) stimulation, and they were perfused 1 hr later. Vaginal-cervical stimulation increased the number of cells expressing pDARPP-32 immunoreactivity by 92% in the medial preoptic nucleus, 134% in the caudal ventromedial hypothalamic nucleus, 123% in the posterodorsal medial amygdala, and 103% in the bed nucleus of the stria terminalis. These results suggest that some of the neuronal effects of vaginal-cervical stimulation, and perhaps other social or environmental stimuli, are mediated by phosphorylation of DARPP-32, perhaps via stimulation of D1 receptors, within progestin receptor-containing areas.     

Permeability of blood-eye barrier in patients with primary glaucoma combined with lens opacity

The paper focuses on the history and sources of origin of sanology as science, with its brief characterization being given, relating to such items as definition, object and subject of investigation, methodological approaches and tasks, with special emphasis being placed on the significance of sanology in the elaboration of general theory of medicine.     

Wall shear stress in the human common carotid artery as function of age and gender

OBJECTIVES: It has been postulated that in the arterial system mean wall shear stress is maintained at a constant value. The present study was performed to investigate the level of wall shear stress in the common carotid artery (CCA) as function of age and possible interactions between diameter and storage capacity, defined as the absolute area change per heart beat, with mean wall shear stress. METHODS: Wall shear stress (wall shear rate multiplied by whole blood viscosity) was assessed in the right CCA of 111 presumed healthy male (n = 56) and female (n = 55) volunteers, varying in age between 10 and 60 years. Wall shear rate was measured with a high resolution ultrasound system. Simultaneously, arterial diameter and storage capacity were determined. Whole blood viscosity was calculated from haematocrit, plasma viscosity and shear rate. RESULTS: From the second to the sixth age decade peak wall shear stress was significantly higher in males than in females and decreased from 4.3 Pa to 2.6 Pa (r = -0.56, p < 0.001) in males and from 3.3 Pa to 2.5 Pa (r = -0.54, p < 0.001) in females. Mean wall shear stress tended to decrease from 1.5 Pa to 1.2 Pa (r = -0.26, p = 0.057) in males and decreased significantly from 1.3 Pa to 1.1 Pa (r = -0.30, p = 0.021) in females. No significant difference in mean wall shear stress was found between males and females in any age decade. The diameter of the CCA increased significantly in both males (r = 0.26, p < 0.05) and females (r = 0.40, p < 0.003). Storage capacity decreased significantly in both sexes (males: r = -0.63, p < 0.001; females: r = -0.68, p < 0.001). CONCLUSIONS: These observations suggest that the reduction in mean wall shear stress with age results from the concomitant increase in diameter in an attempt of the arterial system to limit the reduction in storage capacity of the arterial system with increasing age.     

A system of immunoenzyme analysis using biotinylated monoclonal antibodies for typing hantavirus antigens

Enzyme immunoassay with biotin-labeled monoclonal antibodies to Puumala virus was used for typing hantavirus antigens. The system is type-specific, that is, it detects Puumala virus only, which was demonstrated by typing 9 hantavirus antigens in infected Vero E5 cells and by epizootological analysis of an HFRS outbreak in the Yegoryevsk district of the Moscow region in November-December 1995. The suggested system may be used as an element of EIA screening of natural samples in analysis of the screening results.     

Acoustic rhinometry in the study of the acute nasal allergic response

Acoustic rhinometry is a recently developed method for the objective assessment of nasal patency. In this study, acoustic rhinometry was used to measure changes in nasal cavity dimensions in the immediate response to nasal allergen challenge in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared with subjective symptoms, as well as histamine in nasal secretions, cytology of nasal mucosal scrapings, and changes in olfactory function. A significantly greater decrease in nasal airway caliber occurred following allergen challenge as compared to buffer diluent challenge in the same individuals (70% +/- 7% versus 22% +/- 5%). During an allergic response, a strong correlation was found between the minimum cross-sectional area and the volume of the nasal cavity measured by acoustic rhinometry (r = .9). However, no correlation was observed between nasal airway caliber and concomitant subjective congestion reported by the subjects. A modest decrease in olfactory function was seen following allergen challenge (3.1 +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the alterations of olfactory function did not correlate with changes in nasal patency. The results presented in this study demonstrate that acoustic rhinometry has great potential as a reproducible method for the objective assessment of nasal obstruction occurring in nasal allergen challenge studies.