Phosphatidate phosphohydrolase and signal transduction

A Mg(2+)-independent and N-ethylmaleimide-insensitive phosphatidate phosphohydrolase (PAP-2) has been identified in the plasma membrane of cells and it has been purified. The enzyme is a multi-functional phosphohydrolase that can dephosphorylate phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate and these substrates are competitive inhibitors of the reaction. The action of PAP-2 could terminate signalling by these bioactive lipids and at the same time generates compounds such as diacylglycerol, sphingosine and ceramide which are also potent signalling molecules. In relation to phosphatidate metabolism, sphingosine (or sphingosine 1-phosphate) stimulates phospholipase D and thus the formation of phosphatidate. At the same time sphingosine inhibits PAP-2 activity thus further increasing phosphatidate concentrations. By contrast, ceramides inhibit the activation of phospholipase D by a wide variety of agonists and increase the dephosphorylation of phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate. These actions demonstrate "cross-talk' between the glycerolipid and sphingolipid signalling pathways and the involvement of PAP-2 in modifying the balance of the bioactive lipids generated by these pathways during cell activation.     

Cross-national interrater reliability of dementia diagnosis in the elderly and factors associated with disagreement

Thirteen researchers from five centers in Australia, Germany, the Netherlands, United Kingdom, and United States applied DSM-III-R and Clinical Dementia Rating (CDR) syndrome-level dementia criteria to written vignettes of 100 elderly people identified in clinics or community surveys. Subjects ranged in type from cognitively intact to severely demented and many were also frail, partially sighted, or deaf. This paper concerns reliability within and between centers, and the relationship between reliability and factors such as diagnostic criteria, dementia severity, and respondents' clinical characteristics. Within-center interrater reliability was high, more so for "yes-no" DSM-III-R diagnoses than the multi-level CDR. Between-center rates were lower but still moderate to good. Concordance was lower for intermediate dementia levels than for no dementia and severe dementia. Physical disability made an additional contribution to uncertainty but deafness, poor vision, anxiety, and depression had no discernible effects. Reliability levels are likely to be lower in representative aged populations than in carefully selected clinical groups.     

A comparison of moderate and high users of Alberta's universal dental plan for the elderly

The characteristics and service utilization of 2,071 high and 2,337 moderate users of Alberta's dental plan from 1978-79 to 1990-91 are reported. High users are those who used the plan for 14 consecutive years; moderate users are those who used the plan in seven of the 14 years. Both groups were over 74 years of age in 1991-92. Compared to high users, moderate users lived in less urbanized regions, visited denturists more often and received far more complete dentures and fewer partial dentures. As a percentage of their total annual plan expenditures, moderate users spent less on diagnostic, preventive, periodontal and restorative services and much more on removable prosthodontic and denturists' services. However, during the study period, the moderate users increased their annual relative expenditures for diagnostic, preventive and, especially, periodontal services, and decreased them for prosthodontic services. With respect to specific preventive and periodontal services, the percentage of total annual expenditures for dental prophylaxis, topical fluoride applications, periodontal scaling, gingival curettage, and combinations of these, was much higher for the high user group. Despite these differences favoring the high user group, during the 14 year period, the moderate user group considerably increased its relative expenditures for dental prophylaxis, topical fluoride and periodontal scaling services. While the observed differences in service expenditures between high and moderate users were anticipated, the shift over time to using more preventive and periodontal services by both groups was an encouraging harbinger of the "new elderly" dental patients.     

Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the "litter effect''

Rats were mated for two or 15 hours and variability of day-12-embryos in weight, protein content, and [3H]thymidine incorporation was compared in the long mating period (LMP) and short mating period (SMP) groups by a 2-level nested analysis of variance. Variability in day-20 fetal weight was similarly compared. In both groups day-12 embryonic weight was relatively more variable than day-20 fetal weight, and variability was less in SMP than LMP animals for each comparison made, although statistical significance was attained only for thymidine incorporation. "Litter effects' were noted but not of the magnitude reported by other investigators. It was concluded that inappropriate statistical methods have encouraged the belief that among-litter variability usually exceeds within-litter fetal weight variability. The teratological implications of reduced development variability and the "litter effect' are discussed.     

Premature incomplete fusion of the growth plate: causes and treatment by resection (physolysis) in fifteen cases

Premature incomplete fusion of the growth plate results in shortening and progressive deformity of bone and joint. A preliminary report is presented of encouraging results following a new operation aimed at a surgical cure by direct attack on the pathological bony bridge. Growth has been reestablished in all of the cases treated in this way, and progressive spontaneous correction of deformity has been observed. Injuries involving high energy dissipation were mostly responsible. A small number of cases followed burns or were of spontaneous onset.     

Amianthoid change: orientation of normal collagen fibrils during aging

High-angle x-ray diffraction provides direct evidence that amianthoid change, occurring during aging of costal cartilage, corresponds to a transformation from an isotropic to a marked anisotropic distribution of collagen fibrils. Low-angle x-ray diffraction and electron microscopy show that the fibrils have the customary 67-nanometer axial periodicity. Electron microscopy shows that wide amianthoid collagen fibrils consist of smaller parallel fibrils fused together. Similarities between amianthoid change and tendon morphogenesis are briefly discussed. Amianthoid change is remarkable in that aging is accompanied by increased order.     

Neural networks for the analysis of small pulmonary nodules

PURPOSE: Small pulmonary nodules can be readily detected by computed tomography (CT). The goal of this detection is to diagnose early lung cancer as the five year survival at this early stage is over 70% in contradistinction to the overall 5-year survival of around 10%. Critical to the efficacy of CT for early lung cancer detection is the ability to distinguish between benign and malignant nodules. We explored the usefulness of neural networks (NNs) to help in this differentiation. METHODS: CT images of 28 pulmonary nodules, 14 benign and 14 malignant, each having a diameter less than 3 cm were selected. All were sufficiently malignant in appearance to require needle biopsy and surgery. The statistical-multiple object detection and location system (S-MODALS) NN technique developed for automatic target recognition (ATR) was used to differentiate between these benign and malignant nodules. RESULTS: S-MODALS was able to correctly identify all but three benign nodules. S-MODALS classified a nodule as malignant because it looked similar to other malignant nodules. It identified the most similar nodules to display them to the radiologist. The specific features of the nodule that determined its classification were also shown, so that S-MODALS is not simply a "black box" technique but gives insight into the NN diagnostics. CONCLUSION: This initial evaluation of S-MODALS NNs using pulmonary nodules whose CT features were very suspicious for lung cancer demonstrated the potential to reduce the number of biopsies without missing malignant nodules. S-MODALS performed well, but additional optimization of the techniques specifically for CT images would further enhance its performance.     

Prolactin stimulates phosphorylation of the human T-cell antigen receptor complex and ZAP-70 tyrosine kinase: a potential mechanism for its immunomodulation

Prolactin (PRL) is an immunomodulatory hormone which promotes T-cell activation and proliferation. However, the intracellular mechanisms of this action in normal lymphocytes are unknown. Because the PRL receptor (PRLR) activates several signals also activated by the T-cell antigen receptor (TCR)/CD3 complex, we evaluated whether signaling "cross-talk" occurs between these distinct receptors. Using human thymocytes, human peripheral blood lymphocytes and the rat Nb2 lymphoma T-cell, we found that PRL induced rapid phosphorylation of multiple, TCR/CD3 complex proteins, an event required for lymphocyte activation. Two of these phosphorylated proteins were identified to be CD3 epsilon and ZAP-70 tyrosine kinase, molecules essential for TCR function. Further, PRL induced tyrosyl phosphorylation of ZAP-70 in each population of T-lymphocytes tested, demonstrating for the first time that ZAP-70 is a target of PRL action. Taken together, our results suggest that the PRLR directly affects T-lymphocyte activation by means of signaling cross-talk with the TCR/CD3 complex.