Scleroderma is a fi brotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not been fully elucidated, a growing body of evidence suggests that the overproduction of extracellular matrix proteins by activated fi broblasts results from an imbalance between synthesis and degradation of connective tissues. A number of mediators, cytokines, chemokines and growth factors secreted by infl ammatory cells and mesenchymal cells (fi broblasts and myofi broblasts) play an important role in the fi brotic process of scleroderma. In this article, we describe recent advances concerning immunological aspects in the pathogenesis of bleomycin-induced murine scleroderma, laying stress on the involvement of interleukin-13 (IL-13) and plasminogen activator inhibitor-1 (PAI-1).

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Masticatory performance of denture wearers was compared with that of the normal subjects by analyzing the behavior of the mechanical properties of the bolus. The index of the ability to comminute bolus was described as the total number of masticatory strokes until swallowing and therefore this was chosen as the fi rst index. Principal Component Analysis (PCA) on the data of six parameters; 80% energy, elasticity, viscosity, hardness, adhesiveness, and cohesiveness, indicated that the cohesiveness was independent of the other parameters and should be evaluated as the second index of the ability to dilute bolus with saliva. Two factor scores of the other parameters were calculated using the standardized scoring coeffi cient obtained from PCA and factor analysis on the data of the normal subjects, which realized to compare two groups on the same plane of factor scores. The movement of factor scores on the factor plane would indicate the total behavior of mechanical properties of bolus and was chosen as the third index of the ability to knead bolus. Triangle Diagram (TD) was completed by using these three indices. On the TD, all the subjects were lower level at least in one index than the normal subjects in all the foods.

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Cre complementation is a process of reconstitution of the activity of DNA recombinase by noncovalent association of multiple segments of Cre recombinase, which are enzymatically inactive by themselves. Cre complementation is potentially useful in restriction of Cre activity in a specifi c subset of cells, with temporal regulation, by limiting overlap in expression of Cre fragments. We analyzed the effi ciency of Cre complementation using three different dimerizing modules in the context of non-neuronal cells and found differential Cre complementation effi ciency. We further tested the effi ciency of Cre complementation in primary hippocampal neurons derived from transgenic mice harboring a reporter gene fl anked by loxP sites and confi rmed differential activity of dimerization modules in Cre-dependent recombination of the transgene. These results suggest possible application of dimerizer-based Cre complementation in inducible expression/inactivation of target genes in a specifi c subset of neurons in the complex environment of nervous tissue in vivo.

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Tissue-nonspecifi c alkaline phosphatase (TNSALP) and Ca-ATPase are known to play roles in bone mineralization, but how these enzymes contribute to appositional mineralization has been illusive. Here we examined the active sites of these enzymes in appositional mineralization using the bones of young rats being administered with 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) for 5 days. The doses of HEBP totally abolished mineralization of newly formed bone matrix except in matrix vesicles (MVs), and hence allowed precise localization of MVs and phosphatase reactions within non-mineralized extracellular matrix. Intense TNSALP and ATPase reactions were confi rmed along the limited portions of osteoblast membranes where intimate cell-cell contacts were maintained. Diffuse reactions of these enzymes were throughout the osteoid implicating effl ux of TNSALP and ATPase molecules into extracellular matrix from the osteoblast membranes. Phosphatase reactions associated with MVs varied both in intensity and location among the individual vesicles; newly formed MVs were almost free of reactions but appeared to gain those activities later in the osteoid. These data suggest that TNSALP and ATPase are released from the osteoblast membrane and later integrated into MVs within the osteoid. The osteoblasts may thus regulate appositional mineralization of bone from a distance at least in part by providing phosphatases via MVs.

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