Epithelial Cell Lineage and Signaling in Murine Salivary Glands.

Maintaining salivary gland function is critical for oral health. Loss of saliva is a common side effect of therapeutic irradiation for head and neck cancer or autoimmune diseases such as Sjögren's syndrome. There is no curative treatment, and current strategies proposed for functional regeneration include gene therapy to reengineer surviving salivary gland tissue, cell-based transplant therapy, use of bioengineered glands, and development of drugs/biologics to stimulate in vivo regeneration or increase secretion. Understanding the genetic and cellular mechanisms required for development and homeostasis of adult glands is essential to the success of these proposed treatments. Recent advances in genetic lineage tracing provide insight into epithelial lineage relationships during murine salivary gland development. During early fetal gland development, epithelial cells expressing keratin 14 (K14) Sox2, Sox9, Sox10, and Trp63 give rise to all adult epithelium, but as development proceeds, lineage restriction occurs, resulting in separate lineages of myoepithelial, ductal, and acinar cells in postnatal glands. Several niche signals have been identified that regulate epithelial development and lineage restriction. Fibroblast growth factor signaling is essential for gland development, and other important factors that influence epithelial patterning and maturation include the Wnt, Hedgehog, retinoic acid, and Hippo signaling pathways. In addition, other cell types in the local microenvironment, such as endothelial and neuronal cells, can influence epithelial development. Emerging evidence also suggests that specific epithelial cells will respond to different types of salivary gland damage, depending on the cause and severity of damage and the resulting damaged microenvironment. Understanding how regeneration occurs and which cell types are affected, as well as which signaling factors drive cell lineage decisions, provides specific targets to manipulate cell fate and improve regeneration. Taken together, these recent advances in understanding cell lineages and the signaling factors that drive cell fate changes provide a guide to develop novel regenerative treatments.

The relationship between interfacial bonding and radiation damage in adsorbed DNA.

We have performed a comparison of the radiation damage occurring in DNA adsorbed on gold in two different configurations, when the DNA is thiolated and bound covalently to the substrate and when it is unthiolated and interacts with the substrate through the bases. Both molecules were found to organize so as to protrude from the surface at ~45 degrees. Changes in the time-dependent C 1s and O 1s X-ray photoelectron (XP) spectra resulting from irradiation were interpreted to arise from cleavage of the phosphodiester bond and possibly COH desorption. By fitting the time-dependent XP spectra to a simple kinetic model, time constants were extracted, which were converted to cross sections and quantum yields for the damage reaction. The radiation induced damage is significantly higher for the thiolated DNA. N 1s X-ray absorption spectrum revealed the N-C=N LUMO is more populated in the unthiolated molecule, which is due to a higher degree of charge transfer from the substrate to this LUMO in the unthiolated case. Since the N-C=N LUMO of the thiolated molecule is comparatively less populated, it is more effective in capturing low energy electrons resulting in a higher degree of damage.

Calreticulin affects beta-catenin-associated pathways.

Calreticulin, a Ca(2+) storage protein and chaperone in the endoplasmic reticulum, also modulates cell adhesiveness. Overexpression of calreticulin correlates with (i) increased cell adhesiveness, (ii) increased expression of N-cadherin and vinculin, and (iii) decreased protein phosphorylation on tyrosine. Among proteins that are dephosphorylated in cells that overexpress calreticulin is beta-catenin, a structural component of cadherin-dependent adhesion complexes, a member of the armadillo family of proteins and a part of the Wnt signaling pathway. We postulate that the changes in cell adhesiveness may be due to calreticulin-mediated effects on a signaling pathway from the endoplasmic reticulum, which impinges on the Wnt signaling pathway via the cadherin/catenin protein system and involves changes in the activity of protein-tyrosine kinases and/or phosphatases.

Cadherins: crucial regulators of structure and function in reproductive tissues.

Cadherins are cell surface proteins that are directly involved in a wide variety of processes such as cell adhesion, cell sorting, cell survival, morphogenesis, formation of intercellular junctions, maintenance of tissue integrity and tumourigenesis. This review discusses the multiple functions of cadherins in reproductive tissues. Furthermore, the role of the intracellular signalling protein beta-catenin in regulating cadherin function is reviewed. Finally, the findings that cadherin concentrations in reproductive tissues are responsive to steroid hormones is discussed. The modulation of cadherin expression by hormones is in agreement with the hypothesis that these proteins are dynamically involved in the maintenance of structure and function in reproductive tissues.

Pyomyositis: an unusual infection due to staphylococcus aureus.

Pyomyositis is a primary pyogenic infection of skeletal muscle, leading to the formation of intramuscular abscesses. Although common in tropical climates, it is infrequent in temperate zones. We report a patient who developed the condition without travelling to tropical areas.

Staphylococcal meningitis following Synchromed intrathecal pump implant: a case report.

Staphylococcal meningitis associated with implantation of an intrathecal drug pump for spasticity was successfully treated by intrathecal vancomycin delivered by the same pump. This produced high CSF antibiotic levels, and the pump and catheter system did not have to be removed. We are unable to identify a similar case reported in the literature to date.

A clinical investigation of pivmecillinam. A novel beta-lactam antibiotic in the treatment of urinary tract infections.

Pivmecillinam (FL 1039) is the pivaloyloxymethyl ester of mecillinam (FL 1060) which has considerable in vitro activity against Enterobacteriaceae. 38 hospital inpatients who had proven urinary tract infections were treated with 400 mg pivmecillinam four times daily for 5-7 days. The MIC of mecillinam to the infecting organisms was determined as were the serum and urinary concentrations of the antibiotic. The patients were followed up for 4-6 weeks after the end of treatment. Three patients were lost to follow-up. Of the 35 patients who were adequately followed up, 29 (83%) were classified as cured and there were 6 failures. Reported side effects were of a minor nature.