The Oral Cavity State in Renal Transplant Recipients.

AIM: Patients with a solid organ transplant can have many different complications in the mouth, as a result of immunosuppression and side effects of drugs. The aim of this study was to examine the frequency and type of oral lesions in renal transplant patients, dental status, oral hygiene, oral lesions related to drugs which patients take and the time of transplantation as well as the frequency of patient's visits to the dentist in the post-transplant period. MATERIAL AND METHODS: The study was performed in a period of two years and included 100 subjects with a renal transplant during their regular control visits to the Department of Nephrology and Dialysis, Clinical Hospital Centre Zagreb and the Department of Oral Medicine, School of Dental Medicine, University of Zagreb and 100 randomly selected control subjects at the Department of Endodontics and Restorative Dentistry, School of Dental Medicine, University of Zagreb. RESULTS: Results showed a significantly higher incidence of oral lesions in patients with renal transplant (31%) compared to control subjects. The most frequent were erythematous (inflammatory changes), keratotic lesions and gingival hyperplasia. The average DMFT index was significantly lower in patients with renal transplant than in the control group. One third of patients had a subjective feeling of dry mouth. Oral hygiene was poor overall, and only a small number of subjects used the additional sustainers for oral hygiene. Most patients did not visit the dentist after the transplantation. CONCLUSION: Renal transplant patients need a comprehensive and regular dental care during the pre- and post-transplant period and a doctor of dental medicine should be part of a multidisciplinary team of medical specialists.

Regulation of TGF-(beta) signalling by N-acetylgalactosaminyltransferase-like 1.

The TGF-beta superfamily of secreted signalling molecules plays a pivotal role in the regulation of early embryogenesis, organogenesis and adult tissue homeostasis. Here we report the identification of Xenopus N-acetylgalactosaminyltransferase-like 1 (xGalntl-1) as a novel important regulator of TGF-beta signalling. N-acetylgalactosaminyltransferases mediate the first step of mucin-type glycosylation, adding N-acetylgalactose to serine or threonine side chains. xGalntl-1 is expressed in the anterior mesoderm and neural crest territory at neurula stage, and in the anterior neural crest, notochord and the mediolateral spinal cord at tailbud stage. Inhibition of endogenous xGalntl-1 protein synthesis, using specific morpholino oligomers, interfered with the formation of anterior neural crest, anterior notochord and the spinal cord. Xenopus and mammalian Galntl-1 inhibited Activin as well as BMP signalling in the early Xenopus embryo and in human HEK 293T cells. Gain- and loss-of-function experiments showed that xGalntl-1 interferes with the activity of the common TGF-beta type II receptor ActR-IIB in vivo. In addition, our biochemical data demonstrated that xGalntl-1 specifically interferes with the binding of ActR-IIB to Activin- and BMP-specific type I receptors. This inhibitory activity of xGalntl-1 was dependent on mucin-type glycosylation, as it was sensitive to the chemical inhibitor benzyl-GalNAc. These studies reveal an important role of a N-acetylgalactosaminyltransferase in the regulation of TGF-beta signalling. This novel regulatory mechanism is evolutionarily conserved and, thus, might provide a new paradigm for the regulation of TGF-beta signalling in vertebrates.

Xenopus Tetraspanin-1 regulates gastrulation movements and neural differentiation in the early Xenopus embryo.

The tetraspanin family of four-pass transmembrane proteins has been implicated in fundamental biological processes, including cell adhesion, migration, and proliferation. Tetraspanins interact with various transmembrane proteins, establishing a network of large multimolecular complexes that allows specific lateral secondary interactions. Here we report the identification and functional characterization of Xenopus Tetraspanin-1 (xTspan-1). At gastrula and neurula, xTspan-1 is expressed in the dorsal ectoderm and neural plate, respectively, and in the hatching gland, cement gland, and posterior neural tube at tailbud stages. The expression of xTspan-1 in the early embryo is negatively regulated by bone morphogenetic protein (BMP) and stimulated by Notch signals. Microinjection of xTspan-1 mRNA interfered with gastrulation movements and reduced ectodermal cell adhesion in a cadherin-dependent manner. Morpholino knock-down of endogenous xTspan-1 protein revealed a requirement of xTspan-1 for gastrulation movements and primary neurogenesis. Our data suggest that xTspan-1 could act as a molecular link between BMP signalling and the regulation of cellular interactions that are required for gastrulation movements and neural differentiation in the early Xenopus embryo.

Identification of a second Xenopus twisted gastrulation gene.

Twisted Gastrulation (Tsg) is a secreted molecule which regulates BMP signalling in the extracellular space as part of an evolutionarily conserved network of interacting proteins. In Xenopus, maternal xTsg mRNA can be found throughout the early embryo. After gastrulation, xTsg is expressed as part of the BMP4 synexpression group until late tadpole stages. Here we report the identification of a second Xenopus Tsg gene (xTsg-2). Xenopus Tsg-2 is highly homologousto xTsg. In particular, amino acid residues which have been shown to be required for the binding of xTsg to BMP and to Chordin are conserved. The expression of Xenopus Tsg-2 mRNA was restricted to late stages of embryonic development; it was detected at tadpole stages in lateral plate mesoderm, neural crest, branchial arches and head mesenchyme. In microinjection experiments, the activity of xTsg-2 mRNA was similar to that of xTsg. We conclude that two Tsg genes act in distinct temporal and spatial territories in the course of Xenopus embryonic development.