Functional morphology of pulp tissue

As compared with mesenchyme no genuine defense cells are developed in the tissue of the dental pulp and the nervous tissue. This is a further hint for the common development from ectoderm. The three dimensional meshwork of pulpa fibroblasts ("mesectoderm") is structured by elongated cell processes connected with each other by a variety of special cell junctions ("electronic cell coupling"). Metabolites from the microcirculation and neuropeptides from vegetative axons influence the activity of fibroblasts synthetizing groundsubstance. The meshwork of the groundsubstance has exclusion effects concerning molecules with a distinct molecular weight and charge. Thus a primitive defense system is established. With this the role of a newly described cell type of the dental pulp, the "lymphocytic pericyte" is discussed. Because of the poor capacity of the pulpa tissue for immunological reactions pathologically disorders may easily become chronically spreading their antigenic components throughout the body.     

Transforming growth factor-beta: multifunctional regulator of differentiation and development

Transforming growth factors-beta (TGF-beta) are 25 kilodalton (kDa) homodimeric peptides with multifunctional actions controlling the growth, differentiation and function of a broad range of target cells of both epithelial and mesenchymal derivation. They are expressed early in embryogenesis and their tissue-specific and developmentally dependent expression is strongly suggestive of an essential role in particular morphogenetic and histogenetic events. Five distinct TGF-beta s have been characterized so far, with 65-80% homology to each other. By using both molecular biological and immunohistochemical techniques, we are currently attempting to define specific sites of expression of the different TGF-beta s and to determine whether TGF-beta s 1-5 might have unique functions in development and in the mature organism. Comparative study of the promoter regions for the different TGF-beta s and for any particular TGF-beta in different species is also underway. Mechanistically, TGF-beta s act to control gene expression of their target cells, many of their actions converging on a complex, multifaceted scheme of control of matrix proteins and their interactions with cells; these effects on matrix are thought to mediate many of the effects of TGF-beta on development.     

Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Characterization of a class Ib gene of the rat major histocompatibility complex

The cDNA and a partial genomic sequence of a rat class I major histocompatibility (RT1) gene, 11/3R, is reported here. The sequence contains several unique amino acid residues at certain positions, mutations in exon 7 (which is not expressed), a mutation of the canonical exon 8 stop codon to a sense codon, and includes a long 3 unstranslated region (utr). The structure of exon 7 differs from that found in most rat class I genes and resembles exon 7 of most H-2K,D,L.Q genes. Parts of the 3 noncoding region are homologous to the RT1.A-4 and certain H-2 genes. Expression is detectable by northern blot analysis in mitogen-stimulated lymphocytes only, by polymerase chain reaction (PCR) in each tissue tested. After transfection into L cells 11/3R can be shown to be expressible at the cell surface. Probes derived from the 3 noncoding part crosshybridize with a number of restriction fragments which map to the RT1.C region, thus defining a subfamily of RT1.C region genes. Several members of this subfamily are deleted in the M1 RT1 mutant. The 11/3R gene presents typical features of a class Ib gene. Aspects of evolution and the potential of the gene are discussed.The nucleotide sequence data reported in this paper have been submitted to the GenBank molecule sequence data base and have been assigned the accession numbers X67503 ande X67504.     

Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells.

Mice deficient for the major lysosomal aspartic proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia at day 26 +/- 1. An atrophy of the ileal mucosa first observed in the third week progresses towards widespread intestinal necroses accompanied by thromboemboli. Thymus and spleen undergo massive destruction with fulminant loss of T and B cells. Lysosomal bulk proteolysis is maintained. These results suggest, that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical.     

Molecular mechanisms of endotoxin activity

Endotoxin (lipopolysaccharide, LPS), a constitutent of the outer membrane of the cell wall of gramnegative bacteria, exerts a wide variety of biological effects in humans. This review focuses on the molecular mechanisms underlying these activities and discusses structure-function relationships of the endotoxin molecule, its interaction with humoral and cellular receptors involved in cell activation, and transmembrane and intra-cellular signal transduction pathways.     

The significance of tryptophan in human nutrition

Summary Aside from its role as one of the limiting essential amino acids in protein metabolism, tryptophan (TRP) serves as precursor for the synthesis of the neurotransmitters serotonin and tryptamine as well as for the synthesis of the antipellagra vitamin nicotinic acid and the epiphyseal hormone melatonin.By involvement in so manifold pathways, TRP and its metabolites regulate neurobehavioral effects such as appetite, sleeping-waking-rhythm and pain perception. TRP is the only amino acid which binds to serum albumin to a high degree. Its transport through cell membranes is competetrvely inhibited by large neutral amino acids (NAA). The TRP/NAA ratio in plasma is essential for the TRP availability and thus for the serotonin synthesis in the brain.Due to its high TRP-concentration, human milk protein provides optimal conditions for the availability of the neurotransmitter serotonin. Low protein cow's milk-based infant formulas supplemented with-lactalbumin — a whey protein fraction containing 5.8% TRP — present themselves as a new generation of formulas, with an amino acid pattern different from the currently used protein mixtures of adapted formulas, resembling that of human milk to a much higher degree.