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Biomedical subjects

P A Tsonis

Publications and source records attributed to P A Tsonis.

At least 19 recordsLinked to original sources
PubMed1992

Newt squamous carcinoma proves phylogenetic conservation of tumors as caricatures of tissue renewal.

Although regeneration-competent newts like Notophthalmus viridescens have been reported to be resistant to carcinogenesis, we have been able to induce transplantable epidermal squamous cell carcinomas with 10-20% incidence by implanting 20-methylcholanthrene s.c. into the scapular region, a tissue that cannot regenerate. As soon as 1 week after exposure to this carcinogen, malignant cells were present in the treated skin, and after 4 weeks, macroscopic tumors of infiltrating squamous carcinoma cells positive for Type IV collagenase and/or rasHa p21 had dissolved areas of the epidermal basement membrane and colonized the dermis. Analysis of Ki-67 expression revealed that these tumors grow via a high growth fraction rather than a short cell cycle time. Morphological and immunohistochemical analyses showed that these tumors caricature the biology of the renewing epidermis: the presence of basal-like cells; differentiating cells; apoptotic cells; and keratinized horn pearls with an exaggerated or overabundant stem cell compartment as compared to the differentiated cell compartment. Immunochemical analyses indicated that the squamous carcinomas arose from the epidermis rather than the mucous glands. Thus, the principle that malignant tumors caricature the process of tissue renewal originally established in rodent tumors appears to be valid down the phylogenetic tree at least to regeneration-competent amphibia. Such a broad conservation indicates that the caricature principle also holds in human tumors.

Animals↗
PubMed1992

The mutant axolotl Short toes exhibits impaired limb regeneration and abnormal basement membrane formation.

The mutant axolotl Short toes develops with abnormal kidneys, Mullerian ducts, and limbs and provides one of the few experimental systems for developmental studies in amphibia. The present paper describes another deviation from this animal's normal physiology, which is very characteristic of the wild type: amputated limbs of Short toes fail to regenerate. A blastema is formed but differentiation does not occur. Detailed histological analysis provides evidence of abnormal formation of the basement membrane and accumulation of extracellular matrix within the blastema, which could be attributed to an imbalance of extracellular matrix and basement membrane proteins. The basement membrane develops much thicker and is convoluted in the arrested blastema of mutant animals. In contrast to the limbs, the tails of Short toes regenerated normally with no apparent abnormalities. No gross genomic aberrations have been detected between normal and mutant DNA, indicating that a large deletion or insertion is not likely to be the cause of this mutation.

Ambystoma↗
PubMed1992

Protein synthesis in the newt regenerating limb. Comparative two-dimensional PAGE, computer analysis and protein sequencing.

Protein synthesis has been studied by two-dimensional PAGE during the early limb regeneration in the adult newt. Quantitative and statistical analyses have provided unique information on overall patterns of protein synthesis as well as on specific protein synthesis during formation of the blastema. Furthermore, from the patterns in the two-dimensional gels and their quantification, a particular protein has been selected and sequenced. Partial sequencing revealed sequence similarities to Xenopus type I keratin B2. Expression of this keratin is 10-fold greater in the blastema than in the intact limb. The implications of keratin expression by the blastema cells are discussed.

Amino Acid Sequence↗
PubMed1992

Protein synthesis in the brain of newts undergoing limb regeneration.

The nervous system plays an important role during the process of amphibian limb regeneration. However, the molecules that are involved in such a control of regeneration are largely unknown. We have attempted to map protein synthesis in the brains of intact newts and from newts undergoing limb or tail regeneration. Our results show unique protein synthesis in the brain of newts undergoing limb regeneration. Such an analysis can lead to the identification and characterization of these proteins.

Animals↗
PubMed1991

Periodicity in DNA coding sequences: implications in gene evolution.

In this paper we have employed Fourier analysis of DNA coding and non-coding sequences in an attempt to identify possible patterns in gene sequences. It was found that while intronic sequences show a rather random pattern, coding sequences show periodicities and in particular a periodicity of 3. We were able to reconstruct such patterns by assuming a gene having one codon occurring in about 40% of the sequence. This could indicate that the predominant presence of codons all starting from the same base could confer the observed periodicities. Indeed, it was found that proteins do obey this rule. Implications of this finding in gene evolution are discussed.

Animals↗
PubMed1991

Cell populations synthesizing cartilage proteoglycan core protein in the early chick limb bud.

Cartilage specific macromolecules are known to be synthesized in the mesenchyme of the embryonic chick limb bud, especially in areas of prechondrogenic condensations (Shinomura et al, 1984). Even though the mesenchyme seems homogeneous according to histological criteria, studies in the past have suggested the presence of different cell populations with different chondrogenic potential (Solursh et al, 1982; Swalla et al, 1984). In this study we have investigated by means of flow cytometry, the synthesis of proteoglycan core protein during early development of the chick limb bud in order to identify the different chondrocyte progenitor cells. We were able to identify by virtue of different size and density a cell population which synthesizes core protein extensively at stage 24 and stage 25 of development. This cell population synthesizes core protein predominantly at the proximal half of the limb bud at stage 24. However at stage 25 the same population synthesizes core protein predominantly at the distal half of the limb bud. These observations indicate that the distal half of stage 25 limb bud is mostly homogeneous with prechondrogenic cells and is in agreement with in vitro experiments that show high chondrogenic potential of the mesenchymal cells from this stage.

Aggrecans↗
PubMed1991

1,25-Dihydroxyvitamin D3 stimulates chondrogenesis of the chick limb bud mesenchymal cells.

Vitamin D has been known to be important for skeletal development and growth but the mechanism whereby it affects these processes is not well understood. We report now that the hormonal metabolite of vitamin D3, namely 1,25-dihydroxyvitamin D3, stimulates chondrogenesis in cultures of stage 24 chick embryo limb bud mesenchymal cells, as evidenced by morphologic changes as well as by increased transcription of collagen type II and core protein genes. This effect appears to be specific to 1,25(OH)2D3 since 24,25(OH)2D3 or D3 does not influence chondrogenesis in this system, and is probably mediated via the specific 1,25(OH)2D3 receptor protein which is undetectable in untreated cells but appears following exposure to the hormone.

Animals↗
PubMed1991

Inhibitory effects of phospholipase D on chondrogenesis in vitro.

Mesenchymal cells from the wing buds of stage 24 chick embryos undergo differentiation to cartilage when plated at high density. Treatment of these cultures with phospholipase D resulted in inhibition of chondrogenesis. Phospholipase D treatment (which produces phosphatidic acid from membrane phospholipids) was found to affect cell proliferation and to dramatically increase intracellular free calcium levels and inositol phosphate production. Intracellular free Ca2+, mobilized as a result of phosphatidylinositol phosphate hydrolysis, may therefore inhibit chondrogenesis in embryonic mesenchymal cells.

Animals↗
PubMed1991

A spontaneous melanoma-like tumor in the adult newt Triturus cristatus.

We present here a case of a spontaneous melanoma-like tumor in the adult newt Triturus cristatus, lying above the scapula. The melanized cellular mass had infiltrated the subcutaneous connective tissue. The presence of this tumor is discussed with respect to the incidence of tumors in amphibia in relation to the animals' regenerative capacity.

Animals↗
PubMed1990

Cell density dependent effect of a tumor promoter on proliferation and chondrogenesis of limb bud mesenchymal cells.

When limb bud mesenchymal cells are cultured at high density, chondrogenesis takes place in vitro. Treatment of such cultures with the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in complete inhibition of chondrogenesis as indicated from staining the cultures for proteoglycans and from RNA hybridization to cDNA probes specific for four cartilage macromolecules. The effect of TPA varied depending on the initial plating density. At high density, TPA inhibited cell proliferation. At low density, cell proliferation was stimulated by TPA and above a certain cell density, chondrogenesis took place even in the presence of TPA. These results are interpreted to mean that the effect of TPA on chondrogenesis is indirect, possibly through its influence on cell proliferation.

Animals↗
PubMed1989

Structure of the gene for cartilage matrix protein, a modular protein of the extracellular matrix. Exon/intron organization, unusual splice sites, and relation to alpha chains of beta 2 integrins, von Willebrand factor, complement factors B and C2, and epidermal growth factor.

The entire gene for chicken cartilage matrix protein (CMP) has been isolated and characterized by restriction mapping, electron microscopy, nuclease S1 mapping, and sequence analysis. The gene, which is present in a single copy in the chicken genome, is 18 kilobase pairs long and comprises eight exons and seven introns. It has two transcription initiation sites, 8 base pairs from each other. A sequence very homologous to the consensus nuclear factor III binding-site sequence, a CAT- and a TATA-like sequence are found in the promoter region and ATTAAA is used as a polyadenylation signal. The nucleotide sequence defines a primary translation product of 493 amino acids which consists of a 23-amino acid signal peptide and two large repeated domains connected by an epidermal growth factor module. Amino acid sequences homologous to those of the repeated domains are present in the type A repeats of von Willebrand factor, complement factors B and C2, and in the alpha chains of the integrins Mac-1, p150,95, and LFA-1. The exon-intron structure indicates that the CMP gene may have arisen by exon duplication and exon shuffling during evolution. The GT-AG splice rule cannot be applied for the excision of the last intron of the CMP pre-mRNA. The donor splice site of intron G is basically different from the consensus sequence indicating that a novel type of splicing mechanism might exist in cartilage.

Amino Acid Sequence↗
PubMed1989

Chaos: principles and implications in biology.

In this paper we review some of the basic principles of the theory of dynamical systems. We introduce the reader to the definition of chaos and strange attractors and we discuss their implications in biology.

Mathematics↗
PubMed1988

Modeling of the homoeo domain suggests similar structure to repressors.

The sequences of the homoeo domain containing the three alpha-helices were modeled based on secondary structure prediction, sequence homologies and coordinates of known helix-turn-helix motif containing DNA-binding proteins. The model reveals very similar three dimensional structure to repressors and suggest binding to DNA with its helix 3.

Amino Acid Sequence↗
PubMed1988

A consensus sequence in the N-terminus of exported proteins: resemblance with metal binding domains and implications in protein translocation across membranes.

By analyzing and comparing the N-terminus of several exported proteins we identified two consensus sequences that resemble metal binding domains. The consensus sequences are part of the signal peptide and part of the adjacent sequences of the mature protein. Three-dimensional modelling of one such domain suggests a conformation with implication in signal peptide insertion.

Amino Acid Sequence↗