PubMed Health⌕ Search

Biomedical subjects

D Toman

Publications and source records attributed to D Toman.

7 recordsLinked to original sources
PubMed2001

delta Ef1 binds to a far upstream sequence of the mouse pro-alpha 1(I) collagen gene and represses its expression in osteoblasts.

The transcription of type I collagen genes is tightly regulated, but few cis-acting elements have been identified that can modulate the levels of expression of these genes. Generation of transgenic mice harboring various segments of the mouse pro-alpha1(I) collagen promoter led us to suspect that a repressor element was located between -10.5 and -17 kilobase pairs. Stable and transient transfection experiments in ROS17/2.8 osteoblastic cells confirmed the existence of such a repressor element at about -14 kilobase pairs and showed that it consisted in an almost perfect three-time repeat of a 41-base pair sequence. This element, which we named COIN-1, contains three E2-boxes, and a point mutation in at least two of them completely abolished its repressor effect. In gel shift assays, COIN-1 bound a DNA-binding protein named delta EF1/ZEB-1, and mutations that abolished the repressor effect of COIN-1 also suppressed the binding of delta EF1. We also showed that the repressor effect of COIN-1 was not mediated by chromatin compaction. Furthermore, overexpression of delta EF1 in ROS17/2.8 osteoblastic cells enhanced the inhibitory effect of COIN-1 in a dose-dependent manner and repressed the expression of the pro-alpha 1(I) collagen gene. Thus, delta EF1 appears to repress the expression of the mouse pro-alpha 1(I) collagen gene, through its binding to COIN-1.

Animals↗
PubMed2000

[Voice disorders in children with gastroesophageal reflux disease].

The study concerns 11 patients with gastroesophageal disease confirmed by pH-metric examination of esophagus. The clinical assessment included lupolaryngoscopy, stroboscopy and acoustic analysis of voice. Basing on the tests there were confirmed inflammatory lesions at the posterior part of larynx (laryngitis posterior) as well as pathological changes of voice acoustic tests.

Adolescent↗
PubMed1999

[Hormonal conditioning of vocal changes in male].

Porophonia pubertum is the change of voice following activation of gonads in puberty. The present paper shows disorders of porophonia pubertum in 3 boys. The objective of the paper was to explain the pathogenesis of these disorders. Basing on clinical and genetic tests, a non-physiological, high position of spoken voice typical for the prolonged porophonia pubertum was proved. The genetic test confirmed the male sex. However, hormonic tests proved a significantly increased level of estradiol. We suppose that excessively increased estradiol level in blood serum caused the porophonia pubertum disorders in our patients.

Adolescent↗
PubMed1991

Reduced amounts of cartilage collagen fibrils and growth plate anomalies in transgenic mice harboring a glycine-to-cysteine mutation in the mouse type II procollagen alpha 1-chain gene.

We have generated transgenic mice harboring a glycine-to-cysteine mutation in residue 85 of the triple helical domain of mouse type II collagen. The offspring of different founders displayed a phenotype of severe chondrodysplasia characterized by short limbs and trunk, cranio-facial deformities, and cleft palate. The affected pups died of acute respiratory distress caused by an inability to inflate lungs at birth. Staining of the skeleton showed a severe retardation of growth for practically all bones. Light microscopic examination indicated a decrease in cartilage matrix density, a severe disorganization of growth plate architecture, and the presence of streaks of fibrillar material in the cartilage matrix. Electron microscopic analysis showed a pronounced decrease in the number of typical thin cartilage collagen fibrils, distension of the rough endoplasmic reticulum of chondrocytes, and the presence of abnormally large banded collagen fibril bundles. The level of expression of the mutant type II procollagen alpha 1 chain transgene in cartilage tissues was approximately equal to that of the endogenous gene in two of the strains. We propose that the principal consequence of the mutation is a considerable reduction in density of the typical thin cartilage collagen fibrils and that this phenomenon causes the severe disorganization of the growth plate. We also postulate that the abnormal thick collagen fibrils are probably related to a defect in crosslinking between the collagen molecules. The cartilage anomalies displayed by these transgenic mice are remarkably similar to those of certain human chondrodysplasias.

Animals↗
PubMed1991

Mouse type II collagen gene. Complete nucleotide sequence, exon structure, and alternative splicing.

Several overlapping clones covering the entire mouse type II collagen gene including 10 kilobases (kb) of 5'- and 15 kb of 3'-flanking sequences were isolated from a cosmid library. The overall gene structure was determined by restriction mapping and sequencing. The gene spans 28.9 kb from the start of transcription to the polyadenylation site and contains 54 exons. It codes for a major mRNA species of 4910 bases which translates into a polypeptide of 1419 amino acids. A less abundant RNA species of 5110 bases contains additional sequences corresponding to an alternatively spliced exon 2. Except for the amino-terminal propeptide (N-propeptide) domain the exon-intron organization of the mouse pro alpha 1(II) collagen gene is remarkably similar to genes for other fibrillar collagen types. The overall identity of the coding sequences of the mouse and human type II collagen genes is 89% at the nucleotide level, but only 37 amino acid changes occur within the mature alpha 1(II) collagen chains between mouse and man. Intron sizes are also conserved between the mouse and human genes but not with the chick alpha 1(II) gene. The promoter of the mouse type II collagen gene is similar to those of the rat and human genes containing a TATA box and several G + C-rich elements but no CCAAT box. The 3'-untranslated sequence contains two regions of high homology between chick, mouse, bovine, and human genes preceding the major polyadenylation site. Additional size variation in the mRNA arises from the use of a minor polyadenylation signal. Information on conserved noncoding sequences will help in studies on the regulation of the pro alpha 1(II) collagen gene. Detailed knowledge of the gene is also necessary for site-directed mutagenesis and work with transgenic mice.

Amino Acid Sequence↗
PubMed1991

Specific hybridization probes for mouse type I, II, III and IX collagen mRNAs.

We have constructed DNA probes for the specific detection of mouse pro alpha 1(I), pro alpha 1(II), pro alpha 1(III) and alpha 1(IX) collagen transcripts. To avoid cross-hybridization the probes for fibrillar collagens cover mainly sequences in the 3' untranslated region of the gene. Sequencing and Northern analysis confirmed that the clones share minimal sequence similarity and detect only the specific mRNAs under normal hybridization and washing conditions. The clone for mouse alpha 1(IX) collagen covers coding sequences but is sufficiently divergent from other collagen transcripts to allow specific detection of the corresponding mRNA.

Amino Acid Sequence↗