Biomedical subjects

T Mattei

Publications and source records attributed to T Mattei.

5 recordsLinked to original sources

PubMed2006

Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets.

Medulloblastoma (MB) results from aberrant development of cerebellar neurons in which altered hedgehog (Hh) signalling plays a major role. We investigated the possible influence of Hh signalling on ErbB-receptor expression in MB, in particular that of the ErbB-4 CYT-1 and CYT-2 isoforms generated by alternative splicing of the cytoplasmic domain. ErbB-4 expression was downregulated in Hh-induced MBs from Patched-1(+/-) mice. Hh signalling (reflected by enhanced expression of the Gli1 transcription factor) inhibited ErbB-4 expression in mouse cerebellar granule progenitors and human MB cells. Analysis of 26 human primary MBs revealed a subset of 11 tumors characterized by low Gli1 levels, upregulated ErbB-4 expression and increased CYT-1:CYT-2 ratios. Interestingly, CYT-1 and Gli1 levels were inversely correlated. ErbB-4 CYT-1 and CYT-2 had different phenotypic effects in cultured MB cells: in response to neuregulin treatment, CYT-2 overexpression inhibited proliferation whereas CYT-1, which includes a phosphatidylinositol 3-kinase (PI3K)-binding site that is missing in CYT-2, enhanced resistance to starvation- and etoposide-induced apoptosis by activating PI3K/Akt signalling. CYT-1:CYT-2 ratios displayed correlation with tumor histotype and ErbB-2 levels, which are established prognostic indices for MB. These findings demonstrate that low-level Hh signalling in human MB is associated with the selective maintenance of high ErbB-4 CYT-1 expression, an alteration that exerts tumor-promoting effects.

Alternative Splicing↗

PubMed1998

Structural features of force-generating cross-bridges. A 2D-X-ray diffraction study.

In several concepts of muscle contraction it was proposed that during force generation cross-bridges assume a rigor-like conformation. However, so far 2D-X-ray diffraction patterns recorded during isometric contraction did not reveal structural features of rigor-like cross-bridges. It was therefore supposed that the number of force generating cross-bridges in isometric steady state contraction is too low to be detected in 2D-X-ray diffraction patterns. To test this concept we studied the features of 2D-X-ray diffraction patterns of different fractions of rigor-like cross-bridges by varying the concentration of the nucleotide analog ATP gamma S at high [Ca++]. Although we had a fully activated system, i.e., that weak binding cross-bridges were attached to the activated thin filament, none of the patterns was like the active pattern. Analysis of the intensity change of the actin layer lines at 1/370 A-1 and at 1/59 A-1 in diffraction patterns recorded during isometric contraction vs. relaxed and rigor conditions as well as mechanical experiments revealed that the fraction of force generating cross-bridges apparently is as high as 55-70%. Yet, in agreement with previous studies, in spite of this large fraction of force generating cross-bridges, no rigor-like features were detected in diffraction patterns recorded during isometric contraction. Moreover, the intensity distribution along the actin layer lines was clearly different in rigor compared to isometric contraction. Taken together these results provide evidence that in contrast to the above mentioned models the majority of the force generating cross-bridges seems to be in a conformation which is different from rigor.

Adenosine Triphosphate↗

PubMed1991

Environmental impact of the Chernobyl accident: mutagenesis in bank voles from Sweden.

An investigation was carried out in Sweden aimed at studying the possible genetic effects of the Chernobyl fallout on wild small mammals. The bank voles (Clethrionomys glareolus Schreb.) were obtained from three differently contaminated areas in Sweden and, for control, in an area with negligible contamination by fallout. Radionuclide determinations to assess the content of 137Cs and mutagenicity tests (bone marrow micronucleus test and sperm abnormality assay) were performed. The results obtained showed a positive correlation between the increase of micronucleated polychromatic erythrocytes (MPCE/1000 PCE) and both 137Cs content in muscle and in soil contamination. The estimated doses absorbed by the animals were far lower than those required for the same effect in laboratory experiments. An explanation of this discrepancy between dose and measured biological effect is not available, yet similar results have been repeatedly reported after the Chernobyl accident and should be a matter for further discussion. An increased frequency of micronucleated cells might occur at minimal dose gradients, and the micronucleus test appears to be a valid tool to show such effects.

Accidents↗

PubMed1990

Small mammals as biological indicators of radioactive contamination of the environment.

An investigation was carried out in Sweden aimed at studying the contamination of small mammals (orders Rodentia and Insectivora) following the Chernobyl accident. The animals were captured in three differently contaminated areas in Sweden and, for control, in an area with negligible fallout. The results obtained show that the activity in the captured animals was correlated with surface deposition. The differences between the species investigated and the influence of feeding habits on the contamination levels are discussed.

Accidents↗

PubMed1990

137Cs determination and mutagenicity tests in wild Mus musculus domesticus before and after the Chernobyl accident.

Wild rodents were collected alive in a suburban area to the north of Rome before, during, 6 months and 1 year after the Chernobyl accident. Radionuclide determinations to assess their content of (137)Cs and mutagenicity tests (bone-marrow micronucleus test and sperm abnormalities assay) were performed on the captured animals. The results obtained for the species Mus musculus domesticus (which was the rodent captured in highest numbers), compared with the results obtained before the fallout, showed an increase of both micronucleated polychromatic erythrocytes (MPCEs/1000 PCEs) and (137)Cs content during and after the fallout.

Journal Article↗