Biomedical subjects

C Gelinas

Publications and source records attributed to C Gelinas.

9 recordsLinked to original sources

PubMed2001

Regulation of estrogenic and nuclear factor kappa B functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells.

The natural polyamines -putrescine, spermidine, and spermine- are essential for cell growth and differentiation. Polyamines are involved in several gene regulatory functions, although their mechanism(s) of action has not been elucidated. We investigated the role of polyamines in the function of NF-kappa B and estrogen receptor-alpha (ER alpha), two transcription factors implicated in breast cancer cell proliferation and cell survival, using MCF-7 breast cancer cells. We found that spermine facilitated the binding of ER alpha and NF-kappa B to estrogen response element (ERE)- and NF-kappa B response element (NRE), respectively, and enhanced ER alpha-mediated transcriptional activation in transient transfection experiments. We also found that the association of the co-regulatory protein CBP/p300 with ER alpha and NF-kappa B was increased by spermine treatment of MCF-7 cells. Spermine also increased the nuclear translocation of NF-kappa B compared to the control. In contrast, treatment of MCF-7 cells with polyamine analogs, BE-3-4-3 and BE-3-3-3, resulted in transcriptional inhibition of both ERE- and NRE-driven reporter plasmids. In addition, polyamine analogs inhibited the association of ER alpha and NF-kappa B with CBP/p300 and were unable to facilitate nuclear translocation of NF-kappa B. APO-BRDU assay demonstrated that polyamine analogs induced apoptosis, with a loss of the anti-apoptotic protein Bcl-2. These data show a gene regulatory function of polyamines involving transcriptional activation of ER alpha and NF-kappa B, potentially leading to the up-regulation of genes involved in breast cancer cell proliferation. Our results with BE-3-4-3 and BE-3-3-3 suggest that down-regulation of ER alpha- and NF-kappa B-regulated genes is a possible mechanism for the action of polyamine analogs in inducing apoptosis of breast cancer cells.

Apoptosis↗

PubMed1999

Occipitocervical neutral position. Possible surgical implications.

STUDY DESIGN: The study defines the occipitocervical neutral position using cervical radiographs from 30 subjects. OBJECTIVE: To identify reproducible radiographic measures of the occipitocervical neutral position that can be used during surgery to optimize fusion position. SUMMARY OF BACKGROUND DATA: When performing rigid internal fixation of the occiput to the cervical spine, the ability to determine that the occiput is in a neutral position in relation to the cervical spine is important. Currently, no objective radiographic measures for the occipitocervical neutral position exist. METHODS: Thirty flexion, extension, and neutral lateral cervical spine radiographs radiographs interpreted as normal by an experienced radiologist were studied. The occipitocervical angle and occipitocervical distance were defined and calculated. Two investigators, an orthopedic resident and an experienced orthopedic spine surgeon, measured the occipitocervical angle and occipitocervical distance independently on all radiographs in a blinded manner. Correlation coefficients were obtained to determine interobserver reliability. RESULTS: The mean occipitocervical angles were 24.2 degrees, 44.0 degrees, and 57.2 degrees in flexion, neutral, and extension, respectively. The mean occipitocervical distances were 21.5 mm in neutral, 28.0 mm in flexion, and 14.8 mm in extension. The differences in the occipitocervical angle and occipitocervical distance in neutral, flexion, and extension were statistically significant (P < 0.05 and < 0.001, respectively). There were no significant interobserver differences in any of the measurements. CONCLUSIONS: The radiographic measures of the occipitocervical neutral position reported in this study are reliable, repeatable, and simple to determine on routine lateral radiographs. These measurements should be a valuable intra-operative tool for achieving occipitocervical fusion in appropriate alignment.

Adult↗

PubMed1991

Auditory lateralization for speech in language-impaired children.

The ability of five language-impaired (LI) children and five matched controls, aged 7-10 years, to discriminate natural pairs of consonant-vowel syllables contrasted on place of articulation and voicing, presented to the right or left ear with white noise in the contralateral ear, was investigated. The general pattern of errors indicated that LI children had more difficulty than controls in discriminating place of articulation contrasts only when they were presented to the left ear, as well as a difficulty in discriminating voice contrasts selective to the right ear. The results are discussed in terms of acoustic integration and suggest that bihemispheric dysfunction is a basis for specific language impairment.

Aphasia↗

PubMed1989

Mutations in polyomavirus middle T antigen affecting tumorigenesis.

P155 is a polyomavirus mlt mutant with normal transforming ability but impaired tumorigenic potential. The mutation, a 12-bp deletion (nucleotides 1348-1359), removes amino acids 372 to 375 from middle T and affects its ability to function in tumorigenesis (C. Gelinas, S. Masse, and M. Bastin, 1984, J. Virol. 51, 242-246). We used deletion loop mutagenesis to introduce point mutations within the wild-type sequence spanned by the P155 deletion. A mutant phenotype resembling that of P155 could be produced by as little as one alanine to valine substitution at residue 373. The mutants were impaired in their ability to induce tumors in rats but they could still transform established cell lines or primary fibroblasts in culture. To define the biochemical defect, we examined the mutant middle T antigen both for association with pp60c-src, the cellular src gene product, as well as its pattern of phosphorylation. No obvious differences explaining the phenotype were observed. The mutant middle T associated with, and activated pp60c-src, but exhibited a slightly altered pattern of phosphorylation, presumably because of additional sites on the middle T protein.

Animals↗

PubMed1984

Tumorigenic activity of polyoma virus and SV40 DNAs in newborn rodents.

A procedure has been developed whereby the oncogenicity of the DNA from polyoma (Py) virus and Simian virus 40 (SV40) can be tested directly by injecting recombinant DNA into newborn rodents. Injection of 0.2-2.0 micrograms of linear DNA induced the development of subcutaneous liposarcomas and fibrosarcomas at the site of inoculation. Coinjection of high-molecular-weight rat DNA as carrier had little or no effect on tumor formation but plasmids pBR322, pAT153 , and pML2 behaved as strong inhibitors. Tumor induction by injecting DNA into newborn rodents provides an in vivo equivalent to a transformation assay but appears to be a more stringent and rigorous criterion of oncogenic transformation. The oncogenic potential of Py virus in newborn hamsters could be expressed by a recombinant encoding only the middle T protein, although with average tumor latencies 5-10 times longer than those observed with wild-type Py DNA. Py middle T required the cooperation from small T to induce tumors in newborn rats. SV40 DNA was tumorigenic only in newborn hamsters. delta 2005 DNA which is unable to produce the SV40 small T antigen was much less active and required a latent period about twice that of wild-type SV40 DNA. However, its tumorigenic potential was restored by addition of the Py small T antigen gene. This indicates that Py and SV40 small T antigens are interchangeable and that they probably play an identical role in malignant transformation. Finally, evidence was provided that intermolecular recombination or recombination between DNA fragments can occur in vivo.

Animals↗

PubMed1984

mlt Mutation in the polyomavirus genome impairing a function of the middle T protein.

The DNA from polyomavirus mlt mutant P155 transforms cells in culture as efficiently as wild-type DNA but has a much lower tumorigenic potential when injected into newborn rodents. The mutant has a 12-base-pair deletion between nucleotides 1347 and 1360, i.e., in a region which encodes parts of the middle and large T antigens (G elinas et al., J. Virol. 43:1072-1081, 1982). To determine which of the two viral gene functions was affected by the mutation, we transferred the latter into a modified polyomavirus genome encoding exclusively the middle T protein. Our results show that the P155 mutation alters a function of the polyomavirus middle T protein required for the induction of the tumorigenic process in vivo. Beside the 12-base-pair deletion at 96.3 map units, there is no other alteration in the coding sequence of P155 middle T with respect to that of P16, the wild-type parental strain. We conclude, therefore, that the deletion is the lesion affecting the tumorigenic potential of mutant P155 .

Amino Acid Sequence↗

PubMed1983

Role of the three polyoma virus early proteins in tumorigenesis.

A modified polyoma virus genome which can encode the middle T protein but not the large or small T proteins transforms rat cells in culture with an efficiency about 20% that of the wild-type genome. Although middle T-transformed cells grow as tumors when transplanted into nude mice or syngeneic rats, the middle T gene alone is totally inactive when used in a more stringent and rigorous assay for tumorigenicity such as the injection of DNA into newborn rats. Thus, functions other than those expressed by middle T antigen are required for the elaboration of all the properties associated with tumorigenesis. To assess whether a complementary function could be exerted by the large or the small T antigen, we constructed plasmids containing two modified early regions which independently encoded middle T and one of the two other proteins. Both recombinants were tumorigenic in newborn rats. Cell lines derived by transfer of these plasmids under no special selective conditions did not acquire the property of growth in low-serum medium but exhibited the same tumorigenic properties as wild-type polyoma DNA-transformed cells. Furthermore, a recombinant which encoded the middle and small T antigens, but not the large T antigen, was tumorigenic in newborn rats. Although the small T antigen provides a complementary function for tumorigenicity, it cannot complement the middle T antigen for an efficient induction of transformation of cultured cells. This suggests that the complementary function exerted by the small T antigen is different from that of the N-terminal fragment of the large T protein.

Animals↗

PubMed1982

Polyoma virus mutant with normal transforming ability but impaired tumorigenic potential.

Cloned DNA from the P155 mutant of polyoma virus transforms cells in culture as efficiently as wild-type DNA, but has a much lower tumorigenic potential when injected into newborn rats. Like cells transformed by wild-type DNA, cells transformed by the mutant DNA grow in low serum concentrations, form colonies in agar suspension, and grow to high saturation densities compared with untransformed cells. They are, however, much less tumorigenic since they transplant 100- to 2,000-fold less efficiently than cells transformed by wild-type DNA. Substitution of the region between 89.7 and 1.8 map units by the corresponding region of P155 DNA decreased the tumorigenicity of wild-type DNA. When this region was isolated from wild-type DNA and substituted in P155 DNA, the tumorigenicity of the latter increased to values comparable to those of wild-type DNA. This showed that the lesion affecting tumorigenicity occurred between 89.7 and 1.8 map units on the polyoma virus genome. Sequence analysis in this region revealed a 12-base-pair deletion between nucleotides 1,347 and 1,360. This identified P155 as an mlt mutant, i.e., a mutant with a deletion from a region which encodes parts of the large and middle T antigens.

Animals↗

PubMedDate not supplied

Comparison of lateral pillar classification and Catterall classification of Legg-Calvé-Perthes' disease.

To compare the predictive value of the Herring lateral pillar and the Catterall classifications of Legg-Calvé-Perthes' disease, 71 hips with radiographic follow-up to maturity were reviewed. The Herring classification was a significantly better predictor of Stulberg outcome than the Catterall classification. Three independent observers classified early fragmentation stage films by both Herring and Catterall classifications. The interobserver reliability of the Herring classification was significantly better than the reliability of the Catterall measure.

Hip Joint↗