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Biomedical subjects

A Mazabraud

Publications and source records attributed to A Mazabraud.

At least 19 recordsLinked to original sources

[Reflections on the classification validation of the most common forms of osteosarcomas by functional isotopic methods].

After noting the limits of a purely morphological approach, either the descriptive methods for classifying certain osteosarcomas, or the techniques connected with these limitations such as particularly limited or non significant sampling, the authors consider the possible contribution of new methods such as immunohistochemistry or in vivo radioisotope tests to improve osseous tumor classification. The latter methods may be particularly useful in clarifying a significant number of difficult diagnoses or in providing information on tumor location, to be combined with morphological observations regarding osteosarcomas.

Diagnosis, Differential

Germ cell-specific expression of a gene encoding eukaryotic translation elongation factor 1 alpha (eEF-1 alpha) and generation of eEF-1 alpha retropseudogenes in Xenopus laevis.

We have studied by in situ hybridization the expression of the genes encoding the somatic form and the oocyte form of Xenopus laevis eEF-1 alpha. The somatic form of eEF-1 alpha (eEF-1 alpha S) mRNA is virtually undetectable in male and female germ cells of the adult gonad but is very abundant in embryonic cells after the neurula stage. In contrast, another form of eEF-1 alpha (eEF-1 alpha O) mRNA is highly concentrated in oogonia and in previtellogenic oocytes but is undetectable in eggs and embryos. eEF-1 alpha O mRNA is also present in spermatogonia and spermatocytes of adult testis. The latter finding identifies eEF-1 alpha O mRNA as a germ cell-specific gene product. Although germ cells contain very little eEF-1 alpha S mRNA, several eEF-1 alpha S retropseudogenes exist in X. laevis chromosomes. These genes are thought to arise in germ cells from reverse transcription of mRNA and subsequent integration of the cDNA copies into chromosomal DNA. We suggest that eEF-1 alpha S pseudogenes are generated in primordial germ cells of the embryo before they differentiate into oogonia or spermatogonia.

Animals

Structural and functional properties of thesaurin a (42Sp50), the major protein of the 42 S particles present in Xenopus laevis previtellogenic oocytes.

Thesaurin a is one of two protein components of a 42 S ribonucleoprotein particle that is very abundant in previtellogenic oocytes of Xenopus laevis. The primary function of the 42 S particle is the long-term storage of 5 S RNA and aminoacyl-tRNA. Thesaurin a is homologous to eukaryotic elongation factor 1 alpha (EF-1 alpha) and to prokaryotic elongation factor Tu (EF-Tu). Sequence comparison with EF-1 alpha and EF-Tu of different species indicates that thesaurin a is rather distantly related to all eukaryotic elongation factors. In spite of this, the secondary structure of thesaurin a, deduced from hydrophobic cluster analysis, is remarkably similar to that of EF-1 alpha and EF-Tu. The binding and catalytic properties of thesaurin a are also similar but not identical to those of EF-1 alpha. Like EF-1 alpha, purified thesaurin a binds tRNA, GDP, and GTP. Unlike EF-1 alpha, thesaurin a binds discharged tRNA more tightly than charged tRNA, and GTP more tightly than GDP. Thesaurin a also hydrolyzes GTP and catalyzes the mRNA-dependent binding of aminoacyl-tRNA to 80 S ribosomes. The functional properties of the 42 S particle are in general agreement with those of purified thesaurin a. In particular, the 42 S particle contains GTP and efficiently transfers aminoacyl-tRNA to 80 S ribosomes without addition of exogenous elongation factor.

Amino Acid Sequence

Two forms of elongation factor 1 alpha (EF-1 alpha O and 42Sp50), present in oocytes, but absent in somatic cells of Xenopus laevis.

We have purified and partially sequenced the EF-1 alpha protein from Xenopus laevis oocytes (EF-1 alpha O). We show that the two cDNA clones isolated by Coppared et al. (Coppard, N. J., K. Poulsen, H. O. Madsen, J. Frydenberg, and B. F. C. Clark. 1991. J. Cell Biol. 112:237-243) do not encode 42Sp50, as claimed by these authors, but two very similar forms of EF-1 alpha O (EF-1 alpha O and EF-1 alpha O1). 42Sp50 is the major protein component of a 42S nucleoprotein particle that is very abundant in previtellogenic oocytes of X. laevis, 42Sp50 differs from EF-1 alpha O not only by its amino acid sequence, but also by several properties already reported. In particular, 42Sp50 has a low EF-1 alpha activity. It is distributed uniformly in the cytoplasm of previtellogenic oocytes, in contrast to EF-1 alpha O which is concentrated in a small region of the cytoplasm, known as the mitochondrial mass or Balbiani body.

Amino Acid Sequence

The genes encoding the major 42S storage particle proteins are expressed in male and female germ cells of Xenopus laevis.

As components of the 42S storage particles (thesaurisomes), thesaurin a and thesaurin b are involved in the long-term storage of tRNA and 5S RNA in previtellogenic oocytes of Xenopus laevis. Thesaurin a and thesaurin b are among the most abundant proteins in previtellogenic oocytes. We show here that the mRNAs encoding thesaurin a and thesaurin b are present not only in previtellogenic oocytes but also in pre-meiotic germ cells (oogonia). These mRNAs can also be detected in spermatogonia and early spermatocytes, and are translated into protein in testis, as they are in ovary. We conclude that male germ cells mimic female germ cells in several aspects of gene activity related to RNA accumulation and metabolism.

Animals

Three genes under different developmental control encode elongation factor 1-alpha in Xenopus laevis.

We have cloned cDNAs encoding two variants of the elongation factor for protein synthesis in Xenopus laevis, called EF-1 alpha. One of these (42Sp50) is expressed exclusively in immature oocytes. It is one of two protein components of a 42S RNP particle that is very abundant in previtellogenic oocytes. The 42S RNP particle consists of various tRNAs, 5S RNA, 42Sp50 and a 5S RNA binding protein (42Sp43). A major function served by 42Sp50 appears to be the storage of tRNAs for later use in oogenesis and early embryogenesis. The second EF-1 alpha variant (EF-1 alpha O) is expressed mainly in oocytes but transiently in early embryogenesis as well. Its mRNA cannot be detected after neurulation in somatic cells. EF-1 alpha O is closely related to a third EF-1 alpha (EF-1 alpha S), discovered originally by Krieg et al. (1). EF-1 alpha S is expressed at low levels in oocytes but actively in somatic cells. The latter two proteins are very similar to known eukaryotic EF-1 alpha from other organisms and presumably function in their respective cell types to support protein synthesis.

Amino Acid Sequence

Biochemical research on oogenesis. RNA accumulation in the oocytes of the newt Pleurodeles waltl.

We have compared the accumulation of 5S RNA and tRNA in oocytes of Pleurodeles waltl with the corresponding process previously studied in Xenopus laevis. 5S RNA synthesis is regulated similarly in both species since different families of 5S RNA genes are transcribed in oocytes and in somatic cells of P. waltl, as in those of X. laevis. Previtellogenic oocytes of P. waltl contain only one prominent kind of storage particles (thesaurisomes). In contrast, X. laevis oocytes of the same size contain two major classes of thesaurisomes, sedimenting at 42S and 7S. The more abundant particles found in P. waltl oocytes are homologous to the larger thesaurisomes (42S) of X. laevis, but they have a lower sedimentation coefficient and a higher tRNA/5S RNA molar ratio than their X. laevis counterparts. Small amounts of particles which we think to be homologous to the 7S particles of X. laevis are present in previtellogenic oocytes of P. waltl. Therefore, the storage function of the 7S particle protein (TFIIIA) is only marginal in this species. In X. laevis oocytes TFIIIA has a second function. It acts as a positive transcription factor involved in the developmentally regulated expression of the 5S RNA genes. In X. laevis expression of the oocyte-type 5S RNA genes is accompanied by a massive accumulation of TFIIIA. This is not the case in P. waltl.

Animals

[A case of epidermoid carcinoma developing from contact with an articular hip prosthesis].

Several cases of sarcomas which developed in contact with joint prosthetic material were reported previously. They were mostly malignant fibrous histiocytoma, but to our knowledge, no case of epidermoid carcinoma was reported. We report here one case of epidermoid carcinoma which developed in contact with a hip prosthesis. Surgery was complicated by local infection and necessitated multiple reoperations, which may be responsible for the implantation of skin cells. It is generally admitted that multiple factors contribute to the development of a tumor clone. In our patient we must take into consideration such factors as chronic infection with fistula and prosthetic material. However carcinomas, even rare, which form on fistulas appear only after many years of suppuration. The short delay between the prosthesis setting and the carcinoma onset in our patients, suggests that a cofactor may have speeded up tumor induction. This cofactor could be the platelet derived growth factor (PDGF) in the case of sarcomas appearing on bone infarcts without foreign body introduction, and possibly other tumors.

Bone Neoplasms

Solitary plasmacytoma of the spine. Long-term clinical course.

The data for 19 patients with solitary plasmacytoma of the spine were reviewed with regard to clinical course and prognosis (median follow-up, 96 months). Eight patients presented with spinal cord compression. A monoclonal immunoglobulin was initially detected in seven of 15 evaluable patients. Treatment included radiotherapy (18 of 19) and/or surgery (11 of 19) and chemotherapy (eight of 19). Spinal cord compression was reversed in every patient. The expected survival rate was 85% at 10 years after diagnosis. Local recurrence or dissemination was observed in 13 patients. It occurred within 5 years of diagnosis in 11 patients and was localized (that is, local recurrence or single bone metastasis) in eight patients. It was always associated with the appearance or an increase of the M component. Dissemination frequently had a "metastatic" pattern with no diffuse bone marrow plasmacytosis. The incidence of local recurrence (five patients) and leukemia (four patients) was high. Local recurrence and/or dissemination were significantly more frequent in patients with the M component at diagnosis than in those without it (P less than 0.05; relative risk, R = 4). The effectiveness of surgery and chemotherapy combined with radiotherapy is also discussed.

Combined Modality Therapy

Desmoid tumors in adults: the role of radiotherapy in their management.

Twenty-six adult patients with the pathologic diagnosis of desmoid tumor were treated between 1964 and 1983 at the Institut Curie in Paris with megavoltage irradiation. Twenty of these patients (76 percent) had extraabdominal tumors. Definitive surgical resection was performed on nine patients (one received preoperative radiotherapy). At last follow-up 1 1/2 to 10 years after treatment, all of the patients had no evidence of disease. Seven of the nine had follow-up examinations from 5 to 10 years after treatment. Seven patients had postoperative radiotherapy with doses from 4,700 to 6,500 rads (47 to 65 Gy) for either microscopic (three patients) or gross (four patients) residual disease. All but one patient had no evidence of disease from 2 to 8 years after treatment. Nine patients had radiotherapy for recurrent inoperable tumors and six had no evidence of disease from 3 to 20 years after treatment. Recurrences developed in three patients; outside the treatment portal in one, and the other two had received less than 5,000 rads (50 Gy). Clinical regression of tumors after treatment was slow, with complete regression taking up to 2 years. Postoperative radiotherapy with doses of at least 5,000 to 6,000 rads (50 to 60 Gy) was effective in achieving local control of inoperable or incompletely resected tumors, thus the need for repeated resections was avoided. Computerized tomography has greatly improved the assessment of tumor extension and should be used routinely before either operation or radiotherapy to obtain adequate margins and minimize the chance of missing disease.

Adolescent

[Pathological anatomy of sarcomas of the bone and soft tissue].

The different pathologic aspects of bone and soft-tissue sarcomas are discussed: usefulness of special techniques, particularly immunohistochemistry, histologic classification and grading, diagnosis of frozen sections and assessment of treatment effects, particularly of postoperative chemotherapy.

Bone Neoplasms

Thesaurin a, the major protein of Xenopus laevis previtellogenic oocytes, present in the 42 S particles, is homologous to elongation factor EF-1 alpha.

We have purified in SDS X.laevis thesaurin a (Mr 50,000) which is part of the 42 S storage particles. Its N-terminal amino acid is blocked and several peptides obtained by V8 protease treatment were purified and sequenced. As expected from one of the functional roles of the 42 S particles (tRNA binding, protection against deacylation and exchange with the ribosome), the amino acid sequence of thesaurin a was found to be closely related to that of the elongation factor EF-1 alpha. We suggest that all three proteins involved in 5 S RNA and tRNA storage in previtellogenic oocytes, TFIIIA, thesaurin a and thesaurin b, have a dual function: storage and a role in transcription or in protein synthesis.

Amino Acid Sequence

Structure and transcription termination of a lysine tRNA gene from Xenopus laevis.

Termination of RNA polymerase III transcripts commonly occurs at clusters of T residues. A T4 tract located 72 base-pairs beyond a lysine tRNA gene from Xenopus laevis serves as an efficient termination site for the tRNA(Lys) precursors synthesized from this gene in homologous cell-free extracts. Nucleotides following this T tract influence the extent of read-through transcription in vitro, but in a way that differs from Xenopus 5 S RNA termination. Only approximately 50% of the transcripts initiated in vitro extend as far as this downstream T cluster. The remainder prematurely terminate at a second T4 tract located within the gene itself. The contrasting behaviour of these two T tracts in injected oocytes indicates that termination can be influenced by more than just RNA polymerase III alone, and that different components may contribute to, or hinder, termination at these sites. Prematurely terminated tRNA(Lys) transcripts are detectable in RNA from ovary tissue but not from a kidney cell line, suggesting that read-through transcription beyond intragenic T clusters can be modulated in vivo.

Animals

[Ewing's sarcoma. Retrospective study of 108 cases with review of the literature].

108 cases of Ewing's Sarcoma are collected at the "Curie Institute" and studied by the authors using the modern Technics of electron microscopy, cytochemistry, immunohistochemistry and cytogenetics. They raise the histogenesis and etiological factors not entirely resolved yet at the light of literature review.

Diagnosis, Differential

[The role of the pathologist in the treatment of osteogenic sarcoma].

The pathologist today has an important role in the treatment of osteosarcoma. He contributes during the operation by advising about the extent of the tumour and after the operation by studying the operative specimen to assess the extent of the tumour, and, when primary chemotherapy has been used, to estimate the effectiveness of the treatment by counting the percentage of viable tumour cells so that the type of chemotherapy used subsequently can be adapted to the situation. Only trained teams can make the best use of these studies.

Humans

Classification of osteosarcoma by 85-Sr scintimetry.

The histologic type of a classical osteosarcoma may be difficult to determine because of insufficient biopsy material and polymorphism of the tumour. Since osteoformation is directly related to the differentiation and functional capacity of the tumour cells, 85-Sr scintimetry was used to evaluate osteoid formation in 90 patients with classical osteosarcoma. Measurements over an 8-day period from isotope injection revealed a separation of the lesions into three groups, with high, medium and low activity. Compared to histologic classification into osteoblastic, chondroblastic/fibroblastic, the 41 tumours classified as osteoblastic had a high 85-Sr uptake. The anaplastic lesions belonged to the group with low 85-Sr uptake. Scintimetric determination of the functional differentiation of tumoral cells may possibly be of prognostic value in osteosarcoma.

Adolescent