PubMed Health⌕ Search

Biomedical subjects

R Gongora

Publications and source records attributed to R Gongora.

At least 19 recordsLinked to original sources
PubMed2001

An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons.

Interferon-alpha and -beta inhibit the interleukin-7-mediated growth and survival of T and B lymphoid progenitors via an unknown, STAT1-independent pathway. Gene expression profile analysis of interferon-beta-treated progenitor B cells revealed enhanced Daxx expression, with concomitant Daxx protein increase and nuclear body translocation. The interferon effects included downregulation of cell cycle regulating genes and cell cycle arrest, followed by Bcl-2 downregulation and apoptosis. Daxx antisense oligonucleotides rescued the interferon-treated pro-B cells from growth arrest and apoptosis in parallel with the reduction of nuclear Daxx. These findings implicate the gene repressor function of Daxx in interferon-induced apoptosis of lymphoid progenitors.

3T3 Cells↗
PubMed2000

Stat-1 is not essential for inhibition of B lymphopoiesis by type I IFNs.

Type I IFNs, IFN-alpha, -beta, and -omega, are cytokine family members with multiple immune response roles, including the promotion of cell growth and differentiation. Conversely, the type I IFNs are potent inhibitors of IL-7-dependent growth of early B lineage progenitors, effectively aborting further B lineage differentiation at the pro-B cell stage. Type I IFNs alpha and beta function via receptor-mediated activation of a Jak/Stat signaling pathway in which Stat-1 is functionally important, because many IFN-induced responses are abrogated in Stat-1-deficient mice. To the contrary, we show here that the inhibition of IL-7-dependent B lymphopoiesis by IFN-alphabeta is unaffected in Stat-1-deficient mice. The present data indicate that the type I IFNs can activate an alternative signaling pathway in which neither Stat-1 nor phosphatidylinositol 3'-kinase are essential components.

Animals↗
PubMed1999

The 1951-98 experience of the Paris Institut Curie Radiopathology Unit: a preliminary report.

From 1 January 1951 to 30 June 1998, 696 patients presented spontaneously or were referred to the French Institut Curie Radiopathology Unit following a more or less severe accidental irradiation. Of these, 568 patients came from France, while 128 were sent by various foreign countries. The very great majority of irradiation accidents occurred in the workplace, particularly in industry. Interestingly, 'non-nuclear' industry was responsible for three times more events than the nuclear industry. While incidental irradiation of the public by lost radioactive sources was exceedingly rare in France, it seemed to be more frequent in our cohort of foreign patients. Radiation phobia accounted for about 10% of cases in the French cohort, but the number of cases did not seem to increase with time. Overall, the accrual of patients over time appears to be stable, with 10 to 25 new cases consulting each year. Fortunately, a majority of cases corresponded to low-level irradiation (and even no irradiation at all). In the French cohort, only 21.6% of patients, showing deterministic effects, required some form of treatment, with 4.9% considered as 'severe' cases. Not unexpectedly, more patients required treatment in the foreign cohort (35.2%), with 24.2% of severe cases, including four deaths. The main features of this database are consistent with the data previously reported by the IAEA, UNSCEAR and REAC/TS. Although the number of severe cases is small, it should still be considered to be too high, especially as most of these accidents could have been easily avoided if a few basic radioprotection rules had been fully respected.

Accidents, Occupational↗
PubMed1998

Independent duplications of Bf and C3 complement genes in the zebrafish.

As part of an ongoing project aimed at the characterization of the MHC system in bony fishes, we have attempted to identify the class III region in the zebrafish (a teleost), a region that in higher vertebrates contains genes coding for complement proteins C2, Bf and C4. We obtained several genomic PAC clones by hybridization with a zebrafish Bf probe, previously identified in our laboratory, and searched these for the presence of other class III genes. We were able to obtain a second Bf-like gene, however, we were unable to detect any C2- or C4-like genes. By using highly degenerated primers, we extended our search to a hepatopancreas cDNA library and amplified from it clones corresponding to three different C3-like genes, and also the Bf genes, but not any C2- or C4-like genes. The zebrafish therefore contains two Bf and three C3 loci but apparently no C2 and C4 loci. Independent duplications of the Bf and C3 genes in bony fishes suggest that complement plays a prominent part in the immune response of this class of vertebrates.

Amino Acid Sequence↗
PubMed1997

Complex origin of the HLA-DR10 haplotype.

The region of the HLA complex occupied by the DRB genes has undergone many rearrangements in the course of primate evolution. The rearrangements have produced a number of haplotypes differing from one another in the number and composition of the DRB genes. Some of the rearrangements also affected the DRB genes themselves. Selective intron sequencing has revealed the DR10 haplotype to be composed of at least three segments, each of different origin. The haplotype carries three DRB genes (gene fragments): DRB1*10, DRB6, and DRB9. The 5' end of the DRB1*10 gene, from the promoter region to a site in intron 1 approximately 500 bp from the beginning of exon 2, is derived from a DRB1*03-like gene. The segment of the DR10 haplotype encompassing the rest of the DRB1*10 gene and extending to the region between the DRB1 and DRB6 genes is of independent origin; it diverged from other DRB genes (DRB1*01 and DRB1*03) approximately 30 million years ago. Finally, the third segment encompassing the remainder of the DR10 haplotype is derived from a DR1-like haplotype. Since the functional part of the DR10 haplotype is of independent origin, there is little justification for the currently common practice of placing the haplotype together with DR1 in the group of DR1 haplotypes. The rearrangements in the DR haplotypes may constitute one of several mechanisms for increasing diversity at the DRB loci. The region of high instability seems to be flanked by conservatively evolving regions.

Base Sequence↗
PubMed1997

HLA-DRB9--possible remnant of an ancient functional DRB subregion.

The DRB subregion of the HLA complex contains, in addition to the functional genes, a number of pseudogenes and gene fragments. Fourteen kilobases of DNA were sequenced from the segment upstream of the DRB9 gene fragment, as well as shorter segments from different HLA and corresponding ape haplotypes. The analysis of the sequences and restriction fragments indicates that the segment is a remnant of an ancient DRB subregion which may have been functional before the primate radiation and which later became the source of extant functional DRB genes in various primate groups, different ones in different groups. The remnant segment has remained constant in its organization for at least 4 million years. This constancy contrasts with the variability of the adjacent functional part of the DRB subregion occupied by the DRB1 and other loci. The constancy may be related to the monomorphism and evolutionary conservation of the DRA locus.

Base Sequence↗
PubMed1996

The HLA-DRB9 gene and the origin of HLA-DR haplotypes.

HLA-DRB9 is a gene fragment consisting of exon 2 and flanking intron sequences. It is located at the extreme end of the DRB subregion, whose other end is demarcated by the DRB1 locus. We sequenced approximately 1400 base pairs of the segment encompassing the DRB9 locus from eight human haplotypes (DR1, DR10, DR2, DR3, DR5, DR6, DR8, and DR9, the DR4 and DR7 having been sequenced by others earlier), as well as two chimpanzee, five gorillas, one orangutan and one macaque haplotype. The analysis of these sequences indicates that the DRB9 locus, which we estimate to be more than 58 million years (my) old, has been coevolving with the DRB1 locus for the last 4.2 my. As a consequence of this coevolution, the human DRB9 alleles fall into groups that correlate with the DRB1 allelic groups and with the gene organization of the human haplotypes. This observation implies that the present-day HLA-DR haplotype groups (DR1, DR51, DR52, DR8, and DR53) were founded more than 4 my ago and have remained intact (barring minor internal rearrangements that did not recombine the DRB1 and DRB9 genes) for this period of time. The haplotypes have been transmitted during speciations from ancestral to emerging species just like allelic lineages at the DRB1 locus. Thus not only allelic but also haplotype polymorphism evolves trans-specifically.

Animals↗
PubMed1995

A new 123I-MIBG whole body scan scoring method--application to the prediction of the response of metastases to induction chemotherapy in stage IV neuroblastoma.

A new semi-quantitative scoring system is proposed, especially designed for the comparative interpretation of sequential whole-body meta-iodo-benzyl-guanidine (MIBG) scans in stage IV neuroblastoma children. This method was applied to assess whether MIBG scan at mid-course of induction chemotherapy could predict the final response. 27 newly diagnosed children were investigated by three sequential 123I-MIBG scans performed at the beginning, at mid-course (6 weeks) and at the end of neoadjuvant chemotherapy (12 weeks). Whole body scans were divided into nine regions in which the extension of bone metastases was separately quoted (score range: 0-3). The overall absolute scores were obtained by adding the scores of the nine regions. Relative scores were calculated by dividing the absolute score at each time by the corresponding pretreatment score. The score at mid-induction correctly predicted the overall response of metastases at the end of induction (P < 0.0001) in most cases. This method is easy to use, reproducible, subject to little inter-investigator variation, and thus well adapted to multicentric trials.

3-Iodobenzylguanidine↗
PubMed1990

Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients.

Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a. Numerical analysis of the scintigraphic records demonstrated that the main organs of elimination were the kidneys, when the calculation was made on the basis of surface area. On the other hand, the apparent total uptake by liver (whose projection surface--i.e. the area exposed to the lens--is greater) was higher, reaching about 25 to 30% of the injected dose. The projection surface of the tumour was able to take up radiolabelled interferon in both cases, resulting in a 4-fold increase in the external radiation count compared with the equivalent region of the contralateral limb (although it is not possible to determine whether the label is present on the tumour itself or on the surrounding inflammatory cells). Thus, interferon-alpha seems able to reach at least the immediate neighbourhood of osteosarcoma mass.

Adult↗
PubMed1988

[Radioisotopic exploration of sarcomas of the bone and soft tissue].

Radioisotopic methods are widely applied to investigations of bone sarcoma and soft tissue neoplasms. We have at our disposal molecules with osseous, tumoral or vascular tropism. Their use, as single agents or combination, is helpful in positive and differential diagnosis and provides nosological informations. They are also useful in treatment monitoring and in long-term follow-up.

Bone Neoplasms↗
PubMed1986

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↗
PubMed1984

[Comparative statistical study of global and local functional respiratory data in 2 groups of patients with pulmonary or pleural tuberculosis].

Two groups of patients with unilateral tuberculosis, either pulmonary (36 cases) or pleural (75 cases) were studied. The clinical and functional results were compared statistically. These two groups were similar in terms of age, sex, tobacco consumption, the radiological unilaterality of their disease and the global reduction of respiratory function (assessed by VC, FEV1, TPC and TLCO), which can be considered to be essentially due to the local disease. In both groups, the radiological image (extent of the lesion, shape of the lesion) is the only clinical factor statistically related to the functional values. The two groups differ in terms of two functional parameters which reflect different pathophysiological mechanisms in the affected lung. The group with pulmonary tuberculosis presents an obstructive ventilatory syndrome (reduction of the FEV1/VC ratio and increase in the RV/TPC ratio), which reflects the bronchial involvement in the disease. The group with pleural tuberculosis presents a pulmonary distention (increased RV/TPC ratio), which is related to disturbed transmission of the pleural pressure to ventilated alveolar zones. Secondly, in the group with pulmonary tuberculosis, the ventilation and perfusion deficits are equivalent, while in the pleural tuberculosis group, the ventilatory deficit is predominant. Thus the global reduction in ventilatory function which is the same in the two group is caused by fundamentally distinct pathophysiological mechanisms in the two groups of patients.

Adult↗
PubMed1982

[Value of the study of the kinetics of 85 strontium for the classification of osteogenic sarcomas ].

Because of the polymorphism of osteogenic sarcomas, examination of a biopsy specimen, which is necessarily small, cannot give an accurate evaluation of the differentiation of the whole tumor. Therefore, a test which provides an overall assessment of the functional capacity of the tumor is needed. For the last ten years, we have been using 85 strontium, which has a metabolism similar to that of calcium and radioactive characteristics that allow external measurements. With this isotope, classification of osteogenic sarcomas is more accurate, ensuring better therapeutic trials.

Adult↗
PubMed1982

[An experimental model of osteosarcomas in rats ].

Satisfactory experimental models for preclinical prediction in cancerology must answer the following criteria: reproducibility of the method used for inducing tumors; clinical, pathological and kinetic similarity with the corresponding human tumors. We have developed a model of osteosarcoma locally induced by insoluble radioactive cerium chloride (144Ce CI3) in Sprague Dawley rats. This method yields over 80% of bone tumors at the injection site, of which approximately half are histologically similar to human tumors. These tumors double their volume fairly slowly (in approximately 20 days); lung metastases occur both early and frequently (80% of animals). A transplantable tumor was developed from an induced osteosarcoma and adapted to the Curie strain. Transplantation in the bone, next to the bone, or under the skin is followed by widespread metastatic dissemination. The kinetics and histological features of the primary tumor are maintained. Tumor 85 strontium uptake is similar to that seen in human osteosarcomas. These new models of osteosarcomas are being used for evaluating new cancer chemotherapeutic agents and interferon, etc.

Animals↗