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J P Bureau

Publications and source records attributed to J P Bureau.

At least 19 recordsLinked to original sources

Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro. Distribution of peripheral blood T lymphocytes and cell cycle progression.

In transplanted mice, the P388 tumor grew better in castrated than in non castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small tumor tissue (<10 mg). The correlation observed between the tumor weight and T cell subset in PBL and in the mice with small tumors could confirm the important intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone (DT) injection reduced strongly weight and tumor growth in mice. On top of that, DT administration induced a significant increase in the percentage of blood CD8+ cells in grafted mice. The effect of DT was studied on the cell cycle progression, in tumor tissue of P388 tumor bearing BDF1 mice and in P388 murine leukemia cell line in culture. The cell cycle analysis in tumor tissue showed that DT decreased both the cells in S phase and the proliferating leukemic cells, with accumulation of cells in G0/G1 phase. The testosterone can inhibit the proliferation of leukemic cells with a pharmacological dose (10(-7) M). This growth inhibition, dose and time dependent, was associated with cell cycle arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation between tumor weight and the percentage of cells in G0/G1 and the relative number of cells in proliferative state (S + G2/M). To conclude, our experiments reported that testosterone prevents the growth of tumor: indirectly by modulation of subsets T cells distribution and directly by the alteration of the cell cycle.

Animals↗

Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro. Distribution of peripheral blood T lymphocytes and cell cycle progression.

In transplanted mice, the P388 tumor grew better in castrated than in non castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small tumor tissue (<10 mg). The correlation observed between the tumor weight and T cell subset in PBL and in the mice with small tumors could confirm the important intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone (DT) injection reduced strongly weight and tumor growth in mice and DT administration induced a significant increase in the percentage of blood CD8+ cells in grafted mice. The effect of DT was studied on the cell cycle progression, in the tumor tissue of P388 tumor bearing BDF1 mice and in the P388 murine leukemia cell line in culture. The cell cycle analysis showed that DT decreased both the cells in S phase and the proliferating leukemic cells, with accumulation of the cells in G0/G1 phase. The testosterone can inhibit the proliferation of leukemic cells with a pharmacological dose (10-7 M). This growth inhibition dose and time dependent was associated with cell cycle arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation between tumor weight and the percentage of cells in G0/G1 and the relative number of cells in proliferative state (S + G2/M). Our experiments showed that testosterone prevents the growth of tumor: indirectly by modulation of subsets T cells distribution and directly by alteration of the cell cycle.

Animals↗

Plasma proteasome level is a potential marker in patients with solid tumors and hemopoietic malignancies.

BACKGROUND: Proteasomes are nonlysosomal proteolytic structures that have been implicated in cell growth and differentiation. Abnormal expression levels of proteasomes have been described in tumor cells, and proteasomes can be detected and measured in plasma. The objective of this study was to characterize differences in proteasome levels between normal, healthy donors and patients with neoplastic disease and to correlate the findings with clinical status and other biologic markers of disease spread. METHODS: Plasma proteasome levels were measured using a sandwich enzyme-linked immunosorbent assay in normal donors (n = 73 donors) and in patients with solid tumors (n = 20 patients), acute leukemia (n = 35 patients), myeloproliferative (n = 37 patients) and myelodysplastic (n = 19 patients) syndromes, chronic lymphocytic leukemia (n = 44 patients), non-Hodgkin lymphoma (n =104 patients), Hodgkin disease (n = 14 patients), other lymphoid disorders (n = 17 patients), and multiple myeloma (n = 27 patients). RESULTS: In the normal donors, the plasma proteasome concentration was 2356 ng/mL +/- 127 ng/mL. Patients with solid tumors exhibited a significantly higher value (7589 ng/mL +/- 2124 ng/mL), similar to the patients with myeloproliferative (4099 ng/mL +/- 498 ng/mL) and myelodysplastic (2922 ng/mL +/- 322 ng/mL) syndromes. Patients with lymphoproliferative disorders, in contrast, had significantly lower values than normal donors (1751 ng/mL +/- 107 ng/mL), except those in aggressive phase of the disease. This low level persisted in patients who were in complete remission. Proteasome levels decreased during the initial phase of treatment. Although there was a significant correlation with serum lactic dehydrogenase levels, frequent discrepancies were noted. There was no correlation with C-reactive protein or beta2-microglobulin levels, even in the group of patients with multiple myeloma. CONCLUSIONS: The plasma proteasome level is a potential new tool for the monitoring of patients with neoplastic disease. It is not correlated solely with cell lysis and may be involved in the pathophysiology of disease progression.

Adult↗

Diabetes insipidus revealing acute myelogenous leukaemia with a high platelet count, monosomy 7 and abnormalities of chromosome 3: a new entity?

We describe three cases of acute myeloid leukaemia revealed by diabetes insipidus. The patients were 42, 38 and 39 yr old and they had marked hyperleukocytosis, circulating immature granular cells and a normal or elevated platelet count. The leukaemia was type AML-M2 according to the FAB classification. Cytogenetic studies showed inversion of chromosome 3 (q21;q26) in 2 cases and a translocation (3;3)(q21;q29?) in the remaining case, both associated with monosomy 7. All the cerebral CT scans were normal. Complete remission was never achieved, and all three patients survived less than 14 months. Desmopressin therapy was active but treatment could not be reduced. The association of dysmegakaryopoiesis with a chromosome 3 abnormality and diabetes insipidus is probably not fortuitous and could represent a new entity.

Adult↗

[Determination, by in situ hybridization on interphasic nucleus, a cytogenetic DNA index; application to breast cancer; comparison of this DNA index to DNA indexes determined by imaging and flow cytometry].

In oncology, flow cytometry (FCM) and image cytometry (ICM) are commonly used to detect DNA aneuploid cell populations in solid tumors. Agreement between these two approaches is good. The use of both techniques in association minimizes the rate of FCM and ICM false negatives and gives better DNA pattern characterization, particularly for detection of any tumoral component in the FCM DNA diploid peak. Nevertheless, discrepancies exist between the FCM and the ICM DNA index values: the ICM DNA index is often greater than the FCM DNA index. The aim of the present study was to establish a cytogenetic DNA index by determining the chromosomal ploidy using a molecular cytogenetic approach and to compare it to the FCM and ICM DNA indexes. We present here the fluorescence in situ hybridization (FISH) technique we have adapted to the study of breast cancer in order to count the number of copies of the 22 + X human chromosomes in interphasic nuclei. This was achieved using a panel of 21 indirect FITC labeled probes which recognize specific chromosomic DNA sequences. Preliminary results obtained from DNA diploid and DNA aneuploid tumors are discussed.

Breast Neoplasms↗

[The proteasome and malignant hemopathies].

Proteasomes are the main non lysosomal proteolytic structures of the cells. They correspond to the major system eliminating abnormal proteins, short half-life proteins and proteins controlling the cell cycle. They are essential for the production of peptides subsequently presented by the MHC-I. They are formed by a proteolytic core (the 20S proteasome) made of 4 rings of 7 proteic subunits associated with regulatory complexes (namely the 19S complex forming the 26S proteasome). Using classical cell biology techniques (cytometry, immunofluorescence microscopy, Western blot) our group has particularly studied the proteasome expression of leukaemic cell lines (U937 and CCRF-CEM) during in vitro differentiation induced by PMA and Vitamin D plus retinoïc acid. During differentiation, the level of proteasome expression and its localization vary. The various monoclonal antibodies used provided different patterns according to the different subunits. There was a general trend to a disappearance of nuclear proteasome and to a decrease in their cytoplasmic expression. In contrast, proteosomal antigens were increased on the cell membrane and in culture supernatants. We derived an ELISA test to measure plasma proteasome concentrations. Preliminary results showed differences between patients with haemopoietic malignancies or solid tumors and normal donors. Proteasome levels varied under treatment. They were correlated with LDH levels. Taken together, these results argue in favor of a role for cellular proteasomes in malignant differentiation process, and emphasize the qualitative changes in proteasome expression. Plasma proteasomes do not only reflect tumor cell mass and could play a role in addition to their proteolytic activity. They seem to be a relevant tool for diagnosis, prognosis and therapeutic monitoring.

Biomarkers, Tumor↗

Relationships between proteasomes and viral gene products.

The interrelationships between proteasomes and viral gene products are very complex. 20S proteasomes associate with a number of viral mRNAs which are cleaved by proteasome's associated endonuclease activity. In addition proteasome's endopeptidase activities are involved in the presentation of viral antigens. Viral proteins of different origin associate with the 20S and 26S complexes and interfere with their enzymatic activities. A major part of this review deals with the interactions between 20S proteasomes and the gene products of the human immunodeficiency virus (HIV) which has been studied in detail by our group.

Adenosine Triphosphatases↗

Increased prosomal proteins in breast cancer cells and in neighboring normal cells in Parsi and non-Parsi populations.

Monoclonal antibodies were raised against the prosomal proteins p27K, p29K and the prosome-like protein p21K (PLP) from normal breast glandular cells and from benign and malignant tumors. They were used to clarify the involvement of prosomes in tumorigenesis of human breast cells. Immunostaining showed the distribution of prosomes in the cytoplasm and nuclei of cells from European normal women (EN) and Parsi (P) and non-Parsi (NP) benign (B) and malignant (M) tissues. The flow-cytometry studies showed an increased mean percentage of labeled cells, particularly with anti-p27K prosomal protein mAb, in malignant tissue from NP compared to EN. The p21K data indicated an increase in the number of cells labeled by flow-cytometry studies in all groups compared to EN, while p29K-expressing cells were more abundant in NPN, PB, PM and NPM. Intergroup comparison showed that the mean percentage of cells labeled with anti-p27K and anti-p29K was significantly higher in PB than in NPB, as seen by flow cytometry, whereas there was a higher production or accumulation of the p21K (PLP) prosomal protein in NPM than in PM, as seen by immunostaining. By comparison with EN, there were also significantly more normal cells containing the three antigens in the apparently normal tissue in the neighborhood of the tumor in NPM, and more cells containing p21K in PM patients than in EN. As prosomes are involved in the cell differentiation and in the cell cycle control, the changes observed in breast tissues may be related to oncogenic processes. Furthermore, the modified subunit pattern of prosomes in cancer and, possibly, pre-cancer tissue may be of interest for diagnosis purposes.

Breast↗

A constructionist model predicting the emergence, complementarity and classification of the nucleotide bases.

We are proposing an analytical matrix that models a logical process simulating the emergence of the bases of vital nucleotides. The construction and properties of the matricial model are outlined. The Graph 1 matrix specifies a unique distribution pattern of eight terms coded in binary triplet configurations and obeys specific dynamic laws. The whole set of binary triplet configurations is in dynamic equilibrium. For that reason, it is possible to carry out an analysis by entering by any one of the eight terms on the condition that the operating mode obeys all the internal laws of orientation and symmetries inherent in the matrix. The four chemical elements at the origin of life are distributed following their atomic structures in the order hydrogen (H), carbon (C), nitrogen (N) and oxygen (O) and organized according to the model. The dynamic properties of the model necessitate the running of three successive circular periodic studies per analysis in order to show the emergence of the four bases--adenine, guanine, cytosine and thymine--precisely in that order. The fifth base of the nucleotides--uracil--shows up twice but always in an intermediate position, thus in transition, as it is the case for messenger ribonucleic acid (mRNA). We show also that the model provides for a logical explanation of the law of complementarity of the bases and their chemical classification. It is proposed that subsequent developments of the dynamic laws of this matrix may lead to the study of the logical operations for the formation of protein sequences and of their analysis and to genetic bioprogramming in general. Thus, a strictly logical and dynamic approach to molecular genetics is possible.

Base Sequence↗

Pallister-Killian syndrome [i(12p)]: first pre-natal diagnosis using cordocentesis in the second trimester confirmed by in situ hybridization.

Pallister Killian syndrome (PKS) is the most frequent form of partial autosomal tetrasomy 12p in humans. Sufferers have a mosaic of isochromosome 12p [i(12p)]. We report the first pre-natal diagnosis on fetal blood cells after cordocentesis during the second trimester. The extra chromosome was first diagnosed by in situ hybridization. Fluorescence in situ hybridization (FISH) was used to count the interphase and/or metaphase cells containing the isochromosome. A review of the literature identified 27 other reports of PKS diagnosed pre-natally. We showed that the most consistent pre-natal ultrasound findings include hypertelorism, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia and hydramnios. Recognition of this congenital malformation pattern pre-natally may allow utilization of FISH.

Adult↗

Changes in the subunit distribution of prosomes (MCP-proteasomes) during the differentiation of human leukemic cells.

The subunit composition of cell-internal and surface prosomes during phorbol myristate acetate (PMA)-induced differentiation of human leukemic T lymphocytes (CCRF-CEM cell line) was studied in relation to clusters of differentiation (CD) markers. PMA inhibited cell growth and decreased the amounts of CD1a and CD4 while CD3, CD8, CD25, CD45, CD57 and MHCI increased it; the p53 anti-oncogene increased while actin levels remained constant. Cells incubated with the inducer PMA for 3 days and placed in fresh inhibitor-free medium resumed growth at a low rate, while the CD values slowly reverted to those of the initial phenotype. The presence and relative amounts of prosome subunits were analyzed by flow cytometry, light and fluorescent microscopy and Western blotting using 3 monoclonal antibodies (p25K, p27K and p30-33K MAbs). The decrease in cytoplasmic antigens on day 3 was remarkable (cells followed for 7 days) while increased surface antigens were observed. Changes in the subcellular distributions of prosome antigens, particularly the p25K and p30-33K subunit, were correlated with a partial arrest of the cell cycle. Interestingly, the composition of cell internal and surface prosomes showed different patterns of change.

Antibodies, Monoclonal↗

Characterization of prosomes in human lymphocyte subpopulations and their presence as surface antigens.

Prosomes, also called "multicatalytic proteinase" (MCP) or "proteasomes," are a new type of ubiquitous RNP particle present in some archeobacteria and in all eukaryotic cells tested from yeast to human. They were discovered as subcomplexes of untranslated messenger-ribonucleoproteins (mRNP) and later found to have a MCP activity putatively involved in antigen processing. Being composed of variable sets of characteristic proteins and associating small RNAs (pRNA), families of individual "mosaic" prosome particles seem to characterize the differentiation type and physiological state of individual cells and tissues. Here, prosomes from human lymphocytes, isolated and characterized biochemically and by Western blot analysis, were found to differ in their subunit composition compared to other human prosomes. Surprisingly, prosomal antigens were discovered at the outer surface of blood cells monitored by flow cytometry with monoclonal antibodies to individual prosomal proteins. It was observed that human T and B lymphocytes have variable and characteristic prosomal antigens at their surface according to their CD classification. Interestingly, the lymphocyte subpopulations most strongly labeled by the anti-p25K and anti-p27K mAbs were the NK and B cells.

Adult↗

Prosomes (proteasomes) changes during differentiation are related to the type of inducer.

The core of the 26S proteasome, the 20S prosome, is a highly organized multi-protein complex found in large amount in malignant cells. Differentiation of several cell lines, including the monoblastic U937 and the lymphoblastoid CCRF-CEM, is accompanied by a general decrease in the prosome concentration when phorbol-myrirtic-acetate (PMA) and retinoic acid plus dihydroxyvitamine D3 (RA+VD) are used. Incubation of U937 cells for three days with PMA or RA+VD causes differentiation, but the resulting patterns of prosome labeling in the cell and on the plasma membrane are not the same. In contrast, the same kind of prosome changes occur in U937 and CCRF-CEM cells when PMA is used as inducer. The intracellular distribution of prosomes is also linked to malignancy and differentiation. Prosomes are found in the nucleus and the cytoplasm of cancer cells; and treatment with RA+VD decreases the prosomes in the nucleus whereas PMA causes various prosome proteins changes. These results indicate that prosomes are important in cell regulation and in the expression of malignancy.

Cell Differentiation↗

Proteasome (prosome) subunit variations during the differentiation of myeloid U937 cells.

20S proteasomes (prosomes/multicatalytic proteinase) are protein particles built of 28 subunits in variable composition. We studied the changes in proteasome subunit composition during the differentiation of U937 cells induced by phorbol-myristate-acetate or retinoic acid plus 1,25-dihydroxy-cholecalciferol by western blot, flow cytometry and immuno-fluoresence. p25K (C3), p27K (IOTA) and p30/33K (C2) subunits were detected in both the nucleus and cytoplasm of undifferentiated cells. Flow cytometry demonstrated a biphasic decrease in proteasome subunits detection during differentiation induced by RA + VD. PMA caused an early transient decrease in these subunits followed by a return to their control level, except for p30/33K, which remained low. Immuno-fluorescence also showed differences in the cytolocalization of the subunits, with a particular decrease in antigen labeling in the nucleus of RA + VD-induced cells, and a scattering in the cytoplasm and a reorganization in the nucleus of PMA-induced cells. Small amounts of proteasomal proteins were seen on the outer membrane of non-induced cells; these membrane proteins disappeared when treated with RA + VD, whereas some increased on PMA-induced cells. The differential changes in the distribution and type of proteasomes in RA + VD and PMA-induced cells indicate that, possibly, 20S proteasomes may play a role in relation to the mechanisms of differentiation and the inducer used.

Animals↗