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Biomedical subjects

P Neve

Publications and source records attributed to P Neve.

At least 19 recordsLinked to original sources
PubMed2005

High survival frequencies at low herbicide use rates in populations of Lolium rigidum result in rapid evolution of herbicide resistance.

The frequency of phenotypic resistance to herbicides in previously untreated weed populations and the herbicide dose applied to these populations are key determinants of the dynamics of selection for resistance. In total, 31 Lolium rigidum populations were collected from sites with no previous history of exposure to herbicides and where there was little probability of gene flow from adjacent resistant populations. The mean survival frequency across all 31 populations following two applications of commercial rates (375 g ha(-1)) of the acetyl-coenzyme A carboxylase (ACCase) inhibiting herbicide, diclofop-methyl was 0.43%. Survivors from five of these populations were grown to maturity and seed was collected. Dose-response experiments compared population level resistance to diclofop-methyl in these selected lines with their original parent populations. A single cycle of herbicide selection significantly increased resistance in all populations (LD(50) R:S ratios ranged from 2.8 to 23.2), confirming the inheritance and genetic basis of phenotypic resistance. In vitro assays of ACCase inhibition by diclofop acid indicated that resistance was due to a non-target-site mechanism. Following selection with diclofop-methyl, the five L. rigidum populations exhibited diverse patterns of cross-resistance to ACCase and ALS-inhibiting herbicides, suggesting that different genes or gene combinations were responsible for resistance. The relevance of these results to the management of herbicide resistance are discussed.

Biological Evolution↗
PubMed2005

Resistance cost of a cytochrome P450 herbicide metabolism mechanism but not an ACCase target site mutation in a multiple resistant Lolium rigidum population.

Costs of resistance are predicted to reduce plant productivity in herbicide-resistant weeds. Lolium rigidum herbicide-susceptible individuals (S), individuals possessing cytochrome P450-based herbicide metabolism (P450) and multiple resistant individuals possessing a resistant ACCase and enhanced cytochrome P450 metabolism (ACCase/P450) were grown in the absence of mutual plant interaction to estimate plant growth traits. Both P450 and ACCase/P450 resistant phenotypes produced less above-ground biomass than the S phenotype during the vegetative stage. Reduced biomass production in the resistant phenotypes corresponded to a reduced relative growth rate and a lower net assimilation rate and rate of carbon fixation. There were no significant differences between the two resistant phenotypes, suggesting that costs of resistance are associated with P450 metabolism-based resistance. There were no differences in reproductive output among the three phenotypes, indicating that the cost of P450 resistance during vegetative growth is compensated during the production of reproductive structures. The P450-based herbicide metabolism is shown to be associated with physiological resistance costs, which may be manipulated by agronomic management to reduce the evolution of herbicide resistance.

Acetyl-CoA Carboxylase↗
PubMed2002

[The general internal medicine department].

The Department of General Internal Medicine is devoted to the evaluation of patients with autoimmune systemic diseases, multiorganic disorders or presenting non specific symptoms such as chronic fatigue, unexplained weight loss or fever of unknown origin. The interest in salt and water metabolisms had led to original contributions in the treatment of hyponatremia in man and to the understanding of the osmotic demyelinating syndrome in a rat model of hyponatremia. The study of ageing in man and rodents had contributed to better understand lymphocyte and thyroid function in the elderly. The care for patients with various autoimmune disorders led to original observations in the pathogenicity of Sjögren's syndrome adult onset Still disease or sarcoidosis as well as the follow up of patients treated with azathioprine. Intensive collaboration with the Department of Immunology led to identify Th2 clonal lymphocytes as the cause of the so-called idiopathic hypereosinophilic syndrome in some patients and to define the clinical and biological features in this subset of patients.

Belgium↗
PubMed2000

Cloning and expression of rat CYP2E1 in Saccharomyces cerevisiae: detection of genotoxicity of N-alkylformamides.

A cDNA coding for rat cytochrome P450 2E1 was cloned into the multicopy vector pYeDP60 and expressed in haploid RSY6 and diploid RS112 yeast strains of Saccharomyces cerevisiae under control of the GAL10-CYC1 promoter. Spectral and catalytic properties of the expressed 2E1 were examined in whole cells or microsomes of both strains. The level of CYP2E1 obtained in RS112 (200 pmol/mg microsomal protein) was the highest among CYP2E1 produced in the various expression systems. The monooxygenase activity in the microsomes of both strains, measured as aniline hydroxylase, was found comparable to that of control rat hepatic microsomes. In a reconstituted system in the presence of exogenous rat P450 reductase, their activity increased about 10-fold. When exposed to the carcinogen NDMA, a known 2E1 substrate, the recombination frequency determined in the 2E1-expressing RS112 cells was enhanced, in a dose-dependent manner, up to 20-fold. The exposure of the same cells to the hepatotoxic solvents, N-methyl- and N-ethylformamide, resulted in an induction of recombination frequency, which was not observed in the void plasmid containing RS112 cells in the presence of S9 hepatic fractions from pyrazole-induced rats, as a specific exogenous metabolic activation system. These results demonstrate that the 2E1-expressing cells metabolize the two N-alkylformamides to genotoxic intermediates and, therefore, they provide an useful tool to study the bioactivation mechanism of potential P450 2E1 substrates.

Animals↗
PubMed1997

Morphologic and phenotypic changes of the leukemic cells in a case of marginal zone B-cell lymphoma.

A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionaly investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL.

Antigens, CD19↗
PubMed1997

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome.

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.

Acute Disease↗
PubMed1997

Nature of the T lymphocytes in lymphocyte predominance Hodgkin's disease.

Little is known about the function of the T lymphocytes in lymphocyte predominance Hodgkin's disease. We report here the case of a 37-year-old man with a diffuse LPHD, featuring a similar increase in T lymphocytes in both the peripheral blood and the tumor, thus allowing for their characterization by functional assays. These cells were CD4+CD45RO+ and produced high amounts of IL-2 and IFN-gamma, consistent with a TH1-type profile. This subset of T helper cells is involved in cellular immunity and could reflect a cytotoxic reaction directed against the neoplastic cells.

Adult↗
PubMed1997

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome.

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.

Aged↗
PubMed1995

A case of pleomorphic T-cell lymphoma with a high content of reactive histiocytes presented with hypereosinophilia.

A case of peripheral T-cell lymphoma classified, according to the updated Kiel classification, as a large pleomorphic T-cell lymphoma with a high content of reactive histiocytes and blood hypereosinophilia is reported. Light microscopic examination revealed a diffuse effacement of the lymph node structure by large pleomorphic lymphoma cells mixed with eosinophils and many histiocytes, some of them presenting discrete features of hemophagocytosis. The neoplastic cells were CD3, CD5, CD8 and HLA-DR positive but failed to show CD30 antigen. DNA molecular analysis displayed simultaneous rearrangements of the genes coding for the delta chain of the T-cell receptor and for the Ig heavy chain. Increased serum levels of angiotensin converting enzyme and ferritin were found and probably induced by the reactive histiocytes. Immunoassays (ELISA) with antibodies directed against some cytokines and against the Tac peptide (sIL-2R) were performed. They demonstrated high serum levels of sIL-2R and a slight increase in GM-CSF, but neither IL-5 nor IL-3. The association of blood hypereosinophilia and histiocytic hyperplasia with a peripheral T-cell lymphoma is discussed.

Adult↗
PubMed1994

Thiobarbiturate and fructosamine assays: significance and interest of the borohydride blank.

The acute-phase reaction (APR) induces the production by the liver of short-lived glycoproteins. The carbohydrate moiety of these proteins is thought to interfere with the thiobarbiturate (TBA) and nitroblue tetrazolium colorimetric tests which are used for assaying non-enzymatic glycosylation (NEG) of serum proteins. The aim of the present study was to assess the effect of the APR on the specificity of the colorimetric tests in non-diabetic and diabetic subjects. A positive correlation was found between C-reactive protein (CRP), an APR glycoprotein, and non-specific TBA reactivity as determined after borohydride reduction (BH4-resistant TBA, BR-TBA), both in non-diabetics (r = 0.61; P < 0.01) and diabetics (r = 0.68; P < 0.01). The BH4-sensitive specific TBA (SP-TBA) was not influenced by glycoproteins, and its increase in diabetics was correlated with the nitroblue tetrazolium assay (r = 0.89; P < 0.01). An independent effect of diabetes and APR on non-specific TBA was also demonstrated, suggesting an effect of hyperglycaemia on both protein glycation and glycosylation. TBA with borohydride reduction is an attractive tool for the study of complex glycoproteins in diabetes.

Acute-Phase Reaction↗
PubMed1993

Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria.

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.

Antigens, CD↗
PubMed1992

Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats.

Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n = 6-8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from sham-operated and ovariectomized animals (n = 10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.

Animals↗
PubMed1992

The number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats.

Four- and 21-month old female Sprague-Dawley rats were sacrificed and their tibiae and femurs isolated for histology and initiation of bone marrow and trabecular bone cultures. The bone loss observed in 21-month old rats was associated with a markedly decreased osteoblastic index. The percentages of mineralizing trabecular surfaces were only slightly decreased in aged rats, whereas the percentages of mineralizing endocortical surfaces were strikingly decreased. Diaphyseal femoral marrows from 21-month old rats were less cellular than those from four-month old rats, and developed in culture fewer fibroblast colony forming units (FCFU) and fewer adherent cells with phenotypic characteristics of osteoblast-like cells. Trabecular bone cultures from 21-month old rats produced as many cells as cultures from four-month old rats, whereas the amount of trabeculae put into culture was much less in aged rats. Moreover, the proliferation rate in secondary culture was significantly increased in 21-month old rats. Similar responses to calcitriol were observed in bone marrow and trabecular bone cells from aged and younger mature rats, while cAMP responses to PTH were decreased in cells from aged rats. Our data confirm the age-related decrease in the FCFU efficiency of the bone marrow and show a stimulated proliferation of trabecular bone cultures from 21-month old rats that could be seen either as the result of the inhibition in vivo of the response to a signal to proliferate, or as a rebound response to factors present in the serum-enriched medium and lacking in vivo.

Aging↗
PubMed1991

CD71 phenotype and the value of gallium imaging in lymphomas.

Tumor cells of 14 cases of non-Hodgkin lymphomas and 2 cases of Hodgkin disease were tested for the presence of the transferrin receptor (CD71) by flow cytofluorimetry before 67gallium imaging. It appeared that expression of CD71 phenotype was closely related to the positivity of gallium scan before therapy. We feel that this test is able to predict the avidity for 67gallium and the clinical implications are discussed.

Bone Marrow↗
PubMed1991

Changing pattern of CD5+ CD20+ double positive lymphocytes with ageing and cytotoxic chemotherapy.

In this cross-sectional clinical study, it was found that two subtypes of CD5+ B-lymphocytes existed either with CD5-high and CD20-low or CD5-low and CD20-high expression, as determined by dual fluorescence analysis with fluorochrome-labeled monoclonal antibodies on a FACScan flowcytometer. In the normal healthy subjects (n = 20), the CD20 positive cells could be broken down into 3 subsets: CD5(2+) CD20+, 25.4 +/- 3.0% (mean +/- S.E.M.), CD5+ CD20(2+), 18.4 +/- 2.4% and CD5- CD20(2+), 56.2 +/- 2.7%. Similar values were observed in a group of patients (n = 29) suffering from a wide variety of benign or untreated malignant disorders. The CD5(2+) CD20+ subset was typically related to age (Spearman coefficient of correlation rho = 0.77, P less than 0.001 in healthy subjects and rho = 0.46, P = 0.02 in pathological cases). The CD5+ CD20(2+) subpopulation was a salient feature of newborns and little infants (n = 6, 75.4 +/- 2.4%, P less than 0.01). The CD5- CD20(2+) subset was characteristically depressed in patients treated with cytotoxics (n = 21, 41.2 +/- 3.6%, P = 0.001). As far as cytotoxic chemotherapy may represent a model of accelerated ageing, it is worth noting that, in patients treated with cytotoxics, the CD5 CD20 pattern was frequently disturbed in a hyperyoung or hyperaged picture. That age and cytotoxics can affect CD5 expression on CD20+ lymphocytes, suggests some specific B-dysregulation and should be put together with the known emergence of autoantibodies, paraproteinemias and lympho-plasmocytic tumors with age and chemotherapy.

Adult↗