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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 685 records · Page 38Linked to original sources
PubMedDate not supplied

Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells.

Cadmium (Cd) is able to decrease preovulatory luteinizing hormone (LH) levels in blood and inhibit ovulation in rats. In this study the direct effects of Cd on steroidogenesis in granulosa cells were investigated. The cells obtained from ovarian follicular aspirates of 41 women undergoing in vitro fertilization (IVF) were cultured. Cadmium-induced alterations in the cellular morphology and in the production of progesterone by the cells was determined after exposure to concentrations of 8, 16, 32 and 64 microM CdCl2 for 2, 4, 8, 24 and 48 h. Progesterone secretion by granulosa cells could be stimulated with increasing concentrations of follicle-stimulating hormone (FSH). Combined effects of Cd and FSH were also studied. Cadmium diminished progesterone production in unstimulated and FSH-supported cells depending on its concentration and the exposure time. Follicle-stimulating hormone (100 ng ml[-1]) protected against Cd-induced suppression of progesterone production. Cadmium interfered with cell-cell junctions and the adherence of cells. No protective effect of FSH on Cd-induced alteration in cell morphology could be observed. Retraction of cytoplasmic extensions occurred at a lower dose and within a shorter exposure than a decrease in progesterone production. In conclusion, Cd exerted a direct effect on both granulosa cell morphology and on steroid biosynthesis. The lowest Cd concentration (16 microM) that was able to reduce progesterone production was about 3.5 times higher than levels reported in the ovary of a female smoker. The presented data can help to define environmental, occupational and life-style (smoking) risk factors in gonadal function during the preconception period of the female reproductive lifespan.

Adult↗
PubMedDate not supplied

Peripheral markers (Clara cell protein and alpha-glutathione S-transferase) and lipidoperoxidation (malondialdehyde) assessment in Sprague-Dawley rats instilled with haematite and benzo[a]pyrene.

The literature suggests that the concomitant exposure to polycyclic aromatic hydrocarbons (PAH) and ferric oxide particles could enhance lung cancer incidence in environmental and occupational settings. High levels of tracheobronchial tumours were obtained in hamsters exposed to benzo[a]pyrene (B[a]P) adsorbed onto ferric oxide carrier particles. Therefore, we have assessed the toxic effects of exposure to haematite (Fe2O3) and B[a]P in male Sprague-Dawley rats. Animals were instilled with the chemicals alone (3 mg of Fe2O3 or B[a]P) or in combination (3 mg Fe2O3 + 3 mg B[a]P). Bronchoalveolar lavages (BAL) and biological samples (serum and urine) were collected 48 h after the intoxication. Clara cell protein (CC16) and alpha-glutathione S-transferase (alpha-GST), as peripheral markers of both tracheobronchial epithelial cell integrity and renal dysfunction, were determined in BAL fluid, serum and urine. Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in BAL fluid and serum. We observed a significant increase of CC16 concentrations in BAL fluid after Fe2O3 + B[a]P instillation (p < 0.05) in serum after Fe2O3 and Fe2O3 + B[a]P exposure (p < 0.01) and in urine after B[a]P administration (p < 0.01). Instillation of Fe2O3 + B[a]P produced an increased amount of alpha-GST in BAL fluid (p < 0.01), whereas B[a]P alone caused a significant elevation of alpha-GST in serum and urine (p < 0.01). Moreover, Fe2O3 or Fe2O3 + B[a]P instillation induced a significant increase in MDA levels in BAL fluid (p < 0.01 and p < 0.05). In conclusion, Fe2O3 may have a low pulmonary toxicity. However, B[a]P manifested a rapid and high toxicity in the respiratory tract and kidneys. When B[a]P was adsorbed on haematite particles, both its retention in the respiratory tract and pulmonary toxicity increased.

Animals↗
PubMedDate not supplied

A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease.

Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.

Aging↗
PubMedDate not supplied

Reshaping primary care: the Healthy Steps Initiative.

The Healthy Steps Initiative, funded by the Commonwealth Fund in New York and developed and implemented by Boston University School of Medicine, is an enhanced approach to pediatric care in the first 3 years of life. The goals of this effort in transforming pediatric care include (a) supporting the physical and emotional development of each infant and young child; (b) supporting a parental sense of confidence in their child-rearing knowledge and skills; and (c) supporting the clinical effectiveness of pediatric primary care practices to meet the needs of young children and families. The Healthy Steps Initiative enhances well-child care to achieve these goals by providing child development information and support as part of an expanded approach to pediatric primary care. Healthy Steps offers both pediatric practices and families a vehicle for meeting the needs of infants and young children within a preventative framework. This unique program, which is being quantitatively and qualitatively evaluated over 3 years, has been initiated in more than 24 pediatric sites nationwide.

Child Development↗
PubMedDate not supplied

The Belgian PCB/dioxin incident: a critical review of health risks evaluations.

The Belgian PCB/dioxin incident is a food contamination that occurred in Belgium in January 1999 when a tank of recycled fats used to produce animal feeds was accidentally contaminated by approximately 100 L of polychlorinated biphenyl (PCB) oil containing 50 kg PCBs expressed as the sum of the seven markers, 1 g (TEQ) dioxins (PCDD/Fs) and 2 g toxic equivalent (TEQ) dioxin-like PCBs. The incident was discovered when a poultry poisoning resembling the classic chick edema disease broke out in several farms that had received contaminated feeds. The delay in making public this incident resulted in a major political and food crisis and caused much concern in the population. We review here the health risk evaluations that were made after this incident and we assess the likelihood of the different scenarios by taking into account recent data on the real scale of the contamination and on the dioxin body burden of the general population in Belgium. These new data confirm that the incident was too limited in time and in scale to have increased the PCB/dioxin body burden of the general population at large, a conclusion supported by a survey of dioxin levels in blood conducted at the end of 1999. Only farmers in poultry farms affected by the incident (about 30 farms) and having regularly consumed their own products could have increased their PCB/dioxin body burden. It is unlikely, however, that these farmers could have increased their PCB/dioxin body burden above levels prevailing in the 1980s or now found in communities regularly consuming seafood.

Accidents↗
PubMedDate not supplied

Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead.

Current evidence suggests that the neurotoxic effects of lead may partially be mediated through interference with the dopaminergic system. The aim of this study was to assess the levels of two peripheral dopaminergic markers--serum prolactin (Pro-S) and urinary homovanillic acid (HVA-U)--in children living around two lead smelters, who are presumed to be exposed to high environmental lead pollution (n = 200), and compare their results with 200 age- and sex-matched controls living in an area unpolluted by heavy metals, giving a total of 400 children (200 boys and 200 girls). The influence of lead exposure on HVA-U and Pro-S was assessed by stepwise multiple regression, testing lead concentrations in blood (Pb-B), age, sex and area of residence as predictors. Though lead levels were significantly higher in boys and in the lead-polluted environment, mean Pb-B values were relatively low, indicating a low uptake of lead in the contaminated environment (39.5 micrograms l-1, range 4.6-165 micrograms l-1, n = 200), and no significant correlation could be found with either Pro-S or HVA-U. However, when the subgroup of 121 children with Pb-B levels above 50 micrograms l-1 were considered, a weak positive correlation was found between Pb-B and HVA-U (r2 = 0.04, p = 0.03), whilst in the even smaller subgroup of 15 children with Pb-B levels above 100 micrograms l-1, Pro-S appeared to be positively correlated with Pb-B, though the numbers of children were too small for the correlation to reach statistical significance (p = 0.095). These weak associations, probably not important in biological terms, indicate that Pro-S and HVA-U are not useful biomarkers at present exposure levels to lead in the environment. Nevertheless, the finding of subtle biochemical alterations in the dopaminergic system at Pb-B levels of around 100 micrograms l-1 supports the recommended setting of the action level at this value.

Biomarkers↗
PubMedDate not supplied

Cryopreservation of human oocytes: a review of current problems and perspectives.

It is well recognized that the ability to cryopreserve unfertilized human oocytes would make a significant contribution to infertility treatment. However, despite considerable interest, very few successful pregnancies have arisen from cryopreserved oocytes after thawing, insemination and transfer of the subsequent embryo. The reasons for this lack of progress may well result from a dearth of information on how the various biophysical changes during a cryopreservation regimen affect human oocyte function. Recently, fundamental studies on the effects of cooling, membrane permeability, cryoprotectant addition and ice formation have been performed on human oocytes by a number of groups, and these form the basis of the current review. It is likely that successful human oocyte cryopreservation will only follow once these factors are fully understood, but the existing base of knowledge should provide a platform for further improvements in the techniques currently employed.

Cell Membrane Permeability↗
PubMedDate not supplied

Exposure to hydrocarbons and renal disease: an experimental animal model.

The association between hydrocarbon exposure and chronic glomerulonephritis is still a controversial scientific issue. Recent epidemiological evidence suggests a role of exposure to hydrocarbons in the progression of glomerulonephritis towards chronic renal failure. The present experimental study on rats has been designed to assess the possible role of styrene in the progression of adriamycin (ADR) nephrosis, a well known model of renal fibrosis following nephrotic syndrome induced by ADR. Female Sprague-Dawley rats were exposed to styrene, 300 ppm, 6 h/day, 5 days/week for 12 weeks (group 1); treated with ADR, 2 mg/Kg, i.v., twice on day 1 and day 15 of the study (group 2); Additional groups of animals received both the styrene and ADR treatments (group 3) or served as controls (group 4). The urinary excretion of total and single proteins (albumin, Retinol-Binding Protein (RBP), Clara Cell 16 Kd protein (CC16), fibronectin) was measured monthly, whereas histopathology and determinations requiring blood sampling were carried out at the end of the experiment. A progressive increase in total proteinuria, falling in the nephrotic range already by the 6th week was observed in ADR-treated groups. Styrene exposure caused up to a 3- to 5-fold increase as compared to controls. Co-exposure to ADR and styrene also resulted in a proteinuria much greater than that caused by ADR alone. The interactive effect of styrene and ADR was statistically significant for albuminuria and urinary fibronectin. A similar response was observed for glomerular filtration rate at the end of the experiment, styrene-exposed animals showing hyperfiltration as compared to their respective control group. At the end of the experiment, histopathological scoring for interstitial infiltration and fibrosis was also significantly higher in styrene-treated animals as compared to their respective control groups. In ADR-treated rats, low molecular weight proteinuria (l.m.w.p.) was only slightly affected, suggesting minimal tubular dysfunction associated with extensive tubular atrophy. However, styrene-exposed animals showed l.m.w.p. higher than their respective controls. In summary, in this animal model we were able to confirm both styrene-induced microproteinuria, mainly albuminuria and minor increases in l.m.w.p., observed among occupationally exposed workers and the role of hydrocarbon exposure as a factor accelerating the progression of renal disease suggested by epidemiological investigations in patients suffering from chronic renal disease. Whereas in rats exposed to styrene only, microproteinuria was stable over time and minor histopathological changes were noted at the end of the experiment, evidence of a role of solvent exposure in the progression of ADR nephropathy was obtained in terms of both renal dysfunction and interstitial fibrosis. The mechanistic basis of styrene-ADR interaction is unclear. However, experimental evidence is consistent with epidemiological findings suggesting the need to avoid solvent exposure in patients suffering from renal diseases.

Albuminuria↗
PubMedDate not supplied

Erucic acid metabolism in rat liver. A combined biochemical and radioautographical study.

Metabolism of erucic acid was studied in rat liver in comparison with oleic acid in relation with diet lipids. Rats were fed for 3 or 60 days a balanced diet containing 30% of the calories of either rapeseed oil rich in erucic acid or sunflower seed oil rich in linoleic acid. They were intravenously injected with tritiated erucic or oleic acid. After 1 or 15 min, the radioactivity recovered in liver lipids was 9 to 26% whatever the diet or the acid injected. One minute after injection of erucic acid a high part of radioactivity was recovered in the free fatty acid fraction and as untransformed erucic acid. After 15 min the major part of radioactivity was recovered in the triacylglycerol fraction which contained a high proportion of labelled oleic acid formed by shortening of erucic acid. The autoradiography did not show any marked difference between the labelling of peroxisomes and mitochondria when tritiated erucic or oleic acid was injected. These data do not bring about arguments for a peroxisomal nor for a mitochondrial location of erucic acid shortening in liver.

Animals↗
PubMedDate not supplied

[Molecular pathways of T lymphocyte activation].

TRIGGERING T CELL ACTIVATION: A quiescent T cell must encounter an antigen presenting cell to become activated. The T receptor for the antigen delivers a first specific signal which alone is insufficient to trigger total T cell activation. A second signal independent of antigen recognition is furnished by the antigen presenting cell, leading to total activation. PATHWAYS CAPABLE OF DELIVERING THE SECOND SIGNAL: CD28 and CTLA-4 are two molecules capable of playing a powerful role in regulating immune response. The fate of B cells depends on the CD40 molecule they carry on their surface as well as on T cells which express its ligand. Adherence molecules CD11a/CD18 induce tight adherence between T cells and antigen presenting cells by binding their CD50 ligand (ICAM-3); this bond activates the T cell, completing the first signal. The CD2 pathway and its ligands, a constitutional expression on two partner cells, is a strong adherence pathway which also transmits two powerful activation signals for T cells. SEVERAL FUNCTIONAL STATES: These different activation pathways illustrate the subtle interaction between surface molecules, capable of inducing different functional states depending on the environment.

Antigens↗
PubMedDate not supplied

[Lymphocytic molecules implicated in rosette phenomenon. Differential effect of antilymphocyte serum on T (CD2+E2+) and B (CD2-E2+) lymphocytes].

The molecule E2 is present on T lymphocytes and thymocytes and is implicated in rosette phenomenon most probably via interaction with CD2. The discrepancy observed between rosette levels and lymphocyte phenotypes in the follow-up of kidney-transplanted patients treated with antilymphocyte globulins (ALG), methylprednisolone and azathioprine leaded us to study the effect of ALG on E2 molecule.

Antigens, CD↗
PubMedDate not supplied

[Indicators of pulmonary epithelial damage among workers at a foundry exposed to airborne pollutants].

Foundry ambient air contains very high concentrations of noxious substances, such as particulate matter and gaseous pollutants, which can target the respiratory epithelium. Serum concentrations of the 16-kDa Clara cell protein (CC16-S) may reflect both the integrity of the epithelial barrier and smoke-induced Clara cell toxicity. To evaluate whether CC16-S is a sensitive biomarker of early respiratory disturbances, it was determined in a group of 35 foundry male workers (aged 41.1 +/- 6.9 years) examined both prior to and at the end of their work-shift (06:00 a.m.-02:00 p.m.). Exposure to inhalable/respirable dusts and PAH was characterized; urinary excretion of 1-hydroxypyrene (1-OH-P) and naphtol was measured to assess exposure to pyrene and naphthalene, respectively. CC16 serum levels decreased at the end of the shift (10.7 +/- 3.82 micrograms/L vs. 8.39 +/- 3.05 micrograms/L; p < 0.01); such decrements were significantly larger in more exposed workers. Although smokers had lower baseline values as compared to non smokers, both subgroups showed an average decrease of 30% in CC16-S concentrations at the end of shift. CC16-S was also negatively correlated with 1-OH-P, but not with naphtol concentrations. Decreased CC16-S levels can result from citotoxicity and would represent an useful biomarker of pneumotoxicity in foundry workers exposed to complex mixtures.

Air Pollution, Indoor↗
PubMedDate not supplied

Role of CD2 in regulation of CD3- LGL function.

CD2 is a differentiation marker present on T cells and NK cells. Cytotoxic T lymphocytes (CTL) can be activated by antibodies directed against the CD3/T-cell receptor complex and CD2 structures; however, the role of CD2 in regulation of CD3- large granular lymphocyte (LGL) functions has only recently been studied. Anti-CD2 monoclonal antibodies (mAbs) may be either augmenting or inhibitory and T-cell activation via the CD2 molecule occurs only when mAb binds defined combinations of the CD2 epitopes. Since LGL can be activated by a single stimulus (e.g., IL-2) to proliferate, produce IFN gamma, and increase their cytolytic potential, these functions were chosen to examine the effects of the anti-CD2 mAb and its combinations. Anti-CD2 mAb (D66, GT2, and X11-1) were incubated with LGL for various times in the absence or presence of IL2 and IFN gamma production was monitored. Single anti-CD2 mAb treatment demonstrated minimal augmentation of IFN gamma production. However, combinations of anti-CD2 (9.6) and the other anti-CD2 mAb resulted in a significant, synergistic enhancement of the IFN gamma production. Anti-CD2 mAb treatment appeared to inhibit production generated by optimal doses of IL-2 (1,000 U/ml). The effect of anti-CD2 mAb on IFN gamma production parallel their effects on LGL NK and LAK activity. These data suggested that mAb against the CD2 molecule were important in regulating LGL functions in the absence of a functional CD3 receptor in LGL.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗