Search

A search has been performed for neutrinos from two sources, the $hep$ reaction in the solar $pp$ fusion chain and the $��_e$ component of the diffuse supernova neutrino background (DSNB), using the full dataset of the Sudbury Neutrino Observatory with a total exposure of 2.47 kton-years after fiducialization. The $hep$ search is performed using both a single-bin counting analysis and a likelihood fit. We find a best-fit flux that is compatible with solar model predictions while remaining consistent with zero flux, and set a one-sided upper limit of $��_{hep} < 30\times10^{3}~\mathrm{cm}^{-2}~\mathrm{s}^{-1}$ [90% credible interval (CI)]. No events are observed in the DSNB search region, and we set an improved upper bound on the $��_e$ component of the DSNB flux of $��^\mathrm{DSNB}_{��_e} < 19~\textrm{cm}^{-2}~\textrm{s}^{-1}$ (90% CI) in the energy range $22.9 < E_��< 36.9$~MeV., 11 pages, 6 figures

The ability to separately identify the Cherenkov and scintillation light components produced in scintillating mediums holds the potential for a major breakthrough in neutrino detection technology, allowing development of a large, low-threshold, directional detector with a broad physics program. The CHESS (CHErenkov/Scintillation Separation) experiment employs an innovative detector design with an array of small, fast photomultiplier tubes and state-of-the-art electronics to demonstrate the reconstruction of a Cherenkov ring in a scintillating medium based on photon hit time and detected photoelectron density. This paper describes the physical properties and calibration of CHESS along with first results. The ability to reconstruct Cherenkov rings is demonstrated in a water target, and a time precision of $338\ifmmode\pm\else\textpm\fi{}12\phantom{\rule{0.16em}{0ex}}\mathrm{ps}$ FWHM is achieved. Monte Carlo--based predictions for the ring imaging sensitivity with a liquid scintillator target predict an efficiency for identifying Cherenkov hits of $94\ifmmode\pm\else\textpm\fi{}1%$ and $81\ifmmode\pm\else\textpm\fi{}1%$ in pure linear alkyl benzene (LAB) and LAB loaded with 2 g/L of a fluor, PPO, respectively, with a scintillation contamination of $12\ifmmode\pm\else\textpm\fi{}1%$ and $26\ifmmode\pm\else\textpm\fi{}1%$.

The prediction that environmental fluctuations may destabilise populations and yet stabilise aggregate community properties has remained largely untested. We examined population and community stability under constant and fluctuating temperatures in simple planktonic assemblages of differing algal richness. Temperature dependent resource competition produced a highly asymmetric community structure where algal community biomass was dominated by one species. For a given level of species richness, temperature fluctuations induced lower community covariance and thus stabilised community biomass. However, increasing algal species richness increased the variability of population abundance and growth rates, as well as population and community variability. Consumer dynamics were directly destabilised by environmental fluctuations. These results confirm recent theoretical studies suggesting a stabilising effect of environmental fluctuations at the community level. However, they also support the theoretical prediction that increasing species richness may be of limited value for community stability, most especially in asymmetric communities, when competition directly affects population variability.

Food survey of three areas of the lower Rhone vaiiey: Codolet, Tresques, and the Camargue. Consumptionniome consumption. In 1996 the IRSN studied the dosimetric impact of the Marcoule site on the inhahitants of reference village, Codolet. The ingestion-related impact highiighted by this study revealed the need for further familiarisation with the eating habits of the villagers, and more precisely their home consumption habits (that is

A chemical kinetic model for gas-phase pyrolysis of propane has been set up, partially reduced, and validated against FTIR measurements in a tubular hot-wall reactor at P = 2 kPa, and T = 900 to 1400 K. It confirms the notion of maturation from propane to lighter hydrocarbons, the to aromatic compounds and PAHs. The gas-phase composition above the substrate has been correlated to pyrocarbon deposition rates and to the deposit nanostructure. It is confirmed that the growth of the rough laminar (RL) form would be related to heavier gaseous species than for th smooth laminar (SL) form.

For the continued safe operation of a fixed offshore steel structure, it is necessary for any damage resulting from fatigue, collision or impact to be prevented from leading to either progressive failure or sudden collapse. The detection of fatigue damage at an early stage in the life of the structure is, however, difficult and costly, especially sub-sea, but the financial and human consequences of structural failure resulting from inadequate inspection are likely to be much greater, and need to be prevented. The paper describes research that has been undertaken to enable sub-sea inspection strategies to be improved. The findings relate the inspection methods used, the locations inspected and the frequency of inspection to the probability of local fatigue damage leading to unacceptable structural consequences. This provides a practical way of targeting offshore inspection in order to reduce overall life-cycle costs whilst maintaining adequate levels of system reliability for the complete structure.

Resume Les polynucleaires neutrophiles et les monocytes-macrophages possedent cette propriete commune qu'est la phagocytose ayant pour but de neutraliser et de detruire l'agent pathogene. Leur capacite de defense de l'organisme contre les agents pathogenes ne se limite cependant pas a cette fonction. Cette revue met l'accent sur l'origine commune ainsi que sur les fonctions que partagent les deux types de phagocytes, en particulier la degranulation, l'activation metabolique oxydative. Elle souligne ensuite les fonctions particulieres du polynucleaire neutrophile qui lui conferent ce role preponderant dans la bactericidie (liberation de proteases, oxydants, proteines antibiotiques). Le monocyte a, en revanche, le privilege du controle de la reaction inflammatoire de par sa capacite a synthetiser une pleiade de cytokines. Cependant, aucune dichotomie fonctionnelle ne s'opere reellement et les deux types de cellules phagocytaires sont a la fois effectrices et regulatrices. Nous citerons l'exemple de l'interleukine-8 synthetisee a la fois par le monocyte et par le polynucleaire neutrophile, et qui represente une de ses cibles privilegiees. Le second exemple est la generation de produits d'oxydation avancee des proteines (ou advanced oxidation protein products ou AOPP) que nous avons recemment decrits et qui resultent de l'interaction entre les oxydants chlores et les proteines plasmatiques. Ces AOPP, generes via la myeloperoxydase des neutrophiles ont la capacite d'activer le metabolisme oxydatif des monocytes. Ainsi, ces AOPP pourraient representer de nouvelles bases moleculaires du stress oxydant, ainsi qu'un lien dans la communication entre polynucleaires neutrophiles et monocytes.

Resume Parmi les nombreux mediateurs impliques dans le developpement de l'activite anti-infectieuse et le role pro-inflammatoire des cellules phagocytaires, les cytokines proinflammatoires jouent un role pivot. Ces cytokines pro-inflammatoires sont remarquables de par la grande variete des sources cellulaires possibles, et d'autre part, par leurs effets pleitropiques sur de nombreuses cibles cellulaires impliquees dans le developpement de la reponse inflammatoire et immunitaire. Cependant, les phagocytes mononuclees, et principalement les monocytes-macrophages — constituent une source majeure de cytokines telles que l'IL-1, le TNF, l'IL-6, le GM-CSF et l'IL-8. La plupart de ces cytokines sont susceptibles de reguler les fonctions essentielles d'adherence a l'endothelium, de chimiotaxie, de phagocytose, d'activation oxydative et de degranulation des polynucleaires neutrophiles, premiere cellule effectrice de la reaction inflammatoire et de l'activite microbicide. La meilleure connaissance des mecanismes de controle et de regulation du reseau des cytokines pro-inflammatoires et de leur mode d'interaction avec les systemes moleculaires effecteurs des cellules phagocytaires devrait permettre de developper des strategies d'immuno-intervention visant a limiter l'effet deletere pro-inflammatoire du polynucleaire neutrophile tout en preservant son role essentiel dans la resistance de l'hote envers les agents pathogenes.

Resume L'aspergillose pulmonaire est devenue la principale cause de deces chez les enfants atteints de granulomatose septique chronique (GSC). Elle peut survenir avant l'âge de 1 an et est alors souvent revelatrice de la GSC. Observation. - Un nouveau-ne de sexe masculin a ete hospitalisea J27 de vie pour une fievre a 39°C, des troubles hemodynamiques et un syndrome inflammatoire biologique, rattaches a une infection pulmonaire. Le scanner thoracique a revele de multiples nodules intraparenchymateux bilateraux. Une biopsie pulmonaire chirurgicale a montre des granulomes histiocytaires avec des cellules geantes multinucleees. Les cultures des differents prelevements (biopsie pulmonaire, trachee, lavage alveolaire) ont permis d'isoler un Aspergillus fumigatus . L'etude de la chemiluminescence des polynucleaires neutrophiles (PN) a permis d'evoquer le diagnostic de GSC, confirme par l'analyse ulterieure des fonctions du PN. L'infection aspergillaire a regresse apres 12 mois de traitement par amphotericine B iv. Conclusion. - L'etude de la chemiluminescence doit etre effectuee chez un petit nourrisson atteint de pneumopathie multifocale en contexte infectieux, qui peut etre revelatrice d'une GSC.

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.

Neutrophils generate potent microbicidal molecules via the oxygen-dependent pathway, leading to the generation of reactive oxygen intermediates (ROI), and via the non-oxygen dependent pathway, consisting in the release of serine proteinases and metalloproteinases stored in granules. Over the past years, the concept has emerged that both ROI and proteinases can be viewed as mediators able to modulate neutrophil responses as well as the whole inflammatory process. This is well illustrated by the oxidative regulation of proteinase activity showing that oxidants and proteinases acts is concert to optimize the microbicidal activity and to damage host tissues. ROI and proteinases can modify the activity of several proteins involved in the control of inflammatory process. Among them, tumour necrosis factor-α and interleukin-8, are elective targets for such a modulation. Moreover, ROI and proteinases are also able to modulate the adhesion process of neutrophils to endothelial cells, which is a critical step in the inflammatory process.

The radioactive Tchernobyl fallout added their effect to those from atmospheric tests, and the liquid wastes from nuclear plants sited along the Rhone river. The radioactive level of the biotic and abiotic river components increased quickly. The radioactivity of nuclides as 110mAg, 103Ru) 106Ru) 134Cs) 137Cs the nuclear plants impact. In the upper Rhone it was in the same order of magnitude than the one found in the Moselle river but very low in comparison to the values obtained in central Europe of Scandinavian countries. After May 1986 the radioactivity decreased. In the fish cesium 134 and 137 have effective half-lives of 200 and 260 days. In 1988, the river radioactivity is in the same order of magnitude than it was before the accident.

Le parc electronucleaire francais est constitue, debut 1991: de 56 tranches installees. Leur fonctionnement entraine l'emission, apres traitement et selon la Iegislation en vigueur, d'effluents liquides et gazeux faiblement radioactifs Une methodologie generale a ete continuellement amelioree depuis 15 ans pour evaluer I'impact radioecologique des centrales dans les ecosystemes terrestres et aquatiques. Avant la divergence d'une installation, un constat radioecologique et un "point zero" de reference sont realises. Ce dernier a necessite apres Tchernobyl une reactualisation pour les centrales n'ayant pas encore diverge. En cours de fonctionnement, des etudes particulieres peuvent etre conduites pour comprendre l'influence de divers parametres du milieu. Un bilan apres dix ans de fonctionnement de chaque centrale est planifie. Un "suivi radioecologique annuel" est actuellement mis en place. Pour les ecosystemes aquatiques, de l'eau, des sediments, des vegetaux et des poissons sont preleves, prepares et conditionnes afin de mesurer les concentrations en radioelements (spectrometrie y, radiochimie pour les Pu, le Sr, le H...). A titre d'exemples, les resultats obtenus depuis les premieres etudes radioecologiques sur les centrales de Golfech, Nogent, Cattenom, Dampierre, Fessenheim et Bugey sont interpretes. L'influence de l'impact de chaque installation est quantifiee par rapport aux autres termes sources : retombees nucleaires anciennes, retombees de Tchernobyl, fonctionnement d'autres installations nucleaires. Au bilan, le fonctionnement des centrales, meme sur une longue periode, se traduit par des niveaux de radioactivite artificielle tres faibles dans le milieu aquatique.

The aim of this retrospective study was to prove the effectiveness of percutaneous cementoplasty in pelvic bone metastases. We studied the data entered in a multicenter prospective database on 18 cancer patients (average age 58 years) who underwent percutaneous computed tomography (CT) or fluoroscopy-guided cementoplasty from September 1996 to September 1998. The metastatic sites were: acetabulum (n = 12), iliac bone (n = 2), and sacrum (n = 4). Indications were pain recurrence (n = 9) or no relief (n = 3) after radiotherapy, and 6 procedures were performed before radiation. Mean follow-up was 4.6 months, ranging from 11 days up to 24 months. Improvement in pain and walking was obtained in 81.8% cases, and it was generally maintained, except in 1 patient who experienced pain again at day 15 because of an acetabular fracture. Percutaneous cementoplasty is a safe and efficient technique, and is mandatory when radiotherapy fails or when rapid resolution of pain is requested.

Hyperhomocysteinemia has been shown to constitute an independent risk factor for premature occlusive arterial disease. Moderate hyperhomocysteinemia is present in chronic uremic patients, who often develop premature atherosclerosis, but no direct evidence of an association between the occurrence of atherosclerotic cardiovascular accidents (CVAs) and hyperhomocysteinemia has yet been reported in such patients. We serially determined total plasma homocysteine (Hcy) levels in a cohort of 93 consecutive chronic renal failure, undialyzed patients (57 males, 36 females) with creatinine clearance (Ccr)50 ml/min.1.73 m2 and ageor = 50 years at start of follow-up, together with serial assessment of Ccr and blood lipid parameters. From January 1989 to December 1995, 24 patients (group 1) experienced myocardial infarction (18 cases, 13 males) or cerebral infarction (6 cases, 3 males) while the remaining 69 (group 2) remained free of CVAs. Patients in groups 1 and 2 did not differ with respect to age (66 +/- 1.8 vs. 65 +/- 1.1 years, mean +/- Se) or serum creatinine (227 +/- 24 vs. 251 +/- 36 mumol/l) at onset of a CVA (group 1) or at the end of follow-up (group 2). The mean Hcy level was significantly higher in group 1 (20.7 +/- 1.6 vs. 12.8 +/- 0.5 mumol/l, p0.0001), as was the proportion of patients with Hcy in excess of 14 mumol/l, the upper limit in healthy controls (83 vs. 30%, p0.0001). Logistic regression analysis identified Hcy as an independent risk factor for CVA, with an odds ratio of 11.4 (95% confidence interval 3.5-37.7), which remained significant after adjustment on other variables. We conclude that an elevated Hcy level is associated with a risk of occlusive arterial accidents in patients with chronic renal failure and that hyperhomocysteinemia contributes to the accelerated atherosclerosis complicating chronic uremia.

Abstract Despite recent technical advances in underwater technology, the inspection of steel jacket structures is still a very costly activity, However it is recognised in the industry that inspection costs could be further reduced by combining technical advances with a much more rigorous planning philosophy. This paper presents the preliminary results of a two-year project carried out jointly by Quest Consulting Ltd. and the University of Aberdeen, Scotland. The aim has been to develop practical methods and tools for targeting the underwater inspection of offshore structures in areas of greatest criticality on a sound scientific basis. The work has involved an evaluation of traditional methods of inspection planning and the development of a practical risk-based strategy capable of minimizing the inspection costs of offshore structures while maintaining effective safeguards against structural deterioration, The benefits of this new inspection planning strategy are discussed hereafter. Introduction Underwater inspection, repair and maintenance (IRM) of offshore structures consumes a major proportion of the overall maintenance budget and consequently any reduction in this area is expected to have significant impact on the overall costs. Regular inspection of offshore jackets is carried out as part of the efforts to guarantee structural integrity and to meet statutory requirements for certification. Actual inspection planning in the UK North Sea is still very much a qualitative process mainly based on engineering judgement and experience. Technical advances have been achieved in recent years, particularly in ROV (Remotely Operated Vehicle) capability, which have led to a general reduction in highly expensive diver time. However there is a common appreciation of the need for scientific inspection planning which would reduce further the total cost of inspection activity whilst at the same time maintaining or improving the effectiveness of the work carried out. The underwater inspection of steel offshore installations is concerned with the examination of specific areas and components which are normally hidden from view, in search of major or minor defects, flaws or other conditions which could affect the integrity of the structure or the functioning of the whole installation. Jacket structures will have some components whose integrity is critical to the reliability of the structure, while others will not have a great effect on the system reliability. Jacket structures are therefore ideal candidates for targeted risk-based inspection planning strategies where both the probability and consequences of failure of each component are taken into account. A new inspection planning strategy, which uses the concept of risk to assess inspection priorities, has already been outlined in a previous publication. This strategy has now been developed further into an applicable scientifically sound inspection planning methodology for jacket structures. This methodology comprises two distinct steps. A semi-probabilistic ranking tree approach is first used in order to make an initial assessment of the areas of greatest criticality. The results of this method are then used in a probabilistic approach to produce a cost effective inspection programme.

Recent knowledge into the pathophysiological mechanisms mediating the immune abnormalities characteristic of end-stage renal disease (ESRD) has focused on the dual activation versus deficiency state of immunocompetent cells. Despite major advances in renal replacement therapy, notably hemodialysis, no significant improvement in the immune status of uremic patients has been achieved. After a brief review of the role of T cells and B cells in the normal immune response, the functional and phenotypic T and B cell abnormalities observed in uremic patients are presented. Special emphasis is placed on our recent findings indicating that these abnormalities are observed at an early stage in the course of chronic renal failure, worsen with the progression of uremia, and are exacerbated by the dialysis procedure. The previous hypotheses that could reconcile the so-called Janus-faced behavior of T cells in uremia are updated in light of the recent findings obtained in the search of therapeutic strategies that could counteract the impaired responsiveness of patients with ESRD to vaccination against hepatitis B virus. Perspectives of research aimed at elucidating the respective role of T helper cell subpopulations (Th1 and Th2) could contribute to understanding of the mechanisms of the multifaceted process of uremia-related immune dysregulation and of the rationale for possible immunointervention strategies.

According to some nephrologists, pregnancy has damaging effects on renal function in primary glomerulonephritis, but the evidence is conflicting. We evaluated the effect of pregnancy on the occurrence of end-stage renal failure (ESRF) in 360 patients with various histological forms of primary glomerulonephritis but with normal renal function (serum creatinine < or = 0.11 mmol/L) at presentation. In actuarial analyses, overall ESRF-free survival did not significantly differ between women who became pregnant after clinical onset of renal disease (n = 171) and those who did not conceive (n = 189). Furthermore, in a case-control study pregnancy did not emerge as a risk factor for progression to ESRF (odds ratio 1.15 [95% CI 0.61-2.18]), whereas the type of glomerulonephritis and hypertension were major determinants. We conclude that pregnancy does not affect the course of renal disease in patients who have normal renal function at conception.

Abstract International competition, and to some extent the CRINE initiative, have stimulated oil and gas operators to minimise production costs wherever possible. Underwater inspection, repair and maintenance (IRM) of the platform jacket consumes a major proportion of the overall maintenance budget and consequently any reduction in this area is likely to have a significant impact on overall costs. All offshore jackets arc inspected regularly to ensure structural integrity and satisfy the strict statutory requirements. Technical advances have been achieved in recent years, particularly in ROV capability, which have led to a general reduction in highly expensive diver time. However, it is widely recognised within the industry that inspection costs could be further reduced by combining such advances with a much more rigorous planning philosophy, the aim being to reduce the total amount of inspection activity whilst maintaining or improving the effectiveness of the work carried out. Quest Consulting Ltd and Aberdeen University are working jointly on a Teaching Company Scheme, part funded by the Government, to develop methods and tools for targeting the inspection of offshore structures at areas of greatest criticality on a sound scientific basis. This paper presents the results of ongoing research and proposes that planned inspection should include a refined risk assessment to rank components and define the most appropriate inspection methods and optimum inspection intervals for a given structure, This will result in the most cost effective approach to underwater inspection being implemented. Introduction Regular inspection of offshore structures is carried out by the offshore industry as part of the efforts to guarantee the continued integrity of structures and to meet statutory requirements for certification. Offshore inspection is expensive, particularly underwater, and despite the technological advances that have been achieved in recent years, it is recognised that there is much to be gained from a rational inspection strategy. The underwater inspection of steel offshore installations is concerned with the examination of specific areas and components which are normally hidden from view, in search of major or minor defects, flaws or other conditions which could affect the integrity of the structure or the functioning of the whole installation. In the UK sector a 5 year subsea recertification programme will generally comprise an annual swim round of the whole structure by ROV equipped with cameras and CP reading probes, as well as flooded member detection (FMD) on key members or selected weld inspection (i.e. close visual inspection with cleaning and NDT such as magnetic particle inspection). The detailed inspection of selected joints and members can be carried out either in one major survey or in a series of continuous surveys conducted over the recertification period. The most difficult aspect of the inspection planning of jacket structures is the selection of the joints and members for inspection, and the optimal inspection methods and frequency. Although steel jacket structures are highly tolerant of defects and contain many highly redundant components, there will be some components whose integrity is critical to the reliability of the structure. Jacket structures are therefore ideal candidates for targeted inspection planning where both the probability and consequences of failure of each component are taken into account. In such a risk-based process the structural consequences of failure of a member can be determined by system reliability analysis. Risk and reliability analysis can allow the operator to target inspection activity to the most critical areas of the structure and define appropriate inspection methods and intervals. Historical Inspection Planning Approach A literature search was undertaken at the beginning of the project to define the current North Sea practices on inspection planning. P. 383

Pulmonary aspergillosis is now the main cause of death in chronic granulomatous disease (CGD); it may occur before the age of one year and then often reveals CGD.A male newborn was referred to hospital at 27 days of age for fever (39 degrees C), hemodynamic failure and biological inflammation syndrome caused by pulmonary infection. Chest CT scan revealed multiple and bilateral intraparenchymatous nodules. An open lung biopsy showed histiocystic granuloma with multinucleated giant cells. Culture of tracheal, bronchoalveolar lavage samples and lung biopsy grew positive for Aspergillus fumigatus. Impaired chemiluminescence production by neutrophils was detected, enabling the diagnosis of CGD. It was later confirmed by the study of neutrophils functions. The child recovered after 12 months of parenteral amphotericin B therapy.A febrile multifocal pneumopathy occurring in infancy should lead to consider the possibility of CGD which may be confirmed by the chemiluminescence test.

Concomitant immune deficiency and activation of immuno-competent cells, together with a disequilibrium between inflammation-inducing cytokines and their specific natural inhibitors is the basis of our current understanding of immune system dysregulation in patients with chronic uraemia. These anomalies may even be accentuated by dialysis. Clinically, bacterial infections, viral hepatitis and amyloidosis all play important roles. Humoral factors include abnormal immunoglobulin response to specific antibodies and complement activation. The response of T lymphocytes, long sought as the origin of the immunodeficiency associated with chronic uraemia, is also significantly decreased in these patients. The decreased antibody responses to specific stimuli may be related to B cell dysfunction. Monocyte and polymorphonuclear cell reactions are also perturbed. A deficiency in natural killer cells is observed although the mechanisms involved and the consequences are still debated. The factors determining the anomalies leading to immune system dysregulation in chronic uraemia and dialysis and their relationship with the reduction in active nephron mass as well as their metabolic and/or endocrine consequences remain to be fully described. A better understanding of the mechanisms involved should lead to new strategies for immuno-intervention in patients with chronic renal failure and help in optimizing haemodialysis.

The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.

Treatment of human beta 2 microglobulin (beta 2m) with defined oxygen-derived species generated by treatment with gamma-radiation was studied. As assessed by SDS/PAGE, the hydroxyl radicals (.OH) caused the disappearance of the protein band at 12 kDa that represents beta 2m, and cross-linked the protein into protein bands stable to both SDS and reducing conditions. However, when .OH was generated under oxygen in equimolar combination with the superoxide anion radical (O2.-), the high-molecular-mass protein products were less represented, and fragmented derivatives were not obviously detectable. Exposure to .OH alone, or to .OH + O2.- in the presence of O2, induced the formation of beta 2m protein derivatives with a more acidic net electrical charge than the parent molecule. In contrast, O2.- alone had virtually no effect on molecular mass or pI. Changes in u.v. fluorescence during .OH attack indicated changes in conformation, as confirmed by c.d. spectrometry. A high concentration of radicals caused the disappearance of the beta-pleated sheet structure and the formation of a random coil structure. Loss of tryptophan and significant production of dityrosine (2,2′-biphenol type) were noted, exhibiting a clear dose-dependence with .OH alone or with .OH + O2.-. The combination of .OH + O2.- induced a pattern of changes similar to that with .OH alone, but more extensive for c.d. and tryptophan oxidation (2 Trp/beta 2m molecule), and more limited for dityrosine formation. Lower levels of these oxidative agents caused the reproducible formation of species at 18 and 25 kDa which were recognized by antibodies against native beta 2m. These findings provide a model for the protein pattern observed in beta 2m amyloidosis described in the literature.

In the first part of this study, we reported that antibody-dependent cellular cytotoxicity (ADCC) mediated by human polymorphonuclear (PMN) and mononuclear (MN) phagocytes against anti-T-cell monoclonal-antibody-(mAb)-coated T lymphocytes, is mainly dependent upon the generation of reactive oxygen intermediates (ROI) for PMN, whereas MN-mediated ADCC depends on both oxidative and non-oxidative cytolytic events. Using mouse effector cells from various organs and at various maturation or activation states, the present report shows that in this ADCC model against mAb-coated normal T cells, resident spleen (SPC) and peritoneal exudate (PEC) cells selectively bound and developed oxidative responses to these mAb-coated normal target cells but remained ineffective in ADCC. Similar data were obtained with inflammatory recruited (thioglycollate-elicited or Biogel granuloma-induced) macrophages, whereas immunologically activated macrophages (from BCG-treated mice) mediated both strong oxidative responses and potent ADCC reactions. In contrast, and as in the human system, both resident (from bone marrow) and inflammatory PMN phagocytes exerted significant lysis of these mAb-sensitized normal lymphoid cells. These findings, which are similar to those reported in ADCC against tumour target cells, strongly suggest that the nature (normal or tumoral) of the target cell does not influence the lytic mechanisms of macrophage-mediated ADCC and that these latter require activated macrophages and, like PMN, involve strong (if not exclusive) ROI participation.

Le radium 226, element radiotoxique naturel, doit etre examine en regard de la radioprotection de la population critique. La consommation de poissons vivant dans l’environnement aquatique des sites miniers contribue, en particulier, au transfert du 226 Ra a l’homme ; une consommation annuelle de 10 kg de ces poissons correspondrait au maximum a 1 ou 2 % de la limite de la dose population. L’etude du transfert dans un ecosysteme simplifie (eau, sediment, algue planctonique, daphnie, gammare, chironome, carpe) dont le dernier maillon est un poisson susceptible d'etre consomme par l’homme (la truite) est envisagee dans le but de mettre en evidence l'importance de cette voie trophique. Ce travail concerne la contamination par l’eau du premier maillon concerne, une algue planctonique ubiquiste ; Scenedesmus obliquus. On montre que la capacite de fixation du radium par cette algue est maximale en debut de croissance et que, dans tous les cas (concentrations en radium dans le milieu comprises entre 360 et 36 000 Bq.1-1 et differents moments de contamination de la culture en fonction du stade de son developpement), le facteur de concentration atteint, apres une periode de contamination de 15 jours, une valeur d'equilibre proche de 10 000.

The study is based on data covering the water, sediments, plants and fish sampled over a 20-year period at 15 stations along French rivers. Three geographic zones were investigated: one containing a uranium mining complex (Zone 1), another including five major rivers along which nuclear power plants are sited (Zone II) and a third unaffected by nuclear activities (Zone III). Natural radioactivity basically involves 238U, 226Ra and 210Pb in the uranium series, 232Th from the thorium series, 40K and 7Be. The natural radioactivity in Zone II is not different from Zone III, and is thus unaffected by waste discharges from nuclear power plants. The most abundant radionuclide is 40K, while the other nuclides are often found in trace amounts near the detection threshold of the analysis method used (Ge gamma spectrometry with a 15-hour counting period). The 226Ra and 238U concentrations observed in Zone I are at least an order of magnitude higher than in the other two zones due to authorised waste discharges from the Lodève mining complex, but only a small stream is affected. The measured 226Ra concentrations would result in an annual whole body committed dose equivalent attributable to a 200 g weekly fish consumption from this stream of 4.4 x 10-5 Sv.y-1, or 0.86% of the maximum permissible dose (5 mSv).

HBs antigen (HBsAg) has been followed up every month in 440 hemodialyzed patients, typed for 26 HLA alleles of the A and B loci. An abnormally high rate of the HL-A-A1, B8 association (18.6%) was found in the group of patients able to eliminate HBsAg, when compared with the normal French population (5.05%, p less than 10(-4), and with the group of patients unable to eliminate HBsAg (7.0%, less than 0.01). Chronic aggressive hepatitis was only found in the latter. This high frequency of the HLA-A1, B8 association has also been found in patients with seronegative active chronic hepatitis and suggests that this phenotype might be associated with high immune response against HBsAg.

Nous avons verifie in situ qu’un test utilisant les mousses aquatiques — introduction dans l'eau de sacs confectionnes avec du grillage plastique et contenant une petite quantite de mousses — est, en particulier, envisageable pour le controle radioecologique d’un complexe minier d’uranium. Ce test possede, en effet, les qualites requises : simplicite de mise en œuvre, fiabilite et faible cout. Il peut, en meme temps, permettre d’evaluer la pollution minerale due, par exemple, a la presence de metaux lourds, et la pollution organique par des produits comme les derives chlores.

Two girls had delayed umbilical cord detachment, recurrent bacterial infection, inability to form pus, and marked leucocytosis. Their phagocytes were defective in tests of adherence, random migration, chemotaxis, and oxidative burst. NK activity was virtually absent. This rare disorder, due to an inherited absence of a 180 kilodalton membrane glycoprotein on polymorphonuclear cells, is usually lethal within 2 years. Allogeneic HLA-matched bone-marrow transplantation done at ages 4 months in one patient and 2 years in the other after intensive conditioning was successful and resulted in nearly complete correction of phagocytic cell function and NK activity within two months. One patient died 9 months after transplantation from severe chronic graft-versus-host disease with obstructive bronchopneumopathy. The other is doing well 1 year after transplantation and showing stable chimerism and normal phagocytic function.

Within the first minute after incubation with the mouse anti-human T cell orthoclone monoclonal antibodies OKT3, OKT4, and OKT8, and in the absence of complement, human monocytes generate a burst of highly reactive oxygen metabolites as detected by a luminol-dependent photometric chemiluminescence (CL) assay. The kinetics of the CL responses to these antibodies are identical to that induced by OKM1, the monoclonal antibody to human monocytes and granulocytes. With regard to CL response intensities, OKM1 induces the maximal response and those of OKT3, OKT4, and OKT8 closely reflect the proportion of T cell subsets recognized by these antibodies in peripheral blood. This reaction is also observed when monoclonal antibodies against mouse Lyt surface determinants (Lyt-1 and Lyt-2) and Thy-1 antigen are tested against murine spleen cells. This murine model was further used to investigate the specificity and the mechanism of this reaction. It was demonstrated that the CL response is Lyt antigen specific, occurs upon addition of monoclonal IgG but not IgM antibodies, requires the concomitant presence of CL-producing cells (CLPC) (promonocytes, monocytes, macrophages, and/or granulocytes) and of fully differentiated T cells, and lastly, is mediated via a T cell opsonization process. Selective blockade of bone marrow cell Fc receptors (FcR II) with monoclonal anti-mouse FcR II antibody inhibits the CL response to IgG2b anti-T cell antibody-coated thymocytes and thus strongly suggests that the stimulation of CLPC oxidative metabolism in this model results from the binding of opsonized T cells to plasma membrane Fc receptors. These observations lend additional support to increasing evidence that the initiation of effector functions by monoclonal anti-T cell antibodies may be strictly dependent upon the presence of monocytes and/or macrophages.