Morphological characterization of the hemocytes of the pulmonate snail Biomphalaria tenagophila

The blood cells of the pulmonate snail Biomphalaria tenagophila, an important transmiter of the trematode Schistosoma mansoni in Brazil, were examined by ligth and transmission electron microscopy (TEM). Two hemocyte types were identified: hyalinocytes and granulocytes. Hyalinocytes are small young (immature), poorly spreading cells, which have a high nucleocytoplasmic ratio and are especially rich in free ribosomes. They do not appear to contain lysosome-like bodies and represent less than 10% of the circulating hemocytes. Granulocytes are larger hemocytes which readily spread on glass surface and which strongly react to the Gomori substrate, indicating the enzyme acid phosphatase usually found in lysosomes. Ultra-structurally, they contain a well-developed rough endoplasmic reticulum, dictyosomes and some some lysosome-like dense bodies. Granulocytes do not exhibit a characteristic granular aspect and the few granules observed in the cytoplasm should correspond to a lysosome system. They were named granulocytes instead of amoebocytes to use the same terminology adopted for Biomphalaria glabrata in order to make easier comparative studies. This is a preface study for more specific investigations on the functional activities of the blood cells of B. tenagophila and their interactions with the trematode parasite.

The Disadvantage of winning an election

This paper analyzes the problem that an incumbent faces during the legislature when deciding how to react to popular initiatives or policy proposals coming from different sources. We argue that this potential source of electoral disadvantage that the incumbent obtains after being elected can jeopardize the reelection possibilities of the incumbent. We analyze the decision of the incumbent when facing reelection and we characterize the conditions under which the advantages that the incumbent obtains can overcome the disadvantages. Finally, we use the results of this analysis to discuss some implications of the use of mechanisms of direct democracy like referenda and popular assemblies on electoral competition.

Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.

Myocardial ischemic postconditioning (PosC) describes an acquired resistance to lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria permeability transition. Recent observations indicated that PostC is associated with free radicals generation, including nitric oxide (NO(.)) and superoxide (O2 (.-)), and that cardioprotection is abrogated by antioxidants. Since NO. And O2 (. -) react to form peroxynitrite, we hypothesized that postC might trigger the formation of peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds ischemia/30 seconds reperfusion) was applied at the end of index ischemia. In a subgroup of rats, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (FeTPPS) was given intravenously (10 mg/kg(-1)) 5 minutes before PostC. Myocardial nitrotyrosine was determined as an index of peroxynitrite formation. Infarct size (colorimetric technique and plasma creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip pressure transducer), were determined. A significant generation of 3-nitrotyrosine was detected just after the PostC manoeuvre. PostC resulted in a marked reduction of infarct size, CK release and LV systolic dysfunction. Treatment with FeTPPS before PostC abrogated the beneficial effects of PostC on myocardial infarct size and LV function. Thus, peroxynitrite formed in the myocardium during PostC induces cardioprotective mechanisms improving both structural and functional integrity of the left ventricle exposed to ischemia and reperfusion in vivo.

Experimental approaches in the targeting of photodynamic therapeutics

RÉSUMÉ : Chez l'homme, le manque de sélectivité des agents thérapeutiques représente souvent une limitation pour le traitement des maladies. Le ciblage de ces agents pour un tissu défini pourrait augmenter leur sélectivité et ainsi diminuer les effets secondaires en comparaison d'agents qui s'accumuleraient dans tout le corps. Cela pourrait aussi améliorer l'efficacité des traitements en permettant d'avoir une concentration localisée plus importante. Le ciblage d'agents thérapeutiques est un champ de recherche très actif. Les stratégies sont généralement basées sur les différences entre cellules normales et malades. Ces différences peuvent porter soit sur l'expression des molécules à leurs surfaces comme des récepteurs ou des transporteurs, soit sur les activités enzymatiques exprimées. Le traitement thérapeutique choisi ici est la thérapie photodynamique et est déjà utilisé pour le traitement de certains cancers. Cette thérapie repose sur l'utilisation de molécules qui réagissent à la lumière, les photosensibilisants. Elles absorbent l'énergie lumineuse et réagissent avec l'oxygène pour former des radicaux toxiques pour les cellules. Les photosensibilisants utilisés ici sont de deux natures : (i) soit ils sont tétrapyroliques (comme les porphyrines et chlorines), c'est à dire qu'ils sont directement activables par la lumière ; (ii) soit ce sont des prodrogues de photosensibilisants comme l'acide 5aminolévulinique (ALA) qui est transformé dans la cellule en protoporphyrine IX photosensibilisante. Dans le but d'augmenter la sélectivité des photosensibilisants, nous avons utilisé deux stratégies différentes : (i) le photosensibilisant est modifié par le greffage d'un agent de ciblage ; (ii) le photosensibilisant est incorporé dans des structures moléculaires de quelques centaines de nanomètres. Les sucres et l'acide folique sont des agents de ciblage largement établis et ont été utilisés ici car leurs récepteurs sont surexprimés à la surface de nombreuses cellules malades. Ainsi, des dérivés sucres ou acide folique de l'ALA ont été synthétisés et évalués in vitro sur de nombreuses lignées cellulaires cancéreuses. La stratégie utilisant l'acide folique est apparue incompatible avec l'utilisation de l'ALA puisque aucune photosensibilité n'a été induite par le composé. La stratégie utilisant les sucres a, par ailleurs, provoquée de bonnes photosensibilités mais pas d'augmentation de sélectivité. En parallèle, la combinaison entre les propriétés anticancéreuses des complexes métalliques au ruthénium avec les propriétés photosensibilisantes des porphyrines, a été évaluée. En effet, les thérapies combinées ont émergé il y a une dizaine d'années et représentent aujourd'hui de bonnes alternatives aux monothérapies classiques. Des ruthenium(I1)-arènes complexés avec la tetrapyridylporphyrine ont ainsi présenté de bonnes cytotoxicités et de bonnes phototoxicités pour des cellules de mélanomes. Des porphyrines ont aussi été compléxées avec des noyaux de diruthénium et ce type de dérivé a présenté de bonnes phototoxicités et une bonne sélectivité pour les cellules cancéreuses de l'appareil reproducteur féminin. L'incorporation de photosensibilisants tétrapyroliques a finalement été effectuée en utilisant des nanoparticules (NP) biocompatibles composées de chitosan et de hyaluronate. L'effet de ces NP a été évalué pour le traitement de la polyarthrite rhumatoïde (PR). Les NP ont d'abord été testées in vitro avec des macrophages de souris et les résultats ont mis en évidence de bonnes sélectivités et photosensibilités pour ces cellules. In vivo chez un modèle marin de la PR, l'utilisation de ces NP a révélé un plus grand temps de résidence des NP dans le genou de la souris en comparaison du temps obtenu avec le photosensibilisant seul. Le traitement par PDT a aussi démontré une bonne efficacité par ailleurs égale à celle obtenue avec les corticoïdes utilisés en clinique. Pour finir, les NP ont aussi démontré une bonne efficacité sur les myelomonocytes phagocytaires humains et sur les cellules contenues dans le liquide synovial de patients présentant une PR. Tous ces résultats suggèrent que les deux stratégies de ciblage peuvent être efficaces pour les agents thérapeutiques. Afm d'obtenir de bons résultats, il est toutefois nécessaire de réaliser une analyse minutieuse de la cible et du mode d'action de l'agent thérapeutique. Concernant les perspectives, la combinaison des deux stratégies c'est à dire incorporer des agents thérapeutiques dans des nanostructures porteuses d'agents de ciblage, représente probablement une solution très prometteuse. SUMMARY : In humans, the lack of selectivity of drugs and their high effective concentrations often represent limitations for the treatment of diseases. Targeting the therapeutical agents to a defined tissue could enhance their selectivity and then diminish their side effects when compared to drugs that accumulate in the entire body and could also improve treatment efûciency by allowing a localized high concentration of the agents. Targeting therapeutics to defined cells in human pathologies is a main challenge and a very active field of research. Strategies are generally based on the different behaviors and patterns of expression of diseased cells compared to normal cells such as receptors, proteases or trans-membrane carriers. The therapeutic treatment chosen here is the photodynamic therapy and is already used in the treatment of many cancers. This therapy relies on the administration of a photosensitizer (PS) which will under light, react with oxygen and induce formation of reactive oxygen species which are toxic for cells. The PSs used here are either tetrapyrolic (i. e. porphyries and chlorins) or prodrugs of PS (5-aminolevulinic acid precursor of the endogenous protoporphyrin Imo. In order to improve PS internalization and selectivity, we have used two different strategies: the modification of the PSs with diseased cell-targeting agents as well as their encapsulation into nanostructures. Sugars and folic acid are well established as targeting entities for diseased cells and were used here since their transporters are overexpressed on the surface of many cancer cells. Therefore sugar- and folic acid-derivatives of 5-aminolevulinic acid (ALA) were synthesized and evaluated in vitro in several cancer cell lines. The folic acid strategy appeared to be incompatible with ALA since no photosensitivity was induced while the strategy with sugars induced good photosensitivites but no increase of selectivity. Alternatively, the feasibility of combining the antineoplastic properties of ruthenium complexes with the porphyrin's photosensitizing properties, was evaluated since combined therapies have emerged as good alternatives to classical treatments. Tetrapyridylporphyrins complexed to ruthenium (I17 arenes presented good cytotoxicities and good phototoxicities toward melanoma cells. Porphyries were also complexed to diruthenium cores and this type of compound presented good phototoxicities and good selectivity for female reproductive cancer cells. The encapsulation of tetrapyrolic PSs was finally investigated using biocompatible nanogels composed of chitosan and hyaluronate. The behavior of these nanoparticles was evaluated for the treatment of rheumatoid arthritis (RA). They were first tested in vitro in mouse macrophages and results revealed good selectivities and phototoxicities toward these cells. In vivo in mice model of RA, the use of such nanoparticles instead of free PS showed longer time of residence in mice knees. Photodynamic protocols also demonstrated good efficiency of the treatment comparable to the corticoid injection used in the clinic. Finally our system was also efficient in human cells using phagocytic myelomonocytes or using cells of synovial fluids taken from patients with RA. Altogether, these results revealed that both strategies of modification or encapsulation of drugs can be successful in the targeting of diseased cells. However, a careful analysis of the target and of the mode of action of the drug, are needed in order to obtain good results. Looking ahead to the future, the combination of the two strategies (i.e. drugs loaded into nanostructures bearing the targeting agents) would represent probably the best solution.

Macroeconomics of extensive margins: a simple model

How do monopolistically competitive industries react to shocks in the context of a New Keynesian macro model? I bridge macroeconomics and trade theory by considering market dynamics. I use an analytically tractable closed-economy model with endogenous entry of firms and show the implications of markets structure for the transmission of real shocks on aggregate variables and welfare. Shock sources become crucial for the results: traditional productivity shocks cause an extensive effect on production; shocks on innovation cause an intensive impact. More patient populations bring the economy to a richer market, although it cushions the extensive effect after an innovation shock.

A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.

État de stress post-traumatique chez les mères et chez les pères d'enfants prématurés: similitudes et différences = Prematurity and parental post-traumatic stress disorder: similarities and differences

Objectifs Évaluer et comparer la présence de symptômes de stress post-traumatique, en fonction de la gravité de la prématurité, chez les mères et chez les pères de bébés nés prématurément. Méthode En fonction du score de risque périnatal (PERI) du bébé, les parents des prématurés (âge gestationnel moins de 34 semaines) ont été divisés en deux groupes : les parents de prématurés à faible risque (n = 16) et à haut risque (n = 26). Les symptômes d'intrusion et d'évitement, de l'état de stress post-traumatique, ont été évalués chez les parents à l'aide d'un questionnaire, l'Impact of Event Scale (IES). Leurs réponses ont été comparées à un groupe témoin de parents de nouveau-nés à terme (n = 24). Les différences entre les réponses des mères et des pères, ont été analysées. Résultats Les parents de bébés prématurés sont plus à risque que les parents de nouveau-nés à terme de présenter des symptômes de stress post-traumatique. Les mères en lien avec le fait même de la prématurité du bébé, les pères en lien avec la gravité de la prématurité. Les mères et les pères des prématurés des deux groupes (prématurés à faible risque, prématurés à haut risque) décrivent des symptômes d'intrusion, alors que les symptômes d'évitement sont décrits par toutes les mères, mais seulement par les pères de prématurés à haut risque périnatal. Conclusion La naissance prématurée est susceptible d'entraîner l'apparition de symptômes de stress post-traumatique chez les parents. Les mères et les pères réagissent différemment. Objectives Evaluation of the symptoms of parental post-traumatic stress disorder (PTSD), according to the severity of the prematurity, in mothers and fathers of premature babies. Materials and methods According to the Perinatal Risk Inventory (PERI), the parents of premature infants (gestational age less than 34 weeks) were divided into two groups, parents of a low-risk premature infants (n = 16) and of high-risk premature infants (n = 26). The symptoms of intrusion and avoidance, as a part of the post-traumatic stress disorder, were evaluated by an autoadministrated questionnaire, the Impact of Event Scale (IES). Their responses were compared with a control group of parents of full-term infants (n = 24). The differences in the answers of mothers and fathers were analysed. Results The occurrence of symptoms of post-traumatic stress disorder is increased in parents of preterm infants compared with the control group. Whereas mothers of premature infants are at risk of presenting symptoms of PTSD, linked to the prematurity, with fathers the infant perinatal risk factors play a greater role. The symptoms of intrusion are present in mothers and fathers of preterm infants of both groups. Mothers of both groups present avoidance symptoms, although only fathers of high-risk preterm infants present them. Conclusions Premature birth has an impact on both parents in terms of post-traumatic stress reactions. However, mothers and fathers react in different ways according to the severity of the prematurity.

Physically based walking simulation

Hem realitzat l’estudi de moviments humans i hem buscat la forma de poder crear aquests moviments en temps real sobre entorns digitals de forma que la feina que han de dur a terme els artistes i animadors sigui reduïda. Hem fet un estudi de les diferents tècniques d’animació de personatges que podem trobar actualment en l’industria de l’entreteniment així com les principals línies de recerca, estudiant detingudament la tècnica més utilitzada, la captura de moviments. La captura de moviments permet enregistrar els moviments d’una persona mitjançant sensors òptics, sensors magnètics i vídeo càmeres. Aquesta informació és emmagatzemada en arxius que després podran ser reproduïts per un personatge en temps real en una aplicació digital. Tot moviment enregistrat ha d’estar associat a un personatge, aquest és el procés de rigging, un dels punts que hem treballat ha estat la creació d’un sistema d’associació de l’esquelet amb la malla del personatge de forma semi-automàtica, reduint la feina de l’animador per a realitzar aquest procés. En les aplicacions en temps real com la realitat virtual, cada cop més s’està simulant l’entorn en el que viuen els personatges mitjançant les lleis de Newton, de forma que tot canvi en el moviment d’un cos ve donat per l’aplicació d’una força sobre aquest. La captura de moviments no escala bé amb aquests entorns degut a que no és capaç de crear noves animacions realistes a partir de l’enregistrada que depenguin de l’interacció amb l’entorn. L’objectiu final del nostre treball ha estat realitzar la creació d’animacions a partir de forces tal i com ho fem en la realitat en temps real. Per a això hem introduït un model muscular i un sistema de balanç sobre el personatge de forma que aquest pugui respondre a les interaccions amb l’entorn simulat mitjançant les lleis de Newton de manera realista.

Cre recombinase-mediated inactivation of H-2Dd transgene expression: evidence for partial missing self-recognition by Ly49A NK cells.

We have established H-2D(d)-transgenic (Tg) mice, in which H-2D(d) expression can be extinguished by Cre recombinase-mediated deletion of an essential portion of the transgene (Tg). NK cells adapted to the expression of the H-2D(d) Tg in H-2(b) mice and acquired reactivity to cells lacking H-2D(d), both in vivo and in vitro. H-2D(d)-Tg mice crossed to mice harboring an Mx-Cre Tg resulted in mosaic H-2D(d) expression. That abrogated NK cell reactivity to cells lacking D(d). In D(d) single Tg mice it is the Ly49A+ NK cell subset that reacts to cells lacking D(d), because the inhibitory Ly49A receptor is no longer engaged by its D(d) ligand. In contrast, Ly49A+ NK cells from D(d) x MxCre double Tg mice were unable to react to D(d)-negative cells. These Ly49A+ NK cells retained reactivity to target cells that were completely devoid of MHC class I molecules, suggesting that they were not anergic. Variegated D(d) expression thus impacts specifically missing D(d) but not globally missing class I reactivity by Ly49A+ NK cells. We propose that the absence of D(d) from some host cells results in the acquisition of only partial missing self-reactivity.

Plaisir et souffrance au travail : une lecture psychodynamique au sein d'un office régional de placement suisse

En Suisse, comme dans la plupart des pays industrialisés, le stress au travail et l'épuisement qui en découle sont devenus, au cours des dernières décennies, une réalité qui ne cesse de s'accentuer. Différentes disciplines scientifiques ont tenté de rendre compte, depuis le milieu du siècle dernier, des difficultés rencontrées par les individus dans le cadre de leur travail, avec une prédominance marquée pour des analyses de type causaliste. Dans le cadre de cette étude doctorale, nous nous sommes penché sur le cas d'un office régional de placement, mais avec une perspective sensiblement différente. La grille de lecture psychodynamique utilisée permet en effet de donner accès au sens des situations de travail et d'ouvrir sur une compréhension originale des mécanismes à l'origine des problèmes de santé mentale au travail. Cette approche permet ainsi de comprendre les rapports complexes que les individus entretiennent avec leur travail tel que structuré et organisé, et d'analyser leur expérience en termes de plaisir, de souffrance, de défenses face à la souffrance et de répercussions sur la santé. Dans ce but, nous avons utilisé une méthodologie basée sur des entrevues collectives, afin de stimuler l'expression libre des travailleurs. L'enquête s'est déroulée en deux temps : une première série d'entretiens de groupe a permis la récolte des données empiriques, puis une seconde série, appelée entretiens de restitution, a donné la possibilité aux participants de réagir sur l'interprétation de leur parole faite par le chercheur, et de valider l'analyse. Nos résultats mettent alors en évidence que le travail, tel qu'organisé au sein de cette institution de service public, apparaît considérablement pathogène, mais heureusement compensé par le pouvoir structurant de la relation d'aide aux assurés. Ils montrent également que l'expérience subjective de travail des participants a pour principales sources de souffrance la perception désagréable d'un manque de reconnaissance, d'autonomie et de pouvoir sur leurs actes. - In Switzerland and in other industrialized countries, work-related stress and resulting burn-out has become an ever increasing problem in recent decades. Many researchers Jrom many different fields have made efforts to understand the difficulties employees encounter at work since the middle of the last century. Most of this research is based on a cause and effect analysis approach. For this doctoral research project, we have analyzed cases handled by an unemployment office in Switzerland. We have taken a novel approach by using a number of psychodynamic criteria which permitted us to interpret situations at work and to open up a new way of understanding the mechanisms at work which lead to mental health problems. This approach allows us to understand account the complex relationship people have towards structured and organized work as well as to take into account and to analyze their experience in terms of pleasure, suffering, defense mechanisms against suffering and the consequences on their mental health. In order to achieve this goal we performed collective interviews in order to encourage workers to express themselves freely. The interviews were divided into two series. The first series of group interviews allowed us to collect empirical statistics and the second series gave the workers an opportunity to react to the researchers ' analysis of their answers and to validate the researchers ' interpretation of their answers. Our results show that work has considerable negative effects on mental health. Fortunately, these negative effects are counterbalanced by the psychological support system offered by the unemployment office. Our project also shows that the subjective negative experiences of workers are caused by their perceptions of being under-appreciated, lack of autonomy and having no power over their acts.

Expression, purification and biochemical characterization of recombinant Ca-dependent protein kinase 2 of the malaria parasite Plasmodium falciparum.

Calcium-dependent protein kinases (CDPKs) are serine/threonine kinases that react in response to calcium which functions as a trigger for several mechanisms in plants and invertebrates, but not in mammals. Recent structural studies have defined the role of calcium in the activation of CDPKs and have elucidated the important structural changes caused by calcium in order to allow the kinase domain of CDPK to bind and phosphorylate the substrate. However, the role of autophosphorylation in CDPKs is still not fully understood. In Plasmodium falciparum, seven CDPKs have been identified by sequence comparison, and four of them have been characterized and assigned to play a role in parasite motility, gametogenesis and egress from red blood cells. Although PfCDPK2 was already discovered in 1997, little is known about this enzyme and its metabolic role. In this work, we have expressed and purified PfCDPK2 at high purity in its unphosphorylated form and characterized its biochemical properties. Moreover, propositions about putative substrates in P. falciparum are made based on the analysis of the phosphorylation sites on the artificial substrate myelin basic protein (MBP).

The role of queen pheromones in social insects: queen control or queen signal?

Queens and workers in social insect colonies can differ in reproductive goals such as colony-level sex allocation and production of males by workers. That the presence of queen(s) often seems to affect worker behaviour in situations of potential conflict has given rise to the idea of queen control over reproduction. In small colonies queen control is possible via direct aggression against workers, but in large colonies queens cannot be effectively aggressive towards all the workers. This, plus evidence that queen-produced chemicals affect worker behaviour, has led to the conclusion that physical intimidation has been replaced by pheromonal queen control, whereby queen(s) chemically manipulate workers into behaving in ways that increase the queen's fitness at the worker's expense. It is argued in this paper, however, that pheromonal queen control has never conclusively been demonstrated and is evolutionarily difficult to justify. Proposed examples of pheromonal control are more likely to be honest signals, with workers' responses increasing their own inclusive fitness. A series of experimental and field studies in which positive results would give prima facie evidence for pheromonal queen control is suggested. Finally, three terms are defined: (1) pheromonal queen control for workers or subordinate queens being chemically manipulated into acting against their own best interests; (2) pheromonal queen signal for situations where workers or subordinate queens react to queen pheromones in ways that increase their, and possibly the queens', inclusive fitness; and (3) pheromonal queen effect where changes in the workers' or subordinate queens' behaviour have an unknown consequence on their inclusive fitness.

Changes induced in Biomphalaria glabrata (Say, 1818) following trials for artificial stimulation of its internal defense system

Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being the dominant feature. However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, exhibiting later a pattern of cercarial shedding and histopatopathological picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its internal defense system. Snails previously inoculated with irradiated miracídia (Group I); treated with S. mansoni antigens (Group II) or with a non-related parasite antigen (Group III) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of antigen injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with Capillaria hepatica. However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located elsewhere within the snail body.

Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.

A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorectal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma patients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumulation of antibody by external photoscanning and tomoscintigraphy, whereas none of the 20 sites of other cancer types gave positive results. One-third of the patients received F(ab')2 fragments of the MAb, which gave a slightly higher percentage (61%) of positive results than did intact MAbs (51%). A few patients scheduled for tumor resection were given injections simultaneously of 131I-labeled MAb and 125I-labeled normal immunoglobulin G. Antibody concentration in resected tumors was 3.6 to 6.3 times higher than the average antibody concentration in adjacent normal tissues (1.5, 3.4, and 9.4 as compared with normal mucosa, serosa, and fat, respectively), and the specificity indices, calculated by differential radioactivity analysis, ranged from 2.1 to 5.1. The results show the potential value and limitations of this particular MAb for tumor detection by immunoscintigraphy.

BAFF and the regulation of B cell survival.

The TNF family member BAFF is a fundamental survival factor for B cells. BAFF binds to three receptors, only one of which, BAFF-R, does not cross-react with the BAFF-related ligand APRIL. The survival function of BAFF on B cells is mediated mainly by BAFF-R and is particularly effective in transitional B cells. BAFF depletion leads to a considerable decrease in mature B cells, without apparent effect on B cell genesis. Consistently, BAFF overexpression results in an expanded B cell compartment and autoimmunity in mice. Elevated amounts of BAFF can be found in the serum of patients suffering from autoimmune diseases. The BAFF system is a promising target for the treatment of autoimmune diseases.