Extracorporeal photochemotherapy in a patient with Ki-1-positive anaplastic large-cell lymphoma

Behavior of hemocytes of the gastropod mollusc Biomphalaria glabrata was markedly changed on plastic by treatment of the substrate with 0.1 mg/ml poly-L-lysine compared to behavior on untreated plastic. On lysine, the cells showed minimal spreading, moved significantly faster, and formed aggregates. Cell-mediated cytotoxicity (CMC) assays were set up on the modified and untreated substrates to compare the killing capacities of B. glabrata hemocytes against Schistosoma mansoni sporocysts. Hemolymph from 1316-R1 (resistant) snails showed higher killing in lysine-treated wells; no significant difference in sporocyst mortality was observed in MO (susceptible) hemolymph between treated and untreated wells. The CMC assays on poly-L-lysine-treated plastic were used to compare the kinetics of parasite killing in hemolymph from 2 susceptible (MO, MRLc) and 2 resistant (1316-R1, 10R2) host strains. Marked differences could be observed between the two resistant snail strains, suggesting different mechanisms of parasite recognition, killing, or both.     

Intragastric alcohol causes endothelin release from feline pancreas

Infection with the digenean parasite Plagiorchis elegans dramatically reduced the reproductive output of Biomphalaria glabrata exposed to the parasite as juveniles or adults. The total number of eggs produced by infected snails was reduced to approximately 7 and 13% of control values, respectively. Parasitic castration was attributed to the presence of mother sporocysts that readily established in the tissues of this incompatible host. Infection did not result in the production of cercariae but significantly shortened the life span of juvenile and adult B. glabrata by approximately 23 and 10%, respectively. Plagiorchis elegans also castrated its compatible host, Stagnicola elodes.     

A time-lapse study of interactions between Echinostoma paraensei intramolluscan larval stages and adherent hemocytes from Biomphalaria glabrata and Helix aspersa

In vitro interactions between intramolluscan stages (sporocyst, daughter rediae, and metacercariae) of the trematode parasite Echinostoma paraensei and adherent hemocytes from the gastropods Biomphalaria glabrata (intermediate host) and Helix aspersa (non-host) were visualized by time-lapse videomicroscopy. Hemocytes of either species not exposed to E. paraensei displayed extensive mobility and activity of cellular extensions. Image analysis disclosed no significant change in the total surface area occupied by hemocytes in a selected field of view over 2 hr. Echinostoma paraensei exerted life stage-specific effects on the behavior of B. glabrata hemocytes; the cells moved away from sporocysts and daughter rediae but not encysted metacercariae. In the presence of sporocysts, hemocytes rounded up, whereas hemocytes adjacent to rediae assumed a stringy, beady appearance. Hemocytes close to the parasite were affected more rapidly than more distant cells. In 2 hr, a hemocyte-free "halo" formed around the parasite larvae, significantly reducing the hemocyte-occupied surface area (to 43% by sporocysts and to 70% by rediae). The changes induced by sporocysts and rediae are similar to those noted in both in vivo and in vitro studies of the B. glabrata-E. paraensei model system and are interpreted as manifestations of parasite-mediated interference with host hemocyte function. Helix aspersa (non-host) hemocytes were not affected, suggesting that E. paraensei-mediated effects on hemocytes exhibit a degree of specificity.     

Tissue reactions induced by Schistosoma mansoni in Biomphalaria glabrata

In Biomphalaria glabrata with a strong natural resistance, Schistosoma mansoni sporocysts are rapidly encapsulated by granulocytes and killed, mainly by the strong phagocytic activity of the cells. Irradiated Echinostoma paraensei sporocysts seem able to suppress the function of the granulocytes. Tissue reactions in snails with self-cure demonstrate: involvement of two types of cells, granulocytes and hyalinocyte-like cells; formation of amoeba-fibrous capsules; limited tendency of granulocytes to become attracted to the parasites; a slow process of parasite destruction; and a possible involvement of humoral factors. It seems that there is partial suppression of the granulocyte function in smails with self-cure.     

A laboratory-based approach to biological control of snails

Development of Schistosoma mansoni in the intermediate host Biomphalaria glabrata is influenced by a number of parasite and snail genes. Understanding the genetics involved in this complex host/ parasite relationship may lead to an often discussed approach of introducing resistant B. glabrata into the field as a means of biological control for the parasite. For the snail, juvenile susceptibility to the parasite is controlled by at least four genes, whereas one gene seems to be responsible for adult nonsusceptibility. Obtaining DNA from F2 progeny snails from crosses between parasite-resistant and -susceptible snails, we have searched for molecular markers that show linkage to either the resistant or susceptible phenotype. Both restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) approaches have been used. To date, using a variety of snail and heterologous species probes, no RFLP marker has been found that segregates with either the resistant or susceptible phenotype in F2 progeny snails. More promising results however have been found with the RAPD approach, where a 1.3 kb marker appears in nearly all resistant progeny, and a 1.1 kb marker appears in all susceptible progeny.     

Investigation of the life cycle and adult morphology of the avian blood fluke Austrobilharzia variglandis (Trematoda: Schistosomatidae) from Connecticut

This study was undertaken to expand the current knowledge of the life cycle and adult morphology of the avian schistosome Austrobilharzia variglandis, which causes a marine cercarial dermatitis in New England. The specific objectives were to: (1) investigate the seasonality of the infection in the molluscan intermediate host, Ilyanassa obsoleta; (2) determine which bird species are acting as natural definitive hosts for the parasite; and (3) characterize the morphology of the parasite using scanning electron microscopy (SEM). One-thousand individuals of I. obsoleta were collected each month for 14 consecutive months and examined for the parasite. Ten to 15 specimens of each of the following avian species, Larus argentatus, Larus delawarensis, Larus marinus, Phalacrocorax auritus, and Branta canadensis, and 2 individuals of Larus atrilla, were collected and examined for schistosomes. Twenty adult male and 10 adult female specimens of A. variglandis were processed for SEM. Ilyanassa obsoleta was found to maintain a relatively low prevalence of infection (0.7-5.1%) throughout the 14-mo study, but no fully developed cercaria were visible in sporocysts recovered from snails collected in winter months. The Larus species had both the highest prevalence (85-92.8%) and highest mean intensity (12.1-34.5 male worms) of infection with A. variglandis. These data suggest that overwintering snail populations can harbor viable infections and in the spring infect shore birds (or humans) with cercaria. The snail and definitive host data suggest that A. variglandis is a year-round resident of the state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraarterial infusion of anti-cancer agents. (A suitable technic introducing a polyethylene tube, with angiographic visualization, through the deep femoral artery directly into the artery in the abdomen selected for injection, using two kinds of guidewires) (author''s transl)

The authors have infected 127 B. glabrata by 2 miracidia of S. mansoni, either on the Same day, or introducing a second miracidium after 3, 7 and 16 days. 1 All the groups of planorbid snails had a low percentage of positivity (31 to 41 %). 2 The first cercarial emissions, in the 4 groups were scattered in the time, the delay being in correlation with the second infection. 3 In the snails reinfected after 3 and 7 days occured the highest emissions, those with the simultaneous double infection or second infection delayed to 16 days, had the lesser emissions. 4 An interval cycle of about 3 weeks was discovered for the highest emissions. All those phenomena are probably due to competition between the sporocysts born from both miracidia. Moreover, evident reduction of the fecundity in the positive snails were shown only after the beginning of the cercarial emissions, while a normal, or even increased fecundity was established in the prepatent period of the infected snails.     

Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the initial events in the pathogenesis of insulin-dependent diabetes mellitus?

When aiming at preventing IDDM in man, knowledge of the molecular mechanisms leading to beta cell destruction may facilitate identification of new possible intervention modalities. A model of IDDM pathogenesis in man suggests that cytokines, and IL-1 in particular, are of major importance in the initial events (Nerup et al 1994) (Fig. 1). In vitro rat experiments demonstrated that rhIL-1 beta inhibits beta cell function and induces beta cell death both in isolated islets of Langerhans and in the isolated perfused pancreatic gland. With the long term goal of identifying new modalities capable of preventing IDDM in man, the aim af this review was to investigate the effects of rhIL-1 beta on beta-cell function and viability in normal rats. This review discussed 1) the pharmacokinetics of IL-1 beta in rats as the basis for choice of route of administration and dose of rhIL-1 beta, 2) the effects and molecular mechanisms of IL-1 beta on temperature and food intake used as control parameters for successful injection of rhIL-1 beta in rats, 3) the effects of one or more injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms leading to IL-1 beta induced beta cell inhibition in vivo, and some possible intervention modalities based on the molecular mechanisms, 5) the effects of IL-1 beta on spontaneous diabetes mellitus in DP BB rats, and 6) the effects and molecular mechanisms of IL-1 beta induced inhibition of thyroid epithelial cell function and aggravated thyroiditis in DP BB rats, compared to the effects of IL-1 beta on rat beta cell function. Finally, this review discussed the effects of IL-1 beta on human beta cells in vitro, and the clinical relevance of these experiments, with special reference to a clinical trial with the aim of preventing IDDM in man. The pharmacokinetic studies suggested that IL-1 beta is distributed according to a two-compartment model with a first-order elimination. Interleukin-1 beta reached all the investigated organs in the rats, was accumulated in kidneys and was excreted in the urine. The data suggested that IL-1 beta also accumulated in the islets of Langerhans. After injection of 4.0 micrograms/kg pathophysiologically relevant concentrations of rhIL-1 beta were reached and intact rhIL-1 beta persisted for up to 5 hrs in plasma. Peripheral injections of IL-1 beta dose-dependently induced fever and anorexia in rats, probably via induction of PGE2 in the brain or in peripheral tissues thereafter passing the blood-brain barrier. Nitric oxide produced by cNOS seems to be a molecular mediator of IL-1 beta induced fever but not of anorexia. Fever and anorexia are well described effects of IL-1 beta in rats, and are as such usefull control parameters of the absorption and biological activity of IL-1 beta after peripheral injection. Injections of rhIL-1 beta to normal, non-diabetes prone rats induced initial beta cell stimulation followed by inhibition, in accordance with in vitro data. Furthermore, induction of peripheral insulin resistance coincided with beta cell inhibition after one daily injection for 5 days, leading to a transient diabetes mellitus-like state, characterized by hyperglycemia and hypoinsulinemia. At this time point, electron-microscopy did not demonstrate beta cell destruction. However, IL-1 beta induced intercellularly edema and microvillous processes on the beta cells, which might be early evidence of apoptosis. The diabetes mellitus-like state was not aggravated if the daily injections were continued beyond 5 days. Daily injections of rhIL-1 beta for 2 to 4 weeks induced formation of blocking IL-1 beta-antibodies in normal rats. Hence, injections exceeding 2 weeks should only be performed using species homologous IL-1 beta. The molecular mechanism of IL-1 beta induced beta cell inhibition in rats in vivo as in vitro, are likely to involve binding of IL-1 beta to the IL-1RtI, since the IL-1RtII is considered to be a decoy receptor. (ABSTRACT TRUNCATED)     

Host choice by larval parasites: a study of Biomphalaria glabrata snails and Schistosoma mansoni miracidia related to host size

Within snail/trematode associations the age/size of the host at infection has consequences with regard to miracidial infection success, further intramolluscan parasite development and reproduction, and the host response, mainly in terms of growth and reproductive effort. Taking into account these differences, we were interested in determining whether miracidia could discriminate and make a choice between snails of different sizes. Using the Schistosoma mansoni/Biomphalaria glabrata system, we compared data on the snail infection rate and the mother sporocyst abundance among three size classes of snails (juvenile, subadult, and adult) exposed separately or together to the parasite larvae. When exposed individually, juvenile snails (3-5 mm) had significantly higher prevalence and abundance values than did subadult snails, followed by adult snails. In contrast, when snails of the three size classes were exposed together in heterogeneous size groups the prevalence and abundance values were always significantly higher for subadult snails of the 7- to 9-mm class than for juvenile and adult snails. A host choice experiment confirmed that significantly more miracidia were attracted by subadult snails, suggesting that the parasite has been selected for specific locating and recognition mechanisms increasing the infection rate of subadult snails when the latter have been exposed in a heterogeneous size group. Selective forces that may be responsible for such a preferential infectivity of the parasite vis-à-vis particular host age/size class are discussed in relation to host resources and host responses.     

Neuro-psychological development of vision in children older than 6 years of age

In snails maintained at 20 degrees C rediae of Fasciola hepatica merge from sporocysts from 11 days after infection onwards. The number of mother rediae rises steadily thereafter until at least 40 days after infection. Daughter rediae are seldom observed in mother rediae dissected from snails maintained at 20 degrees C. Their production can, however, be stimulated by subjecting the snail host to starvation, to low, and to high temperature shocks. The parasite is susceptible to stress from immediately after infection for about 16 days, when maintained at 20 degrees C. In general, the more extreme the shock, the greater is daughter redial production. Increasing the length of the period of stress from 12 h up to 9 days does not increase the production of daughter rediae, nor does repeated on/off cold shocks or continuous maintenance at 10 degrees C. Daughter rediae develop more rapidly than cercariae and leave the mother rediae several days earlier. There is no evidence that presence of daughter rediae coincides with the suppression of cercarial production. The findings are discussed with reference to possible mechanisms by which parasite development might be controlled.     

Inhibition of peripheral interleukin-1 beta-induced hyperalgesia by the intracerebroventricular administration of diclofenac and alpha-melanocyte-stimulating hormone

The present study was undertaken to investigate whether or not the endogeneous mechanisms in the brain can modulate the changes in nociception produced by peripherally-administered interleukin-1 beta (IL-1 beta) in rats. We administered diclofenac and alpha-melanocyte-stimulating hormone (alpha-MSH) into the lateral cerebroventricle (LCV) 10 min before the intraperitoneal (i.p.) injection of recombinant human IL-1 beta (rhIL-1 beta, 1 ng/kg-100 ng/kg) and then observed the changes in nociception using a hot-plate test. The i.p. injection of rhIL-1 beta (10 ng/kg and 100 ng/kg) reduced the paw-withdrawal latency without affecting the colonic temperature. The maximal reduction in the paw-withdrawal latency was observed 30 min after the i.p. injection of rhIL-1 beta at 100 ng/kg. The rhIL-1 beta (100 ng/kg)-induced hyperalgesia was inhibited by the LCV injection of both diclofenac (1 ng) and alpha-MSH (100 ng). The LCV injection of either diclofenac (1 ng) or alpha-MSH (100 ng) was found to have no effect on nociception by itself. These findings therefore suggest that the hyperalgesia induced by peripheral IL-1 beta can be modulated by a cyclooxygenase pathway of the arachidonate and alpha-MSH in the brain.     

The identification of markers segregating with resistance to Schistosoma mansoni infection in the snail Biomphalaria glabrata

Both snail and parasite genes determine the susceptibility of the snail Biomphalaria glabrata to infection with the trematode Schistosoma mansoni. To identify molecular markers associated with resistance to the parasite in the snail host, we performed genetic crosses between parasite-resistant and -susceptible isogenic snails. Because resistance to infection in adult snails is controlled by a single locus, DNA samples from individual F2 and F1 backcross progeny, segregating for either the resistant or susceptible phenotypes, were pooled (bulked segregant). Genotypes for both parents were determined with 205 arbitrary decamer primers by random amplified polymorphic DNA-PCR. Of the 205 primers, 144 were informative, and the relative allele frequencies between the pools for these primers were determined. Two primers, OPM-04 and OPZ-11, produced fragments in the resistant parent of one cross that were inherited in a dominant fashion in the resistant F2 and backcross-bulked segregant progeny. Subsequent typing of DNA samples of individual progeny snails showed that the 1.2-kb marker amplified by primer OPM-04 and the 1.0-kb marker produced by primer OPZ-11 segregated in the same dominant fashion with the resistant phenotype. Sequence analysis of the 1.2-kb marker showed that it corresponds to a repetitive sequence in the snail genome with no homology to existing DNA sequences in the public databases. Analysis of the 1. 0-kb marker showed that it also corresponds to a repetitive sequence in the B. glabrata genome that contains an imperfect ORF, with homology to retrovirus-related group-specific antigens (gag) polyprotein.     

Reducing perineal trauma: implications of flexion and extension of the fetal head during birth

Among the determinant factors in the resistance and susceptibility of Biomphalaria to Schistosoma mansoni, hemocytes play an important role. Aiming at studying S. mansoni/Biomphalaria interactions related to hemocytes, the first step is certainly connected with the standardization of this cell population in uninfected Biomphalaria. In this way, quantification of this cell population in hemolymph, as well as its phagocitary capacity, have been determined for the first time. Furthermore, using susceptible and resistant strains of B. glabrata and B. tenagophila, the hemocytegram and phagocytary capacity of hemocytes after infection with S. mansoni were determined too. Resistant and susceptible strains of B. glabrata (BA and BH, respectively), as well as resistant and susceptible strains of B. tenagophila (TAIM and CF, respectively) were infected with 10 miracidia of the LE and SJ strains of S. mansoni, respectively. These infected snails and respective uninfected controls were assessed in relation to the number of circulating hemocytes and alteration in the phagocytary capacity, by using Zymozan and MTT. Reading was taken by means of a spectrophotometer at 5 hours and 1, 2, 5, 10, 20 and 30 days after infection. The results showed a decrease in population of the circulating phagocytary cells, 5 hours after infection. One day post-infection, the circulating cells of the susceptible snails showed an increased metabolic activity, but the same event could not be observed in the resistant strains. In the subsequent observation periods, significant differences among the strains studied could not be observed until the end of the experiment.     

Invasion of the Nile Valley in Egypt by a hybrid of Biomphalaria glabrata and Biomphalaria alexandrina, snail vectors of Schistosoma mansoni

Two years (1996-1997) of systematic survey showed that a hybrid of Biomphalaria glabrata and Biomphalaria alexandrina has invaded the irrigation and drainage systems in the Nile Delta and the Valley nor the of El-Menya. However, the infestation of water courses by and the population density of this snail were variable in various localities. The infestation rate ranged between 7.1% in El-Fayoum Governorate and 52.6% in El-Dakahliya Governorate and the snail density from 2 snails/site to 69.7 snails/site in the same governorates, respectively. Comparing the survey results of the two study years in the sampling sites indicated that the hybrid snail has relatively increased in population density than B. alexandrina. The hybrid snail of B. glabrata and B. alexandrina was found alone in some sites, but was mostly associated with B. alexandrina. The results showed also that both Biomphalaria have almost the same major physicochemical requirements. However, the hybrid snails and B. alexandrina were found differently associated with aquatic snails and plants. The hybrid snail was found naturally infected with S. mansoni thus giving indication that it is presently participating in schistosomiasis mansoni transmission in Egypt.     

An electrophysiological study on the autonomic innervation of the mesenteric lymph node in the rat

Splanchnic innervation of the mesenteric lymph node was studied by means of electrophysiological technique in the rat. The effect of intravenous (i.v.) injection of recombinant human interleukin-1beta (rhIL-1beta) on the activity of efferent nerve fibers innervating the mesenteric lymph node was observed in the urethane anesthetized rat. An i.v. injection of 10 ng rhIL-1beta caused a gradual increase in efferent activity which lasted longer than 90 min. Dose related responses were observed at doses of 1, 10 and 100 ng. The least effective dose was about 10 ng. The conduction velocities estimated in mesenteric nerve fibers to the lymph node distributed in the range of 1.9-0.9 m/s, and the mean velocity was 1.39+/-0.34 m/s (n = 5). These observations implicate the involvement in the neural modulation of immune function of the mesenteric lymph node.     

Interleukin-1 beta differentially affects interleukin-6 and soluble interleukin-6 receptor in the blood and central nervous system of the monkey

Two studies were conducted to investigate whether behavioral and physiological responses induced by administration of interleukin-1 beta (IL-1 beta) were also associated with changes in interleukin-6 (IL-6) and soluble IL-6 receptor levels (sIL-6R). Following intravenous injection of rhIL-1 beta, blood and cerebrospinal fluid (CSF) samples were collected from juvenile rhesus monkeys. Marked increases in IL-6 levels were evident at 1 h in both blood and intrathecal compartments. IL-1 beta also induced significant elevations in the release of ACTH and cortisol into the blood stream, and following high doses, the monkeys evinced signs of sickness behavior. The second study characterized the IL-beta dose-response relationship showing that these physiological changes were most evident at doses between 0.5 microgram and 1.0 microgram IL-1/kg body weight. Soluble IL-6 receptor concentration was also increased, but only in plasma. There was no detectable sIL-6R in CSF. The large release of IL-6 into CSF suggests that some behavioral symptoms may be due to intrinsic changes in central nervous system activity concomitant with the alterations in peripheral physiology.     

Study on the life cycle of a sexually transmitted nematode parasite of a terrestrial snail

A technique for the artificial infection of the snail Helix aspersa by its parasite the nematode Nemhelix bakeri is described. The snail is relaxed by injection of an anesthetic, and 1 gravid female worm is introduced into the genitalia through the genital pore. Half of the injected snails were successfully infected. Following the course of infection over time indicated a 1:1 sex ratio, that the maximum number of progeny produced by injected female worms was 7, and that the development time of female worms was 56 days. The first generation of gravid females was found 100 days after infection. A survey of naturally parasitized snails was also conducted. The sex ratio of worms was in equilibrium, with a mean number of 2.4 larvae per female. The development time (56 days) and the body size (2.47-4.00 mm) of female N. bakeri are similar to those of a related species Cosmocercoides dukae (52-57 days and 1.66-4.34 mm), although the life cycle and biogeographic distribution for each of them are distinct.     

Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13

Exposure of monocytes to pro-inflammatory cytokines or lipopolysaccharide (LPS) may induce synthesis and expression of tissue factor (TF). In this paper we have focused on the induction of TF-activity in human monocytes by the pro-inflammatory cytokines recombinant human interleukin 1 (rhIL-1 alpha) (rhIL-1 beta) (rhIL-6) and human tumour necrosis factor alpha (rhTNF-alpha), measured as procoagulant activity (PCA) in a microtitre plate-based clot assay. In addition we have studied the modulation of IL-1 alpha/beta induced TF-mRNA and PCA by rhIL-4, rhIL-10 and rhIL13. IL-1 alpha and IL-1 beta induced a concentration dependent increase in TF-activity. Neither IL-6 nor TNF-alpha gave rise to procoagulant activity at the concentrations tested (0.2-20 ng/ml). IL-4, IL-10 and IL-13, all effectively diminished IL-1 alpha/beta induced PCA, shown at the protein- and at the mRNA-level, while cell viability was unaffected. These results add to the previously demonstrated role of IL-4 and IL-10 as inhibitors of LPS-induced TF-activity, showing that these anti-inflammatory cytokines are not specific for LPS-activation but interfere with other stimulating substances such as IL-1, which may be involved in diseases where LPS is not present.