Presence of hsp65 in bacterial extracts (OM-89): A possible mediator of orally-induced tolerance?

Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity, particularly arthritis, and there is suggestive though inconclusive evidence that they may also play a role in human autoimmune disease. The simplest hypothesis is based on molecular mimicry due to the amino-acid sequence homology between mammalian and microbial HSP. Recently OM-89, an extract of several strains ofEscherichia coli, has shown some efficacy in the treatment of rheumatoid arthritis (RA) when taken orally. Using species-specific antibodies, we show here that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in another bacterial extract containing other microorganisms, includingStaphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is a relevant target antigen in the human disease, the efficacy of the preparation could be due to induction of oral tolerance or to switching the Th1 response towards Th2. Alternatively, even if the human hsp65 is not a target molecule in RA joints, OM-89 may evoke bystander suppression of joint inflammation via induction of TGF-secreting effector cells. These hypotheses should be tested in further studies.     

Energy flow and community structure in freshwater ecosystems

The goal of this article is twofold: 1) It aims at providing an overview on some major results obtained from energy flow studies in individuals, populations, and communities, and 2) it will also focus on major mechanisms explaining community structures. The basis for any biological community to survive and establish a certain population density is on the one hand energy fixation by primary producers together with adequate nutrient supply and the transfer of energy between trophic levels (bottom-up effect). On the other hand, predator pressures may strongly control prey population densities one or more trophic levels below (top-down effect). Other interpopulation effects include competition, chemical interactions and evolutionary genetic processes, which further interact and result in the specific structuring of any community with respect to species composition and population sizes.     

Sex pheromone of the pine sawflyDiprion pini (Hymenoptera: Diprionidae): Chemical identification,synthesis and biological activity

The main component of the sex pheromone secretion of femaleDiprion pini L. (Hymenoptera: Diprionidae) from insects collected both in Finland and in France has been identified as athreo-3,7-dimethyl-2-tridecanol (8 ng per female) stereoisomer by GC-MS and synthesis. The secretion also contains lower and higher homologues in small amounts (1–4% of the main component). Combined gas chromatographic-electroantennographic detection showed activity in both natural and esterified extracts (acetates and propionates); the esters of the main component gave the largest responses. The acetates and propionates of the eight stereoisomers of 3,7-dimethyl-2-tridecanol were synthesized from enantiomerically highly enriched (>99% ee) building blocks. The stereochemistry of the main component was established to be (2S,3R,7R)-3,7-dimethyl-2-tridecanol by GC analysis of the natural material. It was purified by liquid chromatography prior to the GC analysis of both its pentafluorobenzoates and its isopropylcarbamates on a non-chiral polar column (ECD) and a chiral column (NPD), respectively. Field tests demonstrated that both the acetate and propionate of the main component (100 g of each applied on cotton roll dispensers) were active in attracting males, with or without the presence of several of the minor compounds. Experiments with smaller amounts of the acetate and the propionate (1 g in France and 50 g in Finland) demonstrated that the propionate was more active than the acetate, and that it also caught more males than a blend of the two compounds.     

Antiviral activities of anthraquinones,bianthrones and hypericin derivatives from lichens

The antiviral activities of some naturally occurring anthraquinones bianthrones, and hypericin derivatives were compared by the end-point CPE (viral cytopathic effects) method and plaque assays. Under optimal conditions of exposure to light, hypericin, 7,7-dichlorohypericin and 5,7-dichloroemodin exhibited strong inhibitory activity against HSV-1 (herpes simplex virus type 1) in both assays. Partial inactivation of the virus was shown by emodin, 7-chloroemodin and 7-chloro-1-O-methylemodin; the bianthrones and other anthraquinones were found to be inactive. Antiviral activity appeared to be, positively correlated with increasing substitution of chlorine in the anthraquinone structure. In the absence of light, only hypericin and 7,7-dichlorohypericin displayed detectable activity.     

Dissection of the pheromone-modulated flight of moths using single-pulse response as a template

The upwind flight of male moths to conspecific females is mediated by the chemical and structural characteristics of a pheromone plume. We describe the reaction of maleCadra cautella, the almond moth, to the interception of single pulses of sex pheromone, the smallest structural units of odour plumes. Following loss of a pheromone plume, males cast, that is fly a crosswind course without progressing upwind. The response of casting males to interception of a pulse of 0.25 s duration was, after a delay of 0.21±0.07 s, to turn and briefly fly straighter upwind, resulting in average net upwind displacements of 18 cm in a 50 cm s^–1 wind. Upwind progress in the single-pulse response was the result of steering more upwind and an increase in airspeed, although average ground speed remained unchanged. During the last third of the surge, males turned crosswind, returning to casting flight. These behavioural reactions to pheromone contact and loss support the phasic-tonic model of odour-modulated flight, in which an underlying tonic counterturning rhythm, expressed upon pheromone loss, is briefly overridden by phasic upwind surges, expressed upon interception of the pheromone filament. The surge portion of the cast-surge-cast response was diminished and more crosswind if individual pulses were shorter (0.02 s), probably due to sub-optimal contact with pheromone. The cast-surge-cast response to interception of a single 0.25 s pulse was used as a template to interpret the form of flight tracks in plumes of known structure. The template matched portions of flight tracks of males flying in plumes of low pheromone pulse frequency, thus reflecting the male's pattern of pulse encounter. In plumes ensuring a high frequency of pulse interception, only the upwind surge portion of the template was expressed, resulting in nearly straight upwind flight tracks. Similar nearly straight upwind flight tracks occurred in flights along plumes of low pulse frequency with large volume. Thus flight tracks of maleC. cautella to point sources of pheromone depend on both the frequency and the size of filaments encountered.     

2-Carboxyethylgermanium sesquioxide,a synthetic organogermanium compound,as an inducer of contrasuppressor T cells

2-Carboxyethylgermanium sesquioxide (Ge-132), a synthesized organogermanium compound with immunomodulaing activities, was shown to be an inducer of anti-suppressor T cells in normal mice. The suppressor cell activity of T6S cells, a clone of burn-induced CD8⁺ IL-4-producing suppressor T cells, was clearly inhibited when a mixed lymphocyte-tumor cell reaction of the clone was conducted with splenic mononuclear cells from mice treated orally with a 100 mg/kg dose of Ge-132. The activity of anti-suppressor cells was demonstrated in spleens of mice 2 days after treatment with Ge-132 and reached its peak on day 3. The anti-suppressor cells induced by the compound were of a contrasuppressor T cell-linage, because they were characterized as CD4⁺ CD28⁺ TCR/⁺ Vicia villosa lectin-adherent T cells. These cells produced IFN- but did not produce IL-2, IL-4, IL-6 or IL-10 in their culture fluids. CD4⁺ anti-suppressor T cells induced by Ge-132 may be different from other subsets of CD4⁺ T cells because Th1 and Th2 cells generated in our laboratory did not adhere toVicia villosa lectin-coated petri dishes, and each produced specific cytokines. Th1 cells produced IFN- and IL-2 while Th2 cells produce IL-4 and IL-10 in vitro. These results suggest that Ge-132 may be useful as an inducer of contrasuppressor T cells in immunocompromised individuals bearing suppressor T cells. To eliminate suppressor T cells from immunocompromised hosts may result in improved resistance from various opportunistic infections.     

Transplantation of human cortex with Alzheimer's disease into rat occipital cortex; a model for the study of Alzheimer disease

Summary Senile dementia of the Alzheimer type (SDAT) is a major problem in the human senescent population. As this pathology cannot be reproduced in animals, research into its development is greatly impeded. The technique of implantation of the nervous tissue has been utilized in order to establish an animal model and to test the possible existence of a transmissible agent. When human temporal cortex with Alzheimer's disease is implanted in the occipital cortex of 7-week-old rats, human cerebral tissue containing abundant tangles induces in the receiver cortex a reactive fibrous gliosis. In the processes of the astrocytes, twisted filaments are evident among bundles of normal filaments. These alterations could be induced by the metabolising of abnormal filament subunits or by some infectious agent introduced by the implant.This study is supported by grant No. 2.4517.82 of Fonds de la Recherche Fondamentale Collective of Belgium.     

Isolation and partial characterization of cuticular collagen from the parasitic nematodeGaigeria pachyscelis

Summary The cuticle from adultGaigeria pachyscelis was isolated by solubilizing the internal tissues with sodium dodecyl sulphate (SDS) at 37°C. Cuticular protein was extracted with guanidine-HCl and -mercaptoethanol and purified by ammonium sulphate fractionation and DEAE-cellulose chromatography. SDS-polyacrylamide gel electrophoresis of purified protein revealed 2 polypeptides with apparent mol. wts of 58,000 and 74,000. As judged from their hydroxyproline content both of them are collagenous in nature. Results of gel filtration indicate that cuticular collagen exists in two forms, a non-associated form at low concentration and an associated form at high concentration.Acknowledgments. We thank Drs L.N. Singh and H.C. Tewari for providing the necessary facilities. Laboratory assistance of Mr Ram Kishore is highly appreciated.     

Excretion of acid hydrolases during molting inPhilosamia ricini

Summary The level of the acid hydrolases -glucuronidase (EC 3.2.3.11), acid phosphatase (EC 3.1.3.2) and acid protease (EC 3.4.4) was studied during larval growth and molting inP. ricini. The level of activity of these enzymes remained low during larval growth; however, the level increased sharply at the time of molting and declined sharply thereafter in the newly ecdysed insect. Interestingly, the diminished activity of these enzymes was almost quantitatively recovered in the cast-off cuticle. The excretion of acid hydrolases through the cast-off cuticle has hitherto not been reported in insects during molting.     

Action ofβ-(4-chlorophenyl-GABA) on uptake and metabolism of GABA in different subcellular fractions of rat brain

Summary -(4-chlorophenyl)-GABA, a GABA mimetic compound, acts as an inhibitor of GABA metabolism in both synaptosomal and extrasynaptosomal compartments. It has no significant action on GABA or Glu uptake by synaptosomes.