Immunotherapy eradicates metastases with reversible defects in MHC class I expression

Tumor or metastatic cells lose MHC class I (MHC-I) expression during cancer progression as an escape mechanism from immune surveillance. These defects in MHC-I may be reversible by cytokines or different agents (soft lesions) or irreversible due to structural defects (hard lesions). The nature of these MHC-I alterations might determine the success or failure of immunotherapy treatments. In this study, we have used an MHC-I-positive murine fibrosarcoma tumor clone, GR9-A7, which generates multiple lung and lymph node metastases with reversible MHC-I alterations after treatment with IFN-γ. Four different antitumor treatments were carried out after primary tumor excision to determine their capacity to inhibit spontaneous metastatic colonization of the GR9-A7 tumor clone. We found that 2 different immunotherapy protocols (CpG plus autologous irradiated-GR9-A7 cells and protein-bound polysaccharide K (PSK) and 1 chemoimmunotherapy (docetaxel plus PSK) induced eradication of metastases. In contrast, chemotherapy with docetaxel alone produced only partial reduction in the number of metastases. Flow cytometric analysis of lymphocyte populations showed an immunosuppression in GR9-A7 tumor-bearing host, which could be reverted by immunotherapy treatments. Our results suggest that irreversible or reversible MHC-I alterations in tumor target cells may determine its progression or regression independently of the type of immunotherapy used.     

Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide.

Ceramide is a lipid second messenger that acts on multiple-target enzymes, some of which are involved in other signal-transduction systems. We have previously demonstrated that endogenous ceramide modifies the metabolism of brain ethanolamine plasmalogens. The mechanism involved was studied. On the basis of measurements of breakdown products, specific inhibitor effects, and previous findings, we suggest that a plasmalogen-selective phospholipase A2 is the ceramide target. Arachidonate-rich pools of the diacylphosphatidylethanolamine subclass were also affected by ceramide, but the most affected were plasmalogens. Concomitantly with production of free arachidonate, increased 1-O-arachidonoyl ceramide formation was observed. Quinacrine (phospholipase A2 inhibitor) and 1-O-octadecyl-2-O-methyl-rac-glycerol-3-phosphocholine (CoA-independent transacylase inhibitor) prevented all of these ceramide-elicited effects. Therefore, phospholipase and transacylase activities are tightly coupled. Okadaic acid (phosphatase 2A inhibitor) and PD 98059 (mitogen-activated protein kinase inhibitor) modified basal levels of ceramide and sphingomyelinase-induced accumulation of ceramide, respectively. Therefore, they provided no evidence to determine whether there is a sensitive enzyme downstream of ceramide. The evidence shows that there are serine-dependent and thiol-dependent enzymes downstream of ceramide generation. Furthermore, experiments with Ac-DEVD-CMK (caspase-3 specific inhibitor) have led us to conclude that caspase-3 is downstream of ceramide in activating the brain plasmalogen-selective phospholipase A2.     

Guaianolides from Centaurea canariensis

The reinvestigation of Centaurea canariensis var. subexpinnata provided, along with three known compounds, three new sesquiterpene lactones of the guaiane series.     

Effect of boron on soluble protein and sugar contents of tomato roots

Summary In relation to a biochemical diagnosis of B-affected plants, the influence of boron on soluble protein and sugar contents in roots of tomato plants was investigated. Differences in protein and sugar contents occur throughout the culture period of tomato plant. Boron deficiency results in an accumulation of proteins and both total and reducing sugars.     

Distribution patterns of aquatic oligochaetes inhabiting watercourses in the Northwestern Iberian Peninsula

Distribution patterns of aquatic oligochaete assemblages, inhabiting largely unpolluted watercourses, in the Northwestern Iberian Peninsula, and their relationships with chemical and physiographical characteristics were analyzed by means of multivariate analyses. Qualitative and quantitative samples from 47 stations were obtained seasonally during 1983/84 and 1988/90. The variables included in this study were altitude, order number, distance from the origin, mean width, mean depth, substrate, current velocity, oxygen content, pH, conductivity, alkalinity and concentration of different ions.From a chemical point of view, major changes in the structure of oligochaete assemblages were related to water mineralization. The correlation between faunal distribution and environmental variables showed a great increase when physiographic parameters were included in the analyses. Substrate type and current velocity are the principal variables explaining the community structure.     

Two new species of freshwater Oligochaeta from the North-west Iberian Peninsula: Krenedrilus realis sp. nov. (Tubificidae) and Cernosvitoviella bulboducta sp. nov. (Enchytraeidae)

Two new species of aquatic Oligochaeta are described from the North-west Iberian Peninsula: Krenedrilus realis sp. nov. (Tubificidae) and Cernosvitoviella bulboducta sp. nov. (Enchytraeidae). Krenedrilus realis is the fourth species in a genus of small and presumably plesiomorphic Tubificinae. It is closely related to K. sergei Giani, Erséus & Martínez-Ansemil, 1990. Cernosvitoviella bulboducta belongs to a genus of small amphibiotic enchytraeids. It is close to C. ampullax Klungland & Abrahamsen, 1981 and C. tatrensis (Kowalewski, 1916). Supplementary data to the diagnosis of C. tatrensis are given. The presence of two small glands attached to the gut immediately behind the pharyngeal bulb is noticed in C. bulboducta and C. tatrensis . This previously unknown character is probably more common in the genus than has been supposed.     

Method for Setting Environmental Targets in Product Development: Incorporating Use‐Phase Impact by Subsystem

In order to address environmental aspects during redesign, the product specification must include related targets that are reachable and challenging. To do so, this article presents a stepwise approach for combining benchmarking information and component impact, out of life cycle assessment (LCA) scaling. This approach requires allocating environmental impacts to each subsystem, which is not commonly done for some life cycle phases in LCAs, most particularly for use phases. This article includes a methodology for allocating such impacts. The underlying criterion is avoiding complex calculations, to make the method more agile. This methodology is presented in a full case study of a complex product: a knuckle boom crane. The case study results in the percentage of impact reduction needed to meet the market average or best competitors. In particular, the results show that the cylinders of the crane have a high contribution to environmental impact, not only because of their weight, but also because of the active power consumed to activate them.     

A study of the os goniale in man.

The anterior process of the malleus of the middle ear develops irrespective of Meckel's cartilage through an intramembranous ossification center that appears in the human embryo of 26.5 mm crown-rump length at a caudomedial position in relation to Meckel's cartilage. The malleus has a double origin: the anterior process originates from the os goniale through intramembranous ossification, and the rest from Meckel's cartilage, through endochondral ossification.     

The freshwater Copepoda (Crustacea) of Costa Rica with notes on some species

Sixteen species of Copepoda were recorded in this first detailed study of Costa Rican zooplankton. Two of these species are halophile. Notes are given on some of the species and their distribution. One new species found will be described elsewhere. The Costa Rican fauna resembles in composition the fauna of other Central American and Caribbean regions. Relatively few species were recorded. This is partly due to a low intensity of sampling but also to the paucity of lentic habitats. The occurrence of two circumtropical species of Mesocyclops is interesting.

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Résumé 16 espèces de Copépodes ont été inventoriées au cours d'une première étude détaillée du zooplankton dulcaquicole de Costa Rica. Deux des espèces trouvées sont halophiles. Des remarques sont faites a propos de quelques espèces et de leur répartition. Une nouvelle espèce est nouvelle — elle sera décrite par ailleurs. La fauna de Costa Rica ressemble par sa composition à celle des autres pays d'Amérique centrale et des îles caraibes. Relativement peu d'espèces sont notées. La faible intensité de l'échantillonnage mais aussi la pauvreté en habitats limniques en sont responsables. La présence de deux espèces circumtropicales de Mesocyclops est intéressante.