Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells.

The causes of the decreased immune responsiveness in tumor-bearing hosts are incompletely understood. The impact of a decreased immune response in cancer patients on the clinical response in immunotherapy trials has not been evaluated. The present report demonstrates a marked decrease in the therapeutic efficacy of adoptively transferred T lymphocytes obtained from murine hosts bearing tumor for greater than 30 days [late tumor-bearing mice (TBM)] as compared with normal mice and mice bearing tumor for less than 21 days (early TBM). In vitro analysis of the functions of the T lymphocytes from late TBM showed an apparently normal proliferative response to anti-CD3 and IL-2 with adequate lymphokine production from CD4+ cells, but a significant decrease in the cytotoxic function of CD8+ cells. The decreased cytotoxicity was not because of cell-mediated suppression. The expression of granzyme B mRNA was significantly delayed and decreased in magnitude in CD8+ cells from late TBM. Culture supernatants from two unrelated tumor cell lines were able to inhibit the cytotoxic activity of normal CD8+ cells in vitro. The tumor-derived suppressive factor is not transforming growth factor-beta (TGF-beta), but it has not been further characterized. The data suggest that one potential mechanism responsible for immunologic defects in patients with large tumor burdens is a tumor-induced defect that compromises the function of CD8+ effector T cells.     

Effect of cold environment on skeletal muscle mitochondria in growing rats

Summary Growing rats (4 weeks old) were kept for 3 weeks at 11° C and 24° C respectively. The cold-adapted animals showed a significantly higher oxygen consumption (64%). Volume density of subsarcolemmal and interfibrillar mitochondria as well as volume density of fat droplets were estimated in M. soleus and the diaphragm of both groups. In cold-adapted animals, the total volume of mitochondria was significantly increased by 24% in diaphragm and 37% in M. soleus. The volume of subsarcolemmal mitochondria was almost doubled in each muscle, but the volume of interfibrillar mitochondria did not change significantly. The surface of the inner mitochondrial membranes per unit volume of mitochondrion in M. soleus was significantly increased both in interfibrillar and subsarcolemmal mitochondria, whereas the surface of the outer mitochondrial membranes per unit volume of mitochondrion was increased only in the subsarcolemmal mitochondria. The volume of fat droplets in the diaphragm and M. soleus of cold adapted animals increased significantly by 62% and 150% respectively.     

Agarose gel electrophoresis and restriction endonuclease analysis of largeStaphylococcus plasmids

Preliminary studies using an improved method for the agarose gel electrophoresis of semipurified, cleared lysates of staphylococci have indicated some distinct differences in plasmid composition between the coagulase-positive speciesStaphylococcus aureus andStaphylococcus intermedius, and various coagulase-negative species. Penicillinase-positive strains ofS. intermedius andS. simulans did not carry large penicillinase plasmids like most penicillinase-positive strains ofS. aureus. Most coagulase-negative species examined demonstrated complex plasmid profiles. Codigestion by the restriction endonucleasesHaeIII andHpaI offered a useful approach for “fingerprinting” large plasmids from various strains and species.     

Comparative studies of the structure and composition of the plasmalemma and the tonoplast in Saccharomyces cerevisiae

The two membranes, plasmalemma and tonoplast (Saccharomyces cerevisiae H 1022), are characterized ultrastructurally by their different texture in the corresponding freeze-fracture faces and their silver staining properties.Biochemical characterization with regard to proteins and lipids indicated that the ratio of protein to lipid is significantly higher in the plasmalemma as compared to the tonoplast. Moreover, a pronounced difference appears to exist for both the amount and the composition of total lipids, phospholipids and sterols. The protein patterns of the plasmalemma and the tonoplast reveal only minor differences, as judged by sodium dodecyl sulphate gel electrophoresis.     

Asymmetry of the cerebral hemispheres in man: a bridge binding the 1st and the 2d temporal gyri, superior face of the 2d temporal gyrus, and fusiform gyrus]

The autors study 76 human brains, 36 of which are dissected. They observe a "T1 T2 bridge" over the first temporal and second temporal gyri more often on the left side than on the right. They find the maximal width of the superior face of the second temporal gyrus predominant on the right side in 70% of cases, on the left side in 15% and equivalent on both sides in 15%. The fusiform gyrus is found wider on the left side in 53% of cases, on the right in 22% and equivalent on both sides in 25%.     

Radiation damage in tripalmitin layers studied by means of infrared spectroscopy and electron microscopy.

Structural deteriorations in biomembranes, as inevitably induced while structural information is gathered by electron optical methods, were evaluated by infrared spectroscopy. Tripalmitin model membranes were irradiated with 100 keV-electrons in an electron microscope. The intensity decay of group vibrations over the dose reveals the sequence of damage in the polar and nonpolar part of the molecule. The C-C backbone, being the most important structural feature, shows a significant latency effect up to 0.6 e-/A2 and is completely disordered by 3 e-/A2, corresponding to about three inelastic processes per molecule.     

Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver

Different species from the Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary disorders in traditional European medicine. In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and luteolin-7-O-β-d-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic compound of Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and luteolin-7-O-β-d-glucuronide was prepared by solid phase extraction from a 20% methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O-β-d-glucuronide was determined by HPLC analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow (23–44–47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined effect of DCCAs and luteolin-7-O-β-d-glucuronide stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they seem to be the choleretic active principles in the traditional application forms of yarrow.     

A note on approximating the cumulative distribution function of the time to tumor onset in multistage models

The general multistage theory of carcinogenesis is a very special type of interconnected birth and death process in which the final state is absorbing and all states except the first one are empty at time zero. An approximation proposed by Whittemore and Keller (1978, SIAM Review 20, 1-30) is assessed. It is shown that the adequacy of this approximation depends on the number of malignant cells resulting from a single normal cell. If more than one malignant cell is likely to occur, the approximation will fail.     

Environment outweighs the effects of fishing in regulating demersal community structure in an exploited marine ecosystem

Global climate change has already caused bottom temperatures of coastal marine ecosystems to increase worldwide. These ecosystems face many pressures, of which fishing is one of the most important. While consequences of global warming on commercial species are studied extensively, the importance of the increase in bottom temperature and of variation in fishing effort is more rarely considered together in these exploited ecosystems. Using a 17 year time series from an international bottom trawl survey, we investigated covariations of an entire demersal ecosystem (101 taxa) with the environment in the Celtic Sea. Our results showed that over the past two decades, biotic communities in the Celtic Sea were likely controlled more by environmental variables than fisheries, probably due to its long history of exploitation. At the scale of the entire zone, relations between taxa and the environment remained stable over the years, but at a local scale, in the center of the Celtic Sea, dynamics were probably driven by interannual variation in temperature. Fishing was an important factor structuring species assemblages at the beginning of the time series (2000) but decreased in importance after 2009. This was most likely caused by a change in spatial distribution of fishing effort, following a change in targeted taxa from nephrops to deeper water anglerfish that did not covary with fishing effort. Increasing bottom temperatures could induce additional changes in the coming years, notably in the cold‐water commercial species cod, hake, nephrops, and American plaice. We showed that analyzing covariation is an effective way to screen a large number of taxa and highlight those that may be most susceptible to future simultaneous increases in temperature and changes in exploitation pattern by fisheries. This information can be particularly relevant for ecosystem assessments.