Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 10(6) ml-1) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ng ml-1 within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-IL6 cells were transplanted into C57BL/6 mice subcutaneously, the mean +/- s.d. of survival times of these mice were 33.3 +/- 9.7, 34.3 +/- 7.1 and 17.0 +/- 3.1 days, respectively. The survival time of LLC-IL6 cells transplanted mice was significantly shorter than that of LLC (P < 0.01) or LLC-Neo (P < 0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-IL6 transplanted mice than in LLC transplanted mice. Mouse IL-1 alpha and mouse TNF-alpha were not detected in the plasma of LLC-IL6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-1 alpha and TNF-alpha in the plasma. This state may be responsible for the shortened survival of LLC-IL6 tumour-bearing mice.     

Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat, dog, monkey and human hepatic parenchymal cells

Tetrahydroaminoacridine (tacrine) causes morphological and functional changes in the endoplasmic reticulum, ribosomes, and mitochondria in the liver of humans and animals. In order to investigate species differences as well as to understand the morphological changes, we examined the effects of tacrine on respiration and electron transport in mitochondria isolated from rat, dog, monkey, and human liver. Tacrine produced significantly decreased respiratory control ratios (RCR) in all species at concentrations ranging from 5 to 25 microg/ml. Human mitochondria were more sensitive to tacrine effects with RCR decreased 24% at 5 microg/ml while other species were unaffected at this concentration. The tacrine effects were characterized by increased hepatic mitochondrial State 4 respiration in rats and decreased State 3 respiration in humans. Mitochondria from aged rats were more sensitive to the effects of tacrine than mitochondria from young animals, with significantly decreased RCR at 10 microg/ml in aged rats while mitochondria from young rats were unaffected at this concentration. Concomitant with the respiratory changes, mitochondrial DNA synthesis was impaired. Since tacrine undergoes extensive biotransformation, we also explored the possibility that metabolites could exert detrimental effects. The ranking order of potency for decreasing RCR caused by monohydroxylated metabolites was: tacrine > 4-OH and 7-OH > 2-OH, 1-OH, and velnacrine with the latter group of metabolites having no effect on mitochondrial respiration at concentrations up to 50 microg/ml. In vivo administration of 20 mg/kg tacrine to rats for up to 20 days caused a paradoxical increase in RCR and P/O on Day 1 and decreased RCR on Days 9 and 20, the later findings being consistent with in vitro data. From these data we propose that tacrine does not necessarily have to be metabolized to exert effects on mitochondria at different sites in the electron transport chain that differ among species. These effects are exacerbated in mitochondria from older animals and humans appear to be more sensitive than the laboratory animals studied.     

Cancer prevention--behavior changes: the short and the long of it

BACKGROUND: Behavioral factors play an important role in the adoption and maintenance of nutritional modifications, delivered either through chemopreventive regimens or through dietary adaptation. A body of research supports a protective role of fruits and vegetables, dietary fiber, and eating a low-fat diet in reducing cancer risk. There is only limited knowledge, however, about the cancer-preventing properties of specific micronutrients, apart from beta-carotene; about optimal levels of intake of differing micronutrients; and about patterns of food intake associated with reduced cancer risk. Thus, it would seem preferable, overall, to be able to recommend cancer prevention through dietary modification rather than through the administration of individual agents. METHODS: Studies of dietary adherence in cancer prevention have yielded varying success rates, but are generally quite promising. We have developed a model that encompasses the range of behavioral, psychological, social, and systemic variables thought to influence adherence to nutritional regimens. RESULTS: The model is being utilized to influence the form and content of nutritional regimens and to promote short-term change which can then be sustained as long-term lifestyle modification. The model can also be applied to evaluate adherence to nutritional or other behavioral modifications and to determine the factors predictive of success.     

Clinical and historical predictors of dental caries on radiographs

Jet injection can be used to introduce genes into the cells of differentiated tissues of living animals and organ cultures. When a solution of plasmid DNA is jet injected into a selected tissue or organ, cells lying in or near the path of the jet injection are transfected with the DNA and the introduced gene(s) are expressed. Since there is minimal morbidity from each jet injection, multiple injections can be performed at the same or nearby sites. Both mRNA and protein expression from transfected genes can be quantitated using standard methods. In addition, the technique is an efficient means of DNA immunization. Methodology for using jet injection to transfer plasmid DNA into the cells of skin, fat, mammary gland, and muscle are described.     

A kinetic investigation into the removal of carbobenzyloxy group from protected amines via hydrogenolysis reaction

Hydrogenolysis of a carbobenzyloxy group (CBz) was studied utilizing molecular hydrogen in the presence of carbon-supported palladium catalyst. It was demonstrated that the kinetics of the reaction are greatly influenced by the presence of the CO₂ by-product. It was found out that the presence of CO₂ determines whether the reaction is first or zero order since it causes deactivation of the catalyst via inhibition. The effect of potassium carbonate (K₂CO₃) and triethylamine (TEA) as additives was investigated. A considerable solvent effect was also observed that may be explained by the variation of dispersion of the catalyst from one solvent to another.     

Influence of Al and Ni concentration on the Martensitic transformation in Cu-Al-Ni shape-memory alloys

The martensitic transformation temperatures and the types of martensitic phases have been determined in a wide concentration range of technological interest for Cu-Al-Ni shape-memory alloys (SMAs) A stability diagram of martensitic phases as a function of alloy concentration has been determined. It is found that when the aluminum content increases, the transformation changes from β ₃ ⇒ β′₃ to β ₃ ⇒ γ′₃, with an intermediate concentration range where both martensites coexist due to a β ₃ ⇒ γ′₃+β′₃ transformation. On the other hand, an increase of nickel content stabilizes the martensite β′₃, changing from a mixed β ₃ ⇒ γ′₃ + β′₃ to a single β ₃ ⇒ β′₃ transformation. Furthermore, linear relationships between M _s and Al and Ni concentrations have been obtained for all types of martensitic phases.     

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