Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing

The effects of mouse interferon-alpha (MuIFN-alpha), -beta (MuIFN-beta), and -gamma (MuIFN-gamma) on macrophage activation for tumor cell killing were determined by using proteose peptone-elicited peritoneal macrophages from C3H/HeN and C3H/HeJ mice under conditions that either included or were free of detectable endotoxin. Alone, under the conditions used, none of the interferons was able to activate macrophages directly for tumor cell killing. However, with a second signal provided to responsive macrophages by contaminating endotoxin, added bacterial lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM), all three types of interferon induced cytolytic activity, with MuIFN-gamma approximately 500 to 1000-fold more active than either MuIFN-alpha or -beta. Thus, all three interferons were able to prime macrophages for killing but required a second signal before cytolytic activity could be expressed. When MuIFN-gamma was mixed with either MuIFN-alpha or -beta and placed on macrophages, little or no killing developed. Mixtures of MuIFN-gamma with either MuIFN-alpha or -beta did increase the sensitivity of macrophages to triggering by LPS, however, compared with macrophages treated with MuIFN-gamma alone. The results are collectively important because they i) confirm that significant quantitative differences exist between the various interferons with regard to their capacity to prime macrophages for tumor cell killing; ii) indicate that to be an efficient activator each type of interferon must be combined with a second stimulus, such as LPS or HKLM; iii) show that neither MuIFN-alpha nor -beta can provide an efficient second triggering signal for macrophages that are primed by MuIFN-gamma; and iv) document that mixtures of MuIFN-gamma with either MuIFN-alpha or -beta are most efficient at inducing priming, compared with any one of the interferons used alone.     

Nucleotide sequence analysis of tetracycline resistance gene tetO from Streptococcus mutans DL5.

Streptococcus mutans DL5, isolated from the dental plaque of a pig, was resistant to high levels of streptomycin (Sm, 20 mg/ml), erythromycin (Em, 1 mg/ml), and tetracycline (Tc, greater than 100 micrograms/ml), but contained no detectable plasmid DNA. The Smr and Emr determinants were cloned from cellular DNA on the self-replicating 5-kilobase-pair (kbp) EcoRI fragment of pAM beta 1 and the 4.2-kbp cryptic plasmid pVA380-1, respectively, by transformation of Streptococcus sanguis Challis. Helper plasmid cloning, with a Challis host containing pVA380-1, was required to clone the Tcr determinant of strain DL5 on this vector. A single-colony isolate of the original Tcr clone contained a hybrid plasmid, pDL421, composed of 2.6 kbp of vector DNA and 11.4 kbp of S. mutans DNA. Plasmid pDL421 did not hybridize to plasmids containing the streptococcal Tcr determinants tetL, tetM, and tetN. A shortened derivative of this hybrid plasmid, pDL422, missing a 4.9-kbp HincII fragment from the S. mutans DNA but still encoding Tcr, was obtained by subcloning in S. sanguis Challis. The Tcr gene was located in a 1,917-base-pair open reading frame (ORF) corresponding to a 72-kilodalton protein. The ORF exhibited 99.4% sequence identity with the 1,917-base-pair tetO gene from a strain of Campylobacter coli (W. Sougakoff, B. Papadopoulou, P. Nordmann, and P. Courvalin, FEMS Microbiol. Lett. 44:153-160, 1987). A 1.67-kbp NdeI fragment, internal to the ORF from strain DL5, as well as pDL421 hybridized under stringent conditions to DNA from 10 of 10 Tcr strains of C. coli and Campylobacter jejuni from human and animal sources, but not to DNA from Tcs isolates of these two species.     

Diminished dietary thermogenesis in exercise-trained human subjects

The influence of exercise-training on dietary-induced thermogenesis (DIT) was investigated in humans. The resting metabolic rate was identical in trained and non-trained subjects, but the response to a meal containing 1,636 kcal (6.9 MJ) was markedly lower in trained subjects. Mean dorsal skin temperature, as measured by thermography, was not influenced by training. A significant correlation was observed between postprandial RQ and DIT, which indicates that the reduced energy expenditure noted in trained subjects is related to a greater lipid oxidation. This sparing effect of exercise-training on energy utilization in the form of carbohydrate, is interpreted as adaptive in the sense that energy is preserved for the purpose of producing work.     

Extinction of an appetitive operant response after administration of MSH

Hungry rats were trained to press a lever in order to obtain food on a fixed ratio (FR) or variable ratio (VR) of reinforcement. Rats trained on the FR schedule and injected with synthetic α-MSH had delayed extinction of the task as compared with control rats injected with diluent. The results show that MSH affects the behavior of rats in another type of behavioral situation involving an appetitive operant response.     

Desiccation-Induced Damage and Changes in Total and Heat-Stable Protein Populations in Two Rapeseed Species

Desiccation-induced damage and the capacity to synthesize heat-stableproteins have been examined in two Brassica species. Desiccationdamage to young seedlings, measured as electrolyte leakage andinhibition of overall protein synthesis, is greater in B. napusthan in B.juncea. Constitutive synthesis of heat-stable proteinsis low and declines during desiccation in B. napus while itis relatively high and further increases during desiccationin the case of B.juncea. (Received September 1, 1992; Accepted March 9, 1993)     

Relative risk trees for censored survival data.

A method is developed for obtaining tree-structured relative risk estimates for censored survival data. The first step of a full likelihood estimation procedure is used in a recursive partitioning algorithm that adopts most aspects of the widely used Classification and Regression Tree (CART) algorithm of Breiman et al. (1984, Classification and Regression Trees, Belmont, California: Wadsworth). The performance of the technique is investigated through stimulation and compared to the tree-structured survival methods proposed by Davis and Anderson (1989, Statistics in Medicine 8, 947-961) and Therneau, Grambsch, and Fleming (1990, Biometrika 77, 147-160).     

Utilité de l'épreuve d'effort sur tapis roulant peu après un infarctus du myocarde.

A program of reconditioning through walking was prescribed for 130 patients following an exercise test on a treadmill 3 weeks after a myocardial infarction. At 8 and at 12 weeks the patients again underwent an exercise test. The protocol is safe and permits the detection of angina, arrhythmias and dyspnea during the exercise, thus avoiding delays in treatment. The heart rate and the systolic blood pressure were measured at the end of each stage of the test and after 3 minutes of recuperation. About 75% of the patients attained the target energy output of the two submaximal tests (4 and 7 mets at 3 and 8 weeks respectively); an output of 7 mets permits a patient to resume his or her usual daily activities. The results of the tests at 3 and 12 weeks (the latter a maximal test) showed that the probability of an aerobic capacity of 7 mets or greater at 12 weeks is 86% if the 3-week test is completed. Clinical observations alone did not have the same prognostic value 3 weeks after the infarction.     

Influence of the lactose plasmid on the metabolism of galactose by Streptococcus lactis.

Streptococcus lactis strain DR1251 was capable of growth on lactose and galactose with generation times, at 30 degrees C, of 42 and 52 min, respectively. Phosphoenolpyruvate-dependent phosphotransferase activity for lactose and galactose was induced during growth on either substrate. This activity had an apparent K(m) of 5 x 10(-5) M for lactose and 2 x 10(-2) M for galactose. beta-d-Phosphogalactoside galactohydrolase activity was synthesized constitutively by these cells. Strain DR1251 lost the ability to grow on lactose at a high frequency when incubated at 37 degrees C with glucose as the growth substrate. Loss of ability to metabolize lactose was accompanied by the loss of a 32-megadalton plasmid, pDR(1), and Lac(-) isolates did not revert to a Lac(+) phenotype. Lac(-) strains were able to grow on galactose but with a longer generation time. Galactose-grown Lac(-) strains were deficient in beta-d-phosphogalactoside galactohydrolase activity and phosphoenolpyruvate phosphotransferase activity for both lactose and galactose. There was also a shift from a predominantly homolactic to a heterolactic fermentation and a fivefold increase in galactokinase activity, relative to the Lac(+) parent strain grown on galactose. These results suggest that S. lactis strain DR1251 metabolizes galactose primarily via the tagatose-6-phosphate pathway, using a lactose phosphoenolpyruvate phosphotransferase activity to transport this substrate into the cell. Lac(-) derivatives of strain DR1251, deficient in the lactose phosphoenolpyruvate phosphotransferase activity, appeared to utilize galactose via the Leloir pathway.