Biochemical characterization and protein kinase C dependency of monokine-inducing activities of Toxoplasma gondii

Previous reports have indicated that the early induction of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-1beta, and IL-10 is crucial for the establishment and regulation of host cell-mediated immunity to the intracellular protozoan parasite Toxoplasma gondii. In this study, we demonstrate that a soluble tachyzoite extract (soluble tachyzoite antigen) can trigger the expression of these four monokines by murine inflammatory macrophages. Further characterization revealed that the parasite molecules in soluble tachyzoite antigen responsible for monokine induction are heat stable at 100 degree C but differ in sensitivity to protease digestion. Thus, the tachyzoite factors that stimulate TNF-alpha and IL-to expression were found to be more resistant to treatment with proteinase K than those responsible for IL-12 and IL-10 induction. Similarly, while the factors responsible for the induction of all four monokines were found to be sensitive to periodate oxidation, the TNF-alpha-stimulating activity was partially resistant to treatment with the compound at a low concentration (1 mM). A further dichotomy in monokine induction signals was inferred from experiments with isoquinoline sulfonamide protein kinase inhibitors. The latter work suggested that the pathways for TNF-alpha and IL-1beta are protein kinase C dependent, while expression of IL-12 and expression of IL-10 share distinct signal transduction mechanisms involving other kinases. Together, these data argue that monokine induction by T. gondii is mediated by glycoproteins that may belong to distinct groups in terms of their biochemical properties and intracellular signaling pathways.     

Significance of an abnormal response during pituitary desensitization in an in vitro fertilization and embryo transfer program

From January 1972 to June 1990, 112 patients (39 to 83 years old), 67 males and 45 females were submitted to surgery for sever calcified aortic stenosis. 68 patients were in NYHA III (60.72%) and 44 in NYHA IV. Early mortality included 8 patients (7.14%), 6 died for cardiac reasons. Late mortality was 27.67%. Actuarial survival rate (including postoperative mortality) was 88.39%, 77.67%, 67.85% and 65.17% at one year, five, ten and fifteen years, respectively. Results were significantly correlated to left branch block on preoperative EKG, episodes of complete heart failure, significant coronary stenosis, the cardioplegia technique and the association with coronary bypass.     

A survey of mortality in slaughter pigs during transport and lairage

Of 2.9 million pigs transported to seven slaughter plants in 1991 and 1992, 1781 (0.061 per cent) died in transit and 314 (0.011 per cent) died subsequently in the lairage. Overall mortality for both years was 0.072 per cent and mortality in 1992 was 0.066 per cent. There was little seasonal variation in the number of pigs dying in lairage, but more pigs died in transit in months when the weather was hotter. The relationship with temperature was curvilinear; above about 15 to 17 degrees C the detrimental effect of high temperatures was far more serious. In 1992, the year for which complete data were available, average mortality in the seven plants ranged from 0.045 to 0.093 per cent, but this variation was not related to the size of the plant. The number of pigs which died in lairage, rather than in transit, ranged from 4 to 21 per cent of all deaths in the different plants, and the average was 15 per cent. The variation might be related to differences in average lairage times or to the policies of individual plants with regard to moribund pigs. The survey provided no evidence that the mortality among transported pigs has increased over the last 20 years.     

A 5-year stability study of common illicit drugs in blood

The present study was designed to determine the stability of common illicit drugs in stored blood at various time intervals for a period of up to 5 years. The drugs of interest were cocaine and benzoylecgonine, methamphetamine and amphetamine, nonconjugated morphine and codeine, and phencyclidine (PCP). All specimens were from live individuals and were collected in gray-top Vacutainer tubes containing sodium fluoride and potassium oxalate; the tubes were stored at ambient temperature. The results of the study showed that cocaine and benzoylecgonine have poor stability and require quantitative confirmation within a reasonable time period for reliable interpretation. Methamphetamine and PCP were both fairly stable and had a high probability of confirmation upon reanalysis. The stability of nonconjugated morphine showed wide variation throughout the study. Initially, the morphine concentration decreased, then increased at the 3-year interval, and finally decreased at the 4- and 5-year intervals. The significance of the analytical findings are discussed in this report.     

Retinoic acid-regulated cellular differentiation and mucin gene expression in isolated rabbit tracheal-epithelial cells in culture

Rabbit tracheal epithelial cells were cultured in a serum-free and hormone-supplemented medium with and without retinoic acid. The cells showed time-dependent mucin gene expression when cultured in the medium with retinoic acid. In the absence of retinoic acid, however, mucin mRNA was barely detectable in the cells. When retinoic acid was added back to the medium, the mucin message was prominent again. Actinomycin D and cycloheximide did not inhibit mucin gene expression. The mucin message was slightly elevated by cAMP agonists. A mucin antisense oligomer inhibited the retinoic acid-induced mucin mRNA expression and secretion, thus offering an alternate approach in the management of mucus hypersecretion in upper airway respiratory diseases such as chronic bronchitis, asthma, and cystic fibrosis.