Inhibition of progesterone secretion by a 3 beta-hydroxysteroid dehydrogenase inhibitor in late pregnant sheep

The role of progesterone in the initiation of parturition in the sheep is unclear. Whether a decrease in plasma progesterone is the essential prerequisite for the initiation of parturition or whether other factors also maintain uterine quiescence until delivery is not known. The effect of withdrawal of progesterone on the initiation of parturition has been investigated by intravenous administration of trilostane, a 3 beta-hydroxysteroid dehydrogenase delta 5-4 isomerase inhibitor, to late pregnant sheep. Twenty-five or 100 mg trilostane caused a precipitous decrease in plasma progesterone to about 30% of preinjection levels. Progesterone remained depressed for up to 7 days after treatment. 13,14-Dihydro-15-keto-prostaglandin F2 alpha (PGFM) became elevated between 7 and 36 h after trilostane injection but gradually returned to preinjection levels during the subsequent 36 h, at a time when plasma progesterone was still depressed. Four of 11 animals treated with 100 or 200 mg trilostane aborted prematurely at a time when plasma PGFM was maximal and plasma progesterone minimal. There were no consistent changes in plasma estradiol-17 beta or ovine placental lactogen concentrations after treatment with trilostane. It is suggested that a decrease in plasma progesterone will cause a transient increase in plasma PGFM concentrations which can lead to the premature initiation of parturition. In some instances the myometrium does not appear to respond to the elevated PGFM concentrations even when the estrogen:progesterone ratio is elevated by a decrease in plasma progesterone.     

The importance of prolactin for initiation of lactation in the pregnant ewe

A single injection of ergocryptine (0.5 mg/kg liveweight) given to ewes 0.5-20 days prepartum or two injections (0.5 mg/kg liveweight per injection) given c. 30 and 10 days prepartum reduced concentrations of plasma prolactin to negligible (less than 5 ng/ml) values for 4 weeks after parturition, but did not affect concentrations of growth hormone and placental lactogen. Milking of treated ewes had no effect on concentrations of plasma prolactin during the first 4 weeks of lactation, but concentrations of growth hormone were increased during the 10-20 min period after milking. The half-life of prolactin in plasma was estimated as 21 min. In spite of the dramatic effect of ergocryptine on plasma prolactin all treated ewes secreted copious quantities of milk of normal composition. Mean daily yields of ewes treated with ergocryptine were not significantly different (P greater than 0.05) from those of untreated control ewes, but the mean +/- s.e.m. of total milk production over the first 3 weeks of lactation for ergocryptine-treated ewes was significantly lower (P less than 0.05) than that of control ewes (9.5 +/- 1.11 v. 14.1 +/- 1.20 kg milk). The results suggest that prolactin is not an essential component of the lactogenic and galactopoietic complexes of hormones in the ewe.     

Effects of anoxia and flooding on alcohol dehydrogenase in roots of Glyceria maxima and Pisum sativum

Flood tolerant Glyceria maxima and intolerant Pisum sativum were compared in respect of the effects of anoxia and flooding on the maximum catalytic activities of alcohol dehydrogenase in their roots. Small (<73%) increases in enzyme activity occurred when excised roots of both species were incubated in nitrogen for up to 2 days. Further incubation in nitrogen rapidly and permanently damaged the roots of both species. Enzyme activity in flooded roots of Glyceria was about double that in corresponding non-flooded roots. A marginally greater difference was found for roots of Pisum. It was concluded that the two species respond so similarly to the above treatments that variation in the extent of induction of alcohol dehydrogenase is unlikely to be a significant factor in determining their ability to tolerate flooding.     

Simple electromyographic biofeedback treatment for chronic pediatric constipation/encopresis: Preliminary report

Pediatric constipation/encopresis is thought to be due, in part, to paradoxical constriction of the external anal sphincter (EAS) muscle during attempted defecation. This inappropriate contraction can lead to delayed, impacted, painful, and infrequent bowel movements. Standard Medical Care (SMC) involves disimpaction with enemas, followed by laxative therapy and diet modification, to maintain frequent soft stools. Using the case control method, the efficacy of SMC alone was compared with SMC plus EAS electromyographic biofeedback aimed at eliminating paradoxical contraction. Thirteen consecutive chronically constipated children received SMC plus biofeedback, and were compared with 13 age- and sex-matched children who received only SMC. Biofeedback subjects demonstrated post-treatment elimination of EAS paradoxical constriction. At 16 months follow-up parents of biofeedback children reported significantly greater improvement in constipation, encopresis, laxative use, and painful bowel movements compared to SMC.This research report was supported by the NIH under grant No. RO1 HD 28160.     

Genetic simplex modeling of Eysenck's dimensions of personality in a sample of young Australian twins.

The relative stability and magnitude of genetic and environmental effects underlying major dimensions of adolescent personality across time were investigated. The Junior Eysenck Personality Questionnaire was administered to over 540 twin pairs at ages 12, 14 and 16 years. Their personality scores were analyzed using genetic simplex modeling which explicitly took into account the longitudinal nature of the data. With the exception of the dimension lie, multivariate model fitting results revealed that familial aggregation was entirely explained by additive genetic effects. Results from simplex model fitting suggest that large proportions of the additive genetic variance observed at ages 14 and 16 years could be explained by genetic effects present at the age of 12 years. There was also evidence for smaller but significant genetic innovations at 14 and 16 years of age for male and female neuroticism, at 14 years for male extraversion, at 14 and 16 years for female psychoticism, and at 14 years for male psychoticism.     

Temperature,hydrochemistry and plankton in Wicken Brickpits, 1930–1931

Temperature, selected chemical constituents and plankton were analysed from three depths, fortnightly, by day and occasionally by night, in two flooded brickpits, between May 1930 and August 1931.Br was 3.3 m deep, with clear water and little weed; III was only 1.8 m deep, with thick submerged weed, more sheltered than Br and becoming eutrophic. Neither had direct inflow nor outlet. Both conformed to the second order for dimictic lakes, with summer and winter stratification, leading, for varying periods, to stagnation marked by pH between 6.6 and 7.2 and O₂ much depleted or absent at the bottom.During stagnation, release of SiO₂, soluble inorganic phosphate-P, ammonium ions and bases from the bottom was shown by sampling water close to the mud. This finding preceded the definition of redox potential by others.Thermistor temperature measurements, used for the first time, showed comparable summer gradients in both ponds: on windy days these were usually sigmoid, with discontinuity at various depths, or else nearly isothermal; on calm days, they were exponential, when transmission of heat, from surface to bottom, was apparently due to radiation alone, without water circulation. Stability was then high.Diatoms were abundant in both ponds; but planktonic Rotifera and Crustacea differed in the two, apart fromDiaptomus gracilis, which was dominant in both.     

Neutral lipids of Aedes aegypti and Aedes albopictus cells cultured in vitro.

Aedes aegypti feeding on chickens infected with Plasmodium gallinaceum take less blood and lay fewer eggs than those feeding on uninfected hosts. Both activities show an inverse correlation with the degree of parasitemia. Mosquitoes feeding on infected chickens ingest blood in amounts directly proportional to the length of time spent on the hosts, whereas there is no relationship between host contact and blood meal size for mosquitoes feeding on uninfected hosts. Feeding and probing choice experiments demonstrate that infected chickens are less attractive to Aedes aegypti than uninfected chickens.     

Development of a Genotyping Microarray for Studying the Role of Gene-Environment Interactions in Risk for Lung Cancer

A microarray (LungCaGxE), based on Illumina BeadChip technology, was developed for high-resolution genotyping of genes that are candidates for involvement in environmentally driven aspects of lung cancer oncogenesis and/or tumor growth. The iterative array design process illustrates techniques for managing large panels of candidate genes and optimizing marker selection, aided by a new bioinformatics pipeline component, Tagger Batch Assistant. The LungCaGxE platform targets 298 genes and the proximal genetic regions in which they are located, using ∼13,000 DNA single nucleotide polymorphisms (SNPs), which include haplotype linkage markers with a minimum allele frequency of 1% and additional specifically targeted SNPs, for which published reports have indicated functional consequences or associations with lung cancer or other smoking-related diseases. The overall assay conversion rate was 98.9%; 99.0% of markers with a minimum Illumina design score of 0.6 successfully generated allele calls using genomic DNA from a study population of 1873 lung-cancer patients and controls.     

CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene–gene interactions

Gene–environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene–gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene–gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1, GSTM1 and GSTT1. The present analyses compare the gene–gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A. This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR=2.8, 95% CI=0.9–8.4). The odds ratio for the interactive term (CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI=0.5–15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1.     

Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis

The vesicular stomatitis virus (VSV) matrix (M) protein plays a major role in the virus-induced inhibition of host gene expression. It has been proposed that the inhibition of host gene expression by M protein is responsible for suppressing activation of host interferon gene expression. Most wild-type (wt) strains of VSV induce little if any interferon gene expression. Interferon-inducing mutants of VSV have been isolated previously, many of which contain mutations in their M proteins. However, it was not known whether these M protein mutations were responsible for the interferon-inducing phenotype of these viruses. Alternatively, mutations in other genes besides the M gene may enhance the ability of VSV to induce interferons. These hypotheses were tested by transfecting cells with mRNA expressing wt and mutant M proteins in the absence of other viral components and determining their ability to inhibit interferon gene expression. The M protein mutations were the M51R mutation originally found in the tsO82 and T1026R1 mutant viruses, the double substitution V221F and S226R found in the TP3 mutant virus, and the triple substitution E213A, V221F, and S226R found in the TP2 mutant virus. wt M proteins suppressed expression of luciferase from the simian virus 40 promoter and from the beta interferon (IFN-beta) promoter, while M proteins of interferon-inducing viruses were unable to inhibit luciferase expression from either promoter. The M genes of the interferon-inducing mutants of VSV were incorporated into the wt background of a recombinant VSV infectious cDNA clone. The resulting recombinant viruses were tested for their ability to activate interferon gene expression and for their ability to inhibit host RNA and protein synthesis. Each of the recombinant viruses containing M protein mutations induced expression of a luciferase reporter gene driven by the IFN-beta promoter and induced production of interferon bioactivity more effectively than viruses containing wt M proteins. Furthermore, the M protein mutant viruses were defective in their ability to inhibit both host RNA synthesis and host protein synthesis. These data support the idea that wt M protein suppresses interferon gene expression through the general inhibition of host RNA and protein synthesis.