Prevalence of squamous abnormalities in women with a recent smear without endocervical cells is lower as compared to women with smears with endocervical cells

The purpose of this study was to determine the prevalence rate ratio of squamous lesions in women with recent smears without endocervical component (ECC-) versus women having a smear with ECC+ and to estimate the true prevalence of these lesions in women with ECC- smears by addition of short-term follow-up results of negative ECC- smears. Results of initial smears in a 3-year period, as well as follow-up results of negative ECC- smears in the same period were retrieved. Women were categorized into two groups: having ECC- and ECC+ smears. The data were analysed for three outcome parameters, ASCUS or higher (ASCUS+), LSIL or higher (LSIL+) and HSIL or higher (HSIL+). Squamous abnormalities occurred far less frequently in women with initial ECC- than with ECC+ smears. Prevalence rate ratio (PRR) was 0.27 for ASCUS+, 0.39 for LSIL+ and 0.36 for HSIL+. Addition of follow-up results of negative ECC- smears, as a correction for false-negative ECC- smears, results in PRRs which are still significantly lower than 1, and most marked in subset HSIL+ (PRR = 0.60). We conclude that the true prevalence of squamous lesions in women with recent ECC- smears is significantly lower as compared with ECC+ smears. These findings lent support to the decision to abolish the repeat of ECC- smears in the Dutch population screening programme.     

Seed production in fens and fen meadows along a disturbance gradient

Question: The seed production in several wetland communities across Europe was investigated and differences in seed output in relation to disturbance intensity were tested. The relationship between the vegetation composition and the seed production profile was examined and the results are discussed in relation to restoration. Location: Poland, Germany and the Netherlands. Methods: The seed production in various plant communities was estimated, based on field counts. In addition, records from available databases were used for missing data. Multivariate methods were used to characterize the vegetation and seed production. Communities were grouped according to level of disturbance and tested for differences in seed production. Similarity between vegetation composition and seed profile was examined using the Sørensen index and Spearman correlation coefficient. Results: It was found that the seed production of the studied communities is large, variable and in general increasing with disturbance intensity. The estimated median seed production was ca. 24 × 10³ seeds m^?2 in fens, 167 × 10³ in fen meadows and 556 × 10³ seeds m^?2 in degraded meadows. The majority of seeds was produced by just a few species. The similarity between the vegetation composition and the seed production profile was low (similarity 52%, correlation coefficient 0.42, P<0.05) and slightly increased with disturbance intensity. Conclusions: Increased disturbance enhances seed production at the community level. The composition of the vegetation is a poor predictor of the seed output. It is estimated that the number of seeds transferred with hay is much lower than the seed production in fens and fen meadows.     

Impaired Antibody Response Causes Persistence of Prototypic T Cell–Contained Virus

CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LCMV), a prototypic mouse model of systemic persistent infection. Mice expressing transgenic B cell receptors of LCMV-unrelated specificity, and mice unable to produce soluble immunoglobulin M (IgM) exhibited protracted viremia or failed to resolve LCMV. Virus control depended on immunoglobulin class switch, but neither on complement cascades nor on Fc receptor γ chain or Fc γ receptor IIB. Cessation of viremia concurred with the emergence of viral envelope-specific antibodies, rather than with neutralizing serum activity, and even early nonneutralizing IgM impeded viral persistence. This important role for virus-specific antibodies may be similarly underappreciated in other primarily T cell–controlled infections such as HIV and hepatitis C virus, and we suggest this contribution of antibodies be given consideration in future strategies for vaccination and immunotherapy.     

Perturbations of model membranes induced by pathogenic dynorphin A mutants causing neurodegeneration in human brain

Several effects of the endogenous opioid peptide dynorphin A (Dyn A) are not mediated through the opioid receptors. These effects are generally excitatory, and result in cell loss and induction of chronic pain and paralysis. The mechanism(s) is not well defined but may involve formation of pores in cellular membranes. In the 17-amino acid peptide Dyn A we have recently identified L5S, R6W, and R9C mutations that cause the dominantly inherited neurodegenerative disorder Spinocerebellar ataxia type 23. To gain further insight into non-opioid neurodegenerative mechanism(s), we studied the perturbation effects on lipid bilayers of wild type Dyn A and its mutants in large unilamellar phospholipid vesicles encapsulating the fluorescent dye calcein. The peptides were found to induce calcein leakage from uncharged and negatively charged vesicles to different degrees, thus reflecting different membrane perturbation effects. The mutant Dyn A R6W was the most potent in producing leakage with negatively charged vesicles whereas Dyn A L5S was virtually inactive. The overall correlation between membrane perturbation and neurotoxic response [3] suggests that pathogenic Dyn A actions may be mediated through transient pore formation in lipid domains of the plasma membrane.     

Entering a New Era of Body Indices: The Feasibility of a Body Shape Index and Body Roundness Index to Identify Cardiovascular Health Status

Background

The Body Mass Index (BMI) and Waist Circumference (WC) are well-used anthropometric predictors for cardiovascular diseases (CVD), but their validity is regularly questioned. Recently, A Body Shape Index (ABSI) and Body Roundness Index (BRI) were introduced as alternative anthropometric indices that may better reflect health status.

Objective

This study assessed the capacity of ABSI and BRI in identifying cardiovascular diseases and cardiovascular disease risk factors and determined whether they are superior to BMI and WC.

Design and Methods

4627 Participants (54±12 years) of the Nijmegen Exercise Study completed an online questionnaire concerning CVD health status (defined as history of CVD or CVD risk factors) and anthropometric characteristics. Quintiles of ABSI, BRI, BMI, and WC were used regarding CVD prevalence. Odds ratios (OR), adjusted for age, sex, and smoking, were calculated per anthropometric index.

Results

1332 participants (27.7%) reported presence of CVD or CVD risk factors. The prevalence of CVD increased across quintiles for BMI, ABSI, BRI, and WC. Comparing the lowest with the highest quintile, adjusted OR (95% CI) for CVD were significantly different for BRI 3.2 (1.4–7.2), BMI 2.4 (1.9–3.1), and WC 3.0 (1.6–5.6). The adjusted OR (95% CI) for CVD risk factors was for BRI 2.5 (2.0–3.3), BMI 3.3 (1.6–6.8), and WC 2.0 (1.6–2.5). No association was observed for ABSI in both groups.

Conclusions

BRI, BMI, and WC are able to determine CVD presence, while ABSI is not capable. Nevertheless, the capacity of BRI as a novel body index to identify CVD was not superior compared to established anthropometric indices like BMI and WC.     

Intergeneric transfer of a partial genome and direct production of monosomic addition plants by microprotoplast fusion

Results are reported on the transfer of single, specific chromosomes carrying kanamycin resistance (Kan^R) and -glucuronidase (GUS) traits from a transformed donor line of potato (Solanum tuberosum) to a recipient line of the tomato species Lycopersicon peruvianum through microprotoplast fusion. Polyethylene glycol-induced mass fusion between donor potato microprotoplasts containing one or a few chromosomes and normal recipient diploid L. peruvianum protoplasts gave several Kan^R calli. A high frequency of plants regenerated from Kan^R calli expressed both Kan^R and GUS, and contained one or two copies of npt-II and a single copy of gus. Genomic in situ hybridization showed that several microprotoplast hybrid plants had one single potato donor chromosome carrying npt-II and gus genes and the complete chromosome complement of the recipient L. peruvianum (monosomic additions). Several monosomic-addition hybrid plants could be regenerated within the short time of 3 months and they were phenotypically normal, resembling the recipient line. These results suggest that the transfer of single chromosomes is tolerated better than is the transfer of the whole donor genome. The unique advantages of microprotoplast fusion are discussed: these include the direct production of monosomic addition lines for the transfer and introgression of economically important traits in sexually-incongruent species, the construction of chromosome-specific DNA libaries, high-resolution physical mapping and the identification of alien chromosome domains related to gene expression.     

Mechanisms of resistance in the rice cultivar Manikpukha to the rice stem nematode Ditylenchus angustus

The incompatible interaction between the rice cultivar Manikpukha and the rice stem nematode Ditylenchus angustus has been reported recently. This research focuses on the underlying mechanisms of resistance in Manikpukha. Invasion, post‐infection development and reproduction of D. angustus were compared in compatible and incompatible interactions to identify the stage in which resistance occurs. The results indicate that resistance in Manikpukha is associated with reduced development and reproduction, implying that resistance acts post‐invasion. We studied the possible involvement of three classical defence hormones, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), in response to infection in a compatible interaction using biosynthesis/signalling‐deficient transgenic rice lines. All three hormones appear to have an influence on the basal defence of Nipponbare against the stem nematode. Although hormone application increases basal defences, expression studies and hormone analyses after nematode infection in Manikpukha did not show a clear involvement of the hormone defense pathways for SA, ET and JA. However, it seems that OsPAL1 plays a pivotal role in resistance, indicating that the phenylpropanoid pathway and its products might be key players in the incompatible interaction. Lignin measurement showed that, although basal levels are similar, Manikpukha had a significantly higher lignin content on nematode infection, whereas it was decreased in the susceptible cultivar. The results presented here show that SA, ET and JA are involved in basal defences, but the resistance of Manikpukha against D. angustus probably relies on products of the phenylpropanoid pathway.     

Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children

Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. Age-dependent brain disposition of morphine could contribute to this variability, as developmental increase in blood-brain barrier (BBB) P-glycoprotein (Pgp) expression has been reported. In addition, age-related pharmacodynamics might also explain the variability in effect. To assess the influence of these processes on morphine effectiveness, a multi-compartment brain physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) model was developed in R (Version 3.6.2). Active Pgp-mediated morphine transport was measured in MDCKII-Pgp cells grown on transwell filters and translated by an in vitro-in vivo extrapolation approach, which included developmental Pgp expression. Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature. Model simulations after single dose morphine were compared with measured and published concentrations of morphine and M6G in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), as well as published drug responses in children (1 day– 16 years) and adults. Visual predictive checks indicated acceptable overlays between simulated and measured morphine and M6G concentration-time profiles and prediction errors were between 1 and -1. Incorporation of active Pgp-mediated BBB transport into the PB-PK/PD model resulted in a 1.3-fold reduced brain exposure in adults, indicating only a modest contribution on brain disposition. Analgesic effect-time profiles could be described reasonably well for older children and adults, but were largely underpredicted for neonates. In summary, an age-appropriate morphine PB-PK/PD model was developed for the prediction of brain pharmacokinetics and analgesic effects. In the neonatal population, pharmacodynamic characteristics, but not brain drug disposition, appear to be altered compared to adults and older children, which may explain the reported differences in analgesic effect.     

Mitochondrial DNA variation and crossability of leek (Allium porrum) and its wild relatives from the Allium ampeloprasum complex

 Mitochondrial (mt) DNA variation in the cultigens leek, kurrat and prei-anak is limited compared to that of their wild relatives in the Allium ampeloprasum complex. The phylogenetic relationships among these cultigens and their wild relatives is quite close, with the majority of the species clustering within one mitochondrial clade. The presence in leek of an extra-mitochondrial genetic element was noted. Analysis of crossability showed that all species were interfertile with leek. It is suggested that the genetic variation present within the A. ampeloprasum complex could be exploited in order to broaden the genetic basis of leek. Received: 14 August 1996 / Accepted: 23 August 1996