Membrane fusion induced by the HIV type 1 fusion peptide: modulation by factors affecting glycoprotein 41 activity and potential anti-HIV compounds

Peptides representing a sequence of 23 amino acid residues at the N terminus of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 bind and subsequently induce fusion of large unilamellar vesicles (LUV), an activity presumably related to gp41 function in viral infection. These in vitro effects can be modulated by several factors that are known to affect HIV-1 infectivity and gp41-mediated virus-cell fusion. Peptide-induced membrane fusion but not peptide binding can be inhibited by two factors known to block gp41 activity: a polar amino acid substitution V --> E in position 2 and the presence of the N-terminal hexapeptide of gp41 in addition to the parent sequence. Whereas inclusion of the alternative gp120 receptor galactosylceramide in membranes has virtually no effect, membrane cholesterol stimulates fusion activity. In view of its putative physiological relevance, we have used the fusion activity of the peptides as a tool to evaluate the inhibitory effect of antivirals that might target this sequence. We describe three dissimilar effects: Amphotericin B inhibits in a cholesterol-independent way peptide-induced fusion but not binding, human serum albumin inhibits binding and consequently fusion, and dextran sulfate (M(r) 5000) does not affect either binding or fusion.     

Significance of idiopathic preterm birth in relation to previous and future pregnancies

This registry-based cohort study aimed to describe the relationship between pregnancy complications in the first and second pregnancy, focussing on idiopathic and indicated preterm birth of singleton infants in either pregnancy. The cohort consisted of all women living in Denmark with a first singleton birth in 1982 and a second in the period 1982-1987 (13,967 women). The risk of a second preterm birth was not significantly different between women who had an idiopathic or an indicated first preterm birth (15.2 and 12.8% respectively). Adjustment by logistic regression analysis for other risk factors for preterm birth did not influence the relative risk (6.0 before 32 weeks and 4.8 between 32 and 36 weeks) of a second preterm birth subsequent to a first one. Women with idiopathic preterm delivery in their first or second pregnancies give birth to infants with lower birth weight in previous or subsequent pregnancies. Emergency cesarean section in a first term pregnancy was a risk factor for subsequent idiopathic preterm birth.     

Modelling ordinal responses from co-twin control studies

The co-twin control design has been widely used in studying the effects of environmental factors on the development of diseases. For binary outcomes that arise from co-twin control studies, the conditional likelihood method is commonly used. This approach, however, does not readily extend to ordinal response data because the standard conditional likelihood does not exist for cumulative logit or proportional odds models. In this paper, we investigate the applicability of the random-effects and GEE approaches in analysing ordinal response data from co-twin control studies. Using both approaches, we re-analyse data from a co-twin control study of the impact of military services during the Vietnam era on post-traumatic stress disorders (PTSD). The ordinal models have considerably increased power in detecting the effects of exposure when compared to the analyses using a dichotomized response. We discuss the interpretation of the estimates from GEE and random-effect models in the context of the twin data.     

Prefrontal involvement in "temporal bridging" and timing movement

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.     

Development and differentiation of the anuran auditory brainstem during metamorphosis: an acetylcholinesterase histochemical study

The time course of cell differentiation and the presence of histochemically defined areas in brainstem auditory nuclei were examined in developing bullfrogs, Rana catesbeiana, using cresyl violet staining and acetylcholinesterase (AChE) histochemistry. In the medulla, the dorsolateral nucleus (DLN) can be seen as a distinct structure in its adult location only at Gosner stage 40 and beyond. The majority of cells in the DLN are not fully differentiated until late metamorphic climax (stages 45-46) and early postmetamorphosis. The more ventral vestibular nucleus differentiates earlier (stage 37) than the DLN. Adult-like organization of auditory nuclei in the torus semicircularis (TS) of the midbrain cannot be reliably discerned until metamorphic climax stages. Cellular masses in the brainstem reveal AChE from the earliest stage examined (stage 27) but the intensity of staining differs among cell groups. Staining intensity in the DLN is at a peak in recently metamorphosed froglets. The time course of cell differentiation in the DLN precedes slightly or is coincident with the increased, transient presence of AChE. Staining of the superior olive stabilizes at a moderate level in early postmetamorphic stages. Ventral regions of the principal nucleus in the TS stain more intensely than dorsal regions beginning at stage 40. This dorsal-ventral gradient in staining persists in adult stages. There is a transient decline in staining of the laminar nucleus in metamorphic climax stages. Staining intensity in the magnocellular nucleus peaks during stages 40-46 and in early postmetamorphic froglets and then declines in adults, paralleling the pattern seen in the DLN. These data suggest that metamorphic climax and early froglet periods are an important developmental window for major differentiation and maturational events in the auditory brainstem.     

The Roter Interaction Analysis System (RIAS) in oncological consultations: psychometric properties

One of the most frequently used systems to analyse doctor-patient communication is the Roter Interaction Analysis System (RIAS). However, it has mostly been applied and evaluated in primary care settings. Two studies are presented in which the psychometric properties of the RIAS are investigated in an oncological setting. In the first study (N = 25) the feasibility, inter-rater reliability and content validity of the RIAS was investigated. In the second study, we evaluated the discriminant validity of the RIAS. Results of the first study showed that coding of tapes was more time consuming than indicated by the Roter manual. The inter-rater reliability proved to be high for both physician communication (0.68-1) and patient communication (0.60-1). The content validity proved to be acceptable: all utterances could be classified. However, coding dilemmas regarding affective communication occurred. The RIAS provided no option to classify communication of a third person present. Some communication categories were never or rarely used. Results of the second study indicate that the RIAS was able to discriminate between communicative behaviors in oncological consultations (N = 60) and three different GP-samples (random-GP sample N = 329, hypertension sample N = 103, gynaecology sample N = 65). To conclude, the psychometric properties of the RIAS are satisfactory in an oncological setting.     

Relative stability of a minimal CTG repeat expansion in a large kindred with myotonic dystrophy

The genetic basis for myotonic dystrophy (DM) is a CTG trinucleotide repeat expansion. The number of CTG repeats commonly increases in affected individuals of successive generations, in association with anticipation. We identified a large DM family in which multiple members had minimal CTG repeat expansions, and in which the number of CTG repeats remained in the minimally expanded range through at least three, and possibly four, generations. This relative stability of minimal CTG repeat expansions may help to maintain the DM mutation in the population.     

Chromosome variation and anomalous karyotypes in the red-backed mouse Clethrionomys rufocanus (Rodentia, Microtinae)

G-banding and C-banding of chromosomes were studied in populations of the red-backed mouse Clethrionomys rufocanus from 11 localities of eastern Russia. Intrapopulation polymorphism of autosome 3 caused by the deletion-duplication of the short-arm heterochromatin (2n = 56; NFa = 56-58) was demonstrated. The karyotype of Cl. rufocanus from continental populations and Sakhalin Island was shown to have a large subtelocentric chromosome of pair 3 (NFa = 58), whereas in the population from Kunashir Island, chromosomes of this pair were acrocentric (NFa = 56). One animal from the population of the Kedrovaya Pad' Reserve (Primorsk krai) had a pericentric inversion (acrocentric morphology) of the Y chromosome. In two animals, a female from the Ussuriiskii Reserve (Primorsk krai) and a male captured near the Tomari Settlement (Sakhalin Island), a pericentric inversion of one chromosome of pair 6 was found (NFa = 59). The inversion detected in the animal from the Sakhalin population was accompanied by the loss of the centromeric heterochromatin. In contrast, the inversion of the chromosome pair 6, which was found in the mouse from the Primorsk krai population, did not involve the loss of centromeric heterochromatin. Analysis of our results and data from the literature showed that the karyotype of Cl. rufocanus is not constant, as was thought earlier. The percentage of animals with abnormal karyotype (1.6%) was higher than in other groups of red-backed mice studied (0.12-0.7%).     

Clinical trials and tribulations: lessons learned from recruiting pregnant ex-smokers for relapse prevention.

The development of smoking cessation and relapse prevention interventions for pregnant and postpartum women is a public health priority. However, researchers have consistently reported substantial difficulty in recruiting this population into clinical trials. The problem is particularly acute for relapse prevention studies, which must recruit women who have already quit smoking because of their pregnancy. Although these individuals are an important target for tobacco control efforts, they represent an extremely small subgroup of the general population. This paper describes multiple recruitment strategies used for a clinical trial of a self-help relapse prevention program for pregnant women. The effectiveness of the strategies and the direct expense per participant recruited are provided. A proactive recruitment strategy (telephoning women whose phone numbers were purchased from a marketing firm) was ultimately much more successful than a variety of reactive strategies (advertisements, press releases, direct mail, Web placement, health care provider outreach). We found few differences between proactively and reactively recruited participants on baseline variables. The primary difference was that the former had smoked fewer cigarettes per day and reported lower nicotine dependence prior to quitting. Strengths and limitations of the recruitment strategies are discussed.