Cystic fibrosis screening: a fetus with hyperechogenic bowel may be the index case.

BACKGROUND: The potential of hyperechogenic fetal bowel to act as a hallmark for prenatal cystic fibrosis screening in the general population is controversial. METHODS: Our goal was to evaluate the incidence of cystic fibrosis in 209 fetuses with hyperechogenic bowel diagnosed at routine ultrasonography and with no family history of cystic fibrosis. The diagnosis of cystic fibrosis was based on prenatal screening for the eight mutations most frequently observed in France (deltaF508, deltaI507, 1717-1G-->A, G542X, G551D, R553X, W1282X, N1303K) and at postnatal follow up. RESULTS: The overall incidence of cystic fibrosis was 7/209 (3.3%) which is 84 times the estimated risk of CF in the general population (112500). Of these seven cases, six were diagnosed prenatally based on DNA analysis (deltaF508/deltaF508, n=5; deltaF508/G542X, n=1). One case in which only one mutation had been recognised was diagnosed clinically after birth (deltaF508/unidentified mutation). Of the seven cases, none was diagnosed at 16-19 weeks, four at 16-24 weeks, and three after this. The incidence of heterozygous fetuses (15/209, 7%) was not significantly higher than the 5% expected in the general population. The mutations involved in these heterozygous cases were deltaF508 (n=13), G542X (n=1), and G551D (n=1). CONCLUSIONS: Screening for cystic fibrosis should be offered to families in which fetal hyperechogenic bowel is diagnosed at routine ultrasonography. This underlines the need to review genetic counselling in this situation where the fetus is the index case for a genetic disease.     

Increase in the number of presynaptic large intramembrane particles during synaptic transmission at the Torpedo nerve-electroplaque junction

Small pieces of Torpedo electric organ were treated with 4-aminopyridine, a drug which greatly increases the duration of transmitter release in a single nerve impulse, transforming the normally brief electroplaque potential to a giant discharge. Specimens of tissue were cryofixed by rapid freezing using liquid coolants at precise time intervals during transmission of a single giant discharge, and then examined by freeze fracture. In each experiment, we monitored the electrical response of one specimen during the freezing run to check the physiological responsiveness of the tissue and to determine the precise time of contact with the cryogenic liquid. The general appearance of nerve terminals after cryofixation was similar to that of terminals from chemically fixed and cryoprotected tissue. The major morphological change observed during the time course of the giant discharge was a marked increase in the density of intramembrane particles larger than 10 nm on both the protoplasmic and external faces of the presynaptic membrane. This change appeared in specimens frozen within the first few milliseconds after the stimulus, that is, at a time corresponding to the onset of the rising phase of the potential (3 ms). At the end of the giant discharge, the particle density returned to control values with the same time course as the potential trace. Pits of 20 nm or larger, probably due to vesicle-membrane interaction, were found in a small proportion of nerve terminals. Their occurrence increased only at 120-150 ms after the stimulus, that is, a long time after the beginning of the giant potential and of the change in intramembrane particles. The size distribution of particles was also determined in the membrane of synaptic vesicles exposed by cross fracture of terminal boutons; it was found to be similar to that of the unstimulated presynaptic membrane and it did not change during the giant discharge. Stimulation experiments were also carried out in a modified solution containing no added calcium, 20 mM magnesium and 4-aminopyridine. The propagation of impulses along the nerves to the electric organ was not inhibited in the modified solution but acetylcholine release was prevented and no increase in particle density was found on the presynaptic membrane. These and previous biochemical experiments on this tissue suggest that the release of the neuro-transmitter acetylcholine is associated with a transient occurrence of large intramembrane particles on the two fracture faces of the presynaptic membrane.(ABSTRACT TRUNCATED AT 400 WORDS)     

Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein Evidence of non-random pairing of T and B cell epitopes

The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31–75; 111–145; 151–165; 191–215; 271–320; 421–440; 481–530) which include the major hydrophobic segment (111–145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides.     

BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

Avoiding deceptive imprinting of the immune response to HIV-1 infection in vaccine development

Lymphocyte clonal restriction is caused by priming the immune system with an antigen and has been referred to infectious disease study as "original antigenic sin" (OAS), described first for influenza by Francis. OAS is a dominant feature of a normal immune response. Benefits of OAS come from the initial contact with the pathogen, which induces immunological memory. Memory is achieved by priming B and T cells of an immunologically na?ve host, and confers protection against infection with the antigen-related pathogen. Thus, a restricted antibody response to viral or parasite antigens is not per se pathogenic. However, the interplay between a "locked-in" immune response and the high genetic variation of the pathogenic agent can result in a deception of the immune system. In the following, clonal restriction of the immune response to HIV is described by giving examples of restricted anti-HIV antibody formation in maternally infected children. Clonal restriction results in host resistance of infected individuals to emerging HIV variants and quasispecies. The problems of classical approaches of vaccine design in AIDS and the lack of protection in vaccinated patients is reviewed.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.     

Growth of Aboriginal infants

Aboriginal infants at Cherbourg Aboriginal Settlement in Queensland now have growth rates which are similar to those of white Australian infants. The proportion of children under 90% of the standard weight-for-age appears to be the same as for white Australian children and meets the international standards. Apart from premature infants, no children have been found in the accepted "at risk" categories.     

Firing properties of hippocampal neurons in a visually symmetrical environment: contributions of multiple sensory cues and mnemonic processes

The location-specific firing of hippocampal place cells can easily be brought under the control of experimenter-defined cues. Nevertheless, there is evidence that these firing fields are not determined just by immediate sensory input, but also by earlier states of the nervous system (O'Keefe and Speakman, 1987). Here, we report further on the roles of multiple visual cues and mnemonic processes in determining the firing of place cells. Rats were trained to chase food pellets in a cylinder with homogeneous gray walls and 1 white cue card. After a cell's field was recorded in this "standard" condition, probe sessions were conducted in which a second card was placed 180 degrees away from the first. This configuration created a diametrically symmetrical environment in which pairs of locations 180 degrees apart were identical with respect to views of the wall and cards. If place cells are strongly controlled by these immediately available views, firing in the 2-card configuration should be diametrically symmetrical. Alternatively, because the rat moves freely in the cylinder, information is available that pairs of visually identical places are not truly the same. If some mnemonic process stores and updates information about the rat's paths during the session, it is possible that the firing pattern will be different in 2 such places, especially because the original training was conducted in the 1-card, asymmetrical environment. Thirteen of 18 cells had a single, asymmetric firing pattern after the second card was introduced; the field was the same size and shape as in the 1-card configuration and in the same spatial relation to 1 of the 2 cards. The field position during 2-card sessions could be rotated 180 degrees by starting the rat by one card or the other. In further probe sessions in which the cue cards, entry location, and background cues were, in various combinations, rotated in relation to each other, these cells always showed a single field, similar in size and shape to that in the standard, and in the same relationship as in the standard to as many cues as possible. The remaining 5 cells showed complex changes over repeated 2-card sessions, and 3 of these showed paired fields, 180 degrees apart for at least some of the sessions. In one case, the second field disappeared with repeated exposures to 2 cards; in another, the second field persisted when only 1 card was used. We conclude that place cells are influenced both by the immediate sensory configuration and by internal neural states related to earlier experience in the environment.     

Binding-in: still a relevant concept?

Development of the maternal-fetal relationship was described by Rubin as an intimate "binding-in process." Recent technological advances enabled health care providers to observe, study, diagnose, and treat unborn children and led some to reconsider the relevance of the binding-in concept. Research has focused on prenatal attachment or bonding, maternal characteristics that influence prenatal attachment/bonding, and interventions to promote it. Before binding-in is dismissed as irrelevant, assessment of the prenatal attachment research, consideration of the impact of these ideas on pregnant women and their families, and the implications for maternity nurses must be examined.