Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan.

BACKGROUND: Primary hypogammaglobulinemia disorders are a group of heterogeneous immunodeficiency syndromes with an increased susceptibility to pulmonary complications. METHODS: The aim of this study was to evaluate the extent of lung abnormalities in primary hypogammaglobulinaemic patients by high resolution computed tomography (HRCT) scan and pulmonary function test (PFT). HRCT and PFT were performed in 22 Iranian patients with primary hypogammaglobulinemia. RESULTS: Pathological bronchial findings were observed in thirteen patients: three patients showed only peribronchial thickening and the remaining ten patients suffered from both bronchiectasis and peribronchial wall thickening. Mild type of bronchiectasis and peribronchial wall thickening were the most common type, predominantly observed in the right middle and both right and left lower lobe segments of lungs. Although bullae were not found, emphysema, air-trapping, and collapse/consolidation were observed in two patients. Bronchial involvement was mostly limited to 1 up to 5 bronchopulmonary segments; only one HRCT indicated bronchial involvement in more than nine bronchopulmonary segments. Pathological bronchial findings mostly observed in the proximal bronchi; meanwhile the involvement of the distal bronchi was less common. Decreasing FEVI and FVC were observed in 65% and 55% of patients, respectively. There was a significant correlation between the HRCT score and the predicted values by PFT. The delay of diagnosis in patients with bronchiectasis was significantly higher than those without bronchiectasis. CONCLUSIONS: It seems that the majority of hypogammaglobulinaemic patients suffer from the mild type of bronchiectasis, which is mostly observed in the proximal bronchi of the lower lobe segments. The delay of diagnosis plays an important role in the occurrence of this complication in these patients.

YAC transgene-mediated olfactory receptor gene choice.

In the mouse, individual olfactory neurons express one of a thousand distinct olfactory receptor genes. Furthermore, only one allele of the expressed gene is transcribed. This phenomenon, random allelic inactivation, along with the observation that the olfactory receptor genes reside in large chromosomal arrays, suggests a role for long-range gene regulation in olfactory receptor gene choice. We have constructed a 300-kb yeast artificial chromosome (YAC) transgene in which a single receptor gene is marked while maintaining its coding region. This 300-kb piece of DNA functions as an independent olfactory receptor gene locus in directing olfactory receptor gene choice in both the olfactory system and the accessory olfactory system (vomeronasal organ, VNO). Furthermore, the transgene, like endogenous olfactory receptor loci, is subject to allelic inactivation.

Olfactory neurons are interdependent in maintaining axonal projections.

In mice, individual olfactory neurons express one of the thousand distinct olfactory receptor genes [1] [2] [3]. Neurons that express a given receptor converge on distinct loci in the olfactory bulb to form structures called glomeruli [4] [5] [6]. The olfactory receptor is involved in an instructive manner in this axonal convergence [6] [7] but little is known about the mechanisms involved in maintaining convergence. We have previously created a transgenic olfactory receptor locus that functions independently of the endogenous loci [8]. Here, we show that, although the projections of neurons expressing this ectopic transgenic olfactory receptor always converge in newborn mice, surprisingly, in adult mice, convergence is not always maintained. Moreover, in adult mice there is a positive correlation between the number of neurons expressing the transgenic receptor and the probability of maintaining convergence. These observations, taken together with the variability observed in wild-type [4] [6] and genetically manipulated mice ([6] and our unpublished observations), suggest that olfactory neurons require the presence of other similar axons to maintain a glomerulus. We call this phenomenon interdependence.

The specification of olfactory neurons.

Recent studies have shed light on the different relationships between odorant receptor expression and the specification of neural identity in the olfactory systems of vertebrates and invertebrates. In mice, neuronal identity and axon guidance are specified by the single expressed olfactory receptor, whereas in C. elegans, neuronal identity appears to be independent of receptor expression.

Olfactory G proteins: simple and complex signal transduction.

In both vertebrates and invertebrates, olfactory perception is mediated by G-protein-coupled receptors. Recent work, in both mouse and Caenorhabditis elegans, sheds light on the role of specific G proteins in olfactory signal transduction, neuronal morphology and axon guidance.