The developmental segregation of posterior crista and saccular vestibular fibers in mice: a carbocyanine tracer study using confocal microscopy

The developmental segregation of gravistatic input mediated by saccular fibers and of angular acceleration input mediated by posterior crista (PC) fibers was analyzed for the first time in a developing mammal using carbocyanine dye tracing in fixed tissue. The data reveal a more extensive projection of either endorgan in 7-day-old mice (P7) than has previously been reported in adult mammals. While we confirm and extend many previous findings, we also describe a novel segregation of saccular and posterior crista fibers in the anterior half of the medial vestibular nucleus (Mv) not reported before. Our developmental analysis shows a progressive segregation of posterior crista and saccular fibers to their respective discrete projection areas between embryonic day 15 (E15) and birth (P0). Retention of overlap in young adult animals appears to reflect the early embryonic overlap found in most areas. The vestibular projection does not show a topological projection as has been described in many other sensory systems. We propose that the unique projection features of the vestibular endorgans may relate to the transformation of vestibular signals into a motor output in the three neuron reflex arc of the VOR, of which the primary vestibular projection constitutes the first leg.     

G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population

RATIONALE: Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning. Initial association studies in a Finnish and Canadian population suggested an association with asthma and elevated serum IgE levels. OBJECTIVE: In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed. Methods: Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 children with asthma and/or bronchial hyperresponsiveness) were genotyped for seven polymorphisms in the GPRA gene. MEASUREMENTS: Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. MAIN RESULTS: SNP 546333 increased the risk for asthma (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.88; p = 0.025) and concomitant asthma and bronchial hyperresponsiveness (BHR; OR, 2.38; 95% CI, 1.22-4.66; p = 0.009). Also, SNP 585883 was associated with asthma (OR, 1.34; 95% CI, 1.04-1.72; p = 0.022) and asthma in combination with BHR (OR, 2.71; 95% CI, 1.45-5.09; p = 0.001). Furthermore, SNP 585883 was associated with elevated serum IgE levels (OR, 1.63; 95% CI, 1.10-2.42; p = 0.015). Haplotype combinations of risk alleles increased the OR for asthma to 1.83 (95% CI, 1.08-3.08; p = 0.024) and for asthma and concomitant BHR to OR 3.51 (95% CI, 1.08-11.37; p = 0.036). CONCLUSIONS: These results indicate that GPRA polymorphisms increase the susceptibility for asthma and BHR, and to a lesser degree for the elevation of serum IgE, in a German population, confirming initial observations in other white populations.     

Graduation of gynecological findings from the social-gynecological and industrial health viewpoint (author's transl)

A review is given on the status of the gynecological part of the tabular value of health grades for fitness examinations and checkups in the field of industrial health. It is reported on experiences in carrying out gynecological fitness examinations within the Research Union of Industrial Medicine of the German Democratic Republic during the years 1972 to 1975. With the graduation of gynecological findings and diseases according to four health grades, possibilities are shown, in order to derive statements on development of the state of health under defined working conditions by means of complex industrial health fitness examinations. Thus, health and labour protection of the working woman can be further improved.     

Development and evolution of the vestibular sensory apparatus of the mammalian ear

Herein, we will review molecular aspects of vestibular ear development and present them in the context of evolutionary changes and hair cell regeneration. Several genes guide the development of anterior and posterior canals. Although some of these genes are also important for horizontal canal development, this canal strongly depends on a single gene, Otx1. Otx1 also governs the segregation of saccule and utricle. Several genes are essential for otoconia and cupula formation, but protein interactions necessary to form and maintain otoconia or a cupula are not yet understood. Nerve fiber guidance to specific vestibular end-organs is predominantly mediated by diffusible neurotrophic factors that work even in the absence of differentiated hair cells. Neurotrophins, in particular Bdnf, are the most crucial attractive factor released by hair cells. If Bdnf is misexpressed, fibers can be redirected away from hair cells. Hair cell differentiation is mediated by Atoh1. However, Atoh1 may not initiate hair cell precursor formation. Resolving the role of Atoh1 in postmitotic hair cell precursors is crucial for future attempts in hair cell regeneration. Additional analyses are needed before gene therapy can help regenerate hair cells, restore otoconia, and reconnect sensory epithelia to the brain.     

Keeping sensory cells and evolving neurons to connect them to the brain: molecular conservation and novelties in vertebrate ear development

The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an 'organ' system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.     

Interactions between food components and drugs. Part 8: Effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro

Interactions between quinine and acetylated pectin, amidated pectin and pectin with blockwise arrangement of the free carboxyl groups as well as interactions between quinine and bile salt preparations forming stable mixed bicelles have been investigated. A diffusion cell with two compartments and an artificial lipid membrane and a filter-grown colon carcinoma cell line (Caco-2) have been used. Depending on structural parameters, pectin preparations diminished the rate of permeation of the drug. Above the critical micelle concentration, the bile salt preparations influence the quinine transport stronger than the pectin preparations. The strongest inhibition of the quinine permeation showed a stable mixed micelle preparation consisting of glycodeoxycholate, palmitic acid and lecithin. The Caco-2 cell line appears to be not as suitable as artificial lipid membranes to study drug transport in the presence of the bile salt preparations.     

Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 3rd communication: comparison of various contrast agents employed in contrast echocardiography

Right-ventricular contrast provided by the new standardized sonographic contrast agent SH U 454, which consists of pure galactose microparticles, with 300 mg microparticles/ml and by 5 other currently employed ultrasonic contrast media was examined by 2 D echocardiography in 10 anesthetized female beagle dogs (6.8-12.7 kg) following i.v. administration. With a 5-min interval between injections each animal was given 3 injections of 2 ml of each formulation in random order using an injection speed of approximately 2 ml/s. The echocardiographic investigation was recorded on videotape and the contrast assessed blind using a visual score system (rating 0-5) by two investigators working independently and also by a videodensitometer. Only SH U 454 caused an intense, homogeneous and reproducible opacification of the right heart chambers. By comparison with other formulations for right-heart echocontrast, SH U 454 was significantly superior (p less than 0.05) in every parameter assessed.