Expression of S-100 protein in the human fetal inner ear

The expression of S-100 protein was analyzed in the human fetal inner ear using immunohistochemical methods. In the 11-week-old human fetus, the cochlea was almost negative for S-100 protein, whereas in the 14- and 15-week-old fetuses, the spiral ligament, Reissner's membrane and spiral limbus were positive for the protein. These results suggest that S-100 protein may be a reliable marker for determining functional maturation of the fetal cochlea and the inner ear. In the l l-, 14- and 15-week fetuses, the epithelial cells of the endolymphatic sac were labelled with S-100 protein. These findings demonstrate that the endolymphatic sac, spiral limbus and spiral ligament in the fetal inner ear have a high activity of S-100 protein, with this presence possibly related to fluid and ion transport of endolymph.     

Degradation of the homogeneous substance in the endolymphatic sac

The accumulation and degradation of a homogeneous precipitate in the lumen of the endolymphatic sac (ES) was studied in mice. Filling of the endolymphatic sac was induced by surgical labyrinthectomy and the sacs were studied 1-8 weeks postoperatively. The initial phase (1-2 weeks postlabyrinthectomy) was characterized by filling of the ES with the homogeneous precipitate. The number of freely floating cells in the lumen was increased after two weeks. Three weeks postoperatively the ES lumen was generally clear, with apparently no stainable material. Ultrastructural analysis of the ES showed that this clearance of the endolymphatic space resulted from degradational activity in the epithelial cells initiated in the proximal portion of the sac. Breakdown of the homogeneous substance seemed to result from cellular ingestion with concomitant lysosomal digestion. Four weeks postoperatively cell clusters were observed subepithelially and were filled with densely staining precipitate, indicating that these cells or macrophages were involved in the turnover of the homogeneous substance in the ES. The functional significance of a degradational system of this substance in the ES is discussed.     

Three-dimensional ultrastructure of the endolymphatic sac

Summary The subcellular structures of the epithelial cells of the guinea pig endolymphatic sac were studied. By using a newly developed scanning electron microscopy technique, the intracellular organelles could be studied three-dimensionally and the topographic relationships analyzed. The light epithelial cell has an extensive network of endoplasmic reticulum which is characteristically arranged in a basoapical direction. The connections between the inner surface of the plasmalemma and the endoplasmic reticulum were observed, as were connections between the Golgi complex and the endoplasmic reticulum. Our findings support the hypothesis that the endoplasmic reticulum might form transcellular channels through which the cell can transport water and ions from the lumen of the endolymphatic sac out into the subepithelial tissue. The dark epithelial cells seen in particular contained the smooth type of endoplasmic reticulum. Lysosomes were also observed in the dark cells, indicating that these cells probably have more of a secretory function.     

The development of the endolymphatic duct and sac. A light microscopical study

The development and maturation of the endolymphatic sac were studied in the CBA/CBA mouse. The otocyst is developed at gestational day 10 and the primitive endolymphatic sac is present as a large slit-like appendage at day 12 of gestation. At day 18 the endolymphatic sac is clearly detached from the rest of the otocyst, forming a true sac. The epithelial lining consists of only one layer of immature cells containing large vesicles. The endolymphatic sac is surrounded by a rich network of vessels. One day before birth, the epithelial lining is uneven and the first signs of differentiation into light and dark cells is visible. This situation is more pronounced 2 days post partum when the sac also seems to be filled with a stainable material. At day 6 post partum the otic capsule fuses around the sac, forming the vestibular aqueduct. At 14 days post partum the sac is mature, with clearly developed light and dark cells and widened lateral intercellular spaces, constituting the rugose epithelium. The lumen is filled with a stainable precipitate and a few free-floating cells.     

Discriminability of the quality of amplitude-compressed speech

In an earlier experiment on intelligibility of amplitude-compressed speech, subjects could not hear a difference between noncompressed speech and speech under some conditions of compression. Therefore, compression conditions were determined in which the quality of the two types of speech could be distinguished. When speech average level was 10 dB above a masking noise, compression ratio (CR) was equal to 2.5, and the attack time (Ta) was 3 ms, the release time (Tr) had to be shorter than 120 ms to achieve discrimination by trained normal-hearing subjects. With longer attack times and/or higher compression ratios, the critical value of release times increased. Thus, the range in which the discrimination was observed also increased (for CR = 5 and Ta = 10 ms, the critical Tr was 360 ms). The discrimination of our hearing-impaired subjects was much worse than that of the normal-hearing subjects. For example, speech processed with CR = 10, Ta = 1 ms, and Tr = 10 ms could be distinguished from the noncompressed by only 50% of the impaired subjects.     

The role of the endolymphatic sac in statoconial formation and degradation

In the present investigation we studied the morphology o the endolymphatic sac in guinea pig fetuses (age 20-, 30-, 45-, 60-days-old and newborns). Twenty-day and 30-days-old guinea pig fetuses often displayed small prismatic or hexagonally shaped granules, presumably representing miniature otoconia. The granules appeared freely in the lumen of the endolymphatic sac as well as incorporated in the cytoplasm of the freely floating cells or macrophages. The origin of these "sac otoconia' as well as the possible role of the endolymphatic sac in statoconis turnover and metabolism is discussed.     

Trabecular aspiration in pseudoexfoliative glaucoma--surgery to primarily reduce intraocular pressure

BACKGROUND: Trabecular aspiration has been discussed during the past few years as a new surgical method in the treatment of pseudoexfoliative glaucoma. In this procedure PEX-material, pigment and detritus are aspirated from the trabecular meshwork. Trabecular aspiration has been evaluated mainly in combination with cataract extraction. This study reports on our first experiences concerning the IOP-reducing effect of trabecular aspiration as a primary surgical method in the management of pseudoexfoliative glaucoma. MATERIALS: 17 eyes of 14 patients (7 m, 7 f; 12 OD, 5 OS; age 71 +/- 6 years) with pseudoexfoliative glaucoma were included in this study and operated on by standardised trabecular aspiration (vacuum max. 200 mm Hg, 180 - 270 degrees, 5 min). Therapy success was defined as an IOP reduction by more than 20 % and less than 21 mm Hg. RESULTS: Therapy success was 82 % (14 out of 17) on the first postoperative day, 50 % after 30 days (8 out of 16) and 23 % after 180 days (3 out of 13). IOP was 26.8 +/- 8.5 mm Hg before surgical intervention, 18.1 +/- 11.4 mm Hg after 1 day, 19.1 +/- 7.9 mm Hg after 30 days and 19.2 +/- 5.2 mm Hg after 180 days. Mean quantity of antiglaucomatous eye drops application was 3.1 +/- 0.9 preoperatively, 0.9 +/- 1.6 after 1 day, 0.8 +/- 1.2 after 30 days and 1.0 +/- 1.3 after 180 days. CONCLUSIONS: Trabecular aspiration achieves a good short-term effect in the reduction of IOP in patients with pseudoexfoliative glaucoma. However, this effect was limited to a few weeks in most patients. Trabecular aspiration as a primary surgical method in the management of pseudoexfoliative glaucoma does not appear to be suitable for long-term IOP reduction.     

Blockade of neuropeptide Y(2) receptors and suppression of NPY's anti-epileptic actions in the rat hippocampal slice by BIIE0246

Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y(2) (Y(2)R) and the Y(5) (Y(5)R) receptors have both been implicated in this action. We used the non-peptide, Y(2)R-selective antagonist, BIIE0246, to test the hypothesis that the Y(2)R mediates both the presynaptic inhibitory and anti-epileptic actions of NPY in rat hippocampus in vitro. NPY and the Y(2)R-selective agonist, [ahx(5-24)]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration-dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC(50), in a manner inconsistent with competitive antagonism. BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1 - 3 microM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246. In the stimulus train-induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx(5-24)]NPY inhibited primary afterdischarge (1 degrees AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx(5-24)]NPY in this model. In contrast, the potent Y(5)R-selective agonist, Ala(31)Aib(32)NPY, affected neither 1 degrees AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1. BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y(2)R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist.     

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene

BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.