PubMed Health⌕ Search

Biomedical subjects

A Forge

Publications and source records attributed to A Forge.

At least 55 records · Page 3Linked to original sources
PubMed1985

Structural abnormalities in the stria vascularis following chronic gentamicin treatment.

Freeze-fracture and thin-sectioning have been used to examine the stria vascularis of albino guinea pigs chronically treated with gentamicin. Immediately following the end of treatment, most marginal cells showed lipid bodies in the cell body region and freeze-fracture revealed alterations to the marginal cell plasma membrane. Intermediate cells also showed peculiarities including a dilation of the rough endoplasmic reticulum. A co-incidence was noted in the location in the cochlea in which effects in the stria and in outer hair cells occurred. At 4 weeks post-treatment, the stria was significantly thinner than normal and appeared less structurally complex. A minority of marginal cells degenerated. Some morphological features associated with degeneration resembled those of apoptosis, a process of controlled, cellular self-destruction. There were also indications of turnover of gap-junctions throughout the post-treatment period examined. The results indicate significant ototoxic effects of gentamicin occur in the stria and that changes to plasma membranes are one of the initial alterations.

Animals↗
PubMed1985

Outer hair cell loss and supporting cell expansion following chronic gentamicin treatment.

A sequence of changes in the organ of Corti associated with the destruction of outer hair cells (OHCs) and their replacement by supporting cells following chronic gentamicin treatment has been examined using thin-sections and SEM. The progression of change of OHCs was matched by concomitant expansion of adjacent supporting cells. Hair cells ruptured in the lateral membrane. The apical fragment was retained in the reticular lamina and became surrounded basally by the expanded supporting cells. No large breaches at the surface of the organ of Corti were formed. Rather, it appeared that the tight junctions around the hair cell were maintained until junctions were established between newly adjacent supporting cells in the space once occupied by the hair cell body. Only then was the OHC apex disrupted and the debris released into the sub-tectorial space. Some features of the OHC degeneration process were reminiscent of the controlled, cellular self-destruction phenomenon of apoptosis. The results suggest the possibility that the processes of hair cell loss and replacement may be controlled enabling maintenance of permeability barriers during structural reorganisation.

Animals↗
PubMed1985

Cholesterol distribution in cells of the stria vascularis of the mammalian cochlea and some effects of ototoxic diuretics.

The distribution of cholesterol in cells of the stria vascularis of guinea pigs and gerbils has been investigated at the ultrastructural level by incubation of tissue in filipin, followed by freeze-fracture. Verification of results has been sought by using tomatin. It is shown that in the cell body region of the marginal cells, the apical and lateral membranes reacted intensely with both agents, but the membranes of the basal processes of the marginal cells did not respond significantly to either filipin or tomatin. On basal cell membranes, filipin-cholesterol complexes were present at a high density, even within the strands of the tight-junctional network of these cells and occasionally within the gap-junctional areas also. Complexes were present on intermediate cell membranes at a lower density than on other plasma membranes that showed a positive response. Tissue from animals that had received an ototoxic diuretic, either ethacrynic acid or furosemide, was characterized by the appearance of membrane regions with closely clustered filipin complexes, suggesting some change in cell membrane structure. At an early stage following diuretic administration, such clusters were particularly noticeable on the membranes of intermediate cells. As intercellular spaces enlarged in response to the effects of diuretics, vesicles released into the extracellular spaces appeared to be cholesterol-enriched. The results are discussed in relation to known features of the structure and function of cells in the normal stria vascularis and of the changes that follow from acute diuretic ototoxicity.

Animals↗
PubMed1984

Gap junctions in the stria vascularis and effects of ethacrynic acid.

Gap junctions in the stria vascularis of guinea pigs were studied using freeze-fracture. Nearly all junctions were associated with basal cells. They were present between basal cells and spiral ligament cells, adjacent basal cells, basal and marginal cells and basal and intermediate cells. Following administration of ethacrynic acid, gap junction morphology altered. There was a statistically significant decrease in the centre-to-centre spacing of gap junction subunits and the subunits became regularly packed. Such changes were distinct before any other gross morphological change in the stria had occurred. These morphological alterations suggest that physiological uncoupling of stria cells may occur in response to the effects of ethacrynic acid.

Animals↗
PubMed1982

A tubulo-cisternal endoplasmic reticulum system in the potassium transporting marginal cells of the stria vascularis and effects of the ototoxic diuretic ethacrynic acid.

Sections of metal impregnated tissue and freeze-fracture have been used to examine intracellular membrane systems in marginal cells of the stria vascularis in mammalian cochleae. A continuous network of elements of the smooth endoplasmic reticulum was revealed. Notable features of this system were a series of flattened cisternae just inside and parallel with the lateral plasma membrane in continuity with an apical network of tubules, cisternae and sheets oriented in parallel with the luminal membrane. The whole system was closely associated with mitochondria. These characteristics suggest that the potassium transporting marginal cells possess a tubulo-cisternal endoplasmic reticulum (TER) like that found in many sodium transporting epithelial cells. The lateral elements of the TER dilated, appearing like vacuoles, and opened to the lateral extracellular space in response to the effects of ethacrynic acid. This diuretic impairs ion transport in the stria vascularis. It is suggested that the TER in marginal cells is involved in the transport of ions and fluid from the cell to the intercellular space when ion balance is disturbed and may play a role in cell volume regulation.

Animals↗
PubMed1982

Ultrastructural and electrophysiological studies of acute ototoxic effects of furosemide.

Previous studies of the effects of ethacrynic acid on the inner ear following intraperitoneal injection of the diuretic have shown a progression of reversible changes occurring in the stria vascularis. The time course of these changes approximately parallels alterations in endolymphatic potential (EP). In this report, some preliminary findings concerning the effects of furosemide after intraperitoneal injection of 80 mg/kg are described. EP declined over a longer time course than that recorded with intravenous injection. Cochlear microphonic (CM) and compound action potential (CAP) also declined but to differing degrees. In the stria vascularis a progression of changes was apparent. In general, the changes were similar to those observed following ethacrynic acid intoxication and affected marginal cells, intermediate cells and strial capillaries. The upper basal turn of the cochlea was affected first and the damage spread apically. In the organ of Corti, stereocilia on the outermost row of outer hair cells were disorganized. This was apparent in approximately the same region as initial strial effects and was only observed when strial derangement was quite marked.

Animals↗
PubMed1981

Electron microscopy of the stria vascularis and its response to etacrynic acid. A study using electron-dense tracers and extracellular surface markers.

Lanthanum nitrate (La3+), ruthenium red (RR) and tannic acid (TA) have been used to examine the cell coat and permeability pathways in thin sections of the stria vascularis of normal and etacrynic-acid (EA)-treated guinea pigs. The tight junctions around the stria, at both endolymphatic and spiral ligament sides, excluded tracers even when EA-associated oedema was well advanced. La3+ was also unable to enter oedematous stria from the capillaries. A dense fibrillar coat was revealed on the endolymphatic marginal cell surface. This coat was disorganised during EA intoxication. Both RR and TA crossed the apical membrane and produced enhanced contrast in some, but not all, marginal cells in EA-treated animals. The results suggest that EA may affect the structure of the apical membrane of the marginal cells and that there is heterogeneity amongst the marginal cell population. These possibilities are discussed.

Animals↗
PubMed1980

The endolymphatic surface of the stria vascularis in the guinea-pig and the effects of ethacrynic acid as shown by scanning electron microscopy.

Examination of the endolymphatic surface of the stria vascularis showed, in agreement with previous studies, the marginal cells to be hexagonal in shape and that most possessed microvilli. However, the cells in the apical turns were more profusely covered with microvilli than those at the base and, particularly in the basal turns, there was some variation in the surface detail of the cells. These results may indicate differences in the physiological state of the cells. In the early period of ethacrynic acid intoxication (15-30 minutes post-injection), when rapid changes in endolymphatic potential and ion-fluxes occur, the surface of the marginal cells showed only slight distortion. The most dramatic changes were noted 1 hour post-injection, and involved swelling of the cells and loss of microvilli. This distortion persisted up to 2 hours post-injection. The possible explanation for these findings is discussed.

Animals↗
PubMed1979

Cell membrane alterations in the stria vascularis of the guinea pig after ethacrynic acid treatment studied by freeze-fracture.

A freeze-fracture examination of the stria vascularis during the first 2 h after injection of ethacrynic acid was performed. This showed a re-distribution of the particles on the membrane fracture faces of both marginal and intermediate cells. As oedematous spaces developed, particle-poor, vesicle-like structures were found associated with both cell types. The tight junctions at the apices of the marginal cells and around basal cells were unaffected.

Animals↗
PubMed1978

Morphology of egg phosphatidylcholine-cholesterole single-bilayer vesicles, studied by freeze-etch electron microscopy.

Homogeneous, small, single-bilayer vesicles were prepared from egg phosphatidylcholine with various concentrations of cholesterol by ultrasonic dispersion in 0.1 M KCl, 0.01 M Tris, pH 8.0, buffer, followed by gel chromatography. The shape and size distributions of the fractionated vesicles were investigated for preparations with cholesterol compositions from 0 to 50 moles/100 moles, using freeze-etch electron microscopy. The size distribution was estimated from the shadow width of vesicles which were exposed by etching and the vesicle shape was checked by comparing the images obtained by tilting the replicas. The widths of the vesicle diameter distributions were relatively broad, corresponding to standard deviations in the range 60--90 A, but showing no systematic variation with cholesterol composition. In all cases it was found that 70% of the vesicle diameters lay within 150 A of the modal value. The apparent vesicle diameters remained constant for cholesterol compositions up to 20 moles/100 moles (modal diameter = 330 +/- 20 A, mean diameter = 350 +/- 3 A), but there was a sharp net increase in diameter at 30 moles cholesterol/100 moles reaching a model diameter of 430 +/- 20 A (mean diameter = 430 +/- 3 A) at 50 moles cholesterol/100 moles. Using the tilted microscope stage it was found that all vesicles were spherical at all cholesterol compositions studied, including those above 30 moles cholesterol/100 moles. The molecular mechanism by which cholesterol controls the vesicle size is discussed in terms of the asymmetric distribution of cholesterol across the vesicle bilayer.

Cholesterol↗
PubMed1976

Observations on the stria vascularis of the guinea pig cochlea and the changes resulting from the administration of the diuretic furosemide.

An electron microscope examination of the stria vascularis of guinea pigs and the structural changes occurring after administration of furosemide has been made. The use of ruthenium-red, which stains cell coats, has shown that the atria is impermeable to the passive diffusion of material from both the endolymph and the spiral ligament. The first changes after administration of furosemide are observed 4 hours after injection; small spaces develop between the cells. After 5--6 hours the spaces have enlarged but the tight junctions between marginal cells remain intact. The intermediate cells show signs of atrophy. In severely affected animals the intermediate cells have so shrunk that the spaces are very large and the marginal cells clearly resolved. These latter cells show no structural damage. In this severely affected tissue it is seen that the blood vessels are entirely surrounded by marginal cell extensions. It is suggested that the intermediate cells may have a regulatory function. The damage appears to be recoverable, since 6 hours after injection the spaces have decreased in size although some signs of intermediate cell atrophy are still apparent.

Animals↗
PubMed1973

Freeze-etching and x-ray diffraction of the isolated double-track layer from the cell wall of a gram-negative marine pseudomonad.

The isolated double-track layer of the cell wall of the gram-negative marine pseudomonad studied here contains a cleavage plane. This finding localizes the single cleavage plane of the cell wall and shows that the molecular architecture of this layer provides the lipid-enriched layer which cleaves preferentially in the frozen cell. The observation that the isolated double-track layer of the cell wall is sufficiently ordered at the molecular level to yield a well-defined X-ray diffraction pattern with a d-spacing of 0.44 nm shows that its molecular architecture is very similar to that of true membranes. This specific d-spacing is produced by the highly ordered packing of the hydrophobic portions of phospholipid molecules. Therefore, the double-track layer of the cell wall has been shown, by these two biophysical means, to have a molecular architecture which would allow it to function as the membrane-like "molecular sieve" layer, whose presence has been deduced from physiological data. This layer is important in the retention of cell wall-associated enzymes and in the control of the movement of large molecules through the cell wall.

Bacteria↗
PubMedDate not supplied

Establishment of hair bundle polarity and orientation in the developing vestibular system of the mouse.

The morphological development of the vestibular maculae in the mouse was studied in order to identify elements that may determine how hair-bundle polarity is established. Utricles and saccules develop in parallel. Hair-bundles first appear at embryonic day (E) 13.5. They are initially not polarised and have a kinocilium located at the centre of the cell surface surrounded by stereocilia. Polarisation is rapidly established as the kinocilium becomes eccentrically positioned. The orientation of these polarised bundles is initially not random. It varies systematically across the maculae and the general orientation in utricles is the opposite of that in saccules. At E15.5, in both maculae, hair-bundle orientation angles fall into two populations that differ by approximately 180 degrees defining a line of orientation reversal, the position of which varies little during subsequent maturation. Many more immature hair bundles appear at E15.5 suggesting a second wave of hair cell differentiation is initiated. Otoconial membrane is produced simultaneously across the entire width of both maculae, indicating directional growth of the overlying extracellular matrix is unlikely to influence hair-bundle orientation. Growth of both maculae occurs asymmetrically, essentially outwards from the striola, but it is most pronounced after orientation is defined. Microtubules are prominent in hair cells at the earliest stages of their differentiation, but are oriented parallel to the long axis of the cell and, thus, may not have a role in directing hair-bundle polarity. Microfilament assemblies that are aligned parallel to the apical surface and connect to the adherens junctions in supporting cells could provide a "framework" for hair-bundle orientation. The striated rootlets of ciliary centrioles that are aligned parallel to the cell surface with their tips associated with microfilament assemblies at adherens junctions were the only structural asymmetry identified that might influence the development of hair-bundle polarity.

Acoustic Maculae↗