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Biomedical subjects

G Richardson

Publications and source records attributed to G Richardson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Differential glycosylation of auditory and vestibular hair bundle proteins revealed by peanut agglutinin.

Up to four morphologically distinct types of cross-link are found between the stereocilia in the hair bundles of avian hair cells. These links are involved in mechanotransduction, force transmission across the bundle, and maintenance of hair bundle structure. They appear to be specialisations of the cell coat, but very little is known about their molecular composition. Chick inner ear tissues were therefore screened with a number of different lectins to find markers for specialisations of the hair bundle surface. One lectin, peanut agglutinin (PNA), which recognises the dissacharide Gal beta 1-3GalNAc, was found to be a fairly selective marker for vestibular hair bundles, but it does not stain the stereocilia of auditory hair cells. The staining patterns observed with PNA in the vestibular system closely resemble those seen with a monoclonal antibody (mab) directed against a 275 kD component of the hair cell's apical surface known as the hair-cell antigen (HCA). However, unlike PNA, the mab recognises both vestibular and auditory hair cells. A detailed comparison of the fluorescence staining patterns observed with PNA and the anti-HCA mab indicates that binding sites for both ligands spatially codistribute on the surface of vestibular hair cells. The lectin and the anti-HCA mab binding sites are both sensitive to trypsin treatment, and, with sections of the vestibular system, PNA pretreatment blocks subsequent anti-HCA mab staining. Immunoelectron microscopy of vestibular hair bundles shows that PNA and the anti-HCA mab both label a type of cross-link known as the shaft connector. This link type is present on both auditory and vestibular hair bundles but reacts with PNA only in the vestibular system. The lectin jacalin, which has greater specificity for Gal beta 1-3GalNAc than does PNA, also only labels vestibular and not auditory hair bundles. Although terminal sialic acid residues can block both PNA and jacalin binding, neuraminidase treatment does not unmask cryptic binding sites for these lectins on auditory hair cells but does reveal PNA and jacalin staining at a number of other locations in the inner ear. The results obtained with the lectins PNA and jacalin indicate that either the HCA or other components of the shaft links are differentially glycosylated in the vestibular and auditory epithelia of the bird. The functional significance for such a difference in glycosylation remains to be determined, but auditory and vestibular hair cells operate over different frequency ranges, and variations in glycosylation might confer different micromechanical properties on the hair bundles in these two systems.

Animals↗
PubMed1994

Visualisation of domains in the avian tectorial and otolithic membranes with monoclonal antibodies.

The staining patterns observed with six monoclonal antibodies (mAbs) raised in vitro against a fraction derived from the utricular macula were examined with cryosections of the auditory and vestibular organs of the avian inner ear. These antibodies revealed several distinct domains within the gelatinous membranes. Three different labelling patterns were observed in the tectorial membrane. Staining was seen either throughout the entire tectorial membrane, restricted to its core, or in a narrow zone lying close to the surface of the basilar papilla. In the maculae, the mAbs stained either the striolar region of the otolithic membrane or the entire structure. One monoclonal which labelled otoconia, stained small otoconia in their entirely, whilst larger otoconia were only labelled around their periphery. Only one of the mAbs stained the cupulae of the semi-circular canal ampullae and this antibody stained neither the tectorial nor the otolithic membranes. These results suggest that there are biochemically distinct regions in the gelatinous membranes of the inner ear and indicate that these matrices are not simply homogeneous extracellular structures.

Animals↗
PubMed1994

Virtually unaltered permeability-surface area products imply little capillary recruitment in brain with hypoxia.

OBJECTIVE: To test the capillary recruitment hypothesis for the brain with control and hypoxic rats. METHODS: Local cerebral blood flow (LCBF) was sharply raised by respiring 10% O2 (hypoxia). LCBF as well as local influx rate constants (K1) and permeability-surface area (PS) products of 14C-antipyrine and 14C-3-O-methyl-D-glucose (30MG) were estimated for capillary systems in 44 brain areas. RESULTS: With this testing, an increase in PS product would be suggestive of capillary recruitment. In all brain areas, LCBF was increased by 30-90% by hypoxia. Hypoxia modestly raised the influx of antipyrine in brain but did not appreciably alter its PS products. With hypoxia, K1's and PS products of 30MG were significantly lowered (5-25%) throughout the brain, and the blood levels of glucose were sizeably raised. The latter increase would diminish the transfer of 30MG across the blood-brain barrier by the hexose transporter because of increased glucose competition. By applying a glucose-concentration correction to the data, the apparent PS product of 30MC for the hypoxic group became equal to that for the controls, which agrees with the antipyrine PS product results. CONCLUSIONS: Hypoxia, thus, leads to virtually no increase in PS products and no capillary recruitment in brain, and elevates LCBF mainly, perhaps exclusively, by raising the velocity of flow through already perfused capillaries.

3-O-Methylglucose↗
PubMed1993

Freeze fracture analysis of apical membranes in cochlear cultures: differences between basal and apical-coil outer hair cells and effects of neomycin.

Previous studies have shown that exposure of cochlear cultures to the ototoxic aminoglycoside antibiotic neomycin leads to the rapid formation of numerous membrane filled protrusions on the apical surface of the hair cells but not on the surrounding supporting cells, and that hair cells in basal-coil cultures are more sensitive to these effects of neomycin than those in the distal end of apical-coil cultures. Freeze-fracture has been used to examine and compare the apical surfaces of hair cells and supporting cells in basal and apical-coil cultures in order to look for features that may explain the differential sensitivity of the various cell types to neomycin, and to characterize the membrane type that forms in response to neomycin and compare it with the normal apical membrane of the hair cell. The apical surface of the highly responsive basal-coil outer hair cells differs significantly from the apical surfaces of apical-coil outer hair cells and supporting cells in both regions of the cochlea in both surface area and the number and density of endocytotic vesicles associated with this surface. Basal-coil hair cells have an average of 120 +/- 39 vesicles per cell surface and a density of 3.5 +/- 0.89 vesicles per microns 2, whereas apical-coil hair cells have 14.8 +/- 15.8 vesicles/cell surface and density of 0.73 +/- 0.72 vesicles per microns 2. There are no significant differences in intramembrane particle (IMP) density on the apical surfaces of all the cell types examined, and qualitative observations of filipin-treated specimens indicate that cholesterol densities are also similar. The membrane that accumulates in response to neomycin treatment at the apical pole of the hair cell is IMP free, does not respond to filipin, and fractures in a manner that is indicative of a high content of unsaturated phospholipid in a fluid phase, and is therefore different in several respects from the normal apical surface of the hair cell. The results of this study suggest that apical surface associated endocytotic vesicle numbers may determine the differential sensitivity of apical and basal-coil hair cells to neomycin, and that neomycin may interfere with some aspect of phospholipid metabolism or membrane turnover in sensory hair cells.

Animals↗
PubMed1992

Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear.

The 275 kD hair cell antigen (HCA) is a protein that is specifically associated with the apical surface of sensory hair cells in the chick inner ear. A comparative study of the vestibular and auditory organs of the inner ear, using both wholemounts and cryosections double labelled for the HCA and F-actin, reveals that two distinct types of hair cells can be distinguished on the basis of antibody staining in each of the vestibular epithelia. One type of hair cell has the HCA restricted to the base of the stereocilia bundle and is found in the striolae of the maculae and in a large, centrally located region of each ampulla. The other type of hair cell is found in the extrastriolar regions of the maculae and the peripheral regions of the ampullae and has the HCA distributed over the entire surface of the stereocilia bundle. In the basilar papilla, the auditory epithelium of the chick inner ear, the HCA is, as in the striolar regions of the maculae, restricted to the base of the hair bundles. In all sensory epithelia the HCA is also present on the apical, nonstereociliary surface of the hair cells. Ultrastructural examination of the basilar papilla and the striolar and the extrastriolar regions of the lagenar macula after staining with ruthenium red and tannic acid shows that there are four morphologically different types of interstereociliary connectors (oblique tip connectors, horizontal tip connectors, shaft connectors and basal connectors) associated with the hair bundles. Oblique tip connectors and basal connectors are found on hair cells from all regions and have a similar distribution. Horizontal tip connectors are seen only on hair cells in the basilar papilla and the striolar region of the lagenar macula. Shaft connectors extend all the way to the tips of extrastriolar hair cell bundles, but extend only a short way up the bundles of hair cells in the basilar papilla and striolar region of the lagenar macula. Immunogold labelling confirms the results obtained with immunofluorescence microscopy and demonstrates that the distribution of the HCA on the surface of adjacent stereocilia correlates closely with that of the shaft connectors; i.e., immunostaining is observed up to the tips of the extrastriolar hair cell bundles, but is restricted to the lower regions of hair cell bundles in the striolar region and basilar papilla.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The effects of flosequinan on hemodynamics and oxygen delivery in cor pulmonale.

The hemodynamic effects of a new orally active vasodilator, flosequinan, were compared with placebo (single blind) over 24 h in eight patients with pulmonary hypertension secondary to severe chronic obstructive pulmonary disease. Mean pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189) dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04) and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A significant reduction in systemic vascular resistance was observed, 132 (35,230) dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial blood pressure or arterial blood gas tensions. Flosequinan favorably altered pulmonary hemodynamics relative to systemic and resulted in a significant improvement in oxygen delivery. The hemodynamic and blood gas effects of this compound suggest that it is a promising vasodilator for the treatment of pulmonary hypertension.

Adult↗
PubMed1991

Appearance and distribution of the 275 kD hair-cell antigen during development of the avian inner ear.

The 275 kD hair-cell antigen (HCA) is a protein that was originally identified using immunological techniques in the inner ears of early hatchling and adult chickens. The HCA is specifically associated with the apical surface of sensory hair cells; in the vestibular system the antigen is distributed over the entire stereocilia bundle, but in the auditory system it only extends a short distance up the shafts of the stereocilia. The objectives of this study were to ascertain when the HCA is first expressed during inner ear development, to compare the temporal and spatial patterns of HCA expression with those of neurite ingrowth, and to determine how the distribution of the antigen observed in the auditory system arises during development. Serial sections of otocysts from embryonic day (ED) 4 to ED7.5 (stages 24 to 32) were stained with a monoclonal antibody to the HCA and polyclonal antibodies to the neuron-glial cell adhesion molecule in order to analyse patterns of HCA expression and neurite ingrowth. Nerve fibres are first observed in the anterior pole of the otocyst at ED4.5 (stage 24), and in the evaginating basilar papilla by ED5 (stage 26). The HCA first appears within the vestibular system in the anterior pole of the otocyst at ED5 (stage 26), and within the auditory system in the distal end of the basilar papilla at ED6.5 (stage 29). Serial section analysis indicates that expression of the HCA is always limited to areas of the epithelium where nerve fibres are found, although the delay between the onset of innervation and the onset of HCA expression varies from one region of the otocyst to another. The growth of stereocilia bundles in the auditory system was studied from ED10 to 2 days after hatching in sections from the medial to distal regions of the basilar papilla double labelled with rhodamine phalloidin and monoclonal anti-HCA. At ED12 the stereocilia bundles are 1.7 microns high and the staining observed with both phalloidin and the antibody extend to the same maximum height above the apical surface of the hair cell. The maximum height that anti-HCA staining extends up the stereocilia bundle remains almost constant between ED12 and postnatal day 2, but between ED15 and ED18 the stereocilia bundle grows rapidly in height, with a membrane domain lacking the HCA forming at the distal ends of the stereocilia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

The effects of prenatal alcohol use on the growth of children at three years of age.

In this prospective study of substance use during pregnancy, women were interviewed in their 4th and 7th prenatal months, and women and children were assessed at 24 hr, 8, 18, and 36 months postpartum. Data are presented on the outcome of 519 children at age 3. At 3 years, children who were exposed prenatally to alcohol were smaller in weight, length, and head circumference. They also had an increased number of minor physical anomalies. These effects were found even after controlling for nutritional and environmental factors. The persistence of growth effects at age 3 suggests that children exposed to alcohol prenatally may have a diminished capacity for growth.

Body Height↗
PubMed1991

Prenatal alcohol exposure and offspring growth at 18 months of age: the predictive validity of two measures of drinking.

This is an analysis of the effect of prenatal alcohol exposure on growth of the offspring at 18 months of age. In this prospective study, a cohort of women was interviewed at the end of each trimester of pregnancy, at delivery, and at 8 and 18 months. Offspring were examined at each follow-up point. Two drinking scales, average daily volume (ADV) and frequent heavy drinking (FHD), were used to explore the effect of different patterns of drinking. We found significant relationships between both prenatal FHD and ADV and offspring growth at 18 months. A significant and inverse relationship was found between ADV during the second and the third trimesters of pregnancy and weight, height, and head circumference at 18 months. Frequent heavy drinking during all three trimesters predicted a significant decrease in head circumference at 18 months. FHD during the second trimester was significantly related to weight and height at 18 months. Analyses demonstrated that ADV was a better predictor of growth deficits than FHD.

Adult↗
PubMed1990

Malignant transformation occurring in mature cystic teratomas of the ovary.

Two cases in which tumours of contrasting malignant potential arose in mature cystic teratomas (dermoid cysts) of the ovary are presented: one patient had a spindle-cell sarcoma and the other a trabecular carcinoid. The first patient's clinical course was characterized by rapid recurrence of the tumour and death 3 months after surgery. The second patient is alive and well with no evidence of residual carcinoid, although the follow-up time is short. Since the surgical procedure of choice differs substantially if malignant transformation occurs in an ovarian dermoid cyst, the pathologist should be consulted intraoperatively in selected cases.

Adult↗
PubMed1990

Effect of prenatal alcohol exposure on growth and morphology of offspring at 8 months of age.

In this prospective study of alcohol and other substance use during pregnancy, a cohort of women was interviewed at each trimester of pregnancy and when the offspring were 8 months of age. Data are presented concerning the outcome for 461 infants. A significant relationship was found between alcohol use during pregnancy and the growth and morphology of the offspring at the 8-month follow-up observation. Alcohol use during the second and third trimesters of pregnancy and continuous use of alcohol throughout pregnancy were significantly related to lower weight, length, and head circumference in the exposed infants at the follow-up observation. A significant increase in the risk of minor physical anomalies and fetal alcohol effects was also predicted by prenatal alcohol exposure.

Adolescent↗
PubMed1989

Detectability of emergency lights for underwater escape.

The time to detect each of three underwater lights by six subjects was measured in clear and turbid (attenuation coefficient = 4.2.m-1) water, at distances of 1.54 m and 3.1 m, from two viewing angles, straight ahead (0 degrees) or 65 degrees to one side, and under three levels of ambient illumination. The lights were viewed either through a window, to simulate the use of a face mask, or with the subjects immersed. All lights were detected rapidly (less than 1 s) when viewed through the window in clear water. In turbid conditions, none of the lights was seen at 3.1 m by any subject. At a 1.54 m viewing distance, reliable detection by immersed subjects was found only in the clear water under the two darker ambient illuminations. In turbid water, detection was unreliable. We conclude that the design of underwater escape lighting should not rely on visibility over distances greater than 1.5 m, and that an illuminated guide-bar might provide valuable assistance in directing escape from aircraft.

Accidents, Aviation↗