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Biomedical subjects

R Goodyear

Publications and source records attributed to R Goodyear.

15 recordsLinked to original sources
PubMed2001

Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors.

The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRalpha1 and TRbeta thyroid hormone receptors in the auditory system using receptor-deficient mice. TRalpha1 and TRbeta, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TRbeta is required for hearing because TRbeta-deficient (Thrb(tm1/tm1)) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (I(K,f)) in the cochlear inner hair cells. Here, we show that although TRalpha1 is individually dispensable, TRalpha1 and TRbeta synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrb(tm1/tm1) mice, the deletion of all TRs in Thra(tm1/tm1)Thrb(tm1/tm1) mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction of I(K,f) in inner hair cells was not markedly more retarded than in Thrb(tm1/tm1) mice, suggesting that this feature of hair cell maturation is primarily TRbeta-dependent. These results indicate that distinct pathways mediated by TRbeta alone or by TRbeta and TRalpha1 together facilitate control over an extended range of functions during the maturation of the cochlea.

Animals↗
PubMed2001

Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.

The genes for alpha- and beta-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse alpha-tectorin gene was found to cause loss of cochlear sensitivity (). Here we describe that mRNA levels for beta-tectorin, but not alpha-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of beta-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (), can also lead to permanently reduced beta-tectorin protein levels in the tectorial membrane. beta-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low beta-tectorin levels in the tectorial membrane and suggest for the first time that beta-tectorin may be required for development of normal hearing.

Animals↗
PubMed1999

The ankle-link antigen: an epitope sensitive to calcium chelation associated with the hair-cell surface and the calycal processes of photoreceptors.

A monoclonal antibody, mAb E40, that specifically recognizes hair cells and photoreceptors was derived from a mouse immunized with a membrane fraction prepared from the sensory maculae of the chick inner ear. In the mature chick inner ear, punctate labeling is observed along each stereocilium, but staining is mostly concentrated around the basal end of the sensory hair bundles, where it is closely associated with surface specializations known as ankle links. The epitope recognized by mAb E40 is therefore referred to as the ankle-link antigen (ALA). During early embryogenesis, the ALA is initially distributed evenly over the surface of the hair bundle. As development proceeds, it becomes more restricted to the base of the hair bundle, although a spot of the ALA remains associated with the bundle tip until just before hatching. In the eye, mAb E40 stains the calycal processes of photoreceptors. When maculae and retinae are treated with the calcium chelator BAPTA at room temperature, the ALA disappears. BAPTA-induced loss of the ALA from the hair-bundle surface is substantially reduced by lowering the temperature to 2 degrees C. The ALA and ankle links reappear on the hair-bundle surface when cells are cultured for 20 hr after BAPTA treatment. BAPTA sensitivity and recovery after BAPTA-induced loss are properties similar to those described for the tip link, a surface structure thought to gate the mechanotransducer channel. However, unlike the tip link, the ALA and ankle links are sensitive to subtilisin treatment. The results define a new component of the hair-bundle surface, with properties both common to and distinct from those of the tip link.

Animals↗
PubMed1999

Chick alpha-tectorin: molecular cloning and expression during embryogenesis.

The avian and mammalian tectorial membranes both contain two non-collagenous glycoproteins, alpha and beta-tectorin. To determine whether variations in the primary sequences of the chick and mouse alpha-tectorins account for differences in subunit composition and matrix structure of the tectorial membranes in these two species, cDNAs spanning the entire open reading frame of chick alpha-tectorin were cloned and the derived amino acid sequence was compared with that of mouse alpha-tectorin. Chick alpha-tectorin shares 73% amino acid sequence identity with mouse alpha-tectorin and, like mouse alpha-tectorin, is composed of three distinct modules: an N-terminal region similar to the G1 domain of entactin, a central region that shares identity with zonadhesin and contains three full and two partial von Willebrand factor type D repeats, and a C-terminal region containing a zona pellucida domain. The central region of chick alpha-tectorin contains fewer potential N-glycosylation sites than that of mouse alpha-tectorin and is cleaved at two additional sites. Differences in the glycosylation and proteolytic processing of chick and mouse alpha-tectorin may therefore account for the variation observed in the composition and structure of the collagenase-insensitive matrices of the avian and mammalian tectorial membranes. In situ hybridisation and Northern blot analysis of chick inner ear tissue indicate that the spatial and temporal patterns of alpha and beta-tectorin mRNA expression in the developing chick inner ear are different, suggesting the two tectorins may each form homomeric filaments.

Amino Acid Sequence↗
PubMed1998

Comparative study of the clinical effectiveness of a pyrethrin-based pediculicide with combing versus a permethrin-based pediculicide with combing.

In a randomized, evaluator-blinded clinical trial, 190 patients were treated for Pediculus humanus capitis infestations with a pyrethrin-piperonyl-butoxide pediculicide (RID; Py-PB) and a permethrin pediculicide (NIX; PM). A total of 160 patients were evaluable for nit-combing speed, 156 patients were evaluable for efficacy at day 7, and 150 patients were evaluable for efficacy at day 14. Both Py-PB and PM showed 100% efficacy at day 7. At day 14, one patient in the PM group had an apparent reinfestation. The Py-PB group had significantly lower mean combing times (P=0.04), but because the PM group had more nits, the two groups were not significantly different in combing speed expressed as seconds per nit. Multiple regression and covariance analyses suggested that the greater speed of the Py-PB comb might have been masked by this baseline difference. Three patients had mild adverse experiences (Py-PB: erythema, PM: erythema and tingling sensation). No patients were removed from the study because of adverse events. In conclusion, this controlled clinical study demonstrated that both Py-PB and PM provided 100% efficacy following a single application. Differences attributable to comb design favored the Py-PB "rake" comb, but this requires additional evaluation and confirmation.

Child↗
PubMed1997

Pattern formation in the basilar papilla: evidence for cell rearrangement.

The avian basilar papilla is composed of hair and supporting cells arranged in a regular pattern in which the hair cells are surrounded and isolated from each other by supporting cell processes. This arrangement of cells, in which the apical borders of hair cells do not contact one another, may be generated by contact-mediated lateral inhibition. Little is known, however, about the way in which hair and supporting cells are organized during development. Whole mounts double-labeled with antibodies to the 275 kDa hair-cell antigen and the tight junction protein cingulin were therefore used to examine the development of cell patterns in the basilar papilla. Hair cells that contact each other at their apical borders are seen during early development, especially on embryonic days (E) 8 and 9, but are no longer observed after E12. Hair and supporting cell patterns were analyzed in three different areas of the papilla at E9 and E12. In two of these regions between E9 and E12, the ratio of supporting cells to hair cells does not change significantly, whereas there is an increase in both the number of supporting cells around each hair cell and the number of hair cells that each supporting cell contacts. In the third region examined, there is a dramatic rise in the number of supporting cells around each hair cell, which although accompanied by a small, significant increase in the ratio of supporting cells to hair cells cannot be accounted for by an increase in supporting cell numbers. These data show that a rearrangement of hair and supporting cells with respect to one another may be a fundamental process underlying the development of a regular pattern in the basilar papilla.

Animals↗
PubMed1996

Distribution of beta-tectorin mRNA in the early posthatch and developing avian inner ear.

Expression of beta-tectorin mRNA in the inner ear of the embryonic and early posthatch (PH) chick was studied by in situ hybridisation. In the PH chick, beta-tectorin mRNA is expressed in the basilar papilla, in the clear and the cuboidal cells that lie either side of the papilla, in the striolar regions of the maculae, and in two small groups of cells lying adjacent to the midline in the cristae of the anterior and posterior ampullae. Expression of beta-tectorin is not observed in the lateral ampulla. In the sensory epithelia of the PH chick in which beta-tectorin mRNA is detected, expression is restricted to the supporting cell population. During development of the cochlear duct, beta-tectorin expression begins between embryonic (E) days 5 and 6. At E6, expression is observed throughout the length of the duct but is highest at the distal end. By E7, the pattern of expression is reversed and is highest at the proximal end of the cochlea, suggesting that a wave of high beta-tectorin expression passes disto-proximally along the papilla during E6 and E7. Expression of beta-tectorin mRNA is not detected in the homogene cells at any stage during the development of the cochlear duct, indicating that these cells do not synthesise one of the two major proteins of the avian tectorial membrane. The distribution of supporting cells expressing beta-tectorin mRNA in the different epithelia was compared with the distribution of sensory cells that have type B hair bundles, those with shaft links restricted to basal regions of their stereocilia, and sensory cells that have type A bundles, those with shaft links all over the entire surface of their stereocilia. Hair cells with type A hair bundles are never found in association with supporting cells expressing beta-tectorin. Although there is a correspondence in the basilar papilla and the maculae of the utriculus and lagena between the distribution of supporting cells expressing beta-tectorin mRNA and hair cells with type B bundles, this correlation does not generalise to the other sensory epithelia.

Animals↗
PubMed1995

Hair and supporting-cell differentiation during the development of the avian inner ear.

Two monoclonal antibodies and serial section analysis have been used to compare the sites and times at which hair and supporting-cells differentiate in various sensory regions of the chick inner ear during its development. A monoclonal antibody recognising the 275 kD hair-cell antigen, a protein that is specifically associated with the apical surface of hair cells, was used to identify immature hair cells. Another monoclonal antibody, gm-2, which stains the gelatinous membranes of the cochlear duct, sacculus, and utriculus and the epithelial supporting cells of all vestibular structures in the inner ears of early posthatch chicks, was used to detect the onset of supporting-cell differentiation. Although the antigens recognised by the two antibodies are first detected almost simultaneously during the development of each sensory region, their appearance is not always exactly temporally coincident, and their order of appearance, when not coincident, varies between the epithelia but is always the same within any one organ. Also, when the two antigens are first present in any one region, there is not always a very precise overlap in their spatial distribution. These results cannot be explained entirely by a previously proposed model for hair and supporting-cell development in which hair cells differentiate first and prevent undetermined, surrounding cells from becoming hair cells via lateral inhibition. Modified forms of the original model that can accommodate some of these observations are considered and discussed.

Animals↗
PubMed1995

Concern, continuity, and choice: a health promotion formula for advanced practice nurses.

Promoting health in a newly established nurse practitioner family practice was a major undertaking for one advanced practice nurse (APN) in a semi-rural community in southern California. The alignment of the resources necessary to begin such a practice opened many doors not previously traversed by nurses in this community. Likewise, the development of a formula and model for health promotion came about as a result of overcoming the obstacles to starting this private practice as well as the positive rewards of patient encounters over time. Episodes of concern for patients, continuous care, and choices in health care decisions come together to illustrate this formula. The research data supporting the practice further demonstrate the plausibility of the APN becoming a provider of health promotion in the primary care setting.

Adolescent↗
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↗
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↗
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↗
PubMed1989

Conflict resolution: applying the political model to the RCT proposal.

The political model, as described by various authors, provides a powerful and effective approach to dealing with the complex issues that confront nursing. This article demonstrates that the political model may be employed as a useful method for reaching a favorable resultant action on the registered care technologist conflict issue. The problem-solving approach of the political model can be applied to individual, group or organizational conflict. The politically astute person using this model will gain insight into negotiating, policy-making and the allocation of scarce resources.

American Medical Association↗