Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis

Summary The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by barbecuespit (yaw) rotations, vertical eye movements by head-over-heels (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.Supported by Grants NS 01330 from the National Institutes of Health and NGR-14-001-225 from the National Aeronautics and Space Administration     

Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge

The aim of this study was to investigate the potential of a composite matrix, containing esterified hyaluronic acid and gelatin, to facilitate the osteochondral differentiation of culture-expanded, bone marrow-derived mesenchymal progenitor cells. The cell loading characteristics and the effects of the matrix on cell differentiation were examined in vitro and in vivo. Empty and cell-loaded composites were cultivated for up to 28 days in a chemically defined medium with or without transforming growth factor-beta1 (TGF-beta1). A type II collagen-rich extracellular matrix was produced by cells loaded in the matrix and cultured in the presence of TGF-beta1. Empty and cell-loaded matrices were also implanted subcutaneously in immunodeficient mice. Three types of implant were used: empty (group I), cell-loaded matrices (Group II), and cell-loaded matrices cultured for 14 days in vitro in defined medium with TGF-beta1 (group III). No osteochondral differentiation was found in implanted empty matrices; however, the matrix supported osteochondrogenic cell differentiation in the cell-loaded implants. Preculture in vitro in a chondrogenic medium increased the percentage of osteochondral tissue found in the constructs after 3 weeks. These results indicate the potential use of this composite matrix for delivery of bone marrow-derived mesenchymal progenitor cells for the repair of chondral and osseous defects. The results also indicate that this composite matrix is useful for in vitro tissue engineering.     

Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.      

Life events and depression in a community sample of siblings

BACKGROUND: The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. METHODS: We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. RESULTS: Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. CONCLUSIONS: Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Identification of an antigenic determinant of mouse lactate dehydrogenase C4

A peptide bearing an antigenic determinant of the sperm-specific lactate dehydrogenase C₄ isozyme (LDH-C₄) has been isolated from a tryptic digest of the whole protein. This peptide, comprising residues 152–159 (MC_152–159), reacts with rabbit anti-mouse LDH-C₄. Immunization of rabbits with synthetic MC_152–159 conjugated to bovine serum albumin induces an immune response which is specific for the peptide. Anti-MC_152–159 IgG binds ¹²⁵I-labeled mouse LDH-C₄ and competition experiments demonstrate the specificity of this antigen-antibody reaction.     

Stratum-specific likelihood ratios of the general health questionnaire in the community: help-seeking and physical co-morbidity affect the test characteristics

BACKGROUND: In evidence-based medicine, stratum-specific likelihood ratios (SSLRs) are now being increasingly recognized as a more convenient and generalizable method to interpret diagnostic information than an optimal cut-off and its associated sensitivity and specificity. We previously examined the SSLRs of the General Health Questionnaire (GHQ) in primary care settings. The present paper aims to examine if these SSLRs are generalizable to the community settings. METHODS: The Composite International Diagnostic Interview (CIDI) and the GHQ were administered on a representative sample of the Australian population in the Australian National Survey of Mental Health and Well-Being. We first compared the SSLRs of GHQ in urban Australia with the estimates that we had previously obtained from the developed urban centres in the WHO Psychological Problems in General Health Care study. If the SSLRs in the community were found to differ significantly from those in the primary care, we sought for explanatory variables. RESULTS: The SSLRs in urban Australia and in the urban centres in the WHO study were significantly different for three out of the six strata. When we limited the sample to those with physical problems who visited a health professional, however, the SSLRs in the Australian study were strikingly close to those observed for primary care settings. CONCLUSIONS: Different sets of SSLRs apply to primary care and general population samples. For general population surveys in developed countries, the results of the Australian National Survey represent the currently available best estimates. For developing countries or rural areas, the results are less definitive and an investigator may wish to conduct a pilot study.