Search PubMed⌕ Search

Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

Complementary in vivo and in vitro analyses of the interactions between the cis-acting elements of the rat rDNA promoter.

Two transcription factors, rat UBF (rUBF) and rat SL-1 are required for the efficient transcription of the rat promoter in vitro. In vitro studies have established that two broadly defined cis-acting domains, the core promoter element and the upstream promoter element, cooperate to direct correct transcription by RNA polymerase I. The ability of UBF to bind to two linker-scanning mutants of the upstream promoter element, which did not respond to the addition of UBF in in vitro transcription assays, was assessed by DNase footprinting. UBF protected the same region of the promoter in the linker-scanning mutant in BSM 129/124 as it did in the wild-type, but did not yield a typical footprint over the promoter in the linker-scanning mutant BSM 106/101. Previously we reported that promoters with mutant core promoters elements, either the guanine at -16 or -7 substituted by an adenine, were inactive in vitro unless the assays were supplemented with UBF. Those results suggested that the binding of UBF upstream of the core was required for the promotion of transcription. The interactions between the core and upstream promoter elements were assessed by constructing double mutants of the promoter. In two constructs the conserved guanines at either -16 or -7 were altered in a deletion mutant (-86) that did not respond to UBF. In a third construct the guanine at -16 in BSM 129/124 was changed to an adenine. These bidomain mutant constructs did not respond to the addition of UBF in an in vitro transcription assay, confirming that the rescue of the core promoter mutants requires an intact and functional upstream promoter element.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The effects of acceleration on the mechanical impedance response of a primate model exposed to sinusoidal vibration.

Criteria for developing active and passive isolation mechanisms for reducing the effects of whole-body vibration exposure rely on a thorough understanding of the stiffness, damping, and resonance behaviors of the human or human surrogate body. Three Rhesus monkeys were exposed to seated whole-body sinusoidal vibration between 3 and 20 Hz at 0.69 and 3.47 msec-2 rms (0.1 and 0.5 g peak) accelerations. The mechanical impedance magnitude and phase were calculated as the ratio and phase relation between the transmitted force and input velocity, respectively, at the seat. The resultant profiles showed a significant decrease in the primary resonance frequency with increasing acceleration. At the lower acceleration level, a second lower impedance peak was observed at approximately 5 Hz. A three-mass, two degree-of-freedom model, which included upper torso and leg representation, was used to determine the mechanical parameters that best described the measured responses. The mean stiffness coefficients and the mean undamped natural frequencies associated with the upper torso and leg subsystems showed a significant decrease with increases in the acceleration level. The results of this study strongly suggested that nonlinear stiffness properties were responsible for the observed differences in the biodynamic response of the Rhesus monkey with acceleration level.

Acceleration↗
PubMedDate not supplied

Medical genetic evaluation for the etiology of hearing loss in children.

The purpose of the medical genetic evaluation is to identify the etiology of the hearing loss. To do so requires a multidisciplinary team that includes the otolaryngologist, audiologist, medical geneticist, and radiologist. A number of tests and procedures are now available to assist in the search for the cause of hearing losses. The importance of sensitivity when providing genetic counseling is emphasized. Molecular genetics offers potential for continued progress in understanding the etiologies of hearing loss. Recent advances in this area are discussed.

Child↗
PubMedDate not supplied

Single gene influences on radiologically-detectable malformations of the inner ear.

Inner ear malformations associated with hearing loss or vestibular dysfunction are discussed from the viewpoint of the etiologies of the malformation. Symptoms of classification of inner ear malformations are discussed. The significance of malformations of the cochlea and vestibular aqueduct to auditory function are discussed. Genetics features and characteristics of Branchio-oto-renal, Waardenburg's, Pendred's, DiGeorge's, Wildervanck, Fountain, and Treacher Collins syndromes are discussed in relation to ear abnormalities and hearing. Similar attention is given to genetic studies of nonsyndromic hearing loss.

Deafness↗
PubMedDate not supplied

A chromosome 14 inversion in a T-cell lymphoma is caused by site-specific recombination between immunoglobulin and T-cell receptor loci.

Specific chromosomal aberrations are associated with specific types of cancer (for review see ref. 1). The distinctiveness of each association has led to the belief that these chromosomal aberrations are clues to oncogenic events or to the state of differentiation in the malignant cell type. Malignancies of T lymphocytes demonstrate such an association characterized most frequently by structural translocations or inversions of chromosomes 7 and 14 (refs 7-9). Analyses of these chromosomally marked tumours at the molecular level may therefore provide insight into the aetiology of the cancers as well as the mechanisms by which chromosomes break and rejoin. Here we report such an analysis of the tumour cell line SUP-T1 derived from a patient with childhood T-cell lymphoma carrying an inversion of one chromosome 14 between bands q11.2 and q32.3, that is, inv(14) (q11.2; q32.2). These are the same chromosomal bands to which the T-cell receptor alpha-chain (14q11.2) and the immunoglobulin heavy-chain locus (14q32.3) have been assigned. Our analysis reveals that this morphological inversion of chromosome 14 was mediated by a site-specific recombination event between an immunoglobulin heavy-chain variable region (Ig VH) and a T-cell receptor (TCR) alpha-chain joining segment (TCR J alpha). S1 nuclease analysis shows that this hybrid gene is transcribed into poly(A)+ RNA.

Amino Acid Sequence↗
PubMedDate not supplied

A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia.

The leukaemic cells of more than 90% of chronic myelogenous leukaemia (CML) patients and of 10% of acute lymphocytic leukaemia (ALL) patients carry the t(9:22) (q34:q11) translocation which generates the Philadelphia chromosome (Ph1). In CML the abl gene is translocated from chromosome 9 to the centre of the bcr gene on chromosome 22 and this results in production of chimaeric bcr-abl RNA translated into a protein of relative molecular mass (Mr) 210,000 (210K). Our data indicate that in ALL abl is translocated into the 5' region of the bcr gene. The consequence of this is the expression of a fused transcript in which the first exon of bcr is linked to the second abl exon. This transcript encodes a 190K protein kinase.

Amino Acid Sequence↗
PubMedDate not supplied

Reading disability and chromosome 6p21.3: evaluation of MOG as a candidate gene.

Linkage analysis has localized a gene influencing specific reading disability (dyslexia) to 6p21.3. The myelin oligodendrocyte glycoprotein (MOG) gene, which maps to this region, was selected as a candidate. Myelin oligodendrocyte glycoprotein is a membrane protein, a member of the immunoglobin superfamily, that is found on the outermost lamellae of mature myelin. Although the exact function of this protein is unknown, its presence in the central nervous system and the hypothesized relationship between dyslexia and temporal processing rate as well as a suggested relationship with intelligence made this gene a candidate for dyslexia. Analysis of the coding exons and adjacent splice sites in a subset of 22 children with dyslexia from 10 sibships found a missense mutation in exon 4 in 2 of the sibships. This change from the published sequence also occurred in 86 of 96 random controls, making it considerably less frequent in this small sample of individuals with dyslexia. Subsequent typing of this single nucleotide polymorphism (SNP) in 74 nuclear families in which at least one child had reading disability showed no significant difference in frequency from the controls, however. Sib-pair linkage analysis with these families did not show significant linkage with the SNP nor with a separate polymorphic dinucleotide repeat marker in the MOG gene (MOG31/32), but association analysis identified two alleles of MOG31/32 that were associated with reading disability phenotypes with a low level of significance. Thus, although alleles in the MOG gene may be in linkage disequilibrium with a locus that contributes to reading disability, it is unlikely that the MOG gene itself is involved.

Adolescent↗
PubMedDate not supplied

Penetrating keratoplasty vs. epikeratoplasty for the surgical treatment of keratoconus.

PURPOSE: Penetrating keratoplasty and epikeratoplasty have been utilized in the surgical treatment of keratoconus. Comparison of the relative efficacy of each procedure in achieving visual outcomes has not been achieved due to limited numbers of cases and follow-up in previous series. METHODS: All patients who underwent either penetrating keratoplasty or epikeratoplasty for keratoconus between January 1987 and December 1997, and for whom at least 24 months of postoperative follow-up data for visual acuity was documented in the medical record, were included in this retrospective, nonrandomized, sequential comparative trial. The sole criteria for outcome in each group, as well as for comparison of the two groups, was Snellen visual acuity measured at the time of each follow-up with the presenting optical aid. RESULTS: Inclusion criteria were met for 443 eyes treated with penetrating keratoplasty and 161 eyes treated with epikeratoplasty. Mean follow-up was 4.3 years for penetrating keratoplasty and 4.5 years for epikeratoplasty. In each group, approximately 50% of the patients chose rehabilitation with optical correction with either spectacles or contact lenses and 50% chose no optical correction. Final median logMAR visual acuity for all patients, irrespective of means of visual rehabilitation, was 0.30 (20/40) for penetrating keratoplasty and 0.40 (20/50) for epikeratoplasty (P < .00005). In 209 penetrating keratoplasty and 77 epikeratoplasty eyes with optical correction, the final median logMAR visual acuity was 0.18 (20/30) for penetrating keratoplasty and 0.40 (20/50) for epikeratoplasty (P < .00005). The final median logMAR visual acuity in 234 penetrating keratoplasty and 84 epikeratoplasty eyes without optical correction was 0.48 (20/60) in both groups (P-value was not statistically significant). CONCLUSIONS: Although penetrating keratoplasty was statistically superior to epikeratoplasty with respect to visual outcome, results with epikeratoplasty were adequate to recommend its use as a surgical alternative in cases when it is not desirable to perform penetrating keratoplasty.

Adult↗