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Biomedical subjects

R J Smith

Publications and source records attributed to R J Smith.

At least 145 records · Page 8Linked to original sources
PubMed1998

A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene.

Autosomal recessive nonsyndromic sensorineural deafness segregating in a large consanguineous Indian family was mapped to chromosome 11p14-p15.1 defining a new locus, DFNB18. A maximum lod score of 4.4 at theta = 0 was obtained for the polymorphic micro-satellite marker D11S1888. Haplotype analysis localizes this gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and encompasses the region of Usher syndrome type 1C (USH1C). We postulate that DFNB18 and USH1C are allelic variants of the same gene.

Chromosome Mapping↗
PubMed1998

Familial laryngeal paralysis.

Vocal fold paralysis (VFP) is the second most frequent cause of congenital stridor. Although often due to birth trauma, infection, and brainstem abnormalities, most cases are idiopathic. Infrequently, a family history of VFP is elicited, identifying a role for genetic factors in laryngeal function. This study describes a family in which an autosomal dominant form of familial laryngeal abductor paralysis segregates. The typical physical findings, diagnostic and therapeutic considerations, and possible molecular mechanisms of this disorder are discussed in detail.

Adolescent↗
PubMed1998

Fetal mouse NK cell clones are deficient in Ly49 expression, share a common broad lytic specificity, and undergo continuous and extensive diversification in vitro.

NK cells obtained by exposing mouse fetal thymocytes to appropriate combinations of IL-4, IL-2, and PMA are phenotypically indistinguishable from cultured adult splenic NK cells with the exception that they generally lack measurable expression of all of the inhibitory Ly49 molecules that can currently be detected with Abs (Ly49A, -C, -G, and -I) and of the activating molecule Ly49D. Despite this deficiency, fetal NK cells have a similar specificity to Ly49-expressing adult splenic NK cells. Individual fetal NK cell clones display an essentially invariant and broad specificity similar to that of polyclonal populations of fetal or adult NK cells, although significant differences in the fine specificity of clones can occasionally be detected. Most remarkably, cloned fetal NK cell lines display heterogeneous expression of a restricted set of surface molecules that includes 10A7, Ly6C, 3C2, CD8, certain isoforms of CD45, and also, occasionally, Ly49 molecules. This heterogeneity is not related to the cell cycle or activation status of the cells, and micromanipulation recloning demonstrates unambiguously that it is not due to a lack of a single cell origin. Diversity is generated rapidly and the capacity for diversification appears to persist indefinitely in vitro. The expression of individual variable Ags is independent and stochastic, resulting in fetal NK "clones" being potentially composed of hundreds of phenotypically distinct cells. We hypothesize that fetal NK cells behave as progenitor cells that are undergoing a process of rapid, extensive, and continuous diversification and that are individually capable of generating and regenerating a complex NK cell repertoire.

Animals↗
PubMed1998

Insulin-like growth factor-I receptor internalization regulates signaling via the Shc/mitogen-activated protein kinase pathway, but not the insulin receptor substrate-1 pathway.

Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins. Following hormone binding, IGF-I receptors cluster into clathrin-coated pits and are internalized via an endocytotic mechanism. This study investigates the relationship between IGF-I receptor internalization and signaling via IRS-1 and Shc. A mutation in the C terminus of the IGF-I receptor decreased both the rate of receptor internalization and IGF-I-stimulated Shc phosphorylation by more than 50%, but did not affect IRS-1 phosphorylation. Low temperature (15 degrees C) decreased IGF-I receptor internalization and completely inhibited Shc phosphorylation. Although receptor and IRS-1 phosphorylation were decreased in accordance with delayed binding kinetics at 15 degrees C, the ratio of IRS-1 to receptor phosphorylation was increased more than 2-fold. Dansylcadaverine decreased receptor internalization and Shc phosphorylation, but did not change receptor or IRS-1 phosphorylation. Consistent with these findings, dansylcadaverine inhibited IGF-I-stimulated Shc-Grb2 association, mitogen-activated protein kinase phosphorylation, and p90 ribosomal S6 kinase activation, but did not affect the association of phosphatidylinositide 3-kinase with IRS-1 or activation of p70 S6 kinase. These data support the concept that Shc/mitogen-activated protein kinase pathway activation requires IGF-I receptor internalization, whereas the IRS-1 pathway is activated by both cell surface and endosomal receptors.

Animals↗
PubMed1998

Presymptomatic diagnosis of nonsyndromic hearing loss by genotyping.

BACKGROUND: Nonsyndromic hearing loss (NSHL) is the most common type of hereditary hearing impairment (HHI). It is genetically heterogeneous, and although the exact number of genes is not known, 38 loci have been identified. By cloning the relevant genes and studying the function of the encoded proteins at the molecular level, it may be possible to impact the habitation of persons at risk for HHI. Currently, for select families, presymptomatic diagnosis of NSHL by genotyping is possible. OBJECTIVE: To provide presymptomatic diagnosis of HHI to individuals in select families who have participated in linkage studies. DESIGN: In 2 large families with autosomal dominant HHI, genes for NSHL were mapped to chromosomes 6 (DFNA10) and 19 (DFNA4). In each family, the phenotype is one of progressive sensorineural hearing loss that begins in the individual's mid-30s and progresses to a severe-to-profound loss requiring amplification. Presymptomatic diagnosis was requested by, and provided to, 19 at-risk persons in these kindreds. RESULTS: By reconstructing haplotypes through the use of short tandem repeat polymorphisms tightly linked to the disease gene, risk calculations and genetic counseling were provided to these persons. CONCLUSIONS: By simple Mendelian genetics, the risk of inheriting a fully penetrant autosomal dominant NSHL gene from a single affected parent is 50% for each offspring. However, by reconstructing haplotypes in families in which an HHI gene has been localized, this risk can be changed substantially.

Chromosomes, Human, Pair 6↗
PubMed1998

Effects of rigid plate fixation and subsequent removal on craniofacial growth in rabbits.

OBJECTIVE: To examine the effects of rigid plate fixation (RPF) and subsequent removal on craniofacial growth in rabbits. DESIGN: Randomized controlled experiment. SUBJECTS: Thirty-two 6-week-old male New Zealand white rabbits. INTERVENTIONS: Group 1 underwent exposure of the left nasofrontal suture and midzygomatic arch; group 2, RPF of the left nasofrontal suture and midzygomatic arch areas; group 3, single osteotomy at left nasofrontal suture and double osteotomies at midzygomatic arch with RPF of osteotomies; and group 4, controls. At 11 weeks of age, the RPF was removed. Animals were killed at 20 weeks of age. Linear and 3-dimensional measurements (euclidean distance matrix analysis) were used to evaluate craniofacial regions. RESULTS: In comparison with control animals, linear data showed shortening of the left nasal bone in group 3. Groups 1 through 3 also exhibited shortening of the left zygomatic arch, orbital diameter, and anterior midfacial height. Euclidean distance matrix analysis showed significant restrictive shape alterations on both the ipsilateral and contralateral sides in groups 1 through 3. In comparison with animals in which RPF was left in place, linear data showed significant shortening of the orbital diameter in groups 1 through 3 and of anterior midface height in groups 2 and 3. Euclidean distance matrix analysis showed significant restrictive shape alterations on both contralateral and ipsilateral sides. CONCLUSION: Rather than preventing restrictive growth disturbances to the growing midface in rabbits, RPF with subsequent removal produces a greater amount of restrictive shape alteration than RPF that is left in place.

Animals↗
PubMed1998

Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss.

Mutations in the Cx26 gene have been shown to cause autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12. Using direct sequencing, we screened the Cx26 coding region of affected and nonaffected members from seven ARNSHL families either linked to the DFNB1 locus or in which the ARNSHL phenotype cosegregated with markers from chromosome 13q12. Cx26 mutations were found in six of the seven families and included two previously described mutations (W24X and W77X) and two novel Cx26 mutations: a single base pair deletion of nucleotide 35 resulting in a frameshift and a C-to-T substitution at nucleotide 370 resulting in a premature stop codon (Q124X). We have developed and optimized allele-specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status within families. We also have developed a single stranded conformational polymorphism (SSCP) assay which covers the entire Cx26 coding region. This assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the CX26 gene.

Alleles↗
PubMed1998

Sexual dimorphism in primate neonatal body mass.

Data were collected on neonatal body mass for 109 primate species. For 23 species with sample sizes of nine or more for each sex, dimorphism (male/female ratio) in neonatal body mass ranged from 0.94 in Galago senegalensis and Aotus trivirgatus to 1.19 in Pongo pygmaeus. Dimorphism in neonatal body mass was positively correlated both with adult body mass and with dimorphism in adult body mass, but the apparent relationship with adult mass was eliminated after controlling for the relationship with adult dimorphism. Comparative studies concerned with neonatal body mass in primates have almost always ignored sexual dimorphism. However, neonatal sexual dimorphism in primates does exist and appears to be of sufficient magnitude to be biologically significant in some species. It may be important to consider the consequences of neonatal dimorphism for a variety of research questions related to maternal investment, life history, postnatal growth, and the relationship between neonatal size and adult female pelvic dimensions, both in extant and in extinct primates.

Animals↗
PubMed1998

Simplified technique for suturing a temporary keratoprosthesis for pars plana vitrectomy.

PURPOSE: To describe an efficient technique for suturing a Landers wide-field temporary keratoprosthesis for intraocular surgery in an eye with an opaque cornea. METHODS: Two sutures were preplaced at partial thickness into corneal stroma parallel to the corneoscleral limbus. Suture ends were placed through corresponding holes in the keratoprosthesis and tied. RESULTS: The temporary keratoprosthesis was held firmly in place with two sutures and provided clear visualization for extensive intraocular surgery. CONCLUSION: The preplaced two-suture technique for securing a temporary keratoprosthesis to the globe decreased the time that the globe was open.

Cornea↗
PubMed1998

The prediction of surgically induced refractive change from corneal topography.

PURPOSE: To develop a method to predict the refractive power of the cornea from corneal topography. METHODS: We reviewed preoperative and postoperative cycloplegic refraction, keratometry, and corneal topography in 40 eyes of 40 patients who had undergone photorefractive keratectomy, radial keratotomy, myopic keratomileusis in situ, or hyperopic lamellar keratoplasty. For each axial dioptric power map, we calculated the aspheric ellipsoid that best fit that map. Central corneal points were weighted more heavily than peripheral points, based on the Stiles-Crawford effect. The equation of the best-fit ellipsoid yielded the spherical and astigmatic power and axis for each cornea preoperatively and postoperatively. RESULTS: The preoperative corneal spherical and astigmatic powers measured by the best-fit method were consistent with the spherical and astigmatic powers measured by keratometry and simulated keratometry. The change in corneal spherical power predicted by the best-fit method was significantly (P < .05) more accurate at predicting the change in spherical equivalent refraction than change either in spherical equivalent keratometry or in spherical equivalent simulated keratometry. The prediction of the astigmatic change was less precise than that of the spherical, but the best-fit method was the most accurate. CONCLUSIONS: The best-fit method is more accurate than simulated keratometry and standard keratometry are in evaluating corneal refractive power after refractive surgery. An improved method of calculating corneal refractive power may facilitate subjective refraction after refractive surgery, improve the accuracy of intraocular lens power calculation for eyes that have had previous refractive surgery, and improve ablation profiles for excimer laser refractive surgery.

Astigmatism↗
PubMed1998

District nursing in Dominica.

District nurses constitute the basis of the primary health care services in Dominica. All encounters of three district nurses were registered using the international classification of primary care. Information on other aspects of district nursing was collected by participating observation and the use of a questionnaire. Check-ups for hypertension, diabetes, pregnancy and immunisations constituted 40% of all reasons for encounter. The district nurses dealt with 80% of all contacts; only 20% of all patients were referred to the district medical officer. There are several discouragements to the motivation of the nurses. In addition to being a nurse, all have their family and other obligations. Postgraduate training with diversified certification and upgrading of wages could contribute to a continued high motivation and increased job satisfaction.

Adolescent↗
PubMed1998

A new tissue adhesive for laceration repair in children.

To determine the effectiveness of a new tissue adhesive, 2-Octylcyanoacrylate (2-OCA), for laceration repair, 83 children presenting to T.C. Thompson Children's Hospital Emergency Department with lacerations meeting eligibility requirements between February and June 1996 were randomized to receive 2-OCA or nonabsorbable sutures/staples. The length of time for repair was recorded. The length of time for laceration repair was decreased (2.9 minutes 2-OCA vs 5.8 minutes suture/staple; p < 0.001), the parents' assessment of the pain felt by their children in the 2-OCA group was less, and the wounds closed with tissue adhesive had slightly lower cosmesis scores. 2-OCA is an acceptable alternative to conventional methods of wound repair with comparable cosmetic outcome.

Child, Preschool↗
PubMed1998

Effects of dietary protein and tumor necrosis factor on components of the insulin-like growth factor-I pathway in the colon and small intestine in protein-depleted rats.

Intestinal cell growth is markedly affected by nutrient intake and the presence of cytokines. Since insulin-like growth factor-I (IGF-I) is an important hormone regulator of intestinal proliferation, this study examined the effects of dietary protein content and tumor necrosis factor (TNF) on mRNA levels of IGF-I, IGF-I receptor, IGF binding protein-3 (IGFBP-3), and IGFBP-4 and on the histology of the colon, jejunum, and ileum in protein-malnourished rats. After 2 weeks of feeding a 2% casein diet, rats continued on the 2% casein diet or were refed with a 20% casein diet and received daily intraperitoneal injections of either TNF (50 microg/kg) or saline for 4 days. The abundance of mRNA in the intestine was determined by RNA dot-blot analysis, and morphology measurements were performed by light microscopy. Simultaneous refeeding with the 20% casein diet and administration of TNF led to a modest increase in IGF-I and IGFBP-4 mRNA abundance in the colon. However, in the jejunum and ileum, refeeding had no effect but TNF caused a decrease in IGF-I and IGFBP-3 mRNA levels in malnourished rats. Refeeding with the 20% casein diet resulted in relatively modest histologic changes, which were greater in the colon versus the small intestine. The decreased magnitude of histologic changes in the order of the colon, ileum, and jejunum may reflect a response to a gradient of amino acid availability from intraluminal nutrients. These data demonstrate that TNF has distinct effects on colon and small intestine mRNA, but these mild changes had only a slight impact in the colon and did not translate into identifiable histologic changes in the small intestine. Combined protein restriction and TNF administration had only a modest effect on intestinal mRNA levels and mucosal histology.

Animals↗
PubMed1998

Predictability of spherical photorefractive keratectomy for myopia.

OBJECTIVE: This study aimed to examine the effects of purely spherical excimer laser photorefractive keratectomy (PRK) for myopia. DESIGN: Consecutive case series. PARTICIPANTS: A total of 3218 eyes with a mean preoperative mean spherical equivalent (MSE) of -3.75 diopters (D) +/- 1.73 D standard deviation (SD) (range, -1.00 D to -11.88 D) underwent PRK with a Nidek EC-5000 excimer laser. Eyes were divided into groups based on the degree of preoperative myopia in 1 D steps. INTERVENTION: All eyes underwent PRK with a Nidek EC-5000 excimer laser. MAIN OUTCOME MEASURE: Visual and refractive outcome of PRK treatment was measured. RESULTS: After a mean follow-up period of 52.6 weeks (range, 26-150 weeks), the final MSE was -0.07 D (+/-0.68 D) (range, -5.50 D to +4.50 D). Of the 3218 eyes, 2919 (90.7%) were within 1.00 D of emmetropia, and 3038 (94.4%) of eyes had an uncorrected visual acuity of 20/40 or better, with 1886 (58.6%) achieving 20/20 or better visual acuity. Eyes in the lower preoperative myopia groups had a greater chance of attaining 20/40 unaided visual acuity than those in the higher groups (e.g., 98.3% of the -2D group and 53.6% of the -9D group achieved 20/40 unaided visual acuity). Overall, mean postoperative haze was 0.29+/-0.39 SD (scale, 0-3), and 29 eyes (0.9%) lost 0.3 or more logarithm of the minimum angle of resolution (LogMAR) unit of best-corrected visual acuity. CONCLUSIONS: Excimer laser PRK is an effective treatment for myopia of up to -9.00 D. The outcome parameters are less predictable for eyes with greater than -9.00 D of myopia.

Adult↗
PubMed1998

Diffuse lamellar keratitis. A new syndrome in lamellar refractive surgery.

OBJECTIVE: This study aimed to describe a syndrome that the authors call diffuse lamellar keratitis that follows laser in situ keratomileusis (LASIK) and related lamellar corneal surgery. DESIGN: Noncomparative case series and record review. PARTICIPANTS: Thirteen eyes of 12 patients in whom infiltrates developed in the interface after lamellar refractive surgery were studied. INTERVENTION: Topical antibiotics or corticosteroids or both were administered. MAIN OUTCOME MEASURES: Corneal infiltrate appearance, focality, location, and clinical course were measured. RESULTS: Patients presented between 2 and 6 days after surgery with pain, photophobia, redness, or tearing. Ten cases directly followed either myopic keratomileusis or LASIK. Three cases followed enhancement surgery without the use of a microkeratome. All 13 cases had infiltrates that were diffuse, multifocal, and confined to the flap interface with no posterior or anterior extension. The overlying epithelium was intact in each case. Cultures were negative in the two cases cultured. Ten eyes were treated with antibacterial agents; two eyes had fluorometholone four times daily added to the routine postoperative antibacterial regimen, and one eye had the antibacterial agent discontinued and was treated with topical fluorometholone alone. All infiltrates resolved without sequelae. CONCLUSIONS: A distinct syndrome of unknown cause of noninfectious diffuse infiltrates in the lamellar interface is described. It can be distinguished from infectious infiltrates by clinical presentation and close follow-up. Patients with the syndrome should be spared the more invasive treatment of infectious keratitis.

Adult↗
PubMed1998

Aerocele after tracheocutaneous fistula closure.

Tracheocutaneous fistulas (TCF) occasionally follow pediatric tracheotomy decannulation, often requiring surgical treatment. Complications of TCF closure are infrequent, but may include development of a cervical aerocele. A case of cervical aerocele after TCF closure is described. Based on our experience with this problem, we offer guidelines for care of TCFs.

Child↗