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R J Smith

Publications and source records attributed to R J Smith.

At least 217 records · Page 12Linked to original sources
PubMed1996

[Clinical measurement of intraocular gas].

BACKGROUND: Increased use of gases in retinal/vitreous surgery requires a good clinical estimate of intraocular gases. This is needed, if a supplement of gas is intended, its disappearance to be predicted (e.g. to 10% to permit travelling by plane) or the amount to be calculated to cover a break. Clinical estimation of gas in the pupil is limited by its size. Accuracy of pupil measurements will be tested and compared with experimental results obtained by estimating the level of gas meniscus at the retina. MATERIALS AND METHODS: Ten cadaver eyes (5 phakic, 4 aphakic, 1 pseudophakic) were fixed in a plastic mold, vitrectomized and injected with multiple randomized volumes of air. Two observers measured the level of meniscus in disc diameters above or below the superior margin of disc and then anteriorly in the pupil in millimeters from the superior limbus. Measurements were converted to milliliters through tables constructed on mathematical models of the phakic and aphakic eye. RESULTS: Observations at the retina and in the pupil were equally accurate for intermediate gas volumes, for which the meniscus fell within the pupil (P = 0.372). Measurements at the retina proved less vulnerable to error induced by misalignment of the observer's eye. Above the pupil observations at the retina were still reliable for small bubbles up to 4 dd above the disc (error < 5% in the aphakic, < 10% in the phakic eye). Below the pupil observations at the retina yielded a result increasing less than the injected volume because of refraction at the anterior segment gas interface (error > 10% of the ocular volume). CONCLUSION: Observations of the level of gas meniscus at retina with indirect ophthalmoscopy is an accurate method for estimating intraocular gas volumes. It extends the range of measurement significantly beyond the pupil. Tables based on a mathematical model convert disc diameters to milliliters.

Gases↗
PubMed1996

High purity, recovery, and selection of human blood cells with a novel high gradient magnetic separator.

The selective isolation of cell subpopulations from previously cryopreserved human blood mononuclear cells was achieved magnetically using a novel, well-characterized conical funnel filter containing a variety of ordered wire arrays. Tetrameric antibody complexes targeted against the CD8 antigen were used to bind colloidal superparamagnetic dextran-iron particles to the desired cells with very low nonspecific binding. The novel design of the filter was such that the retention of cells at zero magnetic field was on average 0.9%. After two successive magnetic separations, an average purity of 98% was obtained for the desired labeled cells. A third separation gave > 99% purity. Purity was affected by the unlabeled cells, which expressed high intercellular adhesion (0.5% of the total cells). The ultimate recovery of the labeled cells was limited by the degree of nonmagnetic labeling of the cells expressing very low levels of targeted antigen. Recoveries could be as low as 78%, depending on the donor. The separation system described was believed suitable for difficult large-scale separations, that is, cells expressing the CD34 antigen.

Blood Preservation↗
PubMed1996

Localization of the Usher syndrome type ID gene (Ush1D) to chromosome 10.

The Usher syndromes (USH) are a group of autosomal recessive diseases characterized by progressive pigmentary retinopathy and sensorineural hearing loss. Five USH genes have been mapped and at least one additional gene is known to exist. By homozygosity mapping in a consanguineous family, a sixth USH gene has been localized. Clinical findings in the four affected children are consistent with established diagnostic criteria for Ush1. Linkage to known USH loci was excluded, and using two genomic DNA pools, one from the affected children and the other from the parents, 161 polymorphic markers evenly spaced across the autosomal human genome were screened. The location of the Ush1D gene was defined by the only region showing homozygosity by descent in the affected siblings, a 15 cM interval on chromosome 10q bounded by D10S529 and D10S573.

Chromosome Mapping↗
PubMed1996

A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6.

Late-onset non-syndromic hearing impairment is the most common type of neurological dysfunction in the elderly. It can be either acquired or inherited, although the relative impact of heredity on this type of loss is not known. To date, nine different genes have been localized, but none has been cloned. Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6.

Chromosome Mapping↗
PubMed1996

Health and economic implications of a work-site smoking-cessation program: a simulation analysis.

In this article, we examine the health and economic implications of a workplace smoking-cessation program by using a simulation model that includes, among its novel features, consideration of long-term as well as short-term implications and evaluation of the effects of employee turnover on benefits derived by both the firm and the broader community. As a result of employee turnover, approximately half of the program-generated benefits are realized by the community outside the firm. Still, smoking cessation is a very sound economic investment for the firm, and is particularly profitable when long-term benefits are included, with an eventual benefit-cost ratio of 8.75. Saving life-years at a cost of $894 each, the program is more cost-effective than most of the conventional medical care covered by the firm's insurance. Nevertheless, the intervention successfully addresses only a fraction of the costs that smoking imposes on the firm.

Absenteeism↗
PubMed1996

Construction of a YAC contig encompassing the Usher syndrome type 1C and familial hyperinsulinism loci on chromosome 11p14-15.1.

The Usher syndrome type 1C (USH1C) and familial hyperinsulinism (HI) loci have been assigned to chromosome 11p14-15.1, within the interval D11S419-D11S1310. We have constructed a yeast artificial chromosome (YAC) contig, extending from D11S926 to D11S899, which encompasses the critical regions for both USH1C and HI and spans an estimated genetic distance of approximately 4 cM. A minimal set of six YAC clones constitute the contig, with another 22 YACs confirming the order of sequence-tagged sites (STSs) and position of YACs on the contig. A total of 40 STSs, including 10 new STSs generated from YAC insert-end sequences and inter-Alu PCR products, were used to order the clones within the contig. This physical map provides a resource for identification of gene transcripts associated with USH1C, HI, and other genetic disorders that map to the D11S926-D11S899 interval.

Chromosome Mapping↗
PubMed1996

Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose.

The transcription of the yeast FBP1 and PCK1 genes, which encode the gluconeogenic enzymes fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, is repressed by glucose. Here, we show that this repression is both very strong and exceptionally sensitive to glucose, being triggered by glucose at concentrations less than 0.005% (0.27 mM). This repression remains operative in yeast mutants carrying any one of the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 mutant. In addition, 2-deoxyglucose can trigger the repression, but 6-deoxyglucose cannot, suggesting that internalization and phosphorylation of the glucose is essential for repression to occur. While gluconeogenic gene transcription is subject to the Mig 1p-dependent pathway of glucose repression, the exquisite response to glucose is maintained in hxk2 and mig1 mutants, suggesting that this pathway is not essential for the response. The response can also be triggered by the addition of exogenous cAMP, suggesting that the Ras/cAMP pathway can mediate repression of the FPB1 and PCK1 mRNAs. However, the response is not dependent upon this pathway because it remains intact in Ras, adenyl cyclase and protein kinase A mutants. The data show that yeast cells can detect very low glucose concentrations in the environment, and suggest that several distinct signalling pathways operate to repress FPB1 and PCK1 transcription in the presence of glucose.

Cell Cycle Proteins↗
PubMed1996

Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6-phosphate amidotransferase of Candida albicans.

Glutamine:fructose-6-phosphate amidotransferase (glucosamine-6-phosphate synthase) catalyzes the first step of the hexosamine pathway required for the biosynthesis of cell wall precursors. The Candida albicans GFA1 gene was cloned by complementing a gfa1 mutation of Saccharomyces cerevisiae (previously known as gcn1-1; W. L. Whelan and C. E. Ballou, J. Bacteriol. 124:1545-1557, 1975). GFA1 encodes a predicted protein of 713 amino acids and is homologous to the corresponding gene from S. cerevisiae (72% identity at the nucleotide sequence level) as well as to the genes encoding glucosamine-6-phosphate synthases in bacteria and vertebrates. In cell extracts, the C. albicans enzyme was 4-fold more sensitive than the S. cerevisiae enzyme to UDP-N-acetylglucosamine (an inhibitor of the mammalian enzyme) and 2.5-fold more sensitive to N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (a glutamine analog and specific inhibitor of glucosamine-6-phosphate synthase). Cell extracts from the S. cerevisiae gfa1 strain transformed with the C. albicans GFA1 gene exhibited sensitivities to glucosamine-6-phosphate synthase inhibitors that were similar to those shown by the C. albicans enzyme. Southern hybridization indicated that a single GFA1 locus exists in the C. albicans genome. Quantitative Northern (RNA) analysis showed that the expression of GFA1 in C. albicans is regulated during growth: maximum mRNA levels were detected during early log phase. GFA1 mRNA levels increased following induction of the yeast-to-hyphal-form transition, but this was a response to fresh medium rather than to the morphological change.

Amino Acid Sequence↗
PubMed1996

Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration.

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.

Animals↗
PubMed1996

Cerebral blood flow changes in limbic regions induced by unsolvable anagram tasks.

OBJECTIVE: The study addressed the question of whether unsolvable as opposed to solvable cognitive problems activate discrete neuronal systems in the human brain. METHOD: Twelve healthy humans tried to solve unsolvable anagrams. Solvable anagrams and a resting baseline after each anagram task served as control conditions in a within-subject design. Activation was measured with the equilibrium infusion method by using 15O-labeled water and positron emission tomography, with absolute quantitation of anatomically defined regional cerebral blood flow (CBF). RESULTS: Compared to rest, both anagram tasks increased activity in frontal and temporal regions. The soluble task condition increased hippocampal activation and decreased mammillary bodies activity, while unsolvable anagrams were associated with increased CBF to the mamillary bodies and amygdala and decreased hippocampal activity. CONCLUSIONS: A limbic network integrating negative emotion and cognition seems reflected in reciprocal diencephalic and limbic activation with solvable and unsolvable anagrams. Since unsolvable anagrams have been used to induce learned helplessness in humans, this finding may provide an initial step toward clarifying its neural substrate.

Adult↗
PubMed1996

Respiratory manifestations of gastroesophageal reflux disease in pediatric patients.

Respiratory manifestations of gastroesophageal reflux disease (GERD) are being recognized with increasing frequency. We present the evaluation and management of four infants and children with unusual respiratory symptoms attributed to GERD. The advantages and disadvantages of diagnostic studies of GERD are discussed, and an evaluation and treatment protocol is presented. Treatment must be tailored to the nature and severity of the patient's presenting symptoms and includes conservative, pharmacologic, and/or surgical management.

Airway Obstruction↗
PubMed1996

Pediatric exercise-induced laryngomalacia.

Laryngomalacia is a well-recognized cause of airway obstruction and inspiratory stridor in infants. As children grow and become more active, laryngomalacia may manifest in different, unexpected ways. Otherwise healthy athletes may generate enough inspiratory force to draw the aryepiglottic folds into the endolarynx, causing a subtotal glottic obstruction. This problem may be overlooked or attributed to asthma, lack of fitness, or functional abnormalities. The purpose of this report is to review the prevalence, diagnosis, and treatment of exercise-induced laryngomalacia (EIL) in children and young adults. To study the incidence and diagnosis of this disorder, we examined 10 healthy volunteers. Fiberoptic laryngoscopy was used to videotape each subject's larynx during active exercise on a stationary bicycle. All volunteers demonstrated altered laryngeal dynamics with exercise, and 1 of the 10 volunteers developed laryngomalacia. Anatomically, it appears that the aryepiglottic fold serves as the critical point of obstruction. When symptomatic, laryngomalacia may be treated with supraglottoplasty. We have had experience with 2 EIL patients in the last 12 months who have undergone carbon dioxide laser microlaryngoscopy. Both patients benefited significantly from surgery. We conclude that EIL is underdiagnosed but responds well to treatment.

Adolescent↗
PubMed1996

Postoperative care following single-stage laryngotracheoplasty.

Single-stage laryngotracheoplasty (SSLTP) provides a method of correcting mild-to-moderate laryngotracheal stenosis while avoiding the risks of prolonged laryngeal stenting. Pediatric patients are orally intubated for 5 to 7 days postoperatively to ensure an adequate airway while edema resolves and healing begins. During this period, continuous neuromuscular blockade has been advocated in infants and young children to avoid endotracheal tube trauma to the fresh graft and potentially life-threatening accidental decannulation. Pulmonary atelectasis is the most common morbidity associated with prolonged neuromuscular blockade. Neuromuscular weakness also may follow prolonged paralysis and prolong hospitalization. This paper compares the postoperative course of 17 patients who underwent 18 SSLTP procedures by the senior author. The first 8 patients received continuous neuromuscular blockade in the early postoperative period. To reduce perceived morbidity, the last 9 patients were managed with a protocol that incorporated daily 4- to 8-hour "interruptions" of paralysis. Seven patients tolerated this protocol modification. As a group, these patients had less postoperative pulmonary atelectasis prior to extubation (p < .05) and were extubated sooner than patients receiving continuous neuromuscular blockade (p<.05) without compromising the surgical success of the procedure. Intermittent paralysis permitted for more accurate assessment of pain control and protected against accidental drug accumulation. Although self-extubation did not occur, diligent nursing care with adequate sedation and analgesia is necessary to avoid the risk of accidental extubation.

Child↗
PubMed1996

Growth hormone stimulates tyrosine phosphorylation of JAK2 and STAT5, but not insulin receptor substrate-1 or SHC proteins in liver and skeletal muscle of normal rats in vivo.

GH has been shown to stimulate tyrosine phosphorylation of JAK2, several STAT proteins, insulin receptor substrate-1 (IRS-1), and SHC proteins in cultured cells. The goal of this study was to determine GH effects on protein tyrosine phosphorylation in liver and skeletal muscle of normal rats in vivo. Nonfasted male Sprague-Dawley rats (225-250 g) were injected with GH iv, and tissues were obtained after 5, 15, 30, or 60 min. At a maximally effective GH dose (1.5 mg/kg body weight), phosphotyrosine antibody immunoblots demonstrated marked stimulation of the tyrosine phosphorylation of JAK2 (maximal at 5 min) and a 95,000 Mr protein (maximal at 15 min) in both liver and skeletal muscle. The 95,000 Mr protein was recognized and immunodepleted by STAT5 antibody, but not by other STAT protein antibodies. Although basal tyrosine phosphorylation of IRS-1 and SHC was evident, GH did not stimulate tyrosine phosphorylation of either of these proteins in liver or skeletal muscle. In conclusion, GH stimulates the tyrosine phosphorylation of JAK2 and STAT5, but not IRS-1, SHC, or other STAT proteins in liver and skeletal muscle of normal rats. These results differ from findings in cultured cells and support the concept that selectivity for tyrosine kinase substrates is an important determinant of postreceptor signaling specificity in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Type II collagen-induced arthritis in the diabetic-resistant biobreeding rat: inflammatory and histopathological features of joint pathology and effects of antiinflammatory and antirheumatic drugs on this chronic arthritic process.

Diabetic-resistant (DR) BioBreeding (BB) rats developed an erosive hind paw arthritis when immunized with an emulsion of bovine type II collagen (CII) and incomplete Freund's adjuvant. Macroscopic clinical evidence of type II collagen-induced arthritis (CIA) first appeared as periarticular erythema and edema in the hind paws between days 9 and 10 postimmunization with CII. The incidence of CIA was 100% by day 11 in the CII-challenged rats; and CIA severity progressed over a 28-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathology of CIA included an hyperplastic synovium that invaded and eroded articular cartilage at the joint margins, and subchondral bone resorption associated with bone-derived, multinucleated cell-containing granulomatous lesions in the rat hind paw. The corticosteroid, methylprednisolone (medrol), and the nonsteroidal antiinflammatory drug, flurbiprofen (Ansaid), administered at 2 mg/kg (p.o.), suppressed the clinical signs of CIA, and caused 79 to 83% inhibition of hind paw inflammation. However, methylprednisolone, but not flurbiprofen, inhibited the joint pathology in CIA. The antirheumatic drugs, cyclophosphamide (cytoxan, 5 mg/kg, p.o.) and cyclosporin A (CsA, 25 mg/kg, p.o.) suppressed the cartilage erosion in inflamed rat joints, and exerted marked inhibition (89-100%) of hind paw swelling. Methotrexate (0.15 mg/kg, p.o.) treatment reduced hind paw swelling (48%), whereas azathioprine, D-penicillamine (DP) and the oral gold preparation, auranofin, were inactive. Anti-CII antibody titers were completely suppressed by cyclosporin A and cytoxan. Radiographic evidence of protection from bone resorption, osteophyte formation and soft tissue swelling was apparent in the tibiotarsal joints of cytoxan, cyclosporin A, methylprednisolone and methotrexate-treated rat.

Adrenal Cortex Hormones↗
PubMed1996

U-73122: a potent inhibitor of human polymorphonuclear neutrophil adhesion on biological surfaces and adhesion-related effector functions.

We have reported that U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione) an inhibitor of phospholipase C-dependent processes in human polymorphonuclear neutrophils (PMN) and platelets, potently suppresses the responsiveness of suspended PMN and platelets to receptor agonists. We demonstrate here that U-73122 caused a concentration-dependent (10-800 nM) inhibition of N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor-alpha (TNF alpha), interleukin-8 and phorbol myristate acetate (PMA)-triggered PMN adhesion on fibronectin, fetal bovine serum or keyhole limpet hemocyanincoated microtiter plates. U-73122 also inhibited PMN adherence to and transmigration through TNF-alpha-activated endothelium (IC50 < 50 nM). Further, U-73122 suppressed interleukin-8, N-formylmethionyl-leucyl-phenylalanine and PMA-stimulated up-regulation of the beta 2-integrin, Mac-1 (CD11b/CD18), on the PMN surface (IC50 < 1.3 microM). U-73122 also caused a time-(15-120 min) and concentration-dependent inhibition (IC50 = 25-100 nM) of the N-formyl-methionyl-leucyl-phenylalanine-, TNF alpha- and PMA-elicited adhesion-dependent, oxidative burst, measured as hydrogen peroxide (H2O2) production, in PMN. The CD18-dependent extracellular release of lactoferrin from PMN activated with these stimuli was also suppressed by U-73122. U-73343 (1-[6-[[17 beta-3- methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidine dione), a close analog of U-73122, did not affect PMN responsiveness.

Animals↗
PubMed1996

Visually debilitating pterygium: surgical and contact lens treatment.

PURPOSE: We present the management of a patient with large pterygia complicated by irregular astigmatism and corneal opacities. Visual rehabilitation required both surgical excision and contact lens fitting. METHODS: We examined a 30-year-old man with hand motion vision from a large pterygium overgrowing his right cornea. Histopathology was consistent with pterygium. During the first few postoperative weeks, his uncorrected visual acuity improved to 20/60, and manifest refraction yielded no further improvement. In the subsequent months, there were increasing anterior stromal corneal opacities, and the refraction became hyperopic to a variable degree. RESULTS: Best corrected visual acuity was 20/70-20/100. Axial length was 22.64 +/- 0.07 mm. Computerized corneal topography 6 months postoperative was similar to the preoperative topography and revealed irregular and asymmetric astigmatism, with marked variation of the central corneal dioptric power. Slit lamp biomicroscopy suggested that the corneal opacities were responsible for the patient's decreased acuity; however, contact lens fitting provided 20/30 vision with a rigid gas permeable contact lens. CONCLUSIONS: The improved vision with contact lens therapy strongly suggested that the irregular and asymmetric astigmatism were more visually significant than the corneal opacities.

Adult↗