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Biomedical subjects

R S Anderson

Publications and source records attributed to R S Anderson.

At least 55 records · Page 3Linked to original sources

Selenite nuclear cataractogenesis: a scanning electron microscope study.

The sequential changes during selenite nuclear cataractogenesis were examined with a scanning electron microscope (SEM) and correlated with slit lamp observations. A posterior opacity, visible with the slit lamp 1-2 days after injection of sodium selenite, was found to consist of masses of vacuoles in the superficial posterior cortex by SEM. 2-3 days post injection, a biomicroscopic refractile ring around the nucleus was represented by SEM abnormalities suggesting membrane damage and possible loss of cytosol in the perinuclear region. All normal structure in this region was lost by 5 days after injection when the central nucleus had become opaque. SEM also showed evidence for damage in areas which were still clear by slit lamp examination. Changes, characteristic of aging, were found near selenite induced damage in peripheral (younger) fibers.

Animals↗

Review of selenite cataract.

Recent advances in understanding the mechanism of selenite cataract have resulted from locating the cleavage sites on proteolyzed beta-crystallins from the cataract, mimicking the insolubilization of crystallins found in the cataract in an in vitro system, studying cataract produced in lenses cultured in selenite, and permanently or temporarily reducing the rate formation of selenite cataract by use of various inhibitors. The present review discusses the selenite cataract as a useful model for understanding the role calcium-induced proteolysis in cataract formation.

Amino Acid Sequence↗

Calpain in rat cornea.

This study was conducted to provide a description of calpain proteolytic enzyme (EC 3.4.22.17) in normal rat cornea and to document immunohistochemical changes in calpain distribution during maturation. Corneal soluble proteins were fractionated by diethylaminoethyl chromatography on high-performance liquid chromatography. Fractions were analyzed for calpain by enzyme-linked immunosorbent assay, immunoblotting, and caseinolytic enzyme activity with fluorescein isothiocyanate-labeled casein. Calpain II from the soluble fraction of 2-week-old and 3-month-old rat corneas eluted at a similar NaCl concentration (220-240 mmol/l) as calpain II from other tissues, was inhibited by E64, contained an 80-kilodalton subunit in immunoblots, and was present at specific activity of 473 units per gram of protein in 3-month-old rats and 801 units per gram of protein in 2-week-old rats. Calpain antigen also was present in the ethylenediaminetetraacetic acid and EGTA washed insoluble fraction of cornea. Calpain was found (by immunohistochemical analysis) in all layers of the epithelium but not in the stroma. Enzyme-linked immunsorbent assay, immunoblots, and immunohistochemical analysis showed that calpain in the whole cornea did not change with corneal maturation. It was hypothesized that calpain in the cornea may be involved in the turnover of epithelial cells during normal maturation.

Animals↗

Effects of clinical recycling on mechanical properties of nickel-titanium alloy wires.

The purpose of this investigation was to determine the effects of clinical recycling on the load-deflection characteristics and the surface topography of nickel-titanium alloy wires. Thirty wires each of Nitinol and NiTi were subjected to a three-point bending test in an as-received condition (T0) and after clinical exposure of one cycle (T1) and two cycles (T2). Ten wires made up the sample at each of these time points. One cycle was defined as 8 weeks, plus or minus 1 week, of clinical use. Wires undergoing two recycles were cold sterilized after their first clinical exposure. Statistical analyses were done by one-factor repeated measures ANOVA and Scheffe F test. Recycling produced significant changes in both the loading and unloading characteristics of NiTi wires, but only with the loading forces associated with nitinol wires. Representative scanning electron micrographs demonstrated increased pitting of both nitinol and NiTi wires. Several areas were also observed to be smoothened on nitinol wires and scored on NiTi wires.

Alloys↗

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children.

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.

Antibodies, Bacterial↗

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.

This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.

Child↗

2'-Deoxy-6-thioguanosine 5'-triphosphate as a substrate for purified human DNA polymerases and calf thymus terminal deoxynucleotidyltransferase in vitro.

2'-Deoxy-6-thioguanosine 5'-triphosphate (S6dGTP), a metabolite of the antileukemia agent 6-thioguanine, was evaluated as a substrate for purified human DNA polymerases. Using bacteriophage M13 single-strand DNA as a template, S6dGTP substituted efficiently for dGTP and stimulated DNA synthesis in reactions without dGTP, with DNA polymerases alpha, delta, and gamma from the human leukemia cell line K562. The apparent Km values for dGTP and S6dGTP were very similar, i.e., 1.2 microM each for polymerase alpha, 2.8 and 3.6 microM, respectively, for polymerase delta, and 0.8 microM each for polymerase gamma; however, the relative Vmax values for the modified nucleotide were 25-50% lower than those of the corresponding natural substrate. Using a highly sensitive electrophoretic assay of chain elongation across M13mp9 (+)-strand DNA by the aforementioned human DNA polymerases, S6dGTP was shown to be incorporated at the 3' end of the nascent growing DNA chain, and the patterns of chain extension with S6dGTP as substrate were identical to those obtained in the presence of dGTP. There were no major differences using S6dGTP in place of dGTP with these DNA polymerases; however, at higher concentrations (1-10 microM) the analog stimulated primer elongation in reactions without dATP, indicating some misincorporation at sites of S6G.T base pairs during DNA synthesis. Using p(dA)12-18 as the initiator for calf thymus terminal deoxynucleotidyltransferase, S6dGTP inhibited the incorporation of all four natural deoxyribonucleoside 5'-triphosphates into the primer, in a competitive manner. The apparent Ki values for the analog were 6-20 times lower than the Km values for the four endogenous substrates. As a substrate, S6dGTP was added to the 3'-hydroxyl termini of primer, although tailing efficiency with the analog was lower than that in the presence of the natural substrate. These findings indicate that S6dGTP is a relatively good substrate for several mammalian DNA polymerases, including terminal deoxynucleotidyltransferase.

Animals↗

A Vh region synthetic peptide induces antibodies which bind native immunoglobulins and augment an immune response to antigen.

The BALB/c myeloma protein ABPC48 (A48) binds the polysaccharide bacterial levan; its Vh is encoded by a gene derived from the VhX24 family. This antibody has been shown to cross-react idiotypically with the phosphorylcholine-binding BALB/c myeloma protein MOPC167 whose Vh shares homology with A48 from residues 32-44. We have synthesized a peptide corresponding to residues 32-44 of the Vh encoded by a germline gene of the VhX24 family. Anti-peptide antisera from rabbits were purified by affinity chromatography with peptide or intact antibody. Several myeloma proteins and monoclonal antibodies with varying degrees of homology to the peptide have been analyzed for reactivity with purified rabbit antibodies in solid-phase RIA. We observed that the specificities within rabbit antisera are heterogeneous, and that purification with antibody versus peptide yields preparations containing different specificities, albeit demonstrably peptide-related. We also show that injection of mice at birth with small amounts of purified rabbit antibodies can affect the magnitude of the response to bacterial levan and the expression of A48 idiotopes in that response.

Adjuvants, Immunologic↗

Comparative effects of inhaled silica or synthetic graphite dusts on rat alveolar cells.

Alterations in population profiles, morphology, and phagocytic activity of lung cells following in vivo exposure of Fischer 344 rats to a single dose of silica, were compared to similar changes following exposure to synthetic graphite. The effect of silica exposure on alveolar macrophage mycocidal activity was also measured. Acute exposure by inhalation to 100 mg/m3 silica dust produced persistent pulmonary inflammation, as well as long-term changes in pulmonary alveolar macrophages (AM) typical of macrophage activation. Both particles were steadily cleared from the lungs; AM from the silica study, as well as from the 100 and 500 mg/m3 graphite studies, contained ingested particles throughout the entire 3 month experimental period. Lavaged pulmonary cells showed no reduction in viability as a result of exposure to either of the dusts. After silica inhalation, the following changes were observed constantly in bronchopulmonary lavage cell samples: increased numbers of polymorphonuclear leukocytes (PMN), hypersegmented PMN, binucleated AM, increased AM phagocytic indices and capacities, and increased mycocidal activity. Following inhalation of 1-100 mg/m3 synthetic graphite the above-mentioned effects were not seen. Exposure to 500 mg/m3 graphite produced transient inflammation and AM activation for about 24-48 hr.

Air Pollutants↗

Responses of rat alveolar macrophages to inhaled brass powder.

The effects of a single acute exposure to inhaled brass dust on rat pulmonary alveolar macrophages (PAM) were determined. Pulmonary alveolar macrophages lavaged from the lungs of these experimental animals showed both morphological and functional abnormalities. Exposure to brass dust caused a rapid, transient inflammatory response, producing an influx of polymorphonuclear leukocytes into the lavage fluid. Binucleation and multinucleation of PAM were sensitive morphological indicators of pulmonary stress that persisted throughout the 14-day course of the experiment. Pulmonary alveolar macrophages from rats exposed to brass dust were phagocytically activated; both the total numbers of test particulates ingested and the phagocytic index were elevated. Chemotaxis, as measured by direct cellular migration in Boyden chambers, was inhibited for 3 days after exposure, but was markedly stimulated from 7 to 14 days. This was interpreted as a possible consequence of a selective release of lymphokines during the course of the inflammatory response. Some of these results, based on in vivo exposure of PAM to inhaled particulates, differ from those derived from in vitro exposure. This points to the fact that it is virtually impossible to duplicate the native chemical microenvironment of PAM in vitro and emphasizes the necessity of bringing about PAM-particle interactions in the intact lung in order to obtain more physiologically relevant data.

Administration, Inhalation↗

Organofluorophosphate-hydrolyzing activity in an estuarine clam, Rangia cuneata.

1. The bivalve Rangia cuneata can enzymatically detoxify the organophosphorus acetylcholinesterase inhibitors DFP and soman. 2. Digestive gland homogenates contained Mazur-type DFPases based on response to Mn2+ ions, and relative rates of DFP: soman hydrolysis. Squid-type DFPase contributed little to the total organophosphate acid (OPA) anhydrase activity of these preparations. 3. The natural substrate(s) and physiological role(s) of OPA anhydrase in R. cuneata has yet to be determined; however, DFPase specific activity was pronounced in the digestive gland, the primary organ involved in bioconcentration and biotransformation of xenobiotics, and in the gills, which are in continuous contact with water-borne chemicals.

Animals↗

Determining risk for chronic otitis media with effusion.

Chronic otitis media with effusion (OME) has been observed in 10 to 20% of children following acute, symptomatic otitis media. To determine factors that place children at increased risk of chronic OME, we conducted a 6-week prospective study of 386 children who had 3 or more recent episodes of otitis media and who had middle ear effusion present for at least 2 weeks. Of these children 23% developed chronic OME (i.e. effusion lasting 8 continuous weeks or more), and 26% developed chronic OME complicated by acute, symptomatic otitis media. Predictors for chronic OME were (1) bilateral OME, (2) duration of effusion for greater than 2 weeks at enrollment and (3) day care attendance. Children with these 3 factors had twice the risk of developing chronic OME as children lacking all 3 factors. These risk factors can be used to target children for early, aggressive OME therapy.

Child↗