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Biomedical subjects

L A Wilson

Publications and source records attributed to L A Wilson.

At least 55 records · Page 3Linked to original sources

Analysis of envelope glycoprotein-specific antibodies from SIV-infected and gp110-immunized monkeys in ACC and ADCC assays.

Sera collected from SIV-infected or recombinant glycoprotein-immunized monkeys were characterized for antibodies participating in antibody-complement-mediated cytolysis (ACC) and antibody-dependent cellular cytolysis (ADCC) in terms of their IgG subclass and epitope specificity. In a competitive inhibition ELISA, gp110-specific antibody reactivity with nondenatured rgp110 was blocked completely by soluble homologous rgp110 and partially inhibited by heterologous rgp110, suggesting cross-reactivity between viral strains. However, only partial inhibition was observed with denatured recombinant gp140 (rgp140) in selected monkeys, indicating that the majority of gp110-specific antibodies recognized conformational epitopes. ACC activity against recombinant vaccinia-infected, envelope-expressing targets was found in sera from both infected and immunized monkeys, whereas ADCC activity was observed only in sera from infected monkeys. ACC was blocked with denatured rgp140 as well as nondenatured rgp110, indicating that ACC-mediating antibodies recognized mainly linear epitopes. In contrast, rgp140 did not compete as effectively as rgp110 in the ADCC assay, indicating that the majority of ADCC antibodies recognized conformational epitopes. Competitive inhibition using three peptide fragments of gp110 indicated that epitopes recognized by ACC antibodies lie within amino acid residues 214-471, a region that spans V3, whereas ADCC-reactive epitopes lie between amino acid residues 52 and 214 at the N-terminal end of gp110. Column chromatography of rhesus IgG resulted in three subclass-enriched fractions, designated IgG-I, IgG-II, and IgG-III. IgG-I, but not IgG-II or IgG-III, from both infected and immunized monkeys mediated ACC, whereas IgG-I and IgG-II from infected monkeys mediated ADCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurobehavioral and psychosocial functioning of children with opsoclonus-myoclonus syndrome.

Childhood opsoclonus-myoclonus syndrome (OMS) is a movement disorder which typically strikes children in the early preschool years, seriously affecting intellectual, social-emotional and general adaptive development. This series of 13 cases with well-documented neurological histories, aged 1.7 to 16.3 years, provides an initial systematic evaluation of these children's neuropsychological, psychosocial and adaptive status. As expected, children with OMS had significantly reduced intelligence and severe speech and motor output problems; however, most of them also demonstrated a range of preserved neurocognitive abilities and impressive goal-directedness and communicative effort. Psychosocial problems included mild behavioral impairment on the Achenbach Child Behavior Checklist, and severe adaptive limitations on the Vineland Adaptive Behavior Scales despite relatively strong social skills. Developmental factors and likelihood of subcortical localization are discussed, and practical guidelines are provided for behavioral and educational management of these children.

Adolescent↗

Phototherapeutic keratectomy for the treatment of nodular subepithelial corneal scars in patients with keratoconus who are contact lens intolerant.

The management of keratoconus with contact lenses may be complicated by punctate epithelial keratopathy, epithelial breakdown, and nodular, raised subepithelial scars. We report four consecutive cases of contact lens intolerance due to pain in patients with keratoconus and raised, nodular scars. Excimer laser phototherapeutic keratectomy (PTK) was used to treat all patients. Follow-up ranged from 7 to 14 months (mean: 10 months). All patients resumed rigid gas permeable (RGP) contact lens wear 2 to 4 weeks after surgery. Visual acuities ranged from 20/40 to 20/70 before surgery and improved to 20/25 or better in all patients postoperatively. PTK flattened the central cornea by an average of 5.43 D (range: 1.13-10.19 D); and refractive cylinder was reduced an average of 4.00 D (range: 3.25-5.25 D). We conclude that PTK may delay or avoid penetrating keratoplasty in selected patients with keratoconus who are contact lens intolerant due to nodular subepithelial scars.

Cicatrix↗

Resistance of adhered bacteria to rigid gas permeable contact lens solutions.

We examined eight conditioning or disinfecting solutions recommended for use with rigid gas permeable (RGP) or hard contact lenses for their efficacy against planktonic and attached cells of bacteria and Candida albicans. Most solutions, particularly those containing phenylmercuric nitrate and polyaminopropyl biguanide, gave marked inhibition (99.99% reduction within 4 hours) of planktonic cells of bacteria. Planktonic cells of Serratia marcescens and C. albicans survived in certain solutions containing chlorhexidine and benzalkonium chloride. In contrast, cells of all test microorganisms adhered to wells of polyethylene contact lens cases showed various degrees of survival after 4, 6, and 12 hours of exposure to most contact lens solutions. Drying of the lens case with adhered cells for 10 hours prior to addition of the lens solution usually reduced the incidence of recovery. Studies demonstrated that biofilms developed in cases with solutions of low and high efficacy. The enhanced resistance of adhered cells requires the periodic disinfection or replacement of lens cases used with RGP lenses.

Bacteria↗

Complications of hexagonal keratotomy.

We examined 15 eyes of ten patients with complications of hexagonal keratotomy, which included glare, photophobia, polyopia, fluctuation in vision, overcorrection, irregular astigmatism, corneal edema, corneal perforation, bacterial keratitis, cataract, and endophthalmitis. Wound healing abnormalities and anterior displacement of the central cornea adjacent to the incisions were common. Eight eyes lost best-corrected visual acuity of two or more Snellen lines. Three eyes required penetrating keratoplasty for visual rehabilitation. Histologic analysis of two of these corneas disclosed variations in wound depth and abnormalities of wound configuration, including considerable wound gaping. Hexagonal keratotomy appears to be an unpredictable, unsafe surgical procedure with a high complication rate, and it should be abandoned until well-controlled experimental trials establish its safety and efficacy.

Adult↗

Treatment of bleb infection after glaucoma surgery.

OBJECTIVE: To assess the history, clinical course, and response to treatment of 14 patients with a bleb infection (blebitis) following glaucoma surgery. DESIGN: Retrospective study. SETTING: A university referral center in Atlanta, Ga. PATIENTS: Fourteen patients developed a bleb infection that ranged from 1 month to 22 years after glaucoma surgery. Infections were characterized by pain, a whitened bleb surrounded by intense conjunctival injection, marked anterior chamber reaction (hypopyon in six eyes), and a clear vitreous. Before infection, most blebs were described as thin. The results of Seidel's test were positive in six patients, and most patients had a low intraocular pressure without the use of any glaucoma medication. INTERVENTION: Treatment consisted of hospitalization, intravenous antibiotic therapy, and hourly topical fortified cefazolin sodium and gentamicin sulfate. RESULTS: The visual acuity in most patients improved to the level before the bleb infection, with only three eyes losing 2 or more lines of vision. CONCLUSIONS: Bleb infection without vitreous involvement (blebitis) may be a precursor of endophthalmitis. With aggressive treatment, bleb infection appears to have a much better prognosis for visual recovery than endophthalmitis.

Adolescent↗

Experimental regeneration in canine muscular dystrophy--2. Expression of myosin heavy chain isoforms.

The sequential expression of neonatal, fast and slow myosin heavy chain isoforms was examined during the regeneration of normal and dystrophic dog muscle from 1 to 56 days, following necrosis induced by the venom of Notechis scutatis, to assess the regenerative potential of dystrophic muscle. Regeneration was equally rapid in normal and dystrophic dogs but morphological and immunocytochemical abnormalities were more apparent in the dystrophic fibres. New myotubes were formed by 3 days, and by 4 days all myosin isoforms were expressed. Neonatal myosin persisted in normal dogs after morphological restoration of the muscle and after dystrophin and beta-spectrin expression had returned to normal. Neonatal myosin was considerably reduced by 21 days in normal dogs, but persisted beyond 28 days in dystrophic dogs, suggesting a delay in maturation. At 42 and 56 days, dystrophic dogs showed a population of small fibres expressing neonatal myosin, which may represent a second cycle of degeneration and regeneration. The reciprocal pattern of fast and slow myosin was not fully restored in normal or dystrophic regenerating muscle, and co-expression persisted. Thus, dystrophic muscle retains its potential to regenerate, but maturation is slower than normal. The persistent co-expression of isoforms has implications for the long-term function of fibres formed after myoblast therapy, but the results imply that a stable state can be achieved if dystrophin expression is restored by gene or myoblast transfer therapy.

Animals↗

Immune responses induced by prototype vaccines for AIDS in rhesus monkeys.

A battery of assay systems was used to profile both humoral and cell-mediated immune responses induced by immunization with candidate vaccines consisting of recombinant simian immunodeficiency virus (SIV) glycoproteins rgp110 (nondenatured) with SAF-M adjuvant (gp110 + SAF-M) or rgp140 (denatured) with Freund's adjuvant (gp140 + FA). All of the monkeys became infected after intravenous challenge. However, 16 days following infection, viral antigenemia was reduced in both groups of vaccinates compared to controls. After 23 days antigenemia in the gp110 + SAF-M group remained at the same level as on day 16, whereas antigenemia in the gp140 + FA group was significantly reduced further than the level observed on day 16. Both vaccines induced blastogenic responses in PBMC cultures stimulated with rgp140, which decreased after repeated immunizations. Both vaccines induced high ELISA titers of IgG antibody against rgp140 that were equivalent to the titers in asymptomatic long-term survivors (LTSs). gp110 +/- SAF-M induced high titers of neutralizing antibody. In contrast, gp140 + FA failed to induce neutralizing antibody, suggesting that the natural conformation of the antigen may be essential for the induction of neutralizing antibody. High titers of antibodies capable of complement-mediated cytolysis (ACC) were induced by gp110 + SAF-M, whereas minimal ACC antibodies were induced by gp140 + FA. In spite of high titers of antibodies by ELISA, neither gp110 + SAF-M nor gp140 + FA vaccines induced detectable levels of antibody capable of antibody dependent cell-mediated cytolysis (ADCC). Detectable amounts of MHC class I-restricted, CD8+ cytotoxic T lymphocytes (CTLs) were not induced in immunized monkeys before challenge. After challenge and infection, antibody responses to glycoprotein (detected by ELISA and ACC) as well as glycoprotein-specific CTLs were induced in gp140 + FA vaccinates at levels higher than in nonimmunized control animals, indicating a priming effect by gp140 + FA immunization. No priming effect for ADCC antibody induction was observed in monkeys vaccinated with either gp110 + SAF-M or gp140 + FA. Rhesus monkey groups immunized with two different SIV envelope vaccines differed regarding potentially protective humoral and cell-mediated immune responses. The physical state of the immunogens, the type of adjuvant used, and/or the immunization protocol apparently affected these responses in both a qualitative and quantitative manner.

AIDS Vaccines↗

Expression of utrophin (dystrophin-related protein) during regeneration and maturation of skeletal muscle in canine X-linked muscular dystrophy.

The regulation of utrophin, the autosomal homologue of dystrophin, has been studied in the canine X-linked model of Duchenne muscular dystrophy. Dystrophic muscle has been shown to exhibit abnormal sarcolemmal expression of utrophin, in addition to the normal expression at the neuromuscular junction, in peripheral nerves, vascular tissues and regenerating fibres. To establish whether this abnormal presence of utrophin in dystrophic muscle is a consequence of continued expression following regeneration, or is attributable to a disease related up-regulation, the expression of utrophin was compared immunocytochemically with that of dystrophin, beta-spectrin and neonatal myosin in regenerating normal and dystrophic canine muscle, following necrosis induced by the injection of venom from the snake Notechis iscutatis. In normal regenerating muscle, sarcolemmal utrophin and dystrophin were detected concomitantly from 2-3 d post-injection, prior to the expression of beta-spectrin. Down-regulation of utrophin was apparent in some fibres from 7 d, and it was no longer present on the extra-junctional sarcolemma by 14 d. Neonatal myosin was still present in all fibres at this stage, but dystrophin and beta-spectrin had been fully restored. In dystrophic regenerating muscle, down-regulation of utrophin occurred from 7 d, although it persisted on some fibres until 28 d, longer than in normal muscle. At 42 d, however, utrophin in dystrophic muscle was only detected in a population of small fibres thought to represent a second cycle of regeneration, with no immunolabelling of mature fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Variation among inbred and linecross mice in response to fescue toxicosis.

Variation in response to fescue toxicosis was examined in inbred and linecross mice. In Exp. 1, exposure to a 50% endophyte-infected tall fescue diet (E+) reduced ADG of males from six inbred lines, but ADG of males from one line was modestly higher on E+. Lines differed (P < .01) for reproductive organ weight, but the diet x line interaction was not significant. In Exp. 2, an apparently susceptible (C57) and an apparently resistant line (FVB) were mated to produce inbred and linecross offspring. The reduction in weight gain caused by the E+ diet did not differ significantly among the genetic groups. In Exp. 3, C57 and C57 backcrosses had smaller reductions in ADG during E+ vs control feeding periods than FVB and FVB backcrosses (P < .10). In Exp. 4, the E+ diet reduced litter size of mates of C57 males by one pup, whereas litter size of mates of FVB males was four pups larger (interaction P = .07). Neither diet, line, nor their interaction affected male reproductive organ weights or tissue proportions in testis cross-sections. In Exp. 5, the E+ diet did not affect weight gain of C57 or FVB males, but effects of the E+ diet on litter size of mates were similar to those in Exp. 4. Percentage of abnormal sperm was increased in C57 males on the E+ diet but decreased in FVB males (Exp. 5). Differences among inbred lines in susceptibility to fescue toxicosis may depend on severity of the challenge and life cycle stage when the challenge is imposed.

Analysis of Variance↗

Pneumococcal endophthalmitis associated with nasolacrimal obstruction.

Pneumococcal endophthalmitis can be a devastating postoperative infection after cataract extraction or penetrating keratoplasty. Streptococcus pneumoniae was isolated as the causative agent in three of the 124 patients (2%) who were treated for endophthalmitis at our institution between 1984 and 1990. Two of the three patients lost light perception in the affected eye. All three patients had previously unrecognized or untreated chronic nasolacrimal obstruction of varying causes. We studied the role of pneumococcal lacrimal conjunctivitis in the pathogenesis of the postoperative pneumococcal endophthalmitis in these patients.

Aged↗

Pathologic features and immunofluorescent antibody demonstration of ocular microsporidiosis (Encephalitozoon hellem) in seven patients with acquired immunodeficiency syndrome.

We studied the clinicopathologic features of seven patients with acquired immunodeficiency syndrome (AIDS) and ocular microsporidiosis. All patients had decreased levels of CD4-positive cells (mean, 26/ml3) and ocular symptoms; five had bilateral punctate epithelial keratopathy, one had intermittent red eyes with conjunctivitis, and one had red eyes only. Light and electron microscopy of corneal and conjunctival biopsy and cytologic specimens and intact globes disclosed microsporidia belonging to the genus Encephalitozoon. Because E. cuniculi and E. hellem, the two species of the Encephalitozoon genus, are morphologically identical, an immunofluorescent antibody technique was used for species identification. In all seven patients, the agent was identified as E. hellem. Pathologic examination of globes obtained after autopsy disclosed E. hellem infection to be restricted to the corneal and conjunctival epithelium. We studied methods for the routine diagnosis of ocular microsporidiosis in patients with AIDS, including the role of immunofluorescent antibody staining.

AIDS-Related Opportunistic Infections↗

Treatment of microsporidial keratoconjunctivitis with topical fumagillin.

Encephalitozoon hellem is a newly described cause of microsporidial keratoconjunctivitis, occurring chiefly in patients with significantly diminished CD4+ T-lymphocyte levels. This disorder is symptomatically disabling and generally recalcitrant to topical antimicrobial therapy. Two homosexual men with E. hellem keratoconjunctivitis diagnosed by Gram stain, transmission electron microscopy, and specific indirect immunofluorescent assay were treated with topical fumagillin (Fumidil B). Both patients had marked symptomatic improvement with reduction of clinical findings. Symptoms and signs recurred with temporary discontinuation of the drug. Both patients, however, remained symptom-free on maintenance levels of topical fumagillin with no evidence of toxic side effects.

AIDS-Related Opportunistic Infections↗

Bacterial and fungal endophthalmitis after penetrating keratoplasty.

We analyzed 1,010 consecutive penetrating keratoplasties to determine the incidence of postoperative endophthalmitis, the frequency of positive donor rim cultures, and whether a correlation between these two factors exists. There were three cases of bacterial endophthalmitis, all caused by streptococci, and one case of Candida albicans endophthalmitis. In all cases except one case of streptococcal endophthalmitis, the same organism was cultured from the donor rim. We cultured 138 organisms from 128 of 932 donor rims (14%). A remarkable percentage of gram-positive organisms were resistant to gentamicin, the only antibiotic contained in corneal storage media. On the basis of our data and previously published data, we believe that donor material is frequently the source of microorganisms in endophthalmitis after penetrating keratoplasty.

Adult↗

Comparative efficacy of amphotericin B, clotrimazole and itraconazole against Aspergillus spp. An in vitro study.

The susceptibilities of two isolates of Aspergillus flavus, one from a human case of recalcitrant mycotic keratitis, and an environmental isolate of A. fumigatus, to itraconazole, clotrimazole and amphotericin B were measured. Observations of macroscopic growth and microscopic evaluations of conidia germination both indicated that the two isolates of A. flavus were markedly more resistant to amphotericin B than to itraconazole and clotrimazole. Itraconazole was more effective than clotrimazole for all isolates. Our in vitro susceptibility results suggest the use of itraconazole should be a primary consideration in the treatment of Aspergillus keratitis.

Amphotericin B↗

Comparison of vasovasostomy techniques in rats utilizing conventional microsurgical suture, carbon dioxide laser, and fibrin tissue adhesives.

An evaluation of vas reanastomoses in rats comparing suture only, carbon dioxide (CO2) laser-assisted, and fibrin-based tissue adhesive was performed in our laboratory. A cohort of 60 known fertile male Sprague Dawley rats initially underwent lower midline abdominal exploration and transection of their vas deferens bilaterally, followed by immediate microsurgical vasovasostomy by one of the three experimental methods. All groups initially had the severed vasa ends coapted by two or three transmural (mucosa through serosa) sutures of 10-0 nylon under an operating microscope. The conventionally sutured group had an additional four to six nylon 10-0 sutures placed externally in the serosa only to complete the anastomosis. The CO2 laser-assisted group underwent laser welding with denaturation of the serosa to seal the anastomosis. A fibrin-based tissue adhesive, produced by combining human cryoprecipitate and thrombin, was placed topically over the coapted vas ends to seal the anastomosis in the third group. Postoperative evaluation revealed similarities among the three surgical groups with the fibrin-based tissue adhesive group resulting in the highest patency rate (89%) and pregnancy rate (85%) as well as the lowest granulation rate (18%) and shortest operative time (27 minutes). The laser-assisted group resulted in the lowest pregnancy rate (68%), while the sewn anastomosis group had the lowest patency rate (76%). Both laser-assisted and conventionally sewn vasectomy reversals required significantly longer operative time (39 and 46 minutes, respectively) compared with the fibrin-based tissue adhesive-assisted procedures (p < 0.01). This study provides evidence that alternative microsurgical techniques may be utilized to perform uncomplicated, expeditious, and successful vasectomy reversals.

Animals↗

Inner-city pharmacies: can they meet the OBRA '90 mandates?

Visits were made to 21 pharmacies in two poor Chicago neighborhoods as one component of the University of Illinois at Chicago's commitment to help improve health care delivery, ensure that pharmacy services are not overlooked in local health reform efforts, and understand the implications of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90). Pharmacists report that Medicaid reimbursement policies result in: (1) prescribing patterns that have no consistent therapeutic or economic rationale; (2) dispensing of expensive drugs, some of which are then sold on the street or to other pharmacies; and (3) dispensing of unnecessary and often expensive legend drugs when other legend drugs and generics or over-the-counter products would perform just as well. On the positive side, 76% of the pharmacies possess computerized patient-profile systems, and 72% maintain background information on their prescribers. These results suggest that OBRA '90's mandates should contribute toward improving the Medicaid program, but that implementation is likely to be difficult and uneven.

Chicago↗