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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 55 records · Page 3Linked to original sources

AcrySof acrylic intraocular lens implantation in children: clinical indications of biocompatibility.

PURPOSE: To assess the clinical biocompatibility of AcrySof (Alcon, Ft Worth, Tex) acrylic intraocular lenses (IOLs) in the highly reactive eyes of infants and children. METHODS: A database of 230 pediatric IOL implantations was queried to allow retrospective review of all eyes implanted with an AcrySof IOL. Eyes implanted with polymethyl methacrylate (PMMA) IOLs were also reviewed and were used as a historical comparison group. Follow-up examinations were conducted by the surgeon on postoperative day 1, day 7, week 4, and week 8 and every 3 months during the first year and every 6 months thereafter. The presence of synechiae, lens deposits, and posterior capsule opacification were noted in the record at each visit. Examination notes were photocopied, and data were extracted from each visit note and entered into a computerized database. RESULTS: One hundred and ten eyes had an AcrySof IOL at an average age of 60.4 months and had an average postoperative follow-up of 64.6 weeks. In comparison, 120 eyes had PMMA IOLs inserted at an average age of 71.9 months with an average postoperative follow-up of 136.9 weeks. IOL cell deposits were seen at the slit lamp in 7 of 110 (6.4%) AcrySof lenses as compared with 26 of 120 (21.75%) PMMA lenses (P =.002). Posterior synechiae were seen in 5 of 110 (4.5%) AcrySof lenses as compared with 23 of 120 (19.2%) PMMA lenses (P =.001). Twenty-two AcrySof-implanted eyes had an intact posterior capsule. Twenty-eight PMMA-implanted eyes had an intact posterior capsule. The YAG laser capsulotomy rate was similar in the 2 groups at 45.4% for AcrySof and 50% for PMMA (P =.973). The average time from surgery to YAG posterior capsulotomy was 18.6 months with an AcrySof lens and 18.3 months with a PMMA lens (P =.951; t test). A total of 60 patients (68%) implanted with AcrySof IOLs were able to cooperate for Snellen visual acuities. Of their 67 eyes, 48 (72%) had a 20/40 or better visual acuity at the last follow-up examination, and 63 eyes (94%) had a 20/100 or better visual acuity. Thirty-five eyes (52%) required amblyopia therapy, and patching continues as needed. CONCLUSIONS: The AcrySof IOL is representative of a new group of foldable IOLs made from flexible hydrophobic acrylic material. The AcrySof IOL appears clinically to be biocompatible when placed in the eyes of children despite the increased tissue reactivity known to occur in young patients.

Acrylic Resins↗

Relationship between placental vascular endothelial growth factor expression and placental/endometrial vascularity in the pig.

We investigated the temporal association between placental vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis and vascular permeability, and changes in placental/endometrial vascularity on selected days throughout gestation in the pig. Placental and endometrial tissues were collected from sows on Days 25 (n = 4), 36 (n =6), 44 (n = 6), 70 (n =5), 90 (n =5 ), and 112 (n = 7) of gestation. Cross sections of the placental/endometrial interface of each conceptus were used to estimate the number of blood vessels per unit area via image analysis and the intensity of VEGF staining via immunohistochemistry. Placental tissues were also collected on these days to evaluate VEGF mRNA expression. Placental VEGF mRNA expression and the numbers of blood vessels per unit area of placental and adjacent endometrial tissue were low and decreasing from Day 25 to Day 44, before increasing (P < 0.05) markedly and progressively through Day 112. These data are consistent with the marked increase in VEGF immunostaining in the chorionic and uterine luminal epithelium from early to late gestation. Further, these increases in placental VEGF mRNA were positively correlated with fetal weight (r = 0.73; P < 0.0001) and placental efficiency (fetal weight/placental weight ratio; r = 0.66, P < 0.0001). These data are consistent with a role for VEGF in increasing the number of blood vessels at the placental endometrial interface, resulting in an increased capacity for nutrient transfer from the maternal to the fetal compartment.

Animals↗

Structural and genetic analyses of O polysaccharide from Actinobacillus actinomycetemcomitans serotype f.

The oral bacterium Actinobacillus actinomycetemcomitans is implicated as a causative agent of localized juvenile periodontitis (LJP). A. actinomycetemcomitans is classified into five serotypes (a to e) corresponding to five structurally and antigenically distinct O polysaccharide (O-PS) components of their respective lipopolysaccharide molecules. Serotype b has been reported to be the dominant serotype isolated from LJP patients. We determined the lipopolysaccharide O-PS structure from A. actinomycetemcomitans CU1000, a strain isolated from a 13-year-old African-American female with LJP which had previously been classified as serotype b. The O-PS of strain CU1000 consisted of a trisaccharide repeating unit composed of L-rhamnose and 2-acetamido-2-deoxy-D-galactose (molar ratio, 2:1) with the structure -->2)-alpha-L-Rhap-(1-3)-2-O-(beta-D-GalpNAc)-alpha-L-Rhap-(1-->* O-PS from strain CU1000 was structurally and antigenically distinct from the O-PS molecules of the five known A. actinomycetemcomitans serotypes. Strain CU1000 was mutagenized with transposon IS903phikan, and three mutants that were deficient in O-PS synthesis were isolated. All three transposon insertions mapped to a single 1-kb region on the chromosome. The DNA sequence of a 13.1-kb region surrounding these transposon insertions contained a cluster of 14 open reading frames that was homologous to gene clusters responsible for the synthesis of A. actinomycetemcomitans serotype b, c, and e O-PS antigens. The CU1000 gene cluster contained two genes that were not present in serotype-specific O-PS antigen clusters of the other five known A. actinomycetemcomitans serotypes. These data indicate that strain CU1000 should be assigned to a new A. actinomycetemcomitans serotype, designated serotype f. A PCR assay using serotype-specific PCR primers showed that 3 out of 20 LJP patients surveyed (15%) harbored A. actinomycetemcomitans strains carrying the serotype f gene cluster. The finding of an A. actinomycetemcomitans serotype showing serological cross-reactivity with anti-serotype b-specific antiserum suggests that a reevaluation of strains previously classified as serotype b may be warranted.

Actinobacillus Infections↗

Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action.

An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult: it influences memory and cognition, decreases the risk and delays the onset of neurological diseases such as Alzheimer's disease, and attenuates the extent of cell death that results from brain injuries such as cerebrovascular stroke and neurotrauma. Thus, estradiol appears to act at two levels: 1) it decreases the risk of disease or injury; and/or 2) it decreases the extent of injury incurred by suppressing the neurotoxic stimulus itself or increasing the resilience of the brain to a given injury. During the past century, the average life span of women has increased dramatically, whereas the time of the menopause has remained essentially constant. Thus, more women will live a larger fraction of their lives in a postmenopausal, hypoestrogenic state than ever before. Clearly, it is critical for us understand the circumstances under which estradiol exerts protective actions and the cellular and molecular mechanisms that underlie these novel, nonreproductive actions.

Animals↗

The impact of the GH-IGF-I axis on gonadotropin secretion: inferences from animal models.

Given the tight, temporal coupling between growth and reproductive development, the idea that a common signal may regulate both adolescent growth and the initiation of puberty has been the focus of much research. Since the rate-limiting step for the onset of puberty is the appropriate hypothalamic secretion of gonadotropin-releasing hormone (GnRH), any factor important for the initiation of puberty must affect GnRH pulsatility. This review examines the hypothesis that GH and/or IGF-I are growth-related signals that regulate the release of GnRH, initiating puberty. By extension, this review also addresses the hypothesis that the GH axis also impacts GnRH and gonadotropin secretion in post-pubertal individuals and, thus, affects the maintenance of fertility in adults. The review examines data from a range of animal models employing a number of different strategies which directly manipulate the activity of either GH or IGF-I. The success of these strategies for producing the desired effects on the GH-IGF-I axis is somewhat variable. Although IGF-I may only play a permissive role in the maintenance of adult fertility, acting at the level of the gonad to increase sensitivity to gonadotropin stimulation, the data indicate that IGF-I is essential for reproductive maturation. However, in addition to its well-documented effects on the gonad, the specific mode of action of IGF-I on the neuroendocrine hypothalamus and GnRH pulsatility remains to be determined. Available evidence suggests that such action by IGF-I may be mediated through neurotransmitter effects on GnRH neurons, changing the availability of metabolic substrates for neuronal activity, or remodeling of synaptic input into GnRH neurons.

Animals↗

The role of altered uterine-embryo synchrony on conceptus growth in the pig.

This study was conducted to determine whether inducing an embryo-uterine asynchrony during the preimplantation period would alter fetal and(or) placental size at term. Yorkshire gilts (n = 24) were checked twice daily for estrus and bred to a Yorkshire boar 24 h after the first exhibition of estrus. Embryos (1 to 4 cells) were flushed from the oviducts of each donor gilt on d 2.5 of gestation and transferred in equal numbers to the oviducts of a recipient gilt on d 1.5, 2.5, or 3.5 of the estrous cycle. Gilts were slaughtered on d 112 of gestation (calculated on the age of the conceptus) and fetal and placental weight, placental surface area, and implantation site lengths were determined. Although litter sizes were similar (9.1+/-0.9), conceptuses transferred to d 3.5 recipients became heavier fetuses (1.44+/-0.05 vs 1.23+/-0.04 kg, P < 0.001), with larger placental surface areas (1,793+/-60 vs 1,459+/-43 cm2, P < 0.01), and longer implantation sites (32.1+/-1.5 vs 24.9+/-0.6 cm, P < 0.001) than those transferred to recipients on d 2.5. These data demonstrate that oviductal transfer of embryos into a reproductive tract that is more advanced by as little as 24 h can result in alterations in placental growth and function during gestation.

Animals↗

Comparative aspects of placental efficiency.

Litter size is often proposed as the trait that could have the greatest impact in improving reproductive efficiency of pigs. Efforts to select directly for increased litter size have generally been unsuccessful and highly variable. As a result, several attempts have been made to identify critical physiological components that control litter size, with the underlying assumption that augmenting these components would improve this important trait. One attempt at improving physiological components has involved the selection of animals for increased uterine capacity, as measured by the number of fetuses or piglets that a female can carry successfully to term. Recent evidence indicates that one critical component of the uterine capacity in pigs is placental efficiency, or the body weight of a piglet divided by the mass of its placenta. It is easy to determine the average placental efficiency in a litter, but variation among conceptuses within a litter for this trait can be substantial, leading to the conclusion that placental efficiency is an individual conceptus trait. It is suggested that the limited success of selection for an increased uterine capacity results, at least in part, from a misguided view that 'uterine capacity' is strictly a maternal trait. Uterine capacity is better defined as the mass of placental tissue that a pregnant female can support to term, and involves phenotypic variation in both the dam and her offspring. This definition of uterine capacity allows maximization of both uterine size and placental efficiency in future attempts to increase litter size in pigs.

Animals↗

Inducible resistance to oxidant stress in the protozoan Leishmania chagasi.

Leishmania sp. protozoa are introduced into a mammalian skin by a sandfly vector, whereupon they encounter increased temperature and toxic oxidants generated during phagocytosis. We studied the effects of 37 degrees C "heat shock" or sublethal menadione, which generates superoxide and hydrogen peroxide, on Leishmania chagasi virulence. Both heat and menadione caused parasites to become more resistant to H(2)O(2)-mediated toxicity. Peroxide resistance was also induced as promastigotes developed in culture from logarithmic to their virulent stationary phase form. Peroxide resistance was not associated with an increase in reduced thiols (trypanothione and glutathione) or increased activity of ornithine decarboxylase, which is rate-limiting in trypanothione synthesis. Membrane lipophosphoglycan increased in size as parasites developed to stationary phase but not after environmental exposures. Instead, parasites underwent a heat shock response upon exposure to heat or sublethal menadione, detected by increased levels of HSP70. Transfection of promastigotes with L. chagasi HSP70 caused a heat-inducible increase in resistance to peroxide, implying it is involved in antioxidant defense. We conclude that leishmania have redundant mechanisms for resisting toxic oxidants. Some are induced during developmental change and others are induced in response to environmental stress.

Animals↗

Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors.

Estradiol has been shown to exert trophic and protective actions in the brain. Our laboratory has shown that in vivo, low physiological levels of estradiol protect the female rat brain against ischemic injury. In the present study, we used organotypic cortical explant cultures to begin to decipher the mechanisms of estradiol's actions. Injury was induced by exposure to kainic acid or potassium cyanide/2-deoxyglucose (KCN/2-DG) for varying lengths of time, and cell death was monitored by LDH release at 2, 6, 12, 24, 48, 72 and 96 h after injury. We found that exposure to 1 mM KCN/2 mM 2-DG for 2 h produced consistent delayed cell death that was detectable by 24 h. The presence of 17beta-estradiol (E2) during the 7 days prior to injury significantly reduced the extent of cell death; whereas, administration of E2 at the time of injury did not protect. The protective effects of estradiol were dose dependent. Low doses of E2 (1, 10, and 30 nM) significantly reduced cell death; however, higher concentrations of E2 (>60 nM) had no protective effect. The observations that low levels of E2 protect against cell death, and that pretreatment is required suggest that the protective actions of estradiol may involve estrogen receptors. Therefore, we examined the ability of 17alpha-estradiol, which does not efficiently activate the estrogen receptor, and the addition of the estrogen receptor antagonist, ICI 182,780, to influence the extent of cell death induced by KCN/2-DG. 17alpha-Estradiol failed to protect, and ICI 182,780 prevented E2 from protecting against cell death. Furthermore, E2 pretreatment is required for more than 24 h to be neuroprotective. Our results clearly show that in cortical explant cultures, estradiol protects cells against ischemic injury, and suggest that these protective actions involve estrogen receptors.

Animals↗

TGF-beta mediates CTLA-4 suppression of cellular immunity in murine kalaazar.

Recent studies indicate important roles for CTLA-4 engagement in T cells, and for TGF-beta production in the immunopathogenesis of murine kalaazar or visceral leishmaniasis, but a functional link between these two pathways in helping intracellular parasite growth is unknown. Here we report that Ag or anti-CD3 activation of splenic CD4+ T cells from visceral leishmaniasis leads to intense CTLA-4-mediated TGF-beta1 production, as assessed either by CTLA-4 blockade or by direct CTLA-4 cross-linkage. Production of TGF-beta1 accounted for the reciprocal regulation of IFN-gamma production by CTLA-4 engagement. Following CD4+ T cell activation, intracellular growth of Leishmania chagasi in cocultured splenic macrophages required both CTLA-4 function and TGF-beta1 secretion. Cross-linkage of CTLA-4 markedly increased L. chagasi replication in cocultures of infected macrophages and activated CD4+ T cells, and parasite growth could be completely blocked with neutralizing anti-TGF-beta1 Ab. Exogenous addition of rTGF-beta1 restored parasite growth in cultures protected from parasitism by CTLA-4 blockade. These results indicate that the negative costimulatory receptor CTLA-4 is critically involved in TGF-beta production and in intracellular parasite replication seen in murine kalaazar.

Abatacept↗

Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease.

The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells. Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production. LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS. These results suggest that local Ag-specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption.

Abatacept↗

Confirmation of confocal microscopy diagnosis of Acanthamoeba keratitis using polymerase chain reaction analysis.

BACKGROUND: Acanthamoeba keratitis has commonly been identified with in vivo confocal microscopy and confirmed with histologic examination of an epithelial biopsy specimen. OBJECTIVE: To determine if Acanthamoeba keratitis can be verified using polymerase chain reaction (PCR) of epithelial biopsy specimens. METHODS: Epithelial specimens from patients with suspected Acanthamoeba keratitis by confocal microscopy were tested for Acanthamoeba with PCR of Acanthamoeba ribosomal DNA. RESULTS: Twenty-four of 31 patients with evidence of Acanthamoeba keratitis were positive for Acanthamoeba on PCR analysis using 3 sets of primers. In 22 cases, the sequence obtained closely matched Acanthamoeba castellanii. CONCLUSIONS: This study demonstrates that PCR analysis of epithelial biopsy specimens can provide definitive verification of the confocal microscopic and histologic identification of Acanthamoeba organisms associated with keratitis. Acanthamoeba keratitis is probably quite common, especially in contact lens wearers, although more than half of the patients in this study did not wear contact lenses.

Acanthamoeba↗

Differential gene expression during elongation in the preimplantation pig embryo.

On day 12-13 of gestation, the preimplantation pig conceptus undergoes a dramatic morphologic change from an approximately 1-cm sphere to a nearly 1-m long thread. This transformation, referred to as elongation, occurs in just 12-24 h. Elongation is primarily the result of trophectodermal cell shape changes, as there is relatively little mitosis during this stage of development. Thus far, descriptions of elongation have been limited to histologic and immunofluorescent studies of cell morphology and gross biochemical evaluations. We hypothesized that the changes in trophectoderm morphology likely involves significant changes in gene expression. Therefore, we used RNA arbitrarily primed-PCR (RAP-PCR) to characterize potential differential gene expression by trophectodermal cells during pig conceptus elongation. We found that the porcine heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 was shown to be differentially expressed by trophectodermal cells during elongation. We suggest that regulated alternative splicing may contribute to the morphogenetic process of elongation. genesis 26:9-14, 2000. Published 2000 Wiley-Liss, Inc.

Alternative Splicing↗

BCG expressing LCR1 of Leishmania chagasi induces protective immunity in susceptible mice.

Cellular immune responses are required for protective immunity against Leishmania chagasi. Immunization strategies using live intracellular bacteria (e.g., bacille-Calmette Guerin strain of Mycobacterium bovis) expressing recombinant antigens can induce cellular immune responses to these antigens. Previous studies demonstrated that the L. chagasi antigen LCR1 stimulates IFN-gamma production from T cells of infected BALB/c mice, and immunization with recombinant LCR1 partially protects against L. chagasi infection. To determine whether live bacteria could enhance the immunization potential of LCR1, we engineered BCG expressing LCR1 (BCG-LCR1). Subcutaneous immunization with BCG-LCR1, but not with BCG containing plasmid only (BCG-pMV261), elicited better protective immunity against L. chagasi infection than LCR1 protein alone. BCG-LCR1 administered intraperitoneally did not protect. Splenocytes from mice immunized s.c. with either BCG-LCR1 or BCG-pMV261 and then infected with L. chagasi promastigotes had increased antigen-induced IFN-gamma and reduced IL-10 production compared to splenocytes of control mice. We propose that BCG-LCR1 promotes a Th1-type protective immune response, and it may be a useful component of a Leishmania vaccine.

Animals↗

Bilateral intraocular lens implantation in the pediatric population.

PURPOSE: To evaluate bilateral intraocular lens (IOL) implantation in children. DESIGN: Retrospective, noncomparative case series PARTICIPANTS: Thirty pediatric patients with bilateral IOL implants at one institution with more than 6 months of followup. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Complications, visual acuity, axial length, and refractive changes were recorded. RESULTS: Thirty patients (60 eyes) had an average followup of 31 months (range, 7-69 months). Average age at implantation was 73 months (range, 12 days-13 years). At last followup, 91% of eyes had vision better than or equal to 20/40. Patients in the youngest age group (<2 years) demonstrated the most rapid refractive and axial length changes, and there were progressively smaller changes in older age groups. Only four patients had acuity differences between eyes of more than one line. CONCLUSIONS: Bilateral IOLs are safe and effective in pediatric aphakia.

Adolescent↗