Late clouding of an acrylic intraocular lens following routine phacoemulsification.
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Aged↗
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Results for “Polyhydroxyethyl Methacrylate”
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Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells.
The insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype of Ewing's sarcoma (ES) cells, and interference with the IGF-IR pathways by a neutralizing antibody causes reversal of the malignant potential of this neoplasm. In this paper, we stably transfected an IGF-IR antisense mRNA expression plasmid in an ES cell line to determine the effectiveness of antisense strategies against the in vitro and in vivo growth of ES cells. Doxorubicin sensitivity of TC-71 cells expressing antisense targeted to IGF-IR mRNA was also examined. Cells carrying antisense IGF-IR had a reduced expression of the receptor, a modest decrease in cell proliferation, a significant increase in anoikis-induced apoptosis, and a severely reduced ability to form colonies in soft agar. Moreover, TC/AS cells showed a marked reduction in their motility. In vivo, when cells carrying antisense IGF-IR were injected subcutaneously in nude mice, tumor formation was delayed and survival increased. Metastatic ability of ES cells was also significantly reduced. Furthermore, TC/AS clones showed a significantly higher sensitivity to doxorubicin - a major drug in the treatment of ES. These results indicate that inhibiting IGF-IR by antisense strategies may be relevant to the clinical treatment of ES patients by reducing the malignant potential of these cells and enhancing the effectiveness of chemotherapy.
Animals↗
Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion.
The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti-apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have investigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occurs when cells are denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of IGF-I and a sufficient number of functional IGF-I receptors. In this model, IGF-I protection correlates best with ras activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.
3T3 Cells↗
A study of death by anoikis in cultured epithelial cells.
BACKGROUND: Epithelial cells are critically dependent upon cell-matrix and cell-cell adhesion for growth and survival. Anoikis is programmed cell death caused by disruption of cell-substrate adhesion in normal epithelial cells. METHODS: We studied the induction of anoikis in vitro in two cell lines; HaCaT and SW742. PI3K, JAK2 and PKC are key elements in signalling pathways regulating cell survival, and using specific inhibitors we also examined their potential role in the induction of anoikis. RESULTS: When prevented from adhesion by culture on polyHEMA, HaCaT cells underwent apoptosis selectively from the proliferating population; surviving cells underwent cell cycle arrest. In SW742 cells anoikis also occurred, but was balanced by increased cycling. The effects of specific kinase inhibitors indicated that both Janus kinase 2 and protein kinase C partially protect HaCaT cells from anoikis through inducing cell cycle arrest of surviving nonadherent cells; inhibition of Phosphatidylinositol 3-kinase did not induce cycling in HaCaTs prevented from adhesion but did stimulate anoikis. SW742 cells showed markedly different responses: Janus kinase 2 inhibition activated apoptosis directly, Phosphatidylinositol 3-kinase inhibition stimulated both cell cycling and apoptosis, while protein kinase C inhibition stimulated cycling but inhibited apoptosis. CONCLUSIONS: Susceptibility to cell death in adhesion-prevented epithelial cells may thus be regulated by signalling pathways involving Phosphatidylinositol 3-kinase, Janus kinase 2 and protein kinase C. The ability of epithelial tumour cells to invade and metastasize may therefore result from disruption of these pathways.
Anoikis↗
Extracellular matrix regulates apoptosis in human neutrophils.
BACKGROUND: During inflammation, polymorphonuclear neutrophils (PMNs) migrate into the affected tissue interacting with extracellular matrix (ECM) proteins. We tested the hypothesis that PMN-matrix interaction affects PMN apoptosis. METHODS: Apoptosis of human PMNs was detected by DNA-fragmentation assay and was quantitated by flow cytometry, ultraviolet and light microscopy. Cell adhesion was assessed by a toluidine blue assay, and cell spreading was detected by phase contrast microscopy. Protein tyrosine phosphorylation was studied using Western blotting and confocal microscopy. RESULTS: PMN apoptosis was not different in unstimulated cultures on either surface-adherent fibronectin or on PolyHema, a surface that prevents cell adherence. However, tumor necrosis factor-alpha (TNF alpha) treatment significantly increased apoptosis on fibronectin (37 +/- 4%) compared with PolyHema (20 +/- 3%). Tests on other matrix substances revealed that the percentage of apoptotic PMNs in the presence of TNF alpha was 8 +/- 1% on PolyHema, 26 +/- 4% on fibronectin, 17 +/- 2% on collagen I, 16 +/- 2% on collagen IV, and 16 +/- 3% on laminin (P < 0.05 for all matrices compared with PolyHema). Preincubation with genistein (50 microM) significantly inhibited TNF alpha-mediated apoptosis on fibronectin (39 +/- 4% to 21 +/- 4%) but not on PolyHema (21 +/- 4% to 16 +/- 4%). Genistein also reduced PMN spreading on fibronectin. In contrast, inhibitors of mitogen-activated protein kinase and protein kinase C showed no effect on PMN apoptosis. Fibronectin strongly increased tyrosine phosphorylation of three 102, 63, and 54 kDa proteins. Five newly tyrosine-phosphorylated 185, 85, 66, 56, and 42 kDa bands were also visible. Using confocal microscopy, highest tyrosine phosphorylation was localized to sites of cell-matrix interaction. CONCLUSIONS: ECM influences apoptosis in TNF alpha-activated, adherent, spreading PMNs. The process is regulated by tyrosine phosphorylation. Acceleration of apoptosis may shorten the PMN lifespan and thereby locally regulate inflammation.
Apoptosis↗
Devices for use as an artificial articular surface in joint prostheses or in the repair of osteochondral defects.
The covering of ultra high molecular weight polyethylene (UHMWPE) and calcium hydroxyapatite (HA)/tricalcium phosphate (TCP) porous solid substrate with polyHEMA hydrogel has been studied aiming at the development of devices to be used as artificial articular surfaces in joint prosthesis or osteochondral repair grafts. Commercial porous UHMWPE was used. Ceramic porous substrate was prepared by load compaction of an HA and TCP powder mixture obtained by aqueous precipitation technique. Two different compaction loads and grain size distribution was used. Polymer particles were added to the powder mixture in order to increase the substrate porosity after the sintering process. The porous substrate was covered with polyHEMA hydrogel by in situ polymerization. Morphological analysis (SEM) showed that a hydrogel layer formed in the porous solid top surface was fixed to the substrate by mechanical interlocking because the porous surface was filled by the hydrogel. After hydrogel covering, the resultant devices showed a decrease in the compressive elastic modulus that was influenced by the porous substrate material.
Calcium Phosphates↗
Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials.
OBJECTIVES: To assess whether cilostazol, a phosphodiesterase III inhibitor, improves treadmill and community-based walking ability and health-related quality of life (HQL) in patients with intermittent claudication resulting from peripheral arterial disease (PAD). DESIGN: Retrospective meta-analysis of data pooled from six Phase 3, multicenter, double-blind, placebo-controlled, parallel-group, randomized studies. SETTING: Patients were recruited from outpatient ambulatory medical care facilities. PARTICIPANTS: Patients' (n = 1,751) mean age +/- standard deviation was 65 +/- 9, and they had a history of PAD for 6 months or longer and an ankle brachial index (ABI) of 0.90 or less. INTERVENTION: Cilostazol 50 mg bid or 100 mg bid for 12, 16, or 24 weeks. MEASUREMENTS: ABI; maximal walking distance (MWD); pain-free walking distance on a graded and constant-load treadmill; and HQL, measured using the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: Maximal treadmill walking distance improved more in both cilostazol groups than in the placebo group (both P <.0001). WIQ and SF-36 physical summary scores improved significantly more with cilostazol than with placebo (for instance, WIQ distance score, P <.0001 and SF-36 physical summary score, P <.0001, comparing persons taking cilostazol with controls). Improved MWD correlated with improvements in WIQ (correlation with distance score, r = 0.34, P <.0001) and SF-36 physical summary scores (r = 0.29, P <.0001). CONCLUSIONS: Treatment with cilostazol was associated with greater improvements in community-based walking ability and HQL in patients with intermittent claudication than treatment with placebo. These improvements correlated with increased MWD. This analysis of effects of cilostazol on improving walking ability in persons with claudication is the first cilostazol study focused on community-based measures of functional status and HQL. Questionnaires assessing walking ability and HQL provide important patient-based information about clinical outcomes of claudication therapy.
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Insulin and IGF-I receptors signaling in protection from apoptosis.
R-cells are mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes. Because R-cells do not express the IGF-IR, they are ideal for studying the biological effects of the insulin receptor (IR), independently from any contribution by the IGF-IR. By stably transfecting R-cells with constructs expressing the IR, we show here the IR can protect cells from apoptosis induced by anoikis or by okadaic acid. The IR, however, is not as efficient as the IGF-IR in protecting mouse embryo fibroblasts from apoptosis, even when IRS-1, one of its major substrates, is over-expressed. In addition, the protection by the IGF-IR is resistant to inhibitors of phosphatidylinositol 3-kinase (PI 3-ki), while the anti-apoptotic effect of the IR is sensitive. These experiments suggest that the IGF-IR uses an alternative anti-apoptotic pathway, not shared with the IR, which is PI3-ki-independent.
3T3 Cells↗
[Clinical results with soft intraocular lenses of poly-HEMA].
In a prospective study 28 patients were unilaterally implanted with a flexible posterior chamber lens made of poly-HEMA. Clinical results of 18 months follow up is reported. Implantation of the one-piece lens was more difficult in some patients according to the elastic property of the lens in comparison to PMMA-lenses. This is expressed in 8 patients in which a asymmetric sulcus-bag fixation of the lens was found. Postoperative visual acuity of better than 20/40 was found in 21 patients, which is rather the same as with hard intraocular implants. According to a lower refraction index of poly-HEMA the refractive power had to be chosen about 1 dpt higher than in PMMA-lenses. Early observation of the soft intraocular implants revealed 3 decentered lenses, in later follow up 5 implants were in an excentric position. One lens removal was performed due to diplopia. 16 of 28 patients revealed capsular fibrosis after 18 months follow up, in 8 patients a YAG-capsulotomy was performed. As an advantage of soft intraocular implants of poly-HEMA a good biocompatibility can be ruled out which is demonstrated in poor cell deposits on the lens surface and no synechias. The minor tendency to adheresis seems to favour on the other hand a destable fixation of the lens, which is expressed in the number of decentered lenses, possibly also in the observed capsular fibrosis.
Aged↗
[Implantation of folding posterior chamber lenses].
The implantation of foldable intraocular lenses (IOL) takes advantages of the benefit of small incision cataract surgery provided by phacoemulsification. However, even experienced surgeons may find the new implantation techniques required initially difficult. Advantages of small incision techniques include maintaining stability of the globe during surgery, especially in the case of acute IOP elevation caused by choroidal effusion or expulsive hemorrhage, as well as improved postoperative healing. Small incision surgery minimizes induced astigmatism, to less than 1.0 dpt change. Therefore, the patients physical and visual rehabilitation can be accelerated. Soft IOL's composed of p-HEMA or Silicone materials have been investigated for the past ten years and appear to be well biocompatible. The p-HEMA lens most often implanted is the IO-GEL, manufactured by Alcon. 120 p-HEMA IOL's were implanted in our clinic over the past 2 years. Our experiences with this foldable IOL are reported.
Foreign-Body Reaction↗
[Causal mechanisms of intralental changes in hema lenses (author's transl)].
Changes in hema lenses can be divided into three groups: changes within the lens material, surface changes and a combination of the two. The various processes which bring about intralental changes are demonstrated with examples from daily practice. For accurate evaluation it is essential to make sections of the lenses. By doing so proof of the inhomogeneity of the lens material can be obtained.
Contact Lenses, Hydrophilic↗
Use of collagen-hydroxyethylmethacrylate hydrogels for cell growth.
Collagen-hydroxyethylmethacrylate hydrogels were prepared by polymerizing monomeric hydroxyethylmethacrylate in the presence of various concentrations of soluble native collagen. The resulting transparent hydrogels were evaluated as substrata for growth of IMR-90 human embryonic lung fibroblasts. Without collagen no significant growth occurred, whereas a dose-response curve expressing maximal cell growth against collagen concentration could be constructed quite readily by the use of appropriate hydrogels. The method allows for quantification of the collagen contribution to cell growth and, in a more general sense, provides the foundation for a relatively easy procedure to probe mechanisms of cell adhesion and cell differentiation.
Acrylic Resins↗
Effect of cell spreading on cytoplasmic pH in normal and transformed fibroblasts.
Growth of normal fibroblasts requires an adhesive substratum on which to spread, whereas transformed cells can grow in suspension. Since an alkaline cytoplasm has been shown to be required for growth, we measured cytoplasmic pH in individual cells as a function of spreading. The degree of spreading was controlled by coating tissue culture plastic with varying amounts of the nonadhesive polymer polyHEMA. Completely round BALB/c 3T3 cells were 0.15 pH unit more acidic than spread cells. In short-term experiments, cells were treated with the peptide Gly-Arg-Gly-Asp-Ser-Pro to induce rounding or by plating on fibronectin to induce spreading. When cells were induced to change shape, pH changed rapidly and reversibly. All of the anchorage-dependent cell lines tested behaved similarly, but 3T3 cells transformed by the plasma membrane oncogene src or ras were able to maintain a relatively alkaline pH even when completely round. Cells transformed by the nuclear oncogene myc behaved like normal cells. Our results suggest that the requirement for spreading may in part be mediated by cytoplasmic pH. Anchorage-independent growth due to oncogenes that localize to the plasma membrane is associated with loss of this control mechanism.
Animals↗
Augmentation of a retrognathic chin. I. Use of HTR-polymer implants in a long-term prospective clinical and radiographic study.
A total of 37 patients have had chin augmentation procedures with HTR-polymer implants. Indications were mandibular retrognathia in connection with dentofacial deformities in 13 and the remaining 24 had a normal occlusion. Three patients with micrognathia also had juvenile rheumatoid arthritis. The patients have been followed for at least one year and in 17 cases up to five years both clinically and radiographically. Cephalometric measurements of the effects and stability of augmentation showed that chin augmentation has highly predictable results, and few side-effects.
Adolescent↗
Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization.
Most normal cells require adhesion to extracellular matrix for survival, but the molecular mechanisms that link cell surface adhesion events to the intracellular apoptotic machinery are not understood. Bcl-2 family proteins regulate apoptosis induced by a variety of cellular insults through acting on internal membranes. A pro-apoptotic Bcl-2 family protein, Bax, is largely present in the cytosol of many cells, but redistributes to mitochondria after treatment with apoptosis-inducing drugs. Using mammary epithelial cells as a model for adhesion-regulated survival, we show that detachment from extracellular matrix induced a rapid translocation of Bax to mitochondria concurrent with a conformational change resulting in the exposure of its BH3 domain. Bax translocation and BH3 epitope exposure were reversible and occurred before caspase activation and apoptosis. Pp125FAK regulated the conformation of the Bax BH3 epitope, and PI 3-kinase and pp60src prevented apoptosis induced by defective pp125FAK signaling. Our results provide a mechanistic connection between integrin-mediated adhesion and apoptosis, through the kinase-regulated subcellular distribution of Bax.
Animals↗
Developing a model of adolescent friendship formation on the internet.
Previous research has been largely silent about what precisely influences online friendship formation and has ignored motives for online communication as potential explanations. Drawing on a sample of 493 adolescents, this study tested a path model of adolescent friendship formation including as predictors introversion/extraversion, online self-disclosure, motive for social compensation, and frequency of online communication. Our path analysis showed that extraverted adolescents self-disclosed and communicated online more frequently, which, in turn, facilitated the formation of online friendships. Introverted adolescents, by contrast, were more strongly motivated to communicate online to compensate for lacking social skills. This increased their chances of making friends online. Among introverted adolescents, a stronger motive for social compensation also led to more frequent online communication and online self-disclosure, resulting in more online friendships. The model suggests that the antecedents of online friendship formation are more complex than previously assumed and that motives for online communication should be studied more closely.
Adolescent↗
Immobilized concentration gradients of neurotrophic factors guide neurite outgrowth of primary neurons in macroporous scaffolds.
Neurotrophic factors present as concentration gradients are neurotropic cues that direct axonal growth toward their targets. Multiple factors work together in vivo to ensure axons reach the proper targets, likely interacting with one another via intracellular signalling pathways. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are neurotrophins known to guide axons as well as promote axonal growth following injury to both the spinal cord and peripheral nerve. These molecules interact with neurons through different tyrosine kinase receptors. In this study, the receptors for these growth factors were shown to be co-localized on E10 chick dorsal root ganglion (DRG) cells, providing an opportunity for synergism. Well-defined concentration gradients of NGF and NT-3 were immobilized for the first time in a cell-penetrable, cell-adhesive scaffold of poly(2-hydroxyethylmethacrylate) and poly(L-lysine). An NGF concentration gradient of 310 ng/mL/mm was required to guide chick DRG neurites. A lower concentration gradient of 200 ng/mL/mm of NGF was shown to elicit guidance when an NT-3 concentration gradient of 200 ng/mL/mm was also present, indicating a synergistic response in the DRG neurons. These gradient scaffolds may be useful for guided regeneration following injury to the spinal cord or peripheral nerve and may also elucidate the mechanism for intracellular signaling of neurotrophic factors.
Animals↗
Detection of monoclonal B-cell populations in decalcified, plastic-embedded bone marrow biopsies with the polymerase chain reaction.
Polymerase chain reaction (PCR) has been employed successfully for the detection of clonal immunoglobulin gene rearrangements in paraffin-embedded clinical samples. The authors examined whether this technique can also be applied to fixed, decalcified, and plastic-embedded bone marrow biopsies. DNA extracted from 66 glycolmethacrylate-embedded trephine biopsy samples was amplified for the detection of rearranged VDJ regions of the immunoglobulin heavy chain genes using both a single-step and a semi-nested PCR technique. After exclusion of samples with inadequate DNA, clonality was confirmed in 16 (67%) of 24 cases with B cell malignancy, whereas all 11 non-B cell neoplasms, and 6 of 9 cases with normal bone marrow showed evidence of a polyclonal B cell population. Patterns indicating oligo- or monoclonality were observed in three plastic-embedded samples of normal bone marrow, although control PCR of frozen bone marrow samples obtained in parallel showed no evidence of clonality. Repeated PCR of these cases revealed inconsistent bands, probably due to the amplification of rare templates from polyclonal B cells. Decalcified, plastic-embedded bone marrow biopsies are suitable for PCR-based determination of B-cell clonality. To exclude the possibility of false-positive results, monitoring of template DNA quality and independent control amplifications are mandatory.
B-Lymphocytes↗