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PURPOSE: To evaluate near and distance visual performance after implantation of a diffractive multifocal intraocular lens (MIOL) (AcrySof ReSTOR) or a refractive MIOL (Array 2) in bilateral cataract surgery. METHODS: In this prospective, comparative trial, 18 patients with bilateral cataract were selected to have lens surgery with asymmetric MIOL implantation. Eighteen eyes received ReSTOR MIOL and the 18 fellow eyes were implanted with Array 2. Five months after second lens implantation, main postoperative outcomes were uncorrected and distance corrected near visual acuities (VA). Secondary outcomes were distance VA and near acuity with power add, contrast sensitivity with and without glare (Pelly-Robson Contrast Sensitivity Chart, CSV 1000 HGT). Quality of vision was measured by comparing the severity of visual symptoms as referred to a masked interviewer. RESULTS: Patients reported similar postoperative distance visual acuities for both eyes. ReSTORimplanted eyes showed better uncorrected and distance corrected near acuity than eyes with Array 2 (p=0.002 and p=0.003, respectively). Intermediate VA with distance correction was slightly higher with the Array 2 MIOL (p=0.058). No important difference was observed in contrast sensitivity, glare disability, and subjective rating of light sensations. Severe photic phenomena were reported only for one Array 2-implanted eye. CONCLUSIONS: The diffractive MIOL showed better uncorrected and distance corrected near VA. The refractive Array 2 MIOL had a tendency to better value for intermediate distance. Disturbing photic phenomena were observed only in one case with the Array 2 MIOL.

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BACKGROUND: Haiti is regarded as the poorest country of the Western hemisphere. The Hôpital Albert Schweitzer (HAS), founded in 1956 by Larimer Melon, is providing medical care to the Artibonite valley, an area in the centre of Haiti with over 400 000 inhabitants. Until 2001, a three-fold population was without eye care in central Haiti. HISTORY: In 2001, Hans Rudolf Bracher, a retired ophthalmologist from Bern, initiated the eye department at HAS and organised an eye examination unit, a microscope and further surgical equipment. Since then, eye care to the population was provided by short-term visits of ophthalmologists, nurses and orthoptists, mainly from switzerland. Additionally, teaching and surgical training was performed at university hospital in Port-au-Price, the only education centre for ophthalmologists in the country. PRESENT SITUATION: The actual political and security situation complicates visits of western doctors. A development association for the HAS eye department was founded and with its help, an Haitian ophthalmologist is employed in a full-time position. Furthermore, logistic support is provided with drugs and surgical equipment. Today, under difficult circumstances, the eye department is well established as an effective and cost-covering institution at HAS.

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We have developed a tissue model of radiation-induced reproductive cell death in the nematode Caenorhabditis elegans. Reproductive cell death is the primary mode of death in tissue multipotential precursor cells, or "clonogens," the targets of cytotoxic therapy, whose elimination results in normal tissue damage as well as solid-tumor eradication. Through extensive morphologic and genetic analysis, we have confirmed that cell death in this model represents reproductive cell death in isolation from apoptotic cell death, affording the opportunity to define the genetic pathways required for protection from reproductive cell death. We have additionally found that the DNA damage response pathway is necessary for protection from reproductive cell death, supporting the long-held tenet that DNA damage is the cause of reproductive cell death and further validating this model. This genetic tissue model provides a valuable tool for oncology-based research and affords a platform to broaden our insight into responses to cytotoxic therapy in tissues.

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beta-catenins are conserved transcription factors regulated posttranslationally by Wnt signaling. bar-1 encodes a Caenorhabditis elegans beta-catenin acting in multiple Wnt-mediated processes, including cell fate specification by vulval precursor cells (VPCs) and migration of the Q(L) neuroblast progeny. We took two approaches to extend our knowledge of bar-1 function. First, we undertook a bar-1 promoter analysis using transcriptional GFP reporter fusions and found that bar-1 expression is regulated in specific cells at the transcriptional level. We identified promoter elements necessary for bar-1 expression in several cell types, including a 321-bp element sufficient for expression in ventral cord neurons (VCNs) and a 1.1-kb element sufficient for expression in the developing vulva and adult seam cells. Expression of bar-1 from the 321-bp element rescued the Uncoordinated (Unc) phenotype of bar-1 mutants, but not the vulval phenotype, suggesting that a Wnt pathway may act in ventral cord neurons to mediate proper locomotion. By comparison of the 1.1-kb element to homologous sequences from Caenorhabditis briggsae, we identified evolutionarily conserved sequences necessary for expression in vulval or seam cells. Second, we analyzed 24 mutations in bar-1 and identified several residues required for BAR-1 activity in C. elegans. By phylogenetic comparison, we found that most of these residues are conserved and may identify amino acids necessary for beta-catenin function in all species.

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beta-Catenins function both in cell adhesion as part of the cadherin/catenin complex and in Wnt signal transduction as transcription factors. Vertebrates express two related proteins, beta-catenin and plakoglobin, while Drosophila has a single family member, Armadillo. Caenorhabditis elegans expresses three beta-catenin-related proteins, BAR-1, HMP-2, and WRM-1, which are quite diverged in sequence from each other and other beta-catenins. While BAR-1 and WRM-1 are known to act in Wnt-mediated processes, and HMP-2 acts in a complex with cadherin/alpha-catenin homologs, it is unclear whether all three proteins retain the other functions of beta-catenin. Here we show that BAR-1, like vertebrate beta-catenin, has redundant transcription activation domains in its amino- and carboxyl-terminal regions but that HMP-2 and WRM-1 also possess the ability to activate transcription. We show via yeast two-hybrid analysis that these three proteins display distinct patterns of protein interactions. Surprisingly, we find that both WRM-1 and HMP-2 can substitute for BAR-1 in C. elegans when expressed from the bar-1 promoter. Therefore, although their mutant phenotypes and protein interaction patterns strongly suggest that the functions of beta-catenin in other species have been segregated among three diverged proteins in C. elegans, these proteins still retain sufficient similarity to display functional redundancy in vivo.

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The Caenorhabditis elegans vulva develops from the progeny of three vulval precursor cells (VPCs) induced to divide and differentiate by a signal from the somatic gonad. Evolutionarily conserved Ras and Notch extracellular signaling pathways are known to function during this process. To identify novel loci acting in vulval development, we carried out a genetic screen for mutants having a protruding-vulva (Pvl) mutant phenotype. Here we report the initial genetic characterization of several novel loci: bar-1, pvl-4, pvl-5, and pvl-6. In addition, on the basis of their Pvl phenotypes, we show that the previously identified genes lin-26, mom-3/mig-14, egl-18, and sem-4 also function during vulval development. Our characterization indicates that (1) pvl-4 and pvl-5 are required for generation/survival of the VPCs; (2) bar-1, mom-3/mig-14, egl-18, and sem-4 play a role in VPC fate specification; (3) lin-26 is required for proper VPC fate execution; and (4) pvl-6 acts during vulval morphogenesis. In addition, two of these genes, bar-1 and mom-3/mig-14, are known to function in processes regulated by Wnt signaling, suggesting that a Wnt signaling pathway is acting during vulval development.

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OBJECTIVE: The auditory brain stem response (ABR) has been criticized recently as an insensitive measure for the detection of small acoustic neuroma (AN). This study was undertaken to evaluate our experience with the efficacy of ABR in detection of small tumors. STUDY DESIGN: Retrospective case review. Twenty-five patients with surgically proven small ANs measuring 1 cm or less were reviewed. In addition, 568 patients who underwent screening ABR were reviewed to evaluate the rate of false positive results at our institution. RESULTS: ABR was abnormal in 92% of patients with small AN in this series. Screening ABR was abnormal in approximately 19% of cases, one-third of which were found to have AN on magnetic resonance imaging testing. CONCLUSION: With strict adherence to optimal technique and evaluation criteria, the ABR remains a viable option for AN screening, especially in elderly patients or when there is a low index of suspicion.

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Morphological and cytochemical studies have suggested that maturation ameloblasts participate in protein loss by absorbing and degrading enamel proteins as the enamel matures. Several immunocytochemical and autoradiographic studies have suggested other possible explanations for the presence of enamel matrix proteins in maturation ameloblasts. The weakness of these autoradiographic studies is the uncontrolled distribution of systemically injected radioactive amino acids, making it impossible to trace the source of the visualized intracellular isotope. This study used a localized technique to control the targets of the applied isotope and to identify enamel matrix proteins in the maturation ameloblasts with more confidence about their origin. The amount of labelled enamel protein was higher in maturation ameloblasts than transitional ameloblasts. When cycloheximide, a protein-synthesis inhibitor, was applied, there was no effect on the amount of labelled protein in the maturation ameloblasts. These findings support the hypothesis that maturation ameloblasts actively resorb and degrade enamel matrix proteins during enamel formation in the mandibular incisor of the rat.

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In C. elegans, the epithelial Pn.p cells adopt either a vulval precursor cell fate or fuse with the surrounding hypodermis (the F fate). Our results suggest that a Wnt signal transduced through a pathway involving the beta-catenin homolog BAR-1 controls whether P3.p through P8.p adopt the vulval precursor cell fate. In bar-1 mutants, P3.p through P8.p can adopt F fates instead of vulval precursor cell fates. The Wnt/bar-1 signaling pathway acts by regulating the expression of the Hox gene lin-39, since bar-1 is required for LIN-39 expression and forced lin-39 expression rescues the bar-1 mutant phenotype. LIN-39 activity is also regulated by the anchor cell signal/let-23 receptor tyrosine kinase/let-60 Ras signaling pathway. Our genetic and molecular experiments show that the vulval precursor cells can integrate the input from the BAR-1 and LET-60 Ras signaling pathways by coordinately regulating activity of the common target LIN-39 Hox.

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Cyclic AMP receptor proteins (cARP) are present in a variety of cell types. Intracellularly, they are the regulatory (R) subunits of type II cyclic AMP-dependent protein kinase (PKA: E.C.2.7.1.37). Additionally, cARP are secretory products of several cell types.[1] That cARP are present in and secreted by ameloblasts into the enamel matrix of the rat incisor was demonstrated by photoaffinity labeling, Western blotting and immunogold cytochemistry. Gold particles were present over cytoplasmic regions including Tomes' Processes of secretory ameloblasts, secretory granules and in the Golgi region. Specific RII labeling was seen in the enamel matrix, but not in dentin. The enamel matrix was more reactive during early maturation compared to the secretory stage of amelogenesis. Nuclear labeling with the RII antibody showed higher intensity in maturation than in secretory ameloblasts. These results demonstrate that cARP are expressed in ameloblasts and secreted into the enamel matrix. The role(s) of cARP in enamel matrix mineralization and the involvement of PKA-regulated pathways in enamel protein synthesis and secretion remain to be determined.

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BACKGROUND: The present study was designed to investigate the effect of topical antiglaucoma drugs on Peak Pulse Blood Volume (PPBV; German abbreviation: PGBV) in cynomolgus monkey eyes without (CMNG; German abbreviation: RA-KTL) and with lasersurgically induced glaucoma (CMG; German abbreviation: RA-LHDG). METHODS: CMG unilaterally received 2-3 laser treatments so as to develop the lasered-eye glaucoma model. Intraocular pressure (IOP; German abbreviation: IOD) and Ocular Pulse Amplitude were measured and PPBV was determined until the glaucoma model had stabilized. Consecutively topical antiglaucoma drugs (epinephrine, paraaminoclonidine, pilocarpine, timolol) were investigated in 4-8 animals in CMNG and CMG eyes. RESULTS: IOP and PPBV were not significantly altered in CMNG. In the CMG eyes epinephrine and paraaminoclonidine did not significantly alter IOP or PPBV, whereas pilocarpine and timolol sig. (p < 0.01) reduced IOP and significantly (p < 0.05) increased PPBV. CONCLUSION: With respect to improved PPBV in the CMG eye the rank order of drug effectiveness is timolol > pilocarpine > paraaminoclonidine > epinephrine.

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Interaction of the TATA box-binding protein (TBP) with promoters of RNA polymerase II-transcribed genes is an early and essential step in mRNA synthesis. Previous studies have demonstrated that the rate-limiting binding of TBP to a TATA element can be influenced by transcriptional regulatory proteins. To identify additional factors that may regulate DNA binding by TBP in vivo, we performed a genetic selection for extragenic suppressors of a yeast TBP mutant that exhibits altered and relaxed DNA binding specificity. This analysis has led to the discovery of a previously unidentified gene, RTF1. The original rtf1 suppressor mutation, which encodes a single amino acid change in Rtf1, and an rtf1 null allele suppress the effects of the TBP specificity mutant by altering transcription initiation. Differences in the patterns of transcription initiation in these strains strongly suggest that the rtf1 missense mutation is distinct from a simple loss-of-function allele. The results of genetic crosses indicate that suppression of TBP mutants by mutations in RTF1 occurs in an allele-specific fashion. In a strain containing wild-type TBP, the rtf1 null mutation suppresses the transcriptional effects of a Ty delta insertion mutation in the promoter of the HIS4 gene, a phenotype also conferred by the TBP altered-specificity mutant. Finally, as shown by indirect immunofluorescence experiments, Rtf1 is a nuclear protein. Taken together, our findings suggest that Rtf1 either directly or indirectly regulates the DNA binding properties of TBP and, consequently, the relative activities of different TATA elements in vivo.

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BACKGROUND: Multifocal intraocular lenses show a reduction of contrast due to the simultaneous projection of different images to the retina. In this study we examined if there is also a loss of contrast in bilateral implantation of multifocal lenses. MATERIAL AND METHODS: We examined 22 patients with bilateral AMO ARRAY multifocal intraocular lens and compared these to 20 patients with bilateral monofocal intraocular lens. We performed a monocular and binocular examination of contrast acuify by means of Regan's contrast charts and contrast sensitivity by means of B-VAT-II-SG-Video-acuity-tester. RESULTS: Monocular examination of contrast acuity showed significant superiority of the monofocal intraocular lens at the lowest contrast. Bilateral examination of contrast acuity did not show any significant difference. Monocular contrast sensitivity of the monofocal intraocular lens was significantly superior to the multifocal intraocular lens at two spatial frequencies, but under the bilateral condition there was only a significant difference between the two lenses at the highest spatial frequency. CONCLUSIONS: Bilateral implantation of multifocal intraocular lenses enables contrast acuity and contrast sensitivity that comes very close to the performance of the monofocal intraocular lenses.

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The Caenorhabditis elegans let-60 gene encodes a Ras protein that mediates induction of the hermaphrodite vulva. To better understand how mutations constitutively activate Ras and cause unregulated cell division, we have characterized ga89, a temperature-sensitive, gain-of-function mutation in let-60 ras. At 25 degrees, ga89 increases let-60 activity resulting in a multivulva phenotype. At 15 degrees, ga89 decreases let-60 activity resulting in a vulvaless phenotype in let-60(ga89)/Df animals. The ga89 mutation causes a leucine (L) to phenylalanine (F) substitution at amino acid 19, a residue conserved in all Ras proteins. We introduced the L19F change into human H-Ras protein and found that the in vitro GTPase activity of H-Ras became temperature-dependent. Genetic experiments suggest that LET-60 (L19F) interacts with GAP and GNEF, since mutations that decrease GAP and GNEF activity affect the multivulva phenotype of let-60(ga89) animals. These results suggest that the L19F mutation primarily affects the intrinsic rate of GTP hydrolysis by Ras, and that this effect may be sufficient to account for the activated-Ras phenotype caused by let-60(ga89). Our results suggest that a mutation in a human ras gene analogous to ga89 might contribute to oncogenic transformation.

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BACKGROUND: Examination of surface-bound heparin on synthetic polymers can only be performed by few staining methods. These methods are limited by an only approximate detection of heparin visible at high magnification. Other methods only measure heparin quantitatively (per square dimension) and are rather sensitive to artifacts. Due to its homogeneous staining pattern, the modified toluidine blue staining technique, using a non-protein-based substance, allows examination and analysis of the homogeneity of the monomolecular heparin layer even under critical conditions like scanning electron microscopy. MATERIALS AND METHODS: For critical examination of the heparin layer, this method was used for 5 sterile heparin surface-modified (HSM) monofocal (Pharmacia, 809C, 5 mm optical zone), 2 multifocal PMMA (Pharmacia, 811E, 6 mm optical zone) and 1 standard PMMA intraocular lenses (IOLs; Pharmacia, 809P, 5 mm optical zone). A special mixture containing a sodium borate buffer was used to avoid cross-reactions of toluidine with phenylimines, which permit a covalent surface linkage of heparin to synthetic polymeric materials via reductive amination. This resulted in less coarse-grained complex agglutination. After light and spectral microscopy of the surface of stained IOLs, scanning electron microscopy was performed to investigated the reliability and validity of this modified staining method. RESULTS: All HSM IOLs showed a homogeneous heparin structure and coating, which could be demonstrated even under critical photographic circumstances. CONCLUSIONS: The modification of the original toluidine blue staining method introduced by Jaques in 1943 is a reliable and reproducible technique for the detailed in vitro analysis of surface-bound heparin with a low artifact rate. Because of the detailed detection of heparin on polymeric surfaces, this staining method is recommended for special problems, e.g. in cataract surgery.

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BACKGROUND: Posterior capsule opacification (PCO) after implantation of a multifocal intraocular lens (MIOL) reduces the visual acuity (VAF) for the far, as well as for the near (VAN). There is no report on results and techniques for Nd:YAG capsulotomy in the presence of PCO after MIOL implantation. PATIENT AND METHODS: Therefore, 31 Nd:YAG capsulotomies in 29 patients with PCO after MIOL implantation were analysed concerning number of expositions, energy, MIOL-damage, results as well as complications after capsulotomy in order to derive individual laser strategies. RESULTS: Nd:YAG capsulotomy was performed after a mean of 14 (+/- 12.5) months. All capsulotomies resulted in a central opening of the posterior capsule. 42 (+/- 25.1) impulses in mean were necessary at a total energy of 71.7 (+/- 47.8) mJ. An average of 4 hits of the MIOL optic occurred and in 5 cases the MIOL remained undamaged. Three capsulotomies were difficult to perform. In eight cases, a dense PCO was present. All capsulotomies were performed without any immediate complication. In 93.6% VAF and in 96.8% VAN increased postoperatively, while in the remaining cases VA did not increase due to other reasons. In one case intraocular pressure increased after YAG laser treatment for a short period of time. In another case, a retinal detachment occurred 5 months postoperatively. No cystoid macular edema occurred until 6 months postoperatively. CONCLUSION: Nd:YAG capsulotomy in PCO after MIOL implantation is a relatively safe, non-invasive method to improve visual acuity. After capsulotomy, the optically effective area of the MIOL mainly depends on the diameter of the pupil, the anterior and posterior capsular opening. Therefore, the opening of the posterior capsule should depend on the individual MIOL design and should include the main MIOL portion for the far and near focus. This allows the patient an unaided profit from the multifocality of the IOL postoperatively.

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Our previous studies revealed intense membrane-associated labeling for Ca(2+)-Mg2+ ATPase (Ca(2+)-pump) in secretory and maturation ameloblasts in the rat incisor, both by enzyme cytochemistry and by immunohistochemical techniques. The purpose of the present study was to map the distribution of Ca(2+)-pump protein at the cellular and subcellular levels by means of a Ca(2+)-pump-specific monoclonal antibody and electron microscopic immunogold cytochemistry. Tissue specimens were dissected from secretory, early, and late enamel maturation zones. We quantified results by comparing gold particle densities over ameloblast lateral and distal plasma membrane regions, supranuclear cytoplasm, regions of the ruffled borders, and nuclei. The highest concentration of gold particles was seen over the distal membranes of early-maturation ameloblasts relative to those in late-maturation and secretory stages. Cytoplasmic labeling was less than that of the distal and lateral membranes, and gold particles located over nuclei were considered to be due to non-specific binding. These results are consistent with our earlier findings and suggest a role for the plasma membrane Ca(2+)-pump in the regulation of calcium availability to mineralizing enamel.

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BACKGROUND: Several clinical studies indicate, that the visual function of multifocal IOLs (MIOL) is impaired by corneal astigmatism. To assess the influence of uncorrected corneal astigmatism on the contrast sensitivity function (CSF) of mono- and multifocal IOLs, an "optical implantation" of physical eyes with astigmatic corneas and IOLs was performed in younger subjects. METHODS: The virtual image of physical eyes with a 40 dpt achromate as artificial cornea and the (M)IOL in a water bath was projected on the retina of the observer by means of an exactly adjusted video objective. Silicone lenses with defined astigmatisms (+1; +2; +4; +6 dpt) were put in front of the achromate to produce an artificial corneal astigmatism. We compared results of a standard monofocal IOL (Pharmacia 811B), a multizone progressive MIOL (AMO Array SSM-26NB) and a diffractive MIOL (Pharmacia 811E). CSF through these IOLs in the physical eyes was measured in ten healthy subjects (mean age: 27.4 y.) with the B-VAT II-SG Video Acuity Tester (Mentor O&O), which uses sine wave gratings of five different spatial frequencies (1.5; 3; 6; 12; 20 cpd). RESULTS: Without astigmatic lenses, all IOLs showed a mean CSF within the age-related norm, but the monofocal IOL yielded significantly better results than both MIOLs at three spatial frequencies (3; 6; 12 cpd). With additional astigmatic lenses of 2 dpt and more, mean CSF of all IOLs was below normal range, but there was no difference in the performance of the three lens styles. CONCLUSION: CSF of MIOLs seems to be less sensitive to uncorrected corneal astigmatism than CSF of the monofocal IOL. This suggests, that a higher preoperative astigmatism does not severely affect the image quality through a multifocal IOL.

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