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Human rhinoviruses (HRVs), the main causative agents of common cold, were originally classified as acid-sensitive picornaviruses (34). Later, based on competition for cellular binding sites, two different groups of viruses using nonidentical receptors for cell attachment were defined within the genus Rhinovirus (18). Subsequently, 24 (1) and finally 100 serotypes (counting the subtypes HRV1A and HRV1B as one strain) were assigned to the two receptor groups by using cross-competition and inhibition of cell binding by a monoclonal antibody recognizing intercellular adhesion molecule 1 (ICAM-1), the receptor of the major group of HRVs (32, 33, 35). According to these reports, 90 serotypes bind ICAM-1, whereas both subtypes of HRV1 (HRV1A and HRV1B) and 8 other serotypes were categorized as belonging to the minor group; they were later shown to use members of the low-density-lipoprotein receptor (LDLR) family for cell entry (12, 20, 36). HRV87 was noted to be an exception in that it binds a sialylated membrane protein. Based on comparison of nucleotide sequences in several genomic regions, HRV87 was subsequently classified as an acid-sensitive enterovirus and found to be a prime strain of enterovirus 68 that uses decay-accelerating factor as a receptor (2, 27). By phylogenetic analysis of capsid protein VP4/VP2 coding sequences of all HRV prototype strains, 74 HRV serotypes, including all the minor receptor group ones, were classified as HRV species A, while the 25 remaining serotypes form HRV species B (27). In a paper from the Colonno group, primary data on the competition with an ICAM-1-blocking antibody were not explicitly presented for all serotypes, in particular not for HRV23 and HRV25, and the presumed allocation of all HRVs to either group was depicted only in the form of a summarizing figure (35). Despite this, it was generally accepted that 90 serotypes, including HRV23 and HRV25, were major group viruses. Later, Crump and colleagues reported that recombinant soluble ICAM-1 and a chimeric ICAM-1/immunoglobulin A molecule failed to neutralize these two serotypes and concluded that they most probably use a receptor different from the major and minor group receptors (4, 5). This finding remained largely unnoticed by the picornavirus community. As soon as the capsid protein VP1 sequences of all human rhinoviruses were determined (15, 16), we became aware of genetic clustering of HRV23 and HRV25 close to certain minor receptor group serotypes and of the presence of a lysine in the HI loop. This residue is strictly conserved in all minor group viruses and is believed to be essential but not sufficient for attachment to members of the LDLR family (37). A lysine is also present at the equivalent position in HRV8, -18, -24, -40, -54, -56, -58, -85, -95, and -98. However, these latter serotypes had been explicitly shown to be neutralized by soluble recombinant ICAM-1 (5). Therefore, we wondered whether at least HRV23 and HRV25 might use members of the LDLR family as receptors. We also wondered whether the other HRVs containing the conserved lysine might eventually possess dual receptor specificity and attach to ICAM-1 as well as to LDLR. The ligand binding domain at the N terminus of LDLR that is implicated in binding minor group HRVs is composed of seven imperfect direct repeats of roughly 40 amino acid residues in length. Three disulfide bridges and a Ca2+ ion within an octagonal cage formed by the carboxylates of three aspartates and one glutamate, together with two backbone oxygens, stabilize this structure (7). The very-low-density lipoprotein receptor (VLDLR) and LDLR-related protein (LRP) possess 8 and 31 such modules, respectively (30). In LRP the modules are not contiguous but are arranged in clusters of 2, 8, 10, and 11. We have previously shown that a soluble recombinant fusion protein composed of the maltose binding protein (MBP) and an artificial concatemer of five copies of repeat 3 (V3) of VLDLR arranged in tandem (MBP-V33333) exhibits strong virus neutralization capacity toward the 10 minor group HRVs (36). Therefore, by using cell protection assays with this protein, ligand blots, and replication in COS-7 cells that do not express ICAM-1, we investigated the nature of the strains containing a lysine residue in the HI loop and found that HRV23 and HRV25 possess all characteristics of minor group viruses. Examination of the major group serotypes with the lysine in the HI loop as mentioned above showed that none was able to use both ICAM-1 and LDLR for cell binding. Therefore, out of the numbered 99 HRV serotypes, altogether, 12 serotypes (if we count HRV1A and -B separately) belong to the minor receptor group.

Human rhinovirus serotype 1A (HRV1A) binds more strongly to the mouse low-density lipoprotein receptor (LDLR) than to the human homologue (M. Reithmayer, A. Reischl, L. Snyers, and D. Blaas, J. Virol. 76: 6957-6965, 2002). Here, we used this fact to determine the binding site of HRV1A by replacing selected ligand binding modules of the human receptor with the corresponding ligand binding modules of the mouse receptor. The chimeric proteins were expressed in mouse fibroblasts deficient in endogenous LDLR and LDLR-related protein, both used by minor group HRVs for cell entry. Binding was assessed by virus overlay blots, by immunofluorescence microscopy, and by measuring cell attachment of radiolabeled virus. Replacement of ligand binding repeat 5 of the human LDLR with the corresponding mouse sequence resulted in a substantial increase in HRV1A binding, whereas substitution of repeats 3 and 4 was without effect. Replacement of human receptor repeats 1 and 2 with the murine homologues also increased virus binding. Finally, murine receptor modules 1, 2, and 5 simultaneously introduced into the human receptor resulted in HRV1A binding indistinguishable from mouse wild-type receptor. Thus, repeats 1 and/or 2 and repeat 5 are involved in HRV1A attachment. Changing CDG GP D in the acidic cluster of module 5 in the human receptor to CDG EA D present in the mouse receptor led to substantially increased binding of HRV1A, indicating an important role of the glutamate residue in HRV1A recognition.

Human rhinoviruses (HRV) of the minor receptor group use several members of the low-density lipoprotein receptor superfamily for cell entry. These proteins are evolutionarily highly conserved throughout species and are almost ubiquitously expressed. Their common building blocks, cysteine-rich ligand binding repeats about 40 amino acids in length, exhibit considerable sequence similarity. Various numbers of these repeats are present in the different receptors. We here demonstrate that HRV type 1A (HRV1A) replicates in mouse cells without adaptation. Furthermore, although closely related to HRV2, it fails to bind to the human low-density lipoprotein receptor but recognizes the murine protein, whereas HRV2 binds equally well to both homologues. This difference went unnoticed due to the presence of other receptors, such as the low-density lipoprotein receptor-related protein, which allow species-independent attachment. The species specificity of HRV1A reported here will aid in defining amino acid residues establishing the contact between the viral surface and the receptor.

We report the case of an immunocompetent 78-year-old woman who developed cytomegalovirus (CMV) retinitis after a single intravitreous injection of triamcinolone acetonide (IVTA). Review of medical records. The patient with macular edema secondary to branch retinal vein occlusion developed peripheral retinitis with hemorrhagic and inflammatory vascular sheathing 3 months after IVTA. A presumptive diagnosis of viral retinitis was confirmed by polymerase chain reaction (PCR) of the aqueous humor tap. The PCR test was positive for CMV DNA. The patient slowly responded to intravenous ganciclovir and oral valganciclovir. After therapeutic vitrectomy for intercurrent vitreous hemorrhage, and while still under treatment, the retinitis resolved completely with final visual acuity of 20/25. CMV retinitis can occur after local immunosuppression with IVTA in an immunocompetent patient with no other systemic risk factors.

Purpose: To study the prevalence of polypoidal choroidal vasculopathy (PCV) in Caucasian patients with occult choroidal neovascularization (CNV); to study the clinical spectrum of PCV in Caucasians and the outcome after laser photocoagulation of such lesions. Methods: (1) A consecutive series of 374 eyes of Caucasian patients at least 58 years old, presenting occult CNV, presumed to have age-related macular degeneration (AMD) on fluorescein angiography (FA) were further characterized by indocyanine green angiography (ICGA) to determine the frequency of PCV. (2) The funduscopic, FA and ICGA findings in a cohort of 36 Caucasian patients with PCV were analyzed. (3) The outcome after laser photocoagulation was studied in 14 PCV eyes with a minimum follow-up of 6 months. Results: (1) Fourteen of 374 eyes (4%) presenting occult CNV in patients at least 58 years old were diagnosed as PCV by means of ICG-A. (2) A polypoidal lesion was found in the macula in 22 of 45 PCV eyes, in the peripapillary area in 16 of 45, under the temporal vascular arcade in 6 of 45 and in the midperiphery in 6 of 45. Large or soft drusen were observed in 15 of 45 eyes with PCV. (3) Regression of fundus signs without persisting polyps 6 months after laser photocoagulation was obtained in 5 of 5 treated peripapillary lesions but in only 5 of 9 treated macular or arcade lesions. Conclusion: Polypoidal choroidal vasculopathy is not rare in Caucasian patients presenting with occult choroidal neovascularization. The fundus abnormalities seen in such eyes overlap with the typical manifestations of AMD. Whereas the prognosis after photocoagulation of peripapillary polypoidal lesions appears to be relatively good, it is more guarded for macular or arcade lesions.

This paper follows an earlier publication in the Advances in Complex Systems journal (Heusse et al., 1998) where we presented a new algorithm based on collaborative agents for routing in communication networks. In this document, we shall investigate its load-balancing capability. This capability is required as a first step to achieve quality of delivery and service. We also compare our new approach to the classical ones and discuss their respective benefits.

The 31 kDa membrane protein stomatin was metabolically labeled with tritiated palmitic acid in the human amniotic cell line UAC and immunoprecipitated. We show that the incorporated palmitate is sensitive to hydroxylamine, indicating the binding to cysteine residues. Stomatin contains three cysteines. By expressing a myc-tagged stomatin and substituting the three cysteines by serine, individually or in combination, we demonstrate that Cys-29 is the predominant site of palmitoylation and that Cys-86 accounts for the remaining palmitate labeling. Disruption of Cys-52 alone does not show any detectable reduction of palmitic acid incorporation. Given the organization of stomatin into homo-oligomers, the presence of multiple palmitate chains is likely to increase greatly the affinity of these oligomers for the membrane and perhaps particular lipid domains within it.

This paper presents a new stochastic heuristic to reveal some structures inherent in large graphs, by displaying spatially separate clusters of highly connected vertex subsets on a two-dimensional grid. The algorithm employed is inspired by a biological model of ant behaviors it proceeds by local optimisations, and requires neither global criteria, nor any a priori knowledge of the graph. It is presented here as a preliminary phase in a recent approach to graph partitioning problems: transforming the combinatorial problem (minimising edge cuts) into one of clustering by constructing some bijective mapping between the graph vertices and points in some geometric space. After reviewing different embeddings proposed in the literature, we define a dissimilarity coefficient on the vertex set which translates the graph‘s interesting structural properties into distances on the grid, and incorporate it into the clustering heuristic. The heuristic‘s performance on a well-known class of pseudo-random graphs is assessed according to several metric and combinatorial criteria.

The 31-kDa integral membrane protein stomatin (protein 7.2b) is not only an important component of the red cell membrane but can also be found in abundance in different tissues and cell lines. The protein is thought to be anchored to the membrane by a hydrophobic domain while both N and C termini are exposed to the cytoplasm. We have previously shown in the human cell line UAC that stomatin concentrates preferentially in plasma membrane folds and protrusions. There is also evidence that stomatin is linked to the cortical actin cytoskeleton, suggesting a role in cortical morphogenesis of the cell. In this study, we demonstrate that the fundamental structure of stomatin is oligomeric. Whereas interaction of stomatin with itself was suggested by cross-linking experiments, we show by density gradient centrifugation analysis that soluble homo-oligomeric complexes of this protein are present in Triton X-100 extracts of UAC cells. We also show the existence of these oligomers by co-immunoprecipitation of the endogenous stomatin and a recombinantly expressed myc-tagged stomatin, using an anti-myc antibody. The data indicate that these complexes comprise between 9 and 12 monomers of stomatin. Two C-terminally truncated forms of stomatin do not incorporate into these oligomers, suggesting an involvement of the C terminus in the homo-oligomeric interaction.

An original coding scheme is introduced to take advantage of the two-dimensional structural information of images within the genetic algorithm framework. Results are presented showing that this new technique outperforms classical optimization methods for the optimization of 32 × 32 and 128 × 128 holograms.

A polymerase chain reaction assay (Lust J.A. et al. (1992). Cytokine 4:96-100) was used to detect a mRNA coding for a soluble IL-6 receptor in human hepatoma cells. In addition to the expected amplification product, we found a sequence (SR4) which could be aligned to it with 78% identity. After cloning and sequencing a genomic 2.5-2.7 kB EcoRI fragment containing SR4, this sequence turned out to be part of a pseudogene corresponding to the transmembrane domain deleted soluble IL-6 receptor. Screening of a panel of interspecies hybrids revealed that it maps to chromosome 9.

AIMS/BACKGROUND--This study was undertaken to confirm the association between diffuse retinal pigment epitheliopathy (DRPE) and systemic corticosteroid therapy. This finding can be of help in determining an aetiological factor in DRPE and associated diseases. Corticosteroids may contribute to the development of leakage in the presence of a retinal pigment epitheliopathy or central serous chorioretinopathy. METHODS--Cases of DRPE were collected from the files of members of the European Fluorescein Angiography Club. There were 34 who developed their ophthalmic symptoms while being treated with corticosteroids. RESULTS--DRPE developed in 34 patients from 10 European eye clinics during systemic treatment with corticosteroids. Thirteen patients were treated with corticosteroids after allotransplantation, 21 other patients developed ocular symptoms while treated with steroids for serious systemic disorders. Symptoms occurred in some patients when the daily corticosteroid dosage was elevated, and the visual complaints ameliorated or even disappeared sometimes on discontinuation of the corticosteroid therapy. CONCLUSION--Corticosteroids can damage the retinal pigment epithelial barrier and predispose a patient to serous retinal detachment, whereas psychological stress may play a role in the development of central serous chorioretinopathy. A decrease of the daily corticosteroid dosage may help to diminish the visual symptoms.

To evaluate the frequency of diabetic retinopathy in Lubumbashi (Democratic Republic of Congo).Descriptive survey including 369 diabetic patients examined in our department of Ophthalmology of Lubumbashi from May 2006 to March 2008. Rates of glycaemia and blood pressure were noted. All the patients had a complete ophthalmological examination including visual acuity measurement, anterior biomicroscopy, intraocular pressure and fundus examination after pupil dilation.At the time of ocular examination, the mean age of diabetic patients was 57 years (range 16 to 85) with a sex ratio of 1.2 males for 1 female. The frequency of type 1 diabetic patients was 28% and of type 2, 72%. High blood pressure was found in 42% of the patients. The frequency of diabetic patients (all forms included) was 13% and diabetes-induced blindness was 0.27%. In our study, the frequency of diabetic retinopathy increased with the patient's age and the duration of the diabetes. Diabetic retinopathy was more frequently found in adults. We did not find correlation between the level of glycaemia and the incidence of diabetic retinopathy.From our epidemiological study, diabetic retinopathy is a concern for adult public health. It requires organized screening and early treatment to prevent blindness of those diabetic patients.

Interleukin 6 (IL-6) is an important mediator of various kinds of inflammatory and immune responses. The human amniotic cell line UAC has an increased number of IL-6 receptors after treatment by glucocorticoids. To find a possible activity of IL-6 on these cells, a cDNA library of IL-6- and dexamethasone-treated cells was screened with cDNA probes from both induced and non-induced cells. Two cDNAs showed a differential hybridization signal. The first one corresponds to metallothionein, a group of small cysteine-rich proteins thought to participate in the metabolism and storage of zinc and to protect cells against oxidative damage. A second cDNA corresponds to the recently cloned cDNA of band 7 integral membrane protein also called stomatin. In hereditary stomatocytosis, absence of this protein in erythrocyte membranes is associated with high Na+ and low K+ intracellular concentrations [Stewart, G. W., Hepworth-Jones, B. E., Keen, J. N., Dash, B. C. J., Argent, A. C. & Casimir, C. M. (1992) Blood 79, 1593-1601]. In UAC cells both metallothionein and stomatin are induced by dexamethasone and IL-6 in a more than additive manner. Western blot analysis shows that stomatin protein is induced in a similar way as its mRNA. IL-6 and dexamethasone induce a state of resistance against hydrogen peroxide toxicity in UAC cells. Metallothionein induction might be partly responsible for this cytoprotection against oxidative stress.

We report a case of bilateral optic neuropathy associated with the CREST syndrome, a variant of scleroderma. Immunosuppressive therapy achieved significant improvement of the visual symptoms for two years. The pathophysiological mechanisms underlying this unique association remain unclear.

The radial position of a gene within its chromosome territory (CT) in the interphase nucleus is thought to depend on the transcriptional activity of the gene and on transcriptional activity, gene density, and conformation of the chromosomal surrounding. In this study we analyzed the position of the cell cycle regulator gene p21 within the CT of human chromosome 6 (HSA6) upon transcriptional activation. Whereas the majority of active p21 genes is located in the interior of the CT of HSA6, induction of p21 transcription correlates with increased variation of gene localization within the CT and with a higher percentage of p21 genes located at the periphery of the CT. Additionally it demonstrates once more that transcription can take place throughout CTs. Comparison of the p21 locus with two non-coding regions on HSA6 showed that both non-coding sequences are located more frequently in the interior of the CT than p21 genes although they are situated in chromosomal neighborhoods with widely differing gene density and regional transcriptional activity. Thus our data support models describing an influence of the transcriptional activity of a gene on the localization within its CT. However, our data also indicate that additional factors such as chromatin remodeling are implicated in the positioning of genes within the respective chromosome territory.

Analysis of the IL-6 Receptor β chain (gp130) mRNA expression on the two human epithelial cell lines UAC and Hep3B reveals that it is enhanced by IL-6, IL-1 and TNF treatment. In the case of UAC cells, TNF action might be mediated by IL-6. For Hep3B cells, TNF seems to exert a direct effect on gp130, as no IL-6 expression is detected after stimulation by this cytokine. On the same cells, increase of the binding of an anti-gp130 monoclonal antibody was observed after treatment by TNF, which denotes the effective appearance of new gp130 molecules on the cell surface. All this cytokines seem to act selectively on the β chain of the IL-6 receptor. This probably reflects the importance for some cells to have gp130 represented on their membrane in inflammatory contexts.

Contains fulltext : 79904.pdf (Publisher’s version ) (Closed access) PURPOSE: To evaluate the long-term outcome after surgery and radiotherapy for patients with sinonasal cancer and assess late toxicity, with special emphasis on hypothalamic-pituitary dysfunction. METHODS AND MATERIALS: A retrospective analysis of 168 patients treated for sinonasal cancer in a single institute between 1986 and 2006. A more detailed analysis was performed on a subgroup of 76 patients with adenocarcinoma or squamous cell carcinoma treated with curative intent. Long-term survivors were evaluated for late toxicity by a multidisciplinary team using the late effects of normal tissues (LENT SOMA) scoring system. Additional endocrinologic tests were performed for assessment of hypothalamic-pituitary function. RESULTS: Five-year actuarial local control and overall survival rates were 62% and 35% for all patients and 64% and 42% for the subgroup with squamous cell carcinoma and adenocarcinoma. In multivariate analysis, T stage was the only significant factor predicting local relapse (79% at 5 years for T1-T3 vs. 53% for T4; p = 0.006). Sinonasal mucosal melanomas had the highest rate of regional failure (33% at 5 years). Thirteen of 21 patients (62%) evaluated at the late morbidity clinic had hormonal disturbances, of whom 5 (24%) had definitive evidence of hypopituitarism with multiple hormonal deficiencies. CONCLUSION: Local failure is the dominant cause of treatment failure for patients with sinonasal cancer, with T4 stage the only independent predictor. Because of a high rate of radiation-induced hypopituitarism, we recommend endocrinologic surveillance for these patients.

Specific fundus changes have been reported in patients with membranoproliferative glomerulonephritis type II (MPGN type II). We studied the clinical course of this retinopathy in four patients who all had a long follow-up with several fundus examinations. Sequential observation was indicative of a slow progression of the retinopathy. Most eyes maintained in the chronic stages a nearly normal visual acuity, and a full visual field despite the existence of marked drusen and atrophic changes. The prognosis however must be somewhat guarded, since choroidal neovascularization developed in three eyes and caused bilateral severe visual loss in one patient.

We describe a case of an acute symptomatic and non-progressive visual field constriction in one eye of a 19-year-old female with optic disc drusen. The fellow eye showed slowly progressive visual field defects. A limited or retrolaminar infarction of the optic nerve head seems a plausible cause of the acute visual field loss. The slow progression in the fellow eye is most probably due to mechanical compression by the drusen. The case is documented with Humphrey perimetry during a follow-up of 11 years and with Color Doppler Imaging (CDI) of the optic nerve.

To analyse short term visual outcomes and macular morphologic changes associated with intravitreal injection of bevacizumab (Avastin) therapy for subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) METHOD: Retrospective study of 59 eyes. Each included eye received 3 intravitreal injections of 1.25 mg bevacizumab at 4 to 6-week intervals. Mean follow-up was 5.5 months (range 3 to 9). Best-corrected visual acuity, ophthalmoscopic examination, optic coherence tomography and fluorescein or green indocyanin angiography were performed before and routinely after the treatment.A total of 160 injections were performed with a mean value of 2.7 (1-6) per eye. Visual acuity improved at least two lines in 17% (10 eyes), worsened at least two lines in 14% (8 eyes) and was stabilized in 69% (41 eyes). Among that last group of 41 eyes, a significative reduction of macular thickness was observed in more than 39% (12 eyes) and a subjective improvement with less metamorphopsia and better visual comfort was noticed in 24% (10 eyes). No intraocular or systemic adverse effects were observed except a self-limited iritis in two cases.Intravitreal bevacizumab therapy resulted in visual and morphologic improvements in a significant number of cases of advanced AMD with CNV. Randomized studies and longer follow-up are needed to confirm these preliminary results.

The first Belgian specimen of Platyperigea kadenii (Freyer, 1836) was observed and photographed at Moen (Province of West-Vlaanderen) on 08 July 2006. In 2007 the species was recorded from four localities in the provinces of Hainaut, Limburg, and Vlaams-Brabant.

4(5)-(2,2-diphenylethyl)imidazole 6a is described as being a potent (pKi = 8.16 for displacement of [3H] p-amino-clonidine) and selective (selectivity = -log (pKiα2 - pKi α1) = 81)α2-adrenoreceptor antagonist (pA2 = 8.73 versus clonidine in the electrically stimulated guinea pig ileum) with additional activity as a norepinephrine uptake inhibitor (IC50 = 0.3 μM). An investigation of the structure-activity relationships of compounds closely related to 6a has been carried out. This included substitution of the phenyl and imidazole rings and modification of the link between these two ring systems. The various synthetic routes used are described. The affinity and the selectivity of the compounds for the α2 site were determined by studying the displacement of [3H] p-aminoclonidine and [3H] WB-4101 from rat forebrain membranes. The efficacy of the compounds was defined by measuring the antagonism of the clonidine effect on the electrically stimulated guinea pig ileum.

Iodinated recombinant human interleukin-6(125I-rhIL-6) was intravenously injected into rats and its fate was studied during 24 h. Between 10–20 min after a single-dose injection, 125I-rhIL-6 accumulated in liver as previously reported [Castell et al. (1988) Eur. J. Biochem. 177, 357–361]. After 1 h. the radioactivity disappeared from the liver and accumulated in skin, reaching 35% of injected 125I-rhIL-6 5–8 h after injection. No comparable accumulation of radioactivity was found in skin when [125I]iodide or rat serum 125I-albumin was administered. Finally the radioactivity was detected as [125I]iodide in urine. Autoradiograhic analysis of skin sections 5 h after 125-I-rhIL-6 injection showed radioactivity in the interstitium. When the experiments were carried out with [35S]rhIL-6, essentially the same results were obtained: a decrease in radioactivity in the liver after 20 min, and a substantial increase in skin 7 h after injection. In vitro experiments showed that 125I-rhIL-6 is degraded by rat and human fibroblasts, whereas no degradation was observed with rat hepatoma cells (Fao) or human hepatocytes. These observations suggest the involvement of skin in the catabolism of IL-6.

Three patients with systemic lupus erythematosus (SLE) associated with anti-phospholipid antibodies are reported. All three had severe vaso-occlusive disease: the first had an unilateral vaso-occlusive retinopathy, the second an unilateral central retinal venous obstruction, and the third a bilateral ischemic choroidopathy. The association of these occlusive ocular vascular diseases with the presence of the lupus anticoagulant and other associated factors in SLE is discussed.

PURPOSE: To report the clinical and imaging features in four male patients presenting with Susac syndrome, a microangiopathy affecting the brain, the retina, and the cochlea. METHODS: Retrospective review of clinical data, fluorescein angiograms, and magnetic resonance imaging findings in these four cases. RESULTS: All four patients were young men (range, 20-35 years). The axiomatic triad of ocular, cochlear, and neurologic involvement was present in three patients. Neurologic symptoms were absent in the fourth one. Fluorescein angiography showed arteriolar wall hyperfluorescence in all four patients. Magnetic resonance images showed in three patients multifocal hyperintense lesions in the white matter and the corpus callosum with typical involvement of the central fibers. Therapeutic modalities and clinical course are described. Three patients had a follow-up of 3, 5, and 13 years with complete remission of the disease within 1 year in all three cases. One patient had severe neuropsychological sequelae. CONCLUSION: Susac syndrome seems to be less unusual in men than previously reported. Though presenting as a self-limited monophasic course disease in most cases, it may result in severe neuropsychological sequelae. Early diagnosis of the syndrome is enabled by the combination of the ophthalmologic, audiometric, and brain magnetic resonance features.

Purpose : To evaluate the safety and efficacy of photodynamic therapy with verteporfin (PDT) for subfoveal classic choroidal neovascularization (CNV) related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Methods : Retrospective review of 16 eyes from 14 patients with subfoveal classic CNV associated with PIC or POHS-like and treated with PDT. Results : The mean visual acuity increased from 4.5/10 (range: 1/10-9/10) to 7/10 (range: 2/10-10/10) after a mean follow-up of 21 months (range: 8-32 months) and a mean number of 2 PDT (range: 1-6). Visual acuity remained stable or improved in 13 of the 16 eyes (81%) and decreased in three. Conclusion : This nearly two-year follow-up study suggests that PDT could be helpful for patients with subfoveal classic CNV related to PIC or POHS-like.

The imputability of a bodily damage to a traumatism and the bond of causality are at the basis of the mission of the medical expert in the procedure that leads to indemnification in reparation of a suffered prejudice. The aim of this paper is to enumerate the bases on which the expert grounds to prove the imputability and the bond of causality. He will also insist on the final role of the jurist who, grounding his opinion on the elements of the expert appraisement, will establish the causality and hence the responsibility and the level of reparation.

HeLa cells were stably transfected with a cDNA clone encoding the B1 isoform of the mouse FcγRII receptor (hereafter referred to as HeLa-FcRII cells). The receptor was expressed at high level at the plasma membrane in about 90% of the cells. These cells bound and internalized mouse monoclonal virus-neutralizing antibodies 8F5 and 3B10 of the subtype immunoglobulin G2a (IgG2a) and IgG1, respectively. Binding of the minor-group human rhinovirus type 2 (HRV2) to its natural receptors, members of the low-density lipoprotein receptor family, is dependent on the presence of Ca 2+ ions. Thus, chelating Ca 2+ ions with EDTA prevented HRV2 binding, entry, and infection. However, upon complex formation of 35 S-labeled HRV2 with 8F5 or 3B10, virus was bound, internalized, and degraded in HeLa-FcRII cells. Furthermore, challenge of these cells with HRV2-8F5 or HRV2-3B10 complexes resulted in de novo synthesis of viral proteins, as shown by indirect immunofluorescence microscopy. These data demonstrate that minor-group receptors can be replaced by surrogate receptors to mediate HRV2 cell entry, delivery into endosomal compartments, and productive uncoating. Consequently, the conformational change and uncoating of HRV2 appears to be solely triggered by the low-pH (pH ≤ 5.6) environment in these compartments.

PURPOSE: To evaluate the effect of photodynamic therapy on subfoveal neovascular membrane related to type 2A idiopathic juxtafoveolar retinal telangiectasia. DESIGN: Interventional case series. METHODS: Retrospective review of four eyes of four patients who underwent photodynamic therapy for subfoveal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasia. Ocular photodynamic therapy with verteporfin was performed in all cases using standard protocols. Results are given in terms of final visual acuity and neovascular membrane activity based on clinical examination, fluorescein and indocyanin green angiography, and, in two cases, optical coherence tomography. RESULTS: Baseline visual acuity of 20/30 and 20/40 (x2) was maintained in three patients after one, two, and three sessions of photodynamic therapy respectively, and a follow-up of 23, 21, and 9 months. Leakage specific to the subfoveal neovascular membrane ceased on the fluorescein angiography. In the other patient, the final vision decreased from 20/50 to 20/200 after four sessions of photodynamic therapy and a follow-up of 14 months. Although there was still mild persistent leakage on the fluorescein angiography, neovascular membrane size was unchanged, and no subretinal fluid was demonstrated on optical coherence tomography. CONCLUSIONS: Data from this case series suggest that photodynamic therapy may be effective in managing subfoveal neovascular membrane associated with idiopathic juxtafoveolar retinal telangiectasia, which usually carries a poor visual prognosis. Prospective study is required to confirm the beneficial effect of this treatment.

The very-low-density lipoprotein receptor (VLDL-R) is a receptor for the minor-group human rhinoviruses (HRVs). Only two of the eight binding repeats of the VLDL-R bind to HRV2, and their footprints describe an annulus on the dome at each fivefold axis. By studying the complex formed between a selection of soluble fragments of the VLDL-R and HRV2, we demonstrate that it is the second and third repeats that bind. We also show that artificial concatemers of the same repeat can bind to HRV2 with the same footprint as that for the native receptor. In a 16-Å-resolution cryoelectron microscopy map of HRV2 in complex with the VLDL-R, the individual repeats are defined. The third repeat is strongly bound to charged and polar residues of the HI and BC loops of viral protein 1 (VP1), while the second repeat is more weakly bound to the neighboring VP1. The footprint of the strongly bound third repeat extends down the north side of the canyon. Since the receptor molecule can bind to two adjacent copies of VP1, we suggest that the bound receptor “staples” the VP1s together and must be detached before release of the RNA can occur. When the receptor is bound to neighboring sites on HRV2, steric hindrance prevents binding of the second repeat.