Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling.

Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin's (HAs) are examined by chemoenzymatic synthesis of N-glycans having 13C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-1H by 13C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.

Bilateral macular edema in sistemic sclerosis.

Systemic sclerosis is a chronic, autoimmune, multisystem disease characterized by vascular dysfunction, chronic inflammation and widespread fibrosis. Although vascular involvement commonly manifests in the skin, it can also affect other organs, including the eyes. The characteristic vascular alteration is an obliterative fibroproliferative vasculopathy leading to hypoxia and tissue ischemia. We present a case of bilateral macular edema in a patient diagnosed with systemic sclerosis, as a consequence of retinal and choroidal vascular changes.

Identification of a new DC-SIGN binding pentamannoside epitope within the complex structure of Candida albicans mannan.

The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune C-type lectin receptor that recognizes carbohydrate-based pathogen associated with molecular patterns of various bacteria, fungi, viruses and protozoa. Although a range of highly mannosylated glycoproteins have been shown to induce signaling via DC-SIGN, precise structure of the recognized oligosaccharide epitope is still unclear. Using the array of oligosaccharides related to selected fragments of main fungal antigenic polysaccharides we revealed a highly specific pentamannoside ligand of DC-SIGN, consisting of α-(1 â†’ 2)-linked mannose chains with one inner α-(1 â†’ 3)-linked unit. This structural motif is present in Candida albicans cell wall mannan and corresponds to its antigenic factors 4 and 13b. This epitope is not ubiquitous in other yeast species and may account for the species-specific nature of fungal recognition via DC-SIGN. The discovered highly specific oligosaccharide ligands of DC-SIGN are tractable tools for interdisciplinary investigations of mechanisms of fungal innate immunity and anti-Candida defense. Ligand- and receptor-based NMR data demonstrated the pentasaccharide-to-DC-SIGN interaction in solution and enabled the deciphering of the interaction topology.

The two domains of human galectin-8 bind sialyl- and fucose-containing oligosaccharides in an independent manner. A 3D view by using NMR.

The interaction of human galectin-8 and its two separate N-terminal and C-terminal carbohydrate recognition domains (CRD) to their natural ligands has been analysed using a synergistic combination of experimental NMR and ITC methods, and molecular dynamics simulations. Both domains bind the minimal epitopes N-acetyllactosamine (1) and Galß1-3GalNAc (2) in a similar manner. However, the N-terminal and C-terminal domains show exquisite and opposing specificity to bind either Neu5Ac- or Fuc-containing ligands, respectively. Moreover, the addition of the high-affinity ligands specific for one of the CRDs does not make any effect on the binding at the alternative one. Thus, the two CRDs behave independently and may simultaneously target different molecular entities to promote clustering through the generation of supramolecular assemblies.

Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring α-Galactose, α-Galactosamine and α-N-Acetyl Galactosamine Linkages.

Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus. GAG is a heteropolysaccharide composed of α-1,4-linked galactose, galactosamine and N-acetylgalactosamine residues. To enable biochemical studies, a library of GAG-fragments was constructed featuring specimens containing α-galactose-, α-galactosamine and α-N-acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di-tert-butylsilylidene directed α-galactosylation methodology and regioselective benzoylation reactions using benzoyl-hydroxybenzotriazole (Bz-OBt). Structural analysis of the Gal, GalN and GalNAc oligomers by a combination of NMR and MD approaches revealed that the oligomers adopt an elongated, almost straight, structure, stabilized by inter-residue H-bonds, one of which is a non-conventional C-H⋅⋅⋅O hydrogen bond between H5 of the residue (i+1) and O3 of the residue (i). The structures position the C-2 substituents almost perpendicular to the oligosaccharide main chain axis, pointing to the bulk solvent and available for interactions with antibodies or other binding partners.

Bacterial polysaccharides: conformation, dynamics and molecular recognition by antibodies.

Bacterial infections are the cause of different severe health conditions and new therapies to combat these pathogens have been widely investigated. Carbohydrates, being complex structures covering the surface of bacteria, are considered relevant targets for antibody and vaccine development. The biological activities in pathogenesis of bacterial capsular polysaccharides and lipopolisaccharides and their unique structures have boosted the study of the minimal antigenic binding epitopes and the structural details of antibody-carbohydrate recognition. This review describes the most recent advances on the field, examining the structure, conformation and dynamics of relevant bacterial carbohydrates and their complexes with antibodies. The understanding of key factors governing the recognition process is fundamental for the progress toward the development of specific and efficient bacterial therapeutics.

Palladium(II)-Catalyzed Intramolecular C-H Alkenylation for the Synthesis of Chromanes.

The intramolecular Pd(II)-catalyzed alkenylation of aryl homoallyl ethers constitutes a mild, versatile, and efficient procedure for the synthesis of highly and diversely substituted chromanes and 2 H-chromenes. The use of p-TsOH as an additive allows more efficient reactions that could be carried out a room temperature in most cases. The procedure has a wide scope, allowing the synthesis of alkylidenechromanes and 2 H-chromenes substituted at C-2 or C-3 of the chromene moiety, thus accessing relevant flavenes and isoflavenes, and even coumarins, in high yields (59 to 91%, 32 examples).

Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of literature on skull sarcoidosis.

Bone sarcoidosis of the skull is an infrequent presentation of sarcoidosis. We describe a 51-year-old man who consulted due to inflammatory-appearing nodulation in the right supraorbital region. Images showed a solitary osteolytic lesion extending to soft tissues with increased scintigraphic uptake. The anatomopathological study revealed the presence of non-caseating epithelioid granulomas, compatible with sarcoidosis. Steroid treatment led to a marked remission of the lesion, without evidence of relapse during a follow-up period of 1 year. The literature dealing with skull sarcoidosis is reviewed.

Optical sensors based on III-nitride photodetectors for flame sensing and combustion monitoring.

Combustion control requires visible photodetectors to sense the CH* CL emission at 430 nm that combined with a visible-blind UV photodetector allows us to obtain the OH*/CH* ratio. UV-visible P-InGaN/GaN multiple quantum well-N photodiodes with 15-18 mm2 areas were fabricated to conduct OH* (308 nm) and CH* CL detection without external filters. Bandpass detectors at 230-390 nm and 360-450 nm presented linear responses over five decades and rejection ratios >10(3) at 430 and 308 nm, respectively. A full optical sensor system was built and detectors operated at 120 degrees C in a combustion chamber, showing linear responses within the dynamic range, maximum signal-to-noise ratios of 103 and response times of <1 s. An exponential association dependence between the optical OH*/CH* CL signals and the gas/air ratios was found.

[Glaucoma drainage device obstruction]. / Obstrucción del tubo de los dispositivos de drenaje.

PURPOSE: To determine the pathophysiology and to discuss possible solutions for tube obstruction since this is a frequent complication in glaucoma drainage device surgery. MATERIAL AND METHODS: 81 eyes with a glaucoma drainage device (GDD) fitted by our Department during the last twelve years (1991-2002) were retrospectively reviewed and eleven cases of tube obstruction were detected. The treatments included Nd-Yag laser, anterior vitrectomy, blood clot removal and intracamerular rTPA. RESULTS: The obstruction was proximal in ten cases and distal in one. Of the former, the obstruction was caused by a blood clot in six cases, by vitreous in three cases and by a fibrinous membrane in one case. The nature of the distal obstruction was not determined. One case of vitreous obstruction occurred after a posterior capsulotomy with Nd-Yag laser two years after positioning the GDD. Complete success was achieved in five cases, and partial success in three where antiglaucoma therapy had to be maintained postoperatively. Complete failure was found in the other three cases. CONCLUSIONS: The material which most frequently caused the tube obstruction was blood and although in some cases this may resolve spontaneously, clot removal with forceps or rTPA intracameral injection may be helpful. In vitreous obstruction, Nd-Yag laser may temporariril clear the tube, but extensive anterior vitrectomy is required to maintain long-term permeability. We suggest carrying out a small posterior capsulotomy in pseudophakic patients with a GDD.

Cutaneous horns of the eyelid: a clinicopathological study of 48 cases.

BACKGROUND: Cutaneous horn (cornu cutaneum) is a morphological designation for a protuberant mass of keratin that resembles the horn of an animal. It results from unusual cohesiveness of keratinized material from the superficial layers of the skin or implanted deeply in the cutis. This lesion may be associated with a benign, premalignant, or malignant lesion at the base, masking numerous conditions. METHODS: A retrospective analysis of 48 cases of cutaneous horns of the eyelid treated between 1992 and 2002 has been performed. RESULTS: Twenty-four men and 19 women, with a mean age of 62 years (range 16-90), were treated by surgery. Histologically, 77.1% were associated with benign specimens at the base pathology, 14.6% were premalignant, and finally, 8.3% were caused by malignant skin tumors. The most common lesion was seborrheic keratosis among the benign lesions, actinic keratosis among the premalignant ones, and basal cell carcinoma and squamous cell carcinoma among the malignant ones. CONCLUSION: Cutaneous horns usually appear on exposed skin areas in elderly men. The important issue in this condition is not the horn itself, which is just dead keratin, but rather the nature of the underlying disease, although the horns are usually benign.

Obstrucción del tubo de los dispositivos de drenaje / Glaucoma drainage device obstruction

Propósito: Determinar la patofisiología y presentar posibles soluciones a la obstrucción del tubo de los dispositivos de drenaje para glaucoma (DDG), ya que es una complicación frecuente en esta cirugía. Material y métodos: Se realizó una revisión retrospectiva de 81 ojos a los que se les había implantado un DDG durante un período de doce años (1991-2002) y se identificaron once casos de obstrucción del tubo. Los tratamientos empleados fueron: lavado de cámara anterior con extracción de coágulo, rTPA intracamerular, vitreolísis con láser Nd-Yag y vitrectomía anterior. Resultados: En diez casos la obstrucción fue proximal, debida a coágulos de sangre en seis ojos, vítreo en tres ojos y una membrana de fibrina en un ojo. En un caso la obstrucción fue distal, no pudiéndose identificar la causa. Un caso de obstrucción por vítreo se produjo tras realizar una capsulotomía posterior con láser Nd-Yag, dos años después de la colocación del DDG. Obtuvimos éxito en cinco casos, en tres éxito parcial que requirió mantener el tratamiento antiglaucomatoso. En tres casos el resultado fue fracaso. Conclusiones: La causa más frecuente de obstrucción del tubo fue sangre y aunque se puede resolver espontáneamente, la inyección de rTPA intracameral o el lavado de cámara anterior con extracción del coágulo son tratamientos eficaces. En la obstrucción por vítreo, una vitrectomía anterior amplia es más eficaz que la vitreolisis con láser Yag. Es recomendable realizar una capsulotomía posterior pequeña en pacientes pseudofáquicos con un DDG(AU)

Purpose: To determine the pathophysiology and to discuss possible solutions for tube obstruction since this is a frequent complication in glaucoma drainage device surgery. Material and Methods: 81 eyes with a glaucoma drainage device (GDD) fitted by our Department during the last twelve years (1991-2002) were retrospectively reviewed and eleven cases of tube obstruction were detected. The treatments included Nd-Yag laser, anterior vitrectomy, blood clot removal and intracamerular rTPA. Results: The obstruction was proximal in ten cases and distal in one. Of the former, the obstruction was caused by a blood clot in six cases, by vitreous in three cases and by a fibrinous membrane in one case. The nature of the distal obstruction was not determined. One case of vitreous obstruction occurred after a posterior capsulotomy with Nd-Yag laser two years after positioning the GDD. Complete success was achieved in five cases, and partial success in three where antiglaucoma therapy had to be maintained postoperatively. Complete failure was found in the other three cases. Conclusions: The material which most frequently caused the tube obstruction was blood and although in some cases this may resolve spontaneously, clot removal with forceps or rTPA intracameral injection may be hepful. In vitreous obstruction, Nd-Yag laser may temporariril clear the tube, but extensive anterior vitrectomy is required to maintain long-term permeability. We suggest carrying out a small posterior capsulotomy in pseudophakic patients with a GDD(AU)