5 research outputs found
Expression of the HNK-1 carbohydrate epitope in human retina and retinoblastoma. An immunohistochemical study with the anti-Leu-7 monoclonal antibody.
Fifty formalin-fixed and paraffin-embedded retinoblastoma specimens and five normal human eyes were studied with the monoclonal anti-Leu-7 antibody, directed against the HNK-1 carbohydrate epitope that is shared by human natural killer cells and many neuronal, glial and neuroectodermal cells. The laboratory method was a sensitive immunohistochemical staining procedure, and neuroectodermal tumours that usually express this epitope were used as positive controls. In the human retina, Müller cell membranes were positively stained, but additional staining of neuronal cells was not excluded at the light microscopical level. A positive cytoplasmic reaction was also seen in ciliary and retinal pigment epithelial cells. All but one intraocular retinoblastomata studied contained cells staining positively for the HNK-1 epitope, but these cells were probably not neoplastic. Although positive reaction has previously been reported in three retinoblastomata, the present results suggest that positive cells are derived from entrapped and infiltrated retina. Staining of adjacent sections against leukocyte common antigen suggested that the positively staining cells were not natural killer cells.Peer reviewe
A lectin cytochemical study of glycoconjugates in the human retina
The binding to morphologically normal human retina of eleven biotin- or peroxidase-coupled lectins with different carbohydrate specificities was studied. Eight formalin-fixed and paraffin-embedded eyes were examined. Photoreceptor cells bound Lens culinaris (LCA), wheat germ (WGA), peanut (PNA) and Ricinus communis (RCAI) agglutinins, and concanavalin A (ConA). The outer segment region was labeled more strongly that the inner segment region, and PNA labeled only cones. All these lectins except PNA bound to both plexiform layers, and all but PNA and RCAI to the nuclear layers. Pretreatment with neuraminidase to remove sialic acid resulted in increased binding of RCAI and PNA, which now labeled both rods and cones, and in decreased binding of WGA. Bandeiraea simplicifolia (BSAI), Dolichos biflorus (DBA), soybean (SBA), Ulex europaeus (UEAI), and Lotus tetragonolobus (LTA) agglutinins, as well as pokeweek mitogen (PWM) reacted only with retinal vascular endothelial cells, which were also labeled with the other lectins. The results indicate that alpha-mannose, alpha-glucose, beta-galactose, N-acetyl-D-glucosamine and N-acetylneuraminic acid are present in glycoconjugates of human neuroretina.Peer reviewe
Carcinoembryonic antigen in retinoblastoma. An immunohistochemical study.
Pathological amounts of carcinoembryonic antigen (CEA) have earlier been reported in the plasma of patients with retinoblastoma, and it has been suggested that CEA determinations be used in the follow-up of treatment of these patients. In the present study, 47 retinoblastoma specimens from the years 1962-1982 were examined. These specimens represented different clinical and pathological tumour types. Colon adenocarcinomata positive for CEA were used as controls. The laboratory method was a highly sensitive immunohistochemical peroxidase-staining procedure. By this method, CEA was not found in any of the retinoblastomata examined. It is probable that retinoblastoma does not produce CEA, but in theory it may indirectly increase the CEA titre or, on the other hand, be fully independent of CEA. Only after this relationship has been thoroughly clarified can determinations of plasma CEA in patients with retinoblastoma be used in clinical work.Peer reviewe
Functional consequences of pathogenic variant c.61G>C in the inflammasome gene NLRP3 underlying keratitis fugax hereditaria
AimsTo elucidate the effect of NLRP3 variant c.61G>C on interleukin-1 beta (IL-1 beta) secretion in keratitis fugax hereditaria (KFH), a cryopyrin-associated periodic syndrome limited to the eye, and to probe the potential modifying role of prednisolone. MethodsPeripheral blood mononuclear cells (PBMCs) isolated from whole blood of patients with KFH and healthy controls were grown under steady-state conditions or primed with lipopolysaccharide (LPS) with or without prednisolone, and subsequently activated with ATP. Cell lysates and proteins precipitated from the cell culture media were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. NLRP3, procaspase-1, and IL-1 beta were visualised by western blotting. The concentration of secreted IL-1 beta in the culture media was quantified by ELISA. ResultsFollowing priming of the NLRP3 inflammasome with LPS, a lower threshold for IL-1 beta secretion was observed in patient-derived PBMCs, compared with healthy controls (median, 124 vs 10 pg/mL, respectively). Interestingly, in PBMCs derived from patients with frequent KFH symptoms, LPS priming alone was able to trigger substantial IL-1 beta secretion (median, 522 pg/mL), whereas those of patients experiencing occasional KFH attacks showed a subtler release of IL-1 beta (median, 85 pg/mL). NLRP3 expression was significantly enhanced with LPS stimulation (p=0.03) whereas procaspase-1 expression was not affected. LPS and ATP treated PBMCs from patients with KFH showed significantly diminished IL-1 beta secretion with prednisolone treatment (p=0.04). ConclusionsPBMCs from patients with KFH are more prone to secrete IL-1 beta, confirming the presumption that the c.61G>C is a gain-of-function variant. Furthermore, prednisolone is confirmed as a potent drug to reduce IL-1 beta secretion in KFH.Peer reviewe