PubMed Health⌕ Search

Biomedical subjects

A Negi

Publications and source records attributed to A Negi.

At least 19 recordsLinked to original sources

Humoral immune response directed against LEDGF in patients with VKH.

Vogt-Koyanagi-Harada disease is an autoimmune systemic disorder. In Vogt-Koyanagi-Harada disease, inflammatory disorders occur in multiple organs containing melanocytes, including uvea (resulting in acute bilateral panuveitis), skin (resulting in vitiligo and alopecia), central nervous system (resulting in meningitis) and inner ears (resulting in hearing loss and tinnitus). These inflammatory aspects are attributed to the destruction of melanocytes through immunological mechanisms. Studies have been carried out to elucidate the exact etiology and target autoantigen in Vogt-Koyanagi-Harada disease, but much remains to be investigated. Identification of target autoantigen is important to understand the etiology of autoimmune diseases, and for development of antigen-specific immuno-modulation therapy. To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada disease. We identified an immunoreactive cDNA clone that encodes bovine lens epithelium derived growth factor. mRNA of human lens epithelium derived growth factor was determined by reverse transcription-polymerase chain reaction and it was expressed in human uvea, retina and melanocytes. Immunoglobulin G (IgG) autoantibodies were quantitated in an enzyme-linked immunosorbent assay, using recombinant human lens epithelium derived growth factor. The prevalence of IgG anti-lens epithelium derived growth factor autoantibodies in patients with Vogt-Koyanagi-Harada disease was significantly higher than that in healthy controls (66.7% versus 21.6%, P<0.001). On the other hand, the prevalence of the autoantibody in patients with panuveitis of other etiology, Behçet's disease and sarcoidosis, was almost same as that in healthy controls. These results suggest that the humoral immune response agonist lens epithelium derived growth factor is not a mere secondary phenomena caused by uveal tissue damage.

Adult↗

Identification of a novel autoantigen UACA in patients with panuveitis.

To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada disease. We identified a novel bovine antigen and homologous human autoantigen and designated it as UACA (uveal autoantigen with coiled coil domains and ankyrin repeats). mRNA of human UACA is expressed most abundantly in skeletal muscles and in various human tissues, including choroid, retina, and epidermal melanocytes. IgG autoantibodies were quantitated in an ELISA, using recombinant C-terminal 18.0% fragment of human UACA. The prevalence of IgG anti-UACA autoantibodies in patients with panuveitis (Vogt-Koyanagi-Harada disease, Behçet's disease, sarcoidosis) was significantly higher than that in healthy controls (19.6-28.1% vs 0%, P < 0.05) indicating that autoimmunity directed against UACA is a common phenomenon in these diseases.

Adolescent↗

Starch and protein digestibility of newly released moth bean cultivars: Effect of soaking, dehulling, germination and pressure cooking.

Effect of soaking (12 h), soaking (12 h) dehulling, germination (60 h) and pressure cooking on starch and protein digestibility of four varieties of moth bean, one Local commonly used by the farmers of the area and three newly released high yielding varieties, Jwala, RMO 225 and RMO 257, was studied. The starch digestibility of raw unprocessed moth bean cultivars differed significantly (P < 0.05) from 25.4-28.2 mg maltose released/g flour being the highest and lowest in RMO 257 and RMO 225, respectively. The protein digestibility differed significantly from 70.3-74.6 per cent among all the unprocessed varieties of moth bean. All the processing treatments namely soaking, dehulling, germination and pressure cooking brought about appreciable enhancement in protein digestibility (1-19%) over the control and starch digestibility (19-115%) of all the four moth bean cultivars. However, out of all the processing treatments, germination (60 h) of soaked seeds (12 h) was the most effective in bringing about improvement in digestibility of starch and protein followed by dehulling and soaking (12 h).

Cooking↗

Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro.

The pathogenesis of pseudomonal keratitis was investigated by focusing on induction and activation of matrix metalloproteinases (MMPs) by pseudomonal virulence factors and proinflammatory cytokines. Corneal lesions and MMP induction in vivo were evaluated in rabbit corneas infected with a clinical isolate of Pseudomonas aeruginosa. Effects of pseudomonal virulence factors [elastase, alkaline protease, exotoxin A and lipopolysaccharide (LPS)], tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta on MMP induction and activation were further examined in vitro in rabbit corneal fibroblasts (RCF) and human fibrosarcoma (HT1080) cells using reverse transcriptase-polymerase chain reaction (RT-PCR), zymography and immunoblotting. Corneal ulcers with typical ring abscesses were observed 12-24 h after infection, and MMPs, particularly MMP-9, were upregulated in infected corneas. Pseudomonal elastase caused the most extensive damage to both cell types. RCF treated with pseudomonal exoproteases or LPS expressed and secreted MMP-9. Exotoxin A had no effect on MMP expression. Both IL-1beta and TNF-alpha augmented MMP-9 expression in HT1080 cells. Pseudomonal elastase proteolytically activated MMP-2 and MMP-9 released from the cells. In conclusion, corneal destruction seen with P. aeruginosa infections may result from enhanced expression of MMPs by corneal stromal cells stimulated with pseudomonal exoproteases and proinflammatory cytokines and the proteolytic activation of MMPs by pseudomonal elastase.

ADP Ribose Transferases↗

Fundus changes corresponding to visual field defects after vitrectomy for macular hole.

OBJECTIVE: Visual field defects are one of the complications of macular hole surgery, and mechanical retinal damage induced by infusion air is a proposed causative factor of this complication. In this study, we examined the fundus to see whether the changes observed corresponded to postoperative visual field defects. DESIGN: Observational case series. PARTICIPANTS: Seventeen eyes of 17 patients who had postoperative visual field defects after vitrectomy for idiopathic macular hole were examined. METHODS: The fundus was examined by ophthalmoscopy and by fluorescein and indocyanine green angiography. MAIN OUTCOME MEASURES: Fundus changes corresponding to postoperative visual field defects. RESULTS: In eight eyes, detectable fundus changes were observed, including regional mottling and degeneration of the retinal pigment epithelium, filling delay of the choroidal circulation, subretinal fibrosis, and epiretinal membrane formation. These findings corresponded exactly to the visual field defects observed. Although the visual field defects had been detected shortly after surgery, fundus changes were detected, on average, more than 8 months after surgery. CONCLUSIONS: Fundus changes become apparent after surgery, and they are progressive. Therefore, it is important to examine eyes with visual field defects for a follow-up period of several years.

Aged↗

N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine reduces intracellular calcium response to noradrenaline in rat visual cortex.

Using the fluorescent indicator Fura-2, we investigated the effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin, on intracellular calcium responses to noradrenaline, N-methyl-D-aspartate, and carbamylcholine chloride in brain slices of the rat visual cortex. Noradrenergic depletion in the visual cortex of young rats was induced by DSP-4, and its selectivity was confirmed by two different methods, i.e., immunostaining with anti-dopamine-beta-hydroxylase antibody and biochemical analysis by high-performance liquid chromatography. The treatment with DSP-4 (25 mg/kg i.p., x2) caused disruption of noradrenergic fibers throughout all cortical layers, and reduced the content of noradrenaline to 6.4% of that in the normal control. In the normal cortex, bath-applied noradrenaline (100 microM) increased the intracellular calcium to 123% of the control in terms of the F(340)/F(380) ratio of Fura-2 fluorescence. Quantitative analysis of the F(340)/F(380) ratio was performed in layers II to IV, since the increase was mainly observed in these layers. The intracellular calcium response to noradrenaline was significantly (P<0.0001) reduced in the DSP-4-treated animals to 63.2% of that in the normal control. The response to N-methyl-D-aspartate (100 microM) was also reduced, whereas the response to carbamylcholine chloride, a muscarinic cholinergic agonist (100 microM), was not affected by the DSP-4 treatment. From these findings we suggest that noradrenergic denervation by DSP-4 reduces the intracellular calcium response to noradrenaline through changes in the intracellular signal transduction.

Adrenergic Agents↗

Selective reduction of the S-cone component of the electroretinogram in Posner-Schlossman syndrome.

PURPOSE: The changes in short wavelength sensitive (S-) cone electroretinograms (ERGs) to ganzfeldt flash stimuli were examined in patients with Posner-Schlossman syndrome to study the differences in S-cone action in both the acute attack phase and the remission phase. METHODS: Ganzfeldt colour flashes under bright white background illumination were used to elicit short wavelength (S-), and mixed long- (L) and middle- (M) wavelength sensitive cone ERGs. Three subjects with unilateral Posner-Schlossman syndrome and 18 age-matched normal controls were compared. To compare the media opacity we obtained the L,M-cone balance, namely, the log density units of the neutral density filter required to produce the L,M-cone b-wave elicited with red stimuli which is identical to those with blue stimuli. RESULTS: Selective reduction of the S-cone ERG b-wave in acute attacks of Posner-Schlossman syndrome was found. Two of three cases showed the recovery of the S-cone b-wave with a decrease in the intraocular pressure. With regard to the implicit time, significant delay of the S-cone b-wave could not be detected in all subjects. CONCLUSION: Selective reduction of the S-cone component of the ERG during raised intraocular pressure was found. The S-cone pathway is thought to be more vulnerable to damage than the L,M-cone systems following elevations of intraocular pressure.

Acute Disease↗

Noradrenaline receptor-mediated potentiation of caffeine-induced Ca( 2+)-activated K(+) currents in bovine ciliary muscle cells.

PURPOSE: Adrenoceptor-mediated modulation of a caffeine (CAF)-induced [Ca(2+)](i) elevation and resulting Ca(2+)-activated K(+) current (I(CAF)) in bovine ciliary muscle (CM) cells were investigated. METHODS: The nystatin-perforated patch clamp technique for the measurement of membrane currents and a microscope based fura-2 fluorescence imaging of [Ca(2+)](i) were applied to CM cells freshly dissociated with collagenase and identified with smooth muscle-specific alpha-isoactin. RESULTS: Under voltage-clamped conditions, noradrenaline (NA) potentiated I(CAF) in a NA concentration-dependent manner without producing current responses to NA when NA was applied alone. NA-induced potentiation of I(CAF) occurred within 20 sec after the application of NA, while the NA-potentiated I(CAF) gradually recovered to the control level within 30 min after removal of NA. Despite the little current response to NA applied alone, NA elicited a [Ca(2+)](i) elevation in a manner similar to that induced by CAF although the NA-induced [Ca(2+ )](i) elevation was smaller than the CAF-induced [Ca(2+ )](i) elevation. In contrast to the significant potentiation of I(CAF) with NA, NA produced little potentiation of the CAF-induced [Ca(2+)](i) elevation. The NA-induced potentiation of I( CAF) was antagonized by an alpha(1) adrenoceptor antagonist, prazosin. Neither clonidine nor isoproterenol had an effect on I(CAF), suggesting that alpha(2) and beta adrenoceptor are not involved in the response to NA. CONCLUSIONS: These results suggest that NA potentiates I( CAF) via alpha(1) adrenoceptor activation and that the NA-induced potentiation occurs at Ca(2+)-activated K(+) channels but not CAF-induced Ca(2+) releasing sites.

Adrenergic alpha-Antagonists↗

[Three ocular sarcoidosis patients examined by indocyanine green angiography].

PURPOSE: To assess the findings of indocyanine green angiography(IA) in patients with ocular sarcoidosis. SUBJECTS AND METHODS: Three active ocular sarcoidosis patients with various retinochoroidal findings diagnosed by biopsy or systemic examination. Two patients were diagnosed pathologically and one patient was diagnosed clinically. IA & fluorescein angiography(FA) were performed before and after treatment with systemic steroid administration. RESULTS: IA revealed hyperfluorescence surrounding the presumed granulomatous lesions. This hyperfluorescence disappeared immediately after the treatment. FA showed hyperfluorescence continuing even after therapy. CONCLUSIONS: It is purposed that the ring-form hyperfluorescence in IA is due to accelerated vascular permeability in the active sarcoid granuloma. IA, which vividly reflects activity of sarcoid lesions, is an important tool for clinical evaluation of ocular sarcoidosis.

Aged↗

Acidic electrolysed water in the disinfection of the ocular surface.

Acidic electrolysed water (AEW) is a colorless solution prepared by the electrolysis of sodium chloride solution, which has potent anti-microbial activity against a wide variety of bacteria, fungi and virus. In this study, the safety and efficacy of an isotonic AEW solution (iAEW) was investigated both in vitro and in vivo using denuded corneas of guinea pigs. Povidone iodine (0.01-1.0%) was used as control. Exposure of P. aeruginosa to iAEW for 5 sec caused total inhibition of bacterial growth in vitro. Comparable results were obtained with 1% povidone iodine, while more dilute solutions required longer exposure times for similar effects. Cytotoxicity of iAEW on corneal epithelial cells in vitro was significantly less compared to 1% povidone iodine (P<0.05), while minimal damage was observed in vivo by irrigation of the cornea with either iAEW or 1% povidone iodine. Treatment of P. aeruginosa with iAEW (15 sec) significantly inhibited the onset of corneal infection in guinea pigs. iAEW may offer an effective and safe method for disinfection of the ocular surface.

Disinfectants↗

Expression of Sonic hedgehog and retinal opsin genes in experimentally-induced myopic chick eyes.

The purpose of this study was to evaluate changes in the expression of different genes in chick retinal tissues after induction of experimental myopia and to evaluate the roles of these genes in the regulation of postnatal eye growth and myopia. Form-deprivation using occlusive goggles and hyperopic defocus by negative spectacle lenses were used to induce myopia in hatched chicks. Expression levels of Sonic hedgehog, its receptor complex, and other retinal cell genes were evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Levels of Sonic hedgehog protein were further evaluated by Western blot analysis. The induction of myopia caused significant increase in expression of Sonic hedgehog mRNA and protein and increased expression of blue and red opsin mRNA. In contrast, the expression of mRNA for Sonic hedgehog receptor complex (Patched-Smoothened), rhodopsin, vimentin, green opsin, violet opsin, and HPC-1 were unaffected by the induction of myopia. The increase in expression of Sonic hedgehog in chick retinas in experimentally-induced myopia suggests involvement in the retina control of postnatal eye growth. Furthermore, Sonic hedgehog may influence the expression of blue and red opsins under myopic conditions.

Animals↗

The process of closure of experimental retinal holes in rabbit eyes.

BACKGROUND: To investigate the healing process of retinal holes, including the identification of the cell types which play an important role in the process, we created experimental retinal holes with minimal damage to retinal pigment epithelium (RPE) in rabbit eyes. METHODS: Pars plana vitrectomy was performed in the rabbit eye. A dome-shaped retinal detachment (bleb; diameter 1.5 mm) was made by injecting balanced salt solution into the subretinal space, followed by making a retinal hole (diameter 0.5 mm) in the center of the bleb with a silicone-tipped extrusion needle. In one group of rabbits, fluid-air exchange was performed and sulfur hexafluoride gas was injected into the vitreous cavity postoperatively. In another group, gas tamponade was not performed. The operated eyes were examined ophthalmoscopically and enucleated at 1, 4, 7, 14, 30, and 90 days after surgery. Tissues were prepared in 5-microm sections for hematoxylin-eosin staining and immunohistochemistry with antibodies to cytokeratin 18 and glial fibrillary acidic protein (GFAP) and examined by light microscopy. RESULTS: In the gas-injected eyes, the retinal holes were ophthalmoscopically closed by 7 days after the surgery. Microscopic examination revealed that the sensory retina around the retinal hole was reattached, and the area of retinal defect was covered with cells which were positive for cytokeratin 18 and GFAP by 7 days after the surgery. In the eyes without gas tamponade, the retinal holes did not close during the observation period. CONCLUSIONS: These findings suggest that early attachment between the sensory retina and RPE could be essential for closure of a retinal hole, where glial and RPE cells might play an important role. This model seems to be useful to investigate the process of closure of retinal holes.

Animals↗

Susac syndrome.

PURPOSE: To report the first Japanese case of the Susac syndrome characterized by microangiopathy of the brain, retina, and cochlea. METHODS: Case report. A 36-year-old Japanese man underwent extensive clinical and laboratory examination for encephalopathy, bilateral recurrent branch retinal arterial occlusion, and hearing loss. RESULTS: This case was initially diagnosed as acute disseminated encephalomyelitis. Despite exhaustive clinical and laboratory examination of the patient, no evidence of a known systemic disease was found. The bilateral recurrent branch retinal arterial occlusions were widely disseminated. Remission occurred 1 year after symptom onset. This patient demonstrated all of the clinical features associated with the Susac syndrome. CONCLUSION: Susac syndrome has been considered rare, but it is probably more common than previously thought and seems to occur in any race. This disorder usually occurs in young women, but it can affect men.

Adult↗

Effect of infusion air pressure on visual field defects after macular hole surgery.

PURPOSE: A defect in the visual field is one of the serious complications of macular hole surgery. We investigated the relationship between the occurrence of visual field defect and the location of infusion cannula and air pressure during fluid-air exchange. METHODS: We studied 100 eyes from 90 patients with macular holes. All patients underwent preoperative and postoperative visual field testing. Vitreous surgery was performed in a standard three-port fashion, with surgically induced posterior vitreous detachment, fluid-air exchange, and sulfur hexafluoride gas injection. We analyzed differences in surgical methods in three groups. In group A, the infusion cannula was placed inferotemporally, and the air pressure was set at 50 mm Hg. In group B, the infusion cannula was placed inferonasally, and the air pressure was set at 50 mm Hg. In group C, the infusion cannula was placed inferotemporally, and the air pressure was set at 30 mm Hg. RESULTS: Eighteen eyes (18%) showed visual field defects after vitrectomy. The defect was always located contralateral to the infusion cannula. There was no statistically significant difference in the incidence of visual field defects in groups A and B. Decreased air pressure reduced the occurrence of visual field defects significantly (24% in group A versus 4% in group C, P = .011). CONCLUSIONS: The location of the visual field defect correlated with the location of the infusion cannula. The incidence of this visual field defect was influenced strongly by the infusion air pressure. The visual field defect may be caused by the mechanical damage of air infusion.

Aged↗

Posterior capsule tear with plate-haptic silicone intraocular lens dislocation.

We report a case of posterior capsule rupture and posterior dislocation of an intraocular lens (IOL) caused by the tip of a silicone plate-haptic lens. The dislocation occurred during IOL implantation after uneventful phacoemulsification in a patient with a small pupil. Discussed are the possible reasons for the complication and measures to prevent it.

Aged↗

New perimetric threshold test algorithm with dynamic strategy and tendency oriented perimetry (TOP) in glaucomatous eyes.

PURPOSE: To investigate the time-wise reliability and efficiency of two new perimetric test algorithms, two computerised static threshold perimetry strategies, namely dynamic strategy (DS) and tendency oriented perimetry (TOP), were compared with the standard full-threshold strategy (normal strategy, NS). METHODS: We examined 41 eyes of 41 normal individuals without any ocular disease and 36 eyes of 36 glaucomatous patients, with the NS (4-to-2 dB), DS and TOP using an Octopus 1-2-3 perimeter. We analysed test time, stimulus time and the two global indices, mean sensitivity (MS) and loss variance (LV). Program 32X was used as test grid pattern. RESULTS: The mean test time for the NS was reduced by 52% with the DS and by 78% with the TOP strategy. Concerning the global indices, the MS value did not differ among the three strategies in the control or glaucoma group. However, the LV value was lower in the TOP strategy compared with the other two strategies in the glaucoma group. This suggested that the TOP strategy underestimated local glaucomatous visual field defects. The ability to detect early-stage glaucoma with the DS and TOP was inferior to that with the NS. CONCLUSIONS: The DS was more efficient than the TOP strategy for the detection of early glaucomatous defects, whereas the TOP strategy required less testing time. The TOP strategy may be an appropriate approach for patients in whom time-consuming perimetry is not possible, or in whom the visual field defect is already advanced.

Adult↗