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An analytical method based on LC-MS/MS was developed for the determination of chlorothalonil metabolite I in livestock products. Chlorothalonil metabolite I in livestock products was extracted with acetone. The crude extracts were defatted by acetonitrile and n-hexane partitioning. Cleanup was carried out using a combination of ethylene diamine-N-propyl silylation silica gel (PSA) and silica gel (SI) mini columns with acidic condition. The sample solution was subjected to LC-MS/MS using an external solvent calibration curve. The average recovery (n=5) of chlorothalonil metabolite I from five types of livestock products (cattle muscle, cattle fat, cattle liver, milk and egg) spike at the maximum residue limits (MRLs) or at a uniform limit of 0.01 mg/kg was 97.1-102.9%, with a relative standard deviation of 1.4-6.8%. The limit of quantitation of the developed method was calculated to be 0.01 mg/kg.

Cardboard boxes used to transport crops are often reused in the distribution process, and therefore transfer of pesticides between crops might occur. So, we designed model experiments to investigate whether or not transfer of pesticide residues from crops to other crops via cardboard boxes occurs. Under severe experimental conditions, 6.2% of the pesticide residues of grapefruit was found to be transferred to spinach via cardboard boxes. In the case of the mandarin orange, 0.57% was transferred. The actual amount of transferred pesticides in the market may be less than that in these model experiments, but it is clear that transfer of pesticide residues to other crops via cardboard boxes can occur. Therefore more attention must be given to reuse of cardboard boxes in the distribution process.

We propose an efficient message-flooding scheme that aims to reduce the number of messages transmitted over the network. The proposed method involves the prior conversion of two-way links into single-way links (in this paper we refer to this as the link-cut technique); by avoiding message link collisions we aim to reduce the number of messages transmitted and by incorporating a time-out transaction, we are able to realize a 50 percent reduction in the number of messages as compared to standard flooding methods while maintaining a delivery success rate of 100 percent. In addition, we show in simulations that by making use of information regarding the number of outgoing links for each node (the number of adjacent nodes), we are able to reduce the number of messages sent while constraining the growth in the message transmission times. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(5): 11–22, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20351

Purpose The dissociated optic nerve fiber layer (DONFL) appearance features numerous arcuate striae after vitrectomy for idiopathic epiretinal membrane or macular hole. We studied the relation between the DONFL appearance and internal limiting membrane (ILM) peeling and performed static microperimetry to explore the possible mechanisms underlying the DONFL appearance. Design Prospective cohort study. Participants Ninety-five eyes of 88 consecutive patients undergoing vitrectomy for idiopathic macular hole. Methods Vitrectomy and gas tamponade were performed with or without ILM peeling. All eyes were examined postoperatively using fundus photography with blue filters. Static microperimetry was performed in 31 eyes with a clearly visible DONFL appearance. Main Outcome Measure The postoperative incidence of the DONFL appearance on blue-filtered fundus photographs. The secondary outcome measure included the microperimetry threshold value in the arcuate striae and the surrounding normal retina within the papillomacular bundle. Results On blue-filtered photographs, 46 (62.2%) of 74 eyes with ILM peeling exhibited the DONFL appearance, compared with 0 (0%) of 21 eyes without ILM peeling ( P = 0.0002). The area of the DONFL appearance was limited to the area of ILM peeling. There was no difference in the microperimetry threshold value between the arcuate striae and the surrounding normal retina ( P = 0.9312). Conclusion The present study indicates that the DONFL appearance might be related to ILM peeling and is not associated with the loss of optic nerve fibers. These results are consistent with the suggestion that the DONFL appearance might be caused by cleavage of the optic nerve fiber bundles due to damage to the Muller cells, which are in close contact with the ILM and act to maintain the close proximity of the nerve fiber bundles.

Acute annular outer retinopathy is an uncommon disorder of uncertain aetiology characterized by a unilateral visual field defect with an irregular annular band of grey-white, deep retinal opacification in a peripapillary location. Acute annular outer retinopathy is considered to be a variant of acute zonal occult outer retinopathy. The case is reported of acute annular outer retinopathy with spontaneous good visual recovery and no ophthalmoscopic sequelae.

A 79-year-old woman presented with sudden unilateral visual loss after an ocular motor disturbance and pulsatile tinnitus. Neuro-ophthalmologic examination showed a presumed right posterior ischemic optic neuropathy (PION), oculosympathetic, and third, sensory fifth, and sixth cranial nerve pareses. Selective angiography of the right internal and external carotid arteries confirmed a posterior-draining dural carotid cavernous sinus fistula (CCF) fed by the right meningohypophyseal trunk and right middle meningeal artery. Angiography also showed an ophthalmic-middle meningeal arterial anastomosis. We postulate that the PION was caused by an arterial steal, because blood was drawn into the fistula and away from the intraorbital optic nerve.

Acinic cell carcinoma is a rare and low-grade malignant tumor of the parotid gland. We treated two acinic cell carcinomas of the parotid gland, each occurring in a young man (18 and 30 years old, respectively). Based on preoperative examination and MRI findings, we expected to find benign tumors, but they were revealed to be acinic cell carcinomas by the permanent pathological specimens. We performed partial parotidectomy in one case, and subtotal parotidectomy in the other, and preserved the facial nerve in both. There has been no metastasis or recurrence for two years after the operations, but we need to follow both patients for a long time.

Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). We exploited the proprietary NMJ-targeting signals of ColQ to treat congenital myasthenia and to explore the mechanisms of autoimmune myasthenia gravis (MG). Mutations in COLQ cause congenital endplate AChE deficiency (CEAD). First, a single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice normalized motor functions, synaptic transmission, and partly the NMJ ultrastructure. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. Second, MuSK antibody-positive MG accounts for 5–15 % of MG. In vitro overlay of AChE/ColQ to muscle sections of Colq−/− mice, as well as in vitro plate-binding of MuSK to ColQ, revealed that MuSK-IgG blocks binding of ColQ to MuSK in a dose-dependent manner. Passive transfer of MuSK-IgG to wild-type mice markedly reduced the size and intensity of ColQ signals at NMJs. MuSK-IgG thus interferes with binding of ColQ to MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq−/− mice and also to reveal underlying mechanisms of anti-MuSK-MG.

Aims To investigate the relationship of aqueous macrophage migration inhibitory factor (MIF) and monocyte chemotactic protein-1 (MCP-1) levels with the clinical stage of diabetic retinopathy. Methods We assayed MIF and MCP-1 levels in aqueous humour samples obtained from 40 diabetic patients (49 eyes) and 24 non-diabetic patients (31 eyes) using enzyme-linked immunosorbent assay. According to the clinical stage of diabetic retinopathy, the diabetic patients were classified into non-diabetic retinopathy (11 eyes), non-proliferative diabetic retinopathy (14 eyes) and proliferative diabetic retinopathy (24 eyes). Results The aqueous levels of MIF (mean ± sd) were 6.34 ± 4.53 ng/ml in proliferative diabetic retinopathy, 3.22 ± 1.71 ng/ml in non proliferative diabetic retinopathy, 1.25 ± 0.96 ng/ml in non-diabetic retinopathy and 1.07 ± 0.94 ng/ml in non-diabetic patients. Significant differences were found among these four groups (P

Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to examine whether or not nuclear factor kappa B (NF-kappaB), a transcription factor that can be activated by various pathological conditions, is involved in the formation of ERMs after PDR.ERM samples were obtained by vitrectomy from 22 cases with PDR aged 56+/-11 years with 18+/-10 years of diabetes and 15 cases with idiopathic ERM. They were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 5 ERM samples from PDR patients aged 51+/-16 years with 15+/-6 years of diabetes were processed for immunohistochemical analysis.NF-kappaB mRNA expression levels were higher (20 out of 22 cases vs. 9 out of 15 subjects in idiopathic ERM, p0.05) in PDR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in all the 5 ERMs derived from PDR patients, and that region was partially double-labelled with interleukin-8 (IL-8) and von Willebrand factor (vWF).These results suggest a possibility that NF-kappaB is involved in the formation of ERMs after PDR, especially for the development of vascular endothelial cell component.

Purpose To report four cases of macular hole formation following ruptured retinal arterial macroaneurysm. Design Case-control study. Methods Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. Macroaneurysms were confirmed using either fluorescein angiography or indocyanine green angiography or both that indicated a telangiectatic retinal vascular change. Clinical data of patients with macroaneurysm with and without macular hole (MH) formation were compared retrospectively. Results Of 75 eyes, four (5.3%; four patients) with macroaneurysm had a macular hole. In one of the four eyes, a macular hole was detected 2 days after the rupture. The distance from the macroaneurysm to the center of the fovea was significantly closer in the four eyes with a macular hole (MH group, 1.1 ± 0.4 (mean ± standard deviation [SD]) disk diameter) than in the 71 eyes without a macular hole (non-MH group, 1.9 ± 0.9 disk diameter) ( P = .0196). The incidence of subretinal hemorrhage in the macula was significantly greater in the MH group (100%) than in the non-MH group (35.2%) ( P = .0195). Conclusions Macular hole formation associated with ruptured macroaneurysm is not as uncommon as previously thought. We suggest that there might be early onset of macular hole formation following ruptured macroaneurysm. Macroaneurysms with early-onset macular hole are present near the center of the macula and are accompanied by subretinal hemorrhage in the macula.

To report the effect of high-dose intravenous corticosteroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy.Nonrandomized clinical trial.We selected 39 Japanese patients (age range, 22-64 years; mean, 48 years; 31 women, 8 men) who had active Graves' ophthalmopathy among 195 consecutive patients. In the first 20 patients, high-dose intravenous methylprednisolone pulse therapy (1 g per day for 3 successive days, repeated 3 times within 3 weeks) followed by 24-Gy orbital radiotherapy was performed. In the other 19 of the 39 patients, high-dose intravenous methylprednisolone pulse therapy without orbital radiotherapy was performed. Coronal computed tomography (CT) of the orbit and exophthalmometry were performed before the corticosteroid pulse therapy, and 1 and 6 months after the corticosteroid pulse therapy. The maximum coronal section area of the most hypertrophic rectus muscle in each eye was measured based on orbital CT imaging.Clinical findings at study entry were not significantly different between the two groups. No significant difference was found in the maximum coronal section area of the most hypertrophic rectus muscle and the results of exophthalmometry measurements in both groups before the therapy. Extraocular muscle hypertrophy was significantly reduced 1 month and 6 months after the therapy (P.01) in both groups. However, no beneficial therapeutic effect on proptosis was observed in either group at 1 month and 6 months after the therapy. No significant difference in the therapeutic effect on extraocular muscle hypertrophy and proptosis was found between the two groups.Orbital irradiation after corticosteroid pulse therapy had no beneficial therapeutic effects on rectus muscle hypertrophy or proptosis of active Graves' ophthalmopathy during the 6-month follow-up period.

OBJECTIVE—Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75NTR]; glial cell line–derived neurotrophic factor receptor-α1 [GFRα1] and GFRα2; and Ret) are involved in the formation of ERMs after PDR. RESEARCH DESIGN AND METHODS—ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 ± 8 years with 17 ± 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 ± 18 years with 13 ± 4 years of diabetes were processed for immunohistochemical analysis. RESULTS—Expressions of trkA, trkB, trkC, p75NTR, and Ret mRNAs were similar in both groups. In contrast, GFRα2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFRα2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFRα1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. CONCLUSIONS—These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.

The behavior of fine particles in a low-pressure parallel plate chemical vapor deposition reactor was investigated by constructing a system that permits particle motion in the reactor to be visualized. The test spherical silica aerosol particles, which were 1.0 μm in diameter and dispersed in argon gas, were fed into the reactor from the outside and particle motion was detected by a laser light scattering method. The effect of operating conditions, such as pressure and temperature, on particle transport in the reactor was investigated. The pressure was varied from 2.0 to 4.0 Torr and the wafer-substrate plate temperature was varied over the range of 25°C to 300°C. A three-dimensional numerical simulation was performed using the commercially available computational fluid dynamics code Fluent. A detailed configuration of the reactor, including the showerhead structure was considered when investigating this mechanism. It is found, both experimentally and by numerical simulation that, when the wafer-substrate plate is not heated, the effect of pressure on particle trajectory in the space between plates cannot be observed. However, at elevated temperature, i.e. when the wafer-substrate plate is heated, the particle trajectory is apparently influenced by pressure. In addition, the effect of thermophoresis, as the result of a temperature gradient by heating of the wafer-substrate plate is very pronounced for gas pressures of both 2.0 and 4.0 Torr . The experimentally observed phenomena were satisfactorily reproduced by simulation.

Purpose: To determine whether visual inputs from the tectothalamocortical pathway influence three-dimensional motion processing within the lateral suprasylvian (LS) area of the cat. Methods: Tungsten microelectrodes were used for recording visual-evoked potentials (VEPs) from the LS area of 4 cats. Random dot stereograms were used as visual stimuli. Three-dimensional, motion-triggered VEPs were recorded from the LS area. Each motion sequence consisted of an abrupt onset of motion disparity with a 2° amplitude followed by an abrupt offset and a stationary phase of 900 ms. The velocity of the motion disparity was varied in eight steps from 10° to 400° per second. The onset of motion disparity was used as the trigger for recording the VEPs. Single or multiple injections (two to three) of muscimol were made mainly into the rostral superior colliculus (SC). The amplitudes of the VEPs before and after the muscimol injection were compared. Results: A large negative wave ( N1) with an implicit time of 92.7 ± 13.5 ms (mean ± SD, n = 98) was recorded consistently. The amplitude of N1 was significantly larger on stereovision of motion disparity than on either binocular vision of two-dimensional lateral motion or monocular vision, indicating that N1 contains neurons sensitive to motion disparity. The amplitude of N1 was not altered by muscimol injection into the SC at velocities ≤50°/s. On the other hand, the amplitude of N1 was reduced to 66–71% of that observed before muscimol injection at velocities ≥75°/s. Conclusions: These findings suggest that the LS area processes three-dimensional motion inputs via two parallel pathways, the geniculostriate pathway and the tectothalamocortical pathway, at velocities of motion disparity ≥75°/s, while the three-dimensional motion inputs project to the LS area only via the geniculostriate pathway at velocities of motion disparity ≤ 50°/s.

PURPOSE: To estimate the prevalence of open-angle glaucoma, including normal-tension glaucoma, in association with Graves disease. METHODS: In a prospective study, a complete ophthalmic examination including applanation tonometry, exophthalmometry, automated static threshold perimetry, and computed tomography of the orbit was performed in 104 consecutive Japanese patients with Graves disease (age range, 11 to 86 years; mean, 42 years; 80 women, 24 men). Ocular hypertension was defined as an intraocular pressure greater than 21 mm Hg on at least two occasions during the period of follow-up. RESULTS: Of the 104 patients, 14 (13%) exhibited typical glaucomatous visual field defects in automatic static threshold perimetry in the absence of compressive optic neuropathy. The intraocular pressure in seven of the 14 patients was consistently less than 21 mm Hg during the follow-up period. Thus, these patients were diagnosed as having normal-tension glaucoma. Of the 104 patients, 23 (22%) were diagnosed as having ocular hypertension. CONCLUSIONS: The prevalence of normal-tension glaucoma as well as open-angle glaucoma and ocular hypertension was significantly higher among patients with Graves disease than in the general population.

Purpose: To assess serial dynamic enhanced computed tomography (serial DE-CT) as a diagnostic tool for carotid-cavernous sinus fistula (CCF). Methods: Serial DE-CT was performed in seven patients (ages 31–74) with CCF. Contrast material was injected intravenously at a dose of 60 mL with an injection speed of 4 mL per second. Serial axial images of the cavernous sinus were undertaken every 3 seconds using a helical computed tomography system. This relatively low-risk technique provides direct evidence of the arteriovenous shunt in the cavernous sinus. Results: In early imaging after the injection, enhancement of the cavernous sinus on the side of the CCF was noted at the arterial phase in all patients, whereas early enhancement of the cavernous sinus was not observed on the contralateral uninvolved side. Conclusions: These findings suggest the usefulness of serial DE-CT as a diagnostic tool for the initial diagnosis of both high- and low-flow CCFs.

PURPOSE: Accumulation of glycosaminoglycans in the orbit may play an important role in the development of Graves ophthalmopathy. Therefore, it might be clinically useful to evaluate the concentration of glycosaminoglycans in the orbit in patients with Graves disease. We investigated the concentration of glycosaminoglycans in retrobulbar tissue using in vivo 1 H-magnetic resonance spectroscopy. METHODS: A model solution of 1% chondroitin sulfate (one of the components of the glycosaminoglycans complex) was initially examined using 1 H-magnetic resonance spectroscopy, and the resonance of chondroitin sulfate was identified. 1 H-magnetic resonance spectroscopy spectra of retrobulbar tissue were obtained in 16 normal volunteers (28 eyes) and 23 patients with Graves ophthalmopathy (36 eyes). The 1 H-magnetic resonance spectroscopy spectrum of chondroitin sulphate in the retrobulbar in vivo tissue was identified by assignments through lineshape comparisons of spectra of the model solutions in vitro and the retrobulbar tissue in vivo. Chondroitin sulphate–peak/H 2 O-peak ratios were calculated. To verify the results of in vivo 1 H-magnetic resonance spectroscopy, retrobulbar tissue samples from five patients, who underwent orbital decompression surgery, were tested for reactivity to chondroitin sulfate proteoglycan by enzyme-linked immunosorbent assay (ELISA). RESULTS: Multiple peaks, with a large peak at 5.24 ppm, were observed in 1 H-magnetic resonance spectroscopy spectra of the model solution. A peak at 5.24 ppm was also observed in spectra of the retrobulbar tissue in all of the normal subjects and the patients. The mean value of the 5.24 ppm–peak/H 2 O-peak ratio was 0.1781 (SD = 0.0498, range, 0.0775 to 0.2282) in the normal subjects and 0.2874 (SD = 0.1357, range, 0.1405 to 0.7377) in the patients. The 5.24 ppm–peak/H 2 O-peak ratios were significantly increased in the patients with Graves ophthalmopathy (P 2 O-peak ratio was correlated with the chondroitin sulphate concentration in retrobulbar tissue samples as evaluated by ELISA (r = .69). CONCLUSIONS: This study suggests that 1 H-magnetic resonance spectroscopy of the retrobulbar tissue allows us to estimate the concentration of chondroitin sulphate proteoglycan in the retrobulbar tissue. 1 H-magnetic resonance spectroscopy of the retrobulbar tissue may be a new clinical tool for the evaluation of Graves ophthalmopathy.

Results of previous studies have suggested that the rostral superior colliculus (SC), which corresponds to the representation of the central visual field, is involved in the control of accommodation and active fixation. To clarify the functional interaction between accommodation and active fixation in the rostral SC, this study was performed to investigate the axon collaterals diverging from the rostral SC to the pretectal accommodation-related areas and the omnipause neuron area in the raphe interpositus (RIP) of the cat by using a fluorescent double-labeling technique. This study was conducted on four cats, weighing 2.5-3.5 kg. Retrogradely labeled neurons in the SC were examined following injections of Fast Blue into the RIP and Diamidino Yellow into the pretectal accommodation-related areas, which were identified with microstimulation techniques. Neurons projecting to the RIP were located mainly in the intermediate layers in the rostral SC, whereas neurons projecting to the pretectal accommodation-related areas were scattered in the superficial and intermediate layers of the rostral SC. The population of double-labeled neurons was highest in the rostral SC, which corresponds to the representation of the central visual field. The presence of double-labeled cells indicated that the accommodation-related area in the rostral SC contains neurons whose axons collateralize to project to both the pretectal accommodation-related areas and the ominipause neuron area in the RIP. Neurons in the rostral SC may be involved in the interaction between accommodation and active fixation.

Purpose: To study the effects of ethmoidal wall (one-wall) decompression using a transmedial-canthal approach (transmedial-canthal ethmoidectomy) for the treatment of dysthyroid optic neuropathy. Methods: The ethmoidal wall and air cells were completely removed using a transmedial-canthal approach in 6 eyes of 4 patients (mean age = 55 years; age range, 46–69 years) with dysthyroid optic neuropathy. Similar surgery was performed on 2 contralateral eyes in 2 of the patients for cosmetic reasons. The preoperative corrected visual acuity in the 6 eyes ranged from hand motion to 20/100. Centrocecal scotomas were detected using automatic static threshold perimetry in the 6 eyes. Results: After transmedial-canthal ethmoidectomy, the corrected visual acuity improved to better than 20/20 in the 6 eyes, and the centrocecal scotomas had almost completely resolved. There were no major complications, such as cerebrospinal fluid leakage or diplopia associated with the surgery. There were no relapses during an average follow-up period of 29 months. Conclusions: These findings suggest that transmedial-canthal ethmoidectomy is an effective and safe therapy for dysthyroid optic neuropathy.

Purpose: The middle temporal (MT) area of the cortex of the monkey is involved in visual motion analysis. Previous studies using brain-imaging techniques have shown that the area around the anterior occipital cortex in man is homologous to the area MT of the monkey. In this study, we investigated the cortical components of motion-triggered visual evoked potentials and their topography in the visual cortex of man. Methods: Visual evoked potentials to the onset of a visual motion stimulus (m-VEPs) were recorded from 5 normal subjects aged 25 to 34 years. A random dot pattern was used as the stimulus for the m-VEPs. The dots moved horizontally to the right and then to the left alternately for 500 milliseconds with interstimulus intervals of 1500 milliseconds. The speed of motion was varied in five steps from 5–25°/s. Fifteen electrodes were placed on the occiput around O z at 5-cm intervals. Color contour maps showing the distribution of voltage over the 15 electrodes at latencies ranging from 0–200 milliseconds with a 20-millisecond interval were made for each subject. These were coregistered with three-dimensional magnetic resonance images of the same brain to specify the topography of the main components of the m-VEPs in relation to the sulcal and gyral pattern of the visual cortex. Results: We consistently observed a positive wave with a peak latency of about 100 milliseconds (P100) and a negative wave with a peak latency of about 150 milliseconds (N150) for all subjects. Topographical analysis showed that P100 was dominant in a relatively wide area caudal to O z , whereas N150 was dominant in a relatively small area posterior to the right anterior occipital sulcus, which included the area corresponding to the area MT in man. Conclusions: These findings suggest that N150 represents the activity of the area MT in the human visual cortex related to motion perception.

To evaluate the association of human leukocyte antigen (HLA) types in Japanese patients with Graves ophthalmopathy.Japanese patients with severe ophthalmopathy (48 patients) and patients without ophthalmopathy (46 patients) were selected prospectively from 234 consecutive patients with hyperthyroid Graves disease. The criteria for severe ophthalmopathy were proptosis of 19 mm or more, or a 3-mm difference in exophthalmometry measurement between the two eyes, or diplopia at the primary eye position. The criteria for the absence of ophthalmopathy were proptosis of 16 mm or less, no diplopia, no lid retraction, and no thickening of extraocular muscles. Serologic HLA typing of class I and II antigens was performed in the two patient groups. The frequency of each HLA antigen in the two patient groups was compared to that in 767 unrelated normal healthy Japanese controls.The frequencies of HLA-DR14 and DQ1 were significantly higher in the patient group with severe ophthalmopathy (35% and 75%, respectively) than in healthy controls (4% and 43%, respectively; corrected P.05), and also greater than in the patient group without ophthalmopathy (13% and 55%, respectively; P.01). On the other hand, the frequencies of HLA-B35, B54, DR4, and DQ4 were significantly higher in the patient group without ophthalmopathy (23%, 23%, 43%, and 30%, respectively) than in the patient group with severe ophthalmopathy (13%, 15%, 25%, and 19%, respectively; P.01).HLA-DR14 and DQ1 antigens may be genetic markers of predisposition to the development of severe ophthalmopathy. In addition, HLA-B35, B54, DR4, and DQ4 may be genetic markers of resistance to severe ophthalmopathy. Variation in the severity of ophthalmopathy associated with Graves disease may depend, in part, on the presence or absence of particular HLA antigens.

Objective The purpose of the study was to describe clinical and serologic features of Fisher syndrome associated with IgG anti-GQ 1b ganglioside antibody following Campylobacter jejuni enteritis. Design A clinical trial. Participants Four consecutive patients with Fisher syndrome were studied. Intervention Samples of sera from four patients were tested for reactivity to GQ 1b ganglioside by enzyme-linked immunosorbent assay (ELISA). Campylobacter jejuni strains isolated from samples of stool from three patients were serotyped by the method of Penner and Hennessy and that of Lior. Main outcome measures Serum IgG anti-GQ 1b antibody titer and serotypes of C. jejuni . Results Diplopia occurred 8 to 14 days after the onset of diarrhea. Campylobacter jejuni was isolated from samples of stool from all of the patients. ELISA revealed a high serum IgG anti-GQ 1b antibody titer for all four patients. Two patients had high serum titers of other antiganglioside antibodies frequently related to Guillain-Barre syndrome. These two patients developed limb weakness following the onset of ophthalmoplegia. The C. jejuni serotype was Penner's serotype 2 for all three of the patients tested. Conclusions These findings suggest that C. jejuni , especially Penner's serotype 2, enteritis could trigger development of Fisher syndrome associated with IgG anti-GQ 1b antibody.

In a recent one decade, we experienced 461 cases of advanced colorectal cancer, 22 cases (4.5%) of which had small colorectal cancer (SCR) less than 20min in size. A clinicopathological study was made to compare SCR and ordinary colorectal cancers (OCR) over 21mm in size. There were no significant differences in the male-to-female ratio and location of the lesions between both groups. The mean age was young and the invasion depth of mp was common in SCRs compared to OCRs. Rates of vascular invasion and lymph nodes metastases were significantly lower in SCRs. Curative resection rate was higher in SCRs and the prognosis was significantly better in SCRs than OCRs. Another analysis of SCRs was conducted. As for the macroscopic type, 10 lesions were elevated type and 12 lesions were depressed type. As for the growth form, five lesions were PG type and 17 lesions were NPG type. In most of the invasive lesions, elevated type and PG type were inner circlar propria muscle. In most of the invasive lesions, depressed type and NPG type were deeper than outer longitudinal propria muscle. Lymphnode metastasis was found in 3 cases in which macroscopic type and growth form were all depressed type and NPG type. Recurrence occurred in two of those three cases. We conclude that depressed type and NPG type SCRs have a malignant potential. But as a whole, the prognosis of SCRs was better than OCRs. It is important to find out these small colorectal cancers (SCRs) .

Aneurysmal bone cyst is an unusual benign solitary lesion of bone occurring rarely in the orbit. In this report, we present computed tomography and magnetic resonance images of an orbital aneurysmal bone cyst involving the frontal bone in a 16-month-old boy. The aneurysmal bone cyst exhibited bone destruction, new bone formation of the orbital roof and fluid-fluid levels in the lesion following hemorrhage. These radiographic features may be useful for diagnosing orbital aneurysmal bone cysts.

Purpose To describe the characteristics of enhanced magnetic resonance imaging of the orbit in a patient with acute paralysis of the inferior division of the oculomotor nerve. Method Using a fat-suppression technique, we performed enhanced magnetic resonance imaging of the orbit of a 36-year-old woman with acute paralysis of the inferior division of the left oculomotor nerve. Results The inferior division of the left oculomotor nerve in the orbit was markedly enhanced, suggesting inflammation of the inferior division of the oculomotor nerve. The severity of paralysis decreased immediately after intravenous corticosteroid (prednisolone acetate) administration. Conclusion These findings suggest that enhanced magnetic resonance imaging with a fat-suppression technique is useful for diagnosing peripheral nerve lesions in the orbit.

The results of our previous studies suggest that the rostral superior colliculus (SC) is involved in the control of accommodation in the cat. The accommodation-related area in the rostral SC projects into the pretectum and the mesencephalic reticular formation (MRF), indicating that these areas may also be involved in the control of accommodation. In this study, we tried to identify cat midbrain areas of accommodation and pupilloconstriction control by systematically mapping microstimulation responses. Three regions were found to evoke the accommodation response: the posterolateral pretectum, including the nucleus of the optic tract and the posterior pretectal nucleus; the posteromedial pretectum, including the nucleus of the posterior commissure (NPC) and adjacent commissural fibers; and the MRF area dorsolateral to the oculomotor nucleus. Pupilloconstriction was evoked by micro-stimulation of the posteromedial pretectum around the NPC and the anterior pretectum around the olivary pretectal nucleus.

The majority of patients with herpes zoster uveitis have relatively good visual prognosis. 1 We report a patient who developed progressive herpes zoster panuveitis despite acyclovir treatment following bone marrow transplantation (BMT).

A survey of pesticide residues in 313 samples of imported spices and herbs on the Tokyo market from April 1997 to March 2011 was carried out. Thirty-seven kinds of pesticides, including organophosphorus, organochlorine, pyrethroid, carbamate and others, were detected between levels of trace (below 0.01 ppm) and 3.3 ppm from 64 samples. The rate of detection was highest in peel (100%) followed by stem (66.7%), fruit (34.5%), bark (33.3%), flower (31.3%) and leaf (14.7%). No residues were detected in root, seed or whole grass. Organochlorine pesticides were detected in all plant parts. The insecticides were detected in products from all production areas, suggesting that their use is common. Residue levels of these pesticides were calculated as less than 1% of their ADI values, based on the daily intake of spices and herbs. Therefore, these spices and herbs should be safe when consumed in customary amounts.

A survey of pesticide residues in 116 imported tea samples on the Tokyo market from April 1992 to March 2010 was carried out. Twenty-two kinds of pesticides, including organophosphorus, organochlorine, pyrethroid and others, were detected at levels between trace (below 0.01 ppm) and 4.0 ppm in 76 samples. The rate of detection was 90% in non-fermented tea, 89% in semi-fermented tea, and 49% in fermented tea. Organophosphorus pesticide was not detected in puer tea, which is fermented with bacteria. The pesticide residues tended to be decreased by a fermentation process. However, organochlorine and pyrethroid pesticides appeared to be chemically stable, so they were still detected in fermented teas. Residue levels of these pesticides were calculated as less than 1% of ADI, except for ethion (45% of ADI) based on the daily intake of tea. Therefore, these teas should be safe when drunk in customary amounts.

PURPOSE: To report a patient who developed accommodation and convergence palsy caused by lesions in the bilateral rostral superior colliculus. DESIGN: Observational case report. METHODS: A 30-year-old right-handed man experienced sudden onset of diplopia and blurred vision at near vision RESULTS: The patient showed accommodation and convergence palsy. Magnetic resonance imaging revealed lesions located in the bilateral rostral superior colliculus. CONCLUSION: These findings suggest that the rostral superior colliculus is involved in the control of accommodation and vergence eye movements.

A survey of pesticide residues in 595 imported frozen products on the Tokyo market from April 1989 to March 2008 was carried out. Forty three kinds of pesticides, including organophosphorus, organochlorine, carbamate, pyrethroid and others, were detected between levels of trace (below 0.01 ppm) and 4.6 ppm from 162 samples. Chlorpyrifos, cypermethrin and omethoate were frequently detected in green vegetables (komatsuna leaf and spinach), cypermethrin and methamidophos were detected in pods and seeds (green soybean and string pea), chlorpropham (CIPC) was detected in potato, and captan and carbaryl were detected in berries (blueberry, raspberry and strawberry). The hydrophilic pesticide methamidophos was detected in flesh of lychee. Residue levels of these pesticides were calculated as between less than 0.5% and 30% of their ADI values according to the daily intake of frozen products. Therefore, these frozen products should be safe when they were eaten in customary amounts.

Accommodative responses were evoked by microstimulation of a circumscribed area in the lateral suprasylvian (LS) cortex of the cat. We studied anatomical connections of this area with WGA-HRP. We identified an accommodation-related area by systematic microstimulation of the LS cortex in each of nine cats. Accommodative and pupillary responses were monitored by an infrared optometer and a pupillometer, respectively. WGA-HRP was injected into the accommodation-related area where accommodative responses were elicited with low-intensity microstimulation, but pupillary responses were not evoked. Retrogradely labeled cells were found mainly in ipsilateral areas 17, 18 and 19, the pulvinar, the lateral posterior nucleus of the thalamus (LP) and the contralateral LS area. Fewer labeled cells were found in ipsilateral areas 20 and 21, the ventral lateral suprasylvian area (VLS), the splenial visual area (SVA) and the lateral geniculate nucleus (LGN). Anterogradely labeled terminals were located mainly in the ipsilateral LP, the rostral portion of the pontine nuclei and the superficial layers of the ipsilateral superior colliculus which corresponds to the representation of the central visual field. Less dense labeled terminals were also found in the ipsilateral nucleus of the optic tract (NOT) in two cats.

We studied vergence eye movements in a patient with limited hemorrhage affecting the right cerebellar peduncles and the hemisphere. The patient showed exotropia of 30 prism dptr during near vision. Some vergence paradigms were investigated in this patient. We studied fusional vergence evoked by placing a wedge prism before one eye. Accommodative vergence was studied by blur stimulus using a servocontrolled optometer. Lens accommodation was also recorded during blur stimulus. Although accommodative responses were normal, accommodative vergence was almost absent as well as fusional convergence in this patient. It has previously been reported that the cerebellum has a role in the control of vergence in the monkey. Our data suggest that the human cerebellum also relates to the control of vergence.

Mossy fiber activity was recorded from the oculomotor vermis (lobules VIc and VII) during visually guided saccades. Saccade-related activities of 99 mossy fiber units were observed in two alert macaque monkeys. Ninety-six units were characterized by high-frequency bursts of firing in response to visually guided saccades (burst unit). These units were silent during all periods of fixation in any gaze position. Three units showed eye position-related tonic discharges with saccadic bursts. The lead time of saccadic bursts ranged from 2.6 to 80.5 ms (mean 27.9 ms, SD 16.6 ms). About 75% of the burst units exhibited a long lead burst characterized by a slow buildup, while the remaining units showed short lead bursts with a sharp onset. About 80% of the units showed burst in association with contralaterally directed saccades. The remaining units exhibited bursts in association with ipsilateral saccades. Preferred directions in this population covered the entire field including the vertical and the oblique. About 68% of long lead burst units exhibited the movement field which consists of a whole sector of the entire oculomotor range (directional type). About 32% of long lead burst units showed the movement field which is a closed area within the oculomotor range (vectorial type). On the other hand, peak frequency of short lead burst units increased in proportion to saccade amplitude. The end of the burst in all units always preceded the completion of saccade. The end of burst was time-locked to the completion of saccade, so that the lead time from the end of burst to the end of saccade was consistent among these units and, was constant regardless of saccadic amplitude. The duration between the peak and the offset of burst was correlated with the amplitude of saccade (0.63 ≦ r ≦ 0.83). Long lead burst of mossy fibers was almost comparable to burst activity in the nucleus reticularis tegmenti pontis (NRTP), while short lead burst of mossy fibers closely resembles activity of excitatory burst neurons in the paramedian pontine reticular formation (PPRF). These findings suggest that the cerebellum receives command signal from the superior colliculus via the NRTP and feedback signal from the PPRF.

A survey of pesticide residues in 600 imported fruit products on the Tokyo market from April 1994 to March 2006 was carried out. Thirty kinds of pesticides, including organophosphorus, organochlorine, carbamate, and pyrethroid, were detected between levels of Tr (below 0.01 ppm) to 0.37 ppm from 75 samples. Residual pesticides were detected from fruit products, dried fruits and pressed juice. A high frequency of pesticide residues was observed in peels, whole body of fruits and products which contained them. Residue levels of these pesticides were calculated as between less than 0.1 and 3.9% of their ADI values according to the daily intake of fruit products. Therefore, these fruit products should be safe when eaten in customary amounts.

Purpose To report bilateral trochlear nerve palsy and its magnetic resonance imaging characteristics in a patient with an arachnoid cyst of the quadrigeminal cistern. Method We performed magnetic resonance imaging of the brainstem of a 54-year-old man who had bilateral trochlear nerve palsy and mild truncal ataxia. Results Magnetic resonance imaging disclosed an arachnoid cyst of the quadrigeminal cistern with enlargement of the lateral, third, and fourth ventricles. The tectum of the midbrain and the ambient and interpeduncular cisterns were markedly compressed by the arachnoid cyst. Conclusion These findings suggest that the bilateral trochlear nerve palsy in this patient was caused by the arachnoid cyst of the quadrigeminal cistern.

Purpose To assess serial dynamic magnetic resonance imaging after rapid intravenous injection of contrast material as a tool for diagnosing orbital cavernous hemangioma. Methods Two patients with orbital cavernous hemangioma were studied. Gadolinium-DTPA, 0.1 mmol/kg, was injected intravenously in 10 seconds. Results On early imaging after the injection, one small point of enhancement was initially noted, and then the tumor was homogeneously enhanced. The initial enhancement point represented the connecting point of feeding vessels to the lesion. Conclusions Dynamic magnetic resonance imaging is useful for diagnosing cavernous hemangioma and for estimating the connecting point of feeding vessels.

Convergent strabismus fixus is classified into congenital and acquired types; however, there are only a few detailed case reports of congenital convergent strabismus fixus. Here, we report a rare case of this condition in which the eyeball was shown by imaging diagnosis to be fixed with a hard cord-like material in the orbit. To our knowledge, there have been no previous reports of congenital convergent strabismus fixus caused by an abnormal cord-like material that was clearly identifiable by imaging.The patient was a 16 year old female who visited our department for consultation regarding restoration of normal appearance of her strabismus. She had undergone strabismus surgery at the age of 3 years, but a forced duction test was strongly positive in all directions, and the eyeball was not mobile at the time. The initial surgery performed was a tenotomy of the medial rectus muscle and inferior rectus muscle and resection of the lateral rectus muscle of the right eye. The eye position and eye movement remained unchanged after surgery. At this time, MRI of the orbital region was performed, and an abnormal cord-like material connecting the posterior eyeball to the orbital wall was detected in the orbit. The cord-like material was pulling strongly on the posterior eyeball, congenitally fixing the eye position internally.We experienced a rare case in which a hard cord-like material in the orbit congenitally fixed the position of the eyeball. On MRI, the intensity of the cord-like material was clearly different from those of the muscle and nerve tissues. Considering the linearity of the cord-like material and the results of a forced duction test, the cord-like material probably consisted of fairly hard tissue, similar to bone.

To the Editor: Angiogenesis is the most important event in proliferative diabetic retinopathy. Previous studies indicated that activator protein-1 (AP-1) is involved in angiogenesis [1, 2]. AP-1 is a transcription factor and a homodimer or heterodimer mainly composed of Jun-Jun and Jun-Fos. The gene encoding Jun was originally identified in avian sarcoma virus 17, and the abbreviation ‘Jun’ is derived from the Japanese ‘ju-nana’, which means 17. cJun (encoded by JUN) is a member of the Jun family and is a principal component of AP-1. The aim of the present study was to assess the potential role of AP-1 in the pathogenesis of proliferative diabetic retinopathy. For this purpose, we examined the expression of JUN mRNA in epiretinal membranes secondary to proliferative diabetic retinopathy. Because perivascular glial cells are essential for the regulation of retinal angiogenesis [3], we also examined levels of phosphorylated c-Jun in glial cells from epiretinal membranes. Epiretinal membranes were surgically removed from consecutive patients with proliferative diabetic retinopathy (23 type 2 diabetic patients) or idiopathic epiretinal membranes (controls, 16 non-diabetic patients) during pars plana vitrectomy. The epiretinal membrane in proliferative diabetic retinopathy is mainly composed of neovascular vessels. On the other hand, idiopathic epiretinal membrane is a non-angiogenic fibroglial membrane that is not associated with diabetes mellitus. Samples derived from 19 of the 23 patients with proliferative diabetic retinopathy and the 16 control patients were processed for RT-PCR analysis. The remaining samples from the diabetic patients were processed for immunohistochemistry. Informed consent was obtained from each patient. The present investigations were carried out in accordance with the principles of the Declaration of Helsinki as revised in 2000. RT-PCR analysis was performed as previously described [4, 5]. The primer sequences used to target the genes in PCR were as follows: JUN: 5′-GCATGA GGA ACC GCA TCG CTG CCT CCA AG-3′ and 5′-GAC CAA GTC CTT CCC ACT CGT GCA CAC TG-3′; and GAPDH: 5′-ACC ACA GTC CAT GCC ATC AC-3′ and 5′-TCC ACC ACC CTG TTG CTG TA-3′. Reactions were conducted under the following conditions: precycling at 94°C for 3 min, then 35 cycles consisting of denaturation at 94°C for 30 s, annealing at either 62°C (JUN) or 55°C (GAPDH) for 30 s and polymerisation at 72°C for 1 min. The expected sizes of the amplified cDNA fragments of JUN and GAPDH were 409 and 452 bp, respectively. Immunohistochemical analysis was performed as previously described [4, 5]. The following antibodies were used to detect antigens: a goat polyclonal antibody against phosphorylated c-Jun (1:200 dilution; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and a mouse monoclonal antibody against vimentin (1:500 dilution; Nichirei, Tokyo, Japan). The antibodies were detected with Cy3-conjugated donkey anti-goat IgG (1:1,000 dilution; Jackson Immunoresearch, West Grove, PA, USA) and Cy2-conjugated donkey anti-mouse IgG (1:200 dilution; Jackson Immunoresearch), respectively. To visualise all nuclei, the Y. Mitamura (*) . A. Tashimo . K. Ohtsuka Department of Ophthalmology, School of Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543 Japan e-mail: ymita@sapmed.ac.jp Tel.: +81-11-611-2111 Fax: +81-11-613-6575

The blood-brain barrier (BBB) is a biological unit composed of capillary endothelial cells and astrocytes. Here we examined the effects of various types of advanced glycation end-products (AGEs) on astrocytes and BBB-forming endothelial cells. While no type of AGE we examined changed the permeability of endothelial sheets, glyceraldehyde-derived AGE induced VEGF expression most significantly in astrocytes. The expression of glial cell line-derived neurotrophic factor (GDNF), which reduces the vascular permeability, was decreased in the astrocytes by treatment with glyceraldehyde-derived AGE. These results indicate that glyceraldehyde-derived AGE is the biologically active substance for astrocytes by regulating the VEGF and GDNF expression, which is causally contributing to an increase in the permeability of the BBB.

We report the case of a 16 year old girl with vertical-torsional oscillations. She had a 4 year history of bilateral horizontal gaze palsy caused by a cavernous angioma in the medial part of the dorsal pons. She presented with vertical oscillopsia that had worsened during the past 3 months. Unilateral three dimensional eye movements and bilateral horizontal eye movements were recorded using a magnetic search coil method and direct current electro-oculography, respectively. She had vertical-torsional oscillations (average frequency: 3.0 Hz) leaving vertical saccades and pursuits intact. The average amplitudes of the vertical and torsional components were 2.0 degrees and 0.6 degrees , respectively. Her horizontal rapid eye movements were severely impaired; however, her horizontal pursuits and slow phases of vestibulo-ocular reflex were only partially impaired (gain0.3, oculomotor range+/-9 degrees ). Convergence and divergence were intact. Lesions involving the medial part of the dorsal pons and bilateral paramedian pontine reticular formation can induce vertical and torsional oscillations without disruption of vertical rapid eye movements.