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Kouichi Ohta, Atsuko Sato, Emi Fukui Department of Ophthalmology, Matsumoto Dental University, Shiojiri, Nagano, JapanCorrespondence: Kouichi OhtaDepartment of Ophthalmology, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano, 399-0781, JapanTel/Fax +81-263-51-2210Email kouichi.ohta@mdu.ac.jpPurpose: A late dislocation of an in-the-bag intraocular lens (IOL) is strongly associated with pseudoexfoliation and less with retinitis pigmentosa, prior vitreoretinal surgery, and uveitis. We present our findings of late in-the-bag IOL dislocation in three patients with multiple chorioretinal atrophy associated with sarcoidosis.Methods: Observational study of three elderly female Japanese patients with a history of uveitis from sarcoidosis who presented with a late dislocation of an in-the-bag IOL.Results: The late in-the-bag IOL dislocation occurred in the convalescent/quiescent stage of the sarcoidosis. Peripheral multifocal chorioretinal atrophy was the main manifestation in all patients who were diagnosed with definite or presumed sarcoidosis. The dislocated IOLs were successfully removed and new IOLs were implanted with scleral suture fixation followed by no remarkable active uveitis.Conclusion: Clinicians should be aware that patients with peripheral multifocal chorioretinal atrophy associated with sarcoidosis can have a late in-the-bag IOL dislocation.Keywords: late in-the-bag IOL dislocation, pigmented chorioretinal atrophy, sarcoidosis, uveitis

Purpose To report a case of a full-thickness macular hole (MH) that developed after cryotherapy and intravitreal bevacizumab injection (IVB) to treat a retinal vasoproliferative tumor (VPT). Methods Case report of a man with a retinal VPT. Results A 64-year-old Japanese man complained of blurred vision in his right eye. At the initial examination, his best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/20 in the left eye. Ophthalmoscopy showed a VPT in the lower peripheral retina of the right eye. An exudative retinal detachment and hard exudates were seen around the tumor. Cryotherapy and intravitreal injections of bevacizumab (IVB) were performed. Although the exudative changes were reduced, a MH developed two months after the initial IVB treatment. He underwent 25-gauge pars plana vitrectomy, and the MH was closed. His postoperative BCVA was 20/32 and the VPT was inactive. The reduced BCVA was due to damage of the outer retinal layers. Conclusion Our findings indicate that cryotherapy and IVB are effective treatments for VPT although the possibility of developing a MH should be considered.

Purpose We have shown distinct morphological changes of the foveal retina such as horizontally asymmetrical retinal thicknesses and displacements of the fovea toward the optic disc after successful idiopathic macular hole (MH) closure by MH surgery with internal limiting membrane (ILM) peeling. The purpose of this study was to determine whether these morphological changes will alter the stereoacuity. Setting This was a non-randomized, retrospective study conducted on patients who underwent MH surgery at the Matsumoto Dental University Hospital, Nagano, Japan. Methods Forty patients (22 women, 18 men) who underwent MH surgery with ILM peeling for a unilateral MH were studied. At >6 months after the PPV, the stereoacuity was measured with the Titmus stereotest (TST) and the TNO stereotest (TNO). The relationship between the stereoacuity and the age, MH size, best-corrected visual acuity (BCVA), foveal retinal thickness, and amount of nasal shift of the retina was determined. Results The mean postoperative BCVA was -0.05 ± 0.11 logarithm of the minimum angle of resolution (logMAR) units. The percentage of cases with good stereoacuity of ≤100 sec of arc was 87.5% with the TST and ≤240" was 90% with the TNO test. A better stereoacuity was significantly correlated with a younger age (r = 0.36, P

BackgroundOcular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.Methods192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.ResultsFor 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.ConclusionOur report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

The effects of hypertonic glycerol solution on erythrocyte (RBC) aggregability were examined in 8 patients with cerebral infarction confirmed by computed tomography scans. Each patient was administered intravenously with 500 ml of 10% glycerol in 5% fructose saline (glycerol solution) over a period of 3 h on the first day, and then with 500 ml of 5% fructose saline without glycerol (control solution) over 3 h on the next day

We have previously shown that the thickness of the parafoveal retina was asymmetrical in spectral-domain optical coherence tomographic (SD-OCT) images after idiopathic macular hole (MH) closure by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. The aim of this study was to determine whether the foveal slopes around the closed MH were also asymmetrical. Forty-three eyes with an MH treated with PPV with ILM peeling at Matsumoto Dental University Hospital were studied. The foveal slope was determined with ImageJ software in both the horizontal and vertical images obtained by SD-OCT at 6 months after the surgery. The possible related factors were also compared. The mean angles of the foveal slopes of the nasal, superior, inferior, and temporal sectors were 31.4° ± 6.2°, 31.2° ± 5.4°, 31.6° ± 7.4°, and 29.9° ± 6.6°, respectively, in the fellow eyes. The corresponding values in the operated eyes were significantly steeper at 50.4° ± 9.1°, 46.9° ± 11.3°, 48.6° ± 11.3°, and 41.3° ± 11.2°, respectively (P

Kouichi Ohta, Atsuko Sato, Nami Senda, Emi Fukui Department of Ophthalmology, Matsumoto Dental University, Nagano, Japan Background: We have shown that the foveal contour was asymmetrical after idiopathic macular hole (MH) closure by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. The purpose of this study was to determine whether these morphological changes differ in eyes after PPV without ILM peeling. Methods: Ten eyes of 10 patients that underwent PPV without ILM peeling and 12 eyes of 11 patients with ILM peeling were studied. The MH in all eyes was 6 months after the surgery. Results: The mean parafoveal retinal thickness in the non-peeled group was 367.1 µm in the nasal (N), 353.0 µm in the temporal (T), 366.9 µm in the superior (S), and 357.3 µm in the inferior (I) sectors. The T, S, and I sectors were significantly thicker than the corresponding sectors in the ILM peeled group (p=0.0008, 0.003, and 0.03, respectively). The mean ganglion cell complex was thicker not only in the N sector but also in the T sector in the non-peeled group. The mean retinal slopes in the non-peeled group (N, 40.2°; T, 37.6°; S, 41.2°; I, 39.5°) were flatter than those in the peeled group (N, 52.3°; T, 43.6°; S, 50.8°; I, 51.9°; p=0.009, 0.09, 0.008, and 0.017, respectively). Conclusion: The symmetrical fovea after MH surgery in the non-ILM peeled eyes indicates that the asymmetrical fovea after ILM peeling was probably due to the ILM peeling. Keywords: idiopathic macular hole, foveal contour, internal limiting membrane, vitrectomy

Kouichi Ohta,Atsuko Sato,Nami Senda,Emi Fukui Department of Ophthalmology, Matsumoto Dental University, Shiojiri, Nagano, Japan Purpose: The purpose of this study was to demonstrate a displacement of the foveal depression toward the optic disk after idiopathic macular hole (MH) surgery with internal limiting membrane (ILM) peeling.Methods: Two patients with a unilateral MH developed an MH in the fellow eyes. Vitrectomy with ILM peeling was performed on the fellow eye to close the MH. Images of spectral-domain optical coherence tomography (SD-OCT) were used to measure the disk-to-fovea distances pre MH formation, after MH formation, and 6months after the closure of the MH.Results: The disk-to-fovea distance was shorter at 6months than after the development of the MH (4,109µm and 4,174µm in Case 1 and 4,001µm and 4,051µm in Case 2).Conclusion: These results indicate that the fovea moves nasally after the MH surgery with ILM peeling. Keywords: idiopathic macular hole, internal limiting membrane, optical coherence tomography, pars plana vitrectomy

Background: Dementia is a new focus of research on improved treatment for Parkinson's disease (PD). In 2007, a screening tool for PD dementia (PD-D) was developed by the Movement Disorder Society (Level I testing), which still requires verification by a large population study. Methods: We conducted a cross-sectional and multicenter study including 13 institutions administering the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to 304 PD patients (mean age: 70.6 ± 8.3 years; mean Hoehn and Yahr stage: 2.7 ± 0.7). Results: In all, 34.5% of the patients had MMSE scores Conclusions: Level I testing with administration of the MMSE and MoCA is a practical and efficient screening tool for PD-D. However, the phonemic fluency and pentagon copying tests should be replaced by more specific/sensitive ones when screening for PD-D.

Background and Aim The Montreal Cognitive Assessment (MoCA) is the most suitable measure for screening cognitive impairment in Parkinson's disease (PD). However, the utility of the MoCA has not been documented sufficiently, especially in Asian populations. The present multicenter study included a large number of Japanese patients, and compared Mini-Mental State Examination (MMSE) and MoCA scores in PD patients. Methods We carried out a cross-sectional study. Idiopathic PD patients (n = 304; age 70.6 ± 8.3 years (mean ± SD); disease duration 6.6 ± 5.1 years; Hoehn and Yahr stage 2.7 ± 0.7) were registered at 13 participating hospitals, and their clinical/neurological/cognitive features were examined using Japanese versions of the MMSE and MoCA. Results The MMSE and MoCA scores were 26.3 ± 3.6 (range 12–30) and 20.9 ± 5.0 (range 5–30), respectively, and showed a strong correlation (R2 = 0.74, P

Purpose: To describe a patient with Hodgkin disease with posterior uveitis who also had a thinning of the retina and an antiretinal autoantibody in his serum. Methods: Our patient was a 58-year-old man who had been diagnosed with Hodgkin disease. He had a complete ophthalmologic examination including fluorescein angiography, electroretinography, perimetry, and spectral-domain optical coherence tomography. A search for antiretinal antibodies in the serum was made by Western blot analysis, and the retinal sites reactive to the antibodies were determined by immunohistochemistry. Results: The ocular signs were mild cellular infiltration in the anterior chamber and vitreous, and small, round chorioretinal lesions in the peripheral retina. The electroretinograms were slightly reduced. Small ring-like scotomas were detected in the Goldmann visual fields. An antiretina-specific 116-kDa antibody was detected in the serum by Western blot analysis, and the antibody reacted with the ganglion cell and inner nuclear layers of mice retinas. Although the visual acuities were maintained for over eight years, the macular thickness measured in the spectral-domain optical coherence tomography images was reduced. Conclusion: The presence of an antiretinal autoantibody, granulomatous uveitis, and retinal thinning in a patient with Hodgkin disease suggests that the patient had a granulomatous uveitis associated with Hodgkin disease or lymphoma-associated uveitis with retinal involvement.

To compare the thickness of each retinal layer in the parafoveal and perifoveal regions of eyes after successful closure of a macular hole (MH) by pars plana vitrectomy with internal limiting membrane (ILM) peeling to the corresponding areas of the normal fellow eyes. Twenty-two eyes of 22 patients with an idiopathic MH who underwent PPV with ILM peeling at the Matsumoto Dental University Hospital were studied. The retinal thickness was measured manually with the volume scan mode of the Spectralis HRA + OCT (Heidelberg Engineering, Germany). The average postoperative parafoveal thickness of the temporal sector was 314.8 μm, and that of the corresponding area of the fellow eyes was 325.0 μm (P = 0.01). The parafoveal thickness of the nasal sector was 360.7 μm, and that of the fellow eyes was 339.6 μm (P

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson’s disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson’s Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p

Objective: The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients. Background: Although camptocormia has been recognized as a prominent phenomenon in PD, the previous epidemiological reports were limited, especially in terms of sample size. Methods: We evaluated 531 PD patients (disease duration: 7.0 ± 5.5 years, mean ± standard deviation). We examined their clinical features and the prevalence of camptocormia. Results: Camptocormia was detected in 22 patients (4.1%) and found in patients who were older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P < 0.05), compared to the patients without camptocormia. Patients with camptocormia showed significantly higher frequencies of autonomic symptoms, such as constipation and urinary incontinence (P < 0.05). Conclusions: Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms. © 2011 Movement Disorder Society

Based on the structural analysis of sample knitted fabrics and the knit geometric theory, we have built an algorithm that can make three-dimensional structure models for weft knitted fabrics such as welt stitches, tuck stitches, cross stitches, rib stitches and purl stitches. In order to reduce computational complexity, we have set the anchoring point on the diametral plane of yarn in the knitting chart. Drawing from the beginning knitting point to the finished knitting point, a smooth knit curve model can be obtained with the cardinal spline curve. Using this algorithm, we have developed the weft knit three-dimensional structure modeling software that can display the three-dimensional model of knitted fabrics including welt stitches; tuck stitches, cross stitches, rib stitches and purl stitches. Our work confirms 3-D modeling of three foundation knits of weft knit (plain stitches, purl stitches, rib stitches), tuck stitches, welt stitches and cross stitches with a commercially available PC. This software can be used by someone with no understanding of knitting to gain an understanding of the knitting process, and determine the structure of a knitted fabric product., 出版者照会後に全文公開

PURPOSE To describe the morphology of the retina at the convalescent stage of acute zonal occult outer retinopathy (AZOOR) from images obtained by spectral domain optical coherence tomography (SD-OCT). METHODS The visual fields, electroretinograms (ERGs), and OCT images were reviewed in two women aged 24 and 33 years. The patients were followed for one and four years, respectively. RESULTS In both cases, the anterior and posterior segments were almost normal, although both patients had a sudden unilateral vision decrease and photopsia. Goldmann perimetry revealed enlarged blind spots and scotomas. The ERGs were reduced in both cases. SD-OCT showed that the junction of the inner and outer segment, the IS/OS line, of the photoreceptors was irregular or lost in the affected retinas. The retina in these areas was thinner due to a decrease in the thickness of both the outer nuclear layer (ONL) and inner nuclear layer (INL) in Case 2. CONCLUSIONS The decrease in retinal thickness at the convalescent stage of AZOOR is most likely due to a shortening of not only the photoreceptors and ONL but also to a thinning of the INL in a severe case.

Purpose: The authors investigate the efficacy of using the cytokine levels and clonal heavy-chain immunoglobulin (IgH) gene rearrangements in the vitreous as adjunctive tools to diagnose intraocular lymphoma (IOL). Methods: The IL-10 and IL-6 levels and IgH gene rearrangements were analyzed in vitreous samples from 8 cases of IOL and in 14 uveitis patients. Results: The level of IL-10 with an IL-10/IL-6 ratio > 1 was significantly higher in all eyes with IOL. B-cell monoclonality was detected in only 5 of 8 eyes with IOL. Conclusions: The measurements of the levels of cytokines are valuable as a reliable biomarker.

To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients.An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included HoehnYahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance.The subjects were 31 PD patients (age 72 ± 8, HoehnYahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment.Twenty four-hour transdermal delivery of rotigotine at doses up to 8 mg/24 hours does not worsen the daytime sleepiness in PD patients and often improves it when switched from other non-ergot DAs. This is achieved together with satisfactory improvement in motor symptoms, demonstrating that this new modality of non-ergot DA is well tolerated and beneficial in PD patients.

Conventionally, CAD for textiles had regarded textiles as a thin plane. For this reason, it was inapplicable to the textiles which have the feature in surface form. In this research, textiles were regarded as a thick solid structure. The research also dealt with the method of carrying out the simulation of the surface form.It has been thought that the surface height of yarn in textiles is influenced by the length of the float yarn. However, as a result of measuring the form of the textile surface using noncontact form measurement equipment, it became clear that the height of yarn is not decided by the length of a float yarn. It is instead decided by the state of the weave in the weaving point circumference and the distribution of float yarn in the large range.Based on these experiment results, a weave figure for surface form was drawn. By applying this formula to computer simulation technology, a system that displays the surface form of textiles in an instant becomes a reality.

For many years the conventional textile CAD treated textiles as thin and superficial. However, development of the textile CAD in recent years is remarkable, and is changing in the research stage of the next generation, such as a display of three-dimensional textiles, and a display of thread structure.In our previous paper, a figure was drawn expressing the relationship between the form of the textile surface and the weave pattern. In this paper, we applied the formula to some textiles which had uneven surface textiles. Mutual relationship was sufficiently estimated from the results of measurements. Consequently, a correlation coefficient has high correlation in the range of 0.74-0.93, and it became clear that the prediction method was appropriate.Applying this formula, we developed a simulation software and the surface form of textiles based on information about a weave figure etc. was realized and displayed in an instant.

We examined the method which creates the three-dimensional model of woven fabric structures from a weave diagram. Consequently, three-dimensional modeling of the fabric structure corresponding to the expression of three-dimensional structures, such as a honeycomb weave or a multi-layered weave. This was attained by using the method of triggering the floating point number of each yarn for the height position. It enabled this to visualize the three-dimensional structure of fabric, which is only from the information of weave diagrams. This was implemented without the use of mathematical knowledge nor three-dimensional graphics technology.

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation. Cytokines, chemokines, and nitric oxide (NO) have been reported to play important roles. We have determined whether heme oxygenase (HO)-1, a heat shock protein, can suppress EIU. EIU was induced by a footpad injection of lipopolysaccharide (LPS) in male Lewis rats. Hemin, an inducer of HO-1, was injected intraperitoneally 1 hr prior to the LPS injection. HO-1 and HO-2 expression in the iris-ciliary body (ICB) was studied by real time PCR and Western blot analysis. The number of infiltrating cells and the protein concentration in the aqueous humor (AqH) were evaluated by microscopy and by protein assay. The expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta mRNA was determined by real time PCR. The concentration of nitrate plus nitrite, and levels of IL-6 and TNF-alpha in the AqH were also evaluated by Griess reagents and by enzyme-linked immunosorbent assay, respectively. The expression of HO-1 mRNA and protein, induced by LPS, was enhanced significantly by pre-injection of hemin (P0.001). HO-2 was constitutively present in the ICB and was not up-regulated by LPS or by hemin. The number of infiltrating cells and the concentration of protein in the AqH was significantly elevated by LPS injection, and hemin significantly reduced the number of cells and the protein concentration (P0.0001). The expression of iNOS and IL-6 mRNA and protein were down-regulated by hemin (P0.001). Hemin is effective in inducing HO-1 and in reducing the ocular inflammation induced by LPS probably by down-regulating NO and pro-inflammatory cytokine expression.

Purpose: To investigate whether conditioned medium from embryonic rat retinas can induce differentiation of adult rat hippocampus-derived neural stem cells (AHSCs) into neurons and glia in vitro. Methods: AHSCs were cultured in 3 types of media: standard culture medium, conditioned medium from embryonic rat retina, and standard culture medium with retinoic acid. Neuronal and glial differentiation of the cultured cells was assessed by cell growth analysis, flow cytometric analysis, immunofluorescent staining, and RT-PCR analysis. Results: Cells cultured in the standard medium showed very little neuronal and glial differentiation. The cells cultured in the conditioned medium and the medium with retinoic acid showed neuronal morphology and growth inhibition. They also expressed mature neuronal markers and glial markers. In addition, the cells cultured in the conditioned medium expressed Thy-1, HPC-1, and calbindin, which were not found in the previous studies with postnatal retinas in vivo. Those cultured in the medium with retinoic acid expressed HPC-1 and calbindin, but not Thy-1. Conclusions: Conditioned medium from embryonic rat retina contains factors that induce neuronal and glial cell differentiation of AHSCs, and promote up-regulation of some types of retinal cell markers.

PURPOSE To report the presence of retinoschises in a case of von Hippel-Lindau disease detected by spectral-domain optical coherence tomography. METHODS Case report of a 23-year-old man with von Hippel-Lindau disease who was seen for a regular follow-up examination. RESULTS Ophthalmoscopy showed several retinal capillary hemangioblastomas in both eyes. Spectral-domain optical coherence tomography showed retinoschises around the retinal capillary hemangioblastoma and also around the feeder and draining vessels of the peripheral larger hemangioblastoma. The retinoschises were found under the internal limiting membrane and also in the inner and outer retinal layers. Intraretinal columns were observed in the retinoschises. CONCLUSION Our observations show that retinoschises can develop in eyes with von Hippel-Lindau disease. The extensiveness of the retinoschises suggests that the retina is fragile in von Hippel-Lindau disease.

The initial phase of brain ischemia sets the scene for final functional disturbance and tissue damage. Important contributors in the course of early events are tissue depolarization and breakdown of ion and of transmitter homeostasis including transmitter-gated ion channel opening. To relate these events to the severity of cerebral blood flow (CBF) reduction, we used two ischemia models in cats: a global model produced complete ischemia and a focal model produced gradual reductions in the CBF. We employed ion-selective microelectrodes in combination with microdialysis/HPLC to detect direct current (DC) potential and extracellular calcium as well as amino acids and purine catabolites. Additionally, we used amperometric glutamate electrodes for rapid detection of glutamate. Most regions exhibited tissue depolarization and were, therefore, denominated as severely ischemic. An extracellular decrease in calcium and an increase in glutamate were associated with depolarization. The temporal pattern of changes differed among models and regions: the initial phase took less than 10 min in global but up to 30 min in focal ischemia. Since extracellular adenosine as a marker of ATP depletion exhibited similar temporal variability in the various regions, we suggest that minor, not easily detectable, perfusional and metabolic differences are responsible for major differences in the pathophysiology of the initial phase of brain ischemia.

PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.

A new subtype of autoimmune encephalitis associated with antibodies against GABAB receptor was recently identified. Although immune-mediated functional abnormalities are suggested for the pathogenesis, functional brain imaging such as perfusion SPECT has not been documented. A 62-year-old woman with anti-GABAB receptor associated encephalitis underwent 123I-IMP SPECT in the beginning and after methylprednisolone pulse therapy. Three-dimensional stereotactic surface projection analysis was used to evaluate the cortical distribution of perfusion abnormality. The patient presented with clinical features of subacute limbic encephalitis. Antibodies to GABAB receptor were identified in her serum and cerebrospinal fluid (CSF), but no tumor was detected. Despite normal magnetic resonance imaging (MRI) findings, the first SPECT revealed hypoperfusion of the frontal, parietal and medial temporal lobes, as well as thalamus, and cerebellum. These areas are known to contain high levels of GABAB receptors. In contrast, the SPECT revealed hyperperfusion in the motor strip and left temporal lobe, which are areas related to some of the patient's symptoms, including seizures, orolingual dyskinesia, and Wernicke aphasia. After treatment with pulses of methylprednisolone, the neuropsychiatric symptoms resolved and the SPECT findings showed substantial improvement in most of these regions. In conclusion, the findings suggest that immunotherapy improved the cortical dysfunction mediated by GABAB receptor antibodies.

The purpose of this study was to report our findings on a patient with cancer-associated retinopathy who had seminoma.A 43-year-old man, who had been diagnosed with Stage 1 seminoma, complained of blurred vision. Fundus examination revealed attenuated retinal arteries, mild optic disk pallor, and a thinning of the outer nuclear layer. Ring scotomas were found in the visual fields of both eyes. The amplitudes of the electroretinograms were moderately reduced. The patient's serum was analyzed for antibodies.Antibodies against recoverin, Hu, and Ma-2 antigens were not detected. However, Western blots of the serum detected 2 bands at 41 and 64 kDa. The 41-kDa band was an anti-retina-specific antibody. Immunoreactivity was identified in the photoreceptor layer of mice retinas. From these findings, we diagnosed the patient with cancer-associated retinopathy. The visual functions remained stable after the removal of the primary lesion at an early stage, treatment with steroids, and intravenous immunoglobulin.This is the first case of cancer-associated retinopathy because of seminoma. The progression of the disease was reduced by removing the seminoma at an early stage, treatment with steroids, and intravenous immunoglobulin.

Background and Purpose —Harmful effects of peri-infarct depolarizations (PIDs) may depend on recurrent Ca 2+ influx. Thus far, few studies have documented the relevance of PIDs in gyrencephalic animals, and the progressive nature of this process has not been investigated over extended periods. We therefore studied in prolonged focal ischemia in cats spatial and temporal profiles of extracellular calcium ([Ca 2+ ] o ) shifts in relation to direct current (DC) potential, nitric oxide (NO) concentration and regional cerebral blood flow alterations, and final pathological outcome. Methods —In halothane-anesthetized cats receiving either vehicle (n=12) or MK-801 treatment (5 mg/kg IV; n=10), the left middle cerebral artery was permanently occluded. Laser-Doppler probes, ion-selective microelectrodes, and NO electrodes measured simultaneously regional cerebral blood flow, DC potential, electrocorticogram, [Ca 2+ ] o , and NO concentrations in ectosylvian and suprasylvian gyri of the left cerebral cortex. Results —Persistent depolarization immediately after middle cerebral artery occlusion occurred in 10 ectosylvian and 4 suprasylvian gyri of vehicle-treated animals and in 9 ectosylvian and 3 suprasylvian gyri of MK-801–treated animals. PIDs associated with transient decreases of [Ca 2+ ] o were detected in suprasylvian gyri of only 4 vehicle-treated animals, of which 3 developed recurrent PIDs. Electrocorticogram was suppressed during PIDs, and electrocorticogram recovery worsened in a stepwise manner with consecutive depolarizations. PID duration increased slightly with ongoing ischemia and evolved to persistent depolarization at a final stage. NO transients were not detected during PID, and regional cerebral blood flow transients were not pronounced. Infarction was larger with initial persistent depolarization than with PID and was smallest in MK-801–treated animals. Conclusions —PID is not a common finding in peri-infarct zones in cats, and it is suppressed by the N -methyl- d -aspartate antagonist MK-801. However, if repeated PIDs are generated, they result in a stepwise, progressive breakdown of neuronal function and ion homeostasis, probably contributing to the growth of infarction in focal cerebral ischemia. Recurrent Ca 2+ influx is a mechanism that presumably contributes to this process.

目的:乾燥迅速Papanicolaou染色 (乾燥Pap.) を試み, 術中迅速診断における有用性について検討した.方法:術中迅速診断例482検体と術中腹腔洗浄液51検体を対象とした. 全身32臓器の組織1が含まれ, 良性311例, 悪性171例であった. 検体到着後, 乾燥Pap. と凍結切片を作成し, それぞれに診断を行った. Papanicolaou染色 (Pap.) とギムザ染色用の標本も作製し, 洗浄液では粘液染色用の標本も作製した.成績:乾燥Pap. の手技は迅速かつ簡便であり, 塗抹後2分以内で鏡検できた. 細胞像はPap. とやや色調が異なったが, 基本的には類似していた. 透明感と色調のバラエティある細胞像が観察され, 核クロマチンや核小体も明瞭であった. また, 背景の赤血球は溶解し, 細胞観察が容易であった. 乾燥Pap. の正診率は97.3%であり, 通常のPap. は96.1%で, 凍結切片は98.2%であった. 乾燥Pap. と凍結切片をあわせた診断では正診率は99%に上昇した.結論:乾燥Pap. は種々の利点を有し, Pap. に勝るとも劣らない染色法と考えられた. 細胞採取や塗抹方法に注意すれば, 術中迅速診断に十分応用でき, 利用価値の高い染色法と考えた.

Aqueous humor (AqH) contains immunosuppressive factors, especially TGF-β2, that contribute to the immune privileged status of the anterior chamber. However, this may not be true when the blood-ocular barrier is compromised by ocular inflammation. To determine the immunosuppressive status of AqH from murine eyes afflicted with experimental autoimmune uveitis, B10.A mice were immunized with interphotoreceptor retinoid-binding protein. AqH was collected from eyes of affected mice periodically after immunization and then evaluated for content of TGF-β, proinflammatory cytokines, and the capacity to suppress anti-CD3-driven T cell proliferation. mRNA expression of selected cytokines in iris and ciliary body from inflamed eyes was analyzed by ribonuclease protection assay. We found that TGF-β levels were significantly increased in AqH from EAU eyes on days 11, 17, and 28. AqH collected on day 11 (onset of disease) failed to suppress T cell proliferation and contained large amounts of locally produced IL-6 that antagonized TGF-β. In contrast, AqH collected at 17 days (when ocular inflammation was progressively severe) re-expressed the ability to suppress T cell proliferation, in this case due to high levels of blood-derived TGF-β1 and eye-derived TGF-β2 in the absence of IL-6. Thus, during the onset of experimental autoimmune uveitis, the ocular microenvironment loses its immunosuppressive properties due to local production of IL-6. But as inflammation mounts, AqH IL-6 content falls, and the fluid reacquires sufficient TGF-β eventually to suppress immunogenic inflammation. The paradoxical roles of IL-6 in antagonizing TGF-β, while promoting TGF-β accumulation during ocular inflammation, is discussed.

· Background: Our purpose was to analyze the expression of Fas antigen on CD4+ lymphocytes in the aqueous humor (AH) and cerebrospinal fluid (CSF) of patients with Vogt-Koyanagi-Harada disease (VKH). · Methods: Using three-color flow cytometry, we assessed T-lymphocyte subsets stained with fluorescence-conjugated anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies in AH, CSF and peripheral blood (PB) from 8 patients with active VKH. · Results: CD3+ T cells constituted the majority of lymphocytes in AH and CSF, in contrast to with PB. The percentages of CD4+ lymphocytes in uveitic AH and CSF were significantly higher than that in PB (P < 0.01). Activated CD4+ and CD8+cells were significantly more frequent in AH than in CSF and PB (P < 0.01). Although the percentages of CD45RA+ cells within CD4+ cells in AH and CSF were extremely low compared with those in PB, the proportions of CD29+ and CD45RO+ (memory) cells within CD4+ were much higher than those in PB (P < 0.01). Fas antigen was also highly expressed on such CD4+ cells in AH, as in other uveitis patients and on such cells in CSF. Moreover, the percentages of Fas+ and memory cells in AH were significantly higher than those in CSF. · Conclusions: The majority of CD4+ lymphocytes in AH and CSF from patients with active VKH were activated memory cells, on which Fas antigen was also highly expressed. Although this Fas expression may not be an apoptosis-related phenomenon, accumulation of Fas+ memory T lymphocytes in AH and CSF probably reflects the immunopathologic mechanism of VKH.

Purpose: To compare the distance between the optic disc and the fovea (disc-to-fovea distance) before and after a successful closure of an idiopathic macular hole (MH) by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. Methods: This was a retrospective observational study of 37 eyes of 36 patients with a MH that had undergone PPV. The distance between the point of intersection of a blood vessel and the disc margin and the center of the opened or closed MH at 6 months after surgery was measured in the Spectralis HRA+OCT (Heidelberg Engineering, Germany) images. Results: The mean disc-to-fovea distance was significantly shorter postoperatively than preoperatively (3,783.7 ±308.5 μm and 3,914.5 ± 320.4 μm, respectively; P

Background and Purpose Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [ 11 C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia. Methods In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined ≈15 hours after MCAO). Results Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images. Conclusions The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.

We aimed to demonstrate different modes of in situ nitric oxide (NO) generation from two NO donors in cerebral cortex of halothane anesthetized cats. NO donors were delivered by in vivo microdialysis into the cortical tissue where an NO electrode measured real-time changes in extracellular NO concentration. In vitro testing in Finger's solution revealed that sodium nitroprusside (SNP) liberates NO spontaneously in the presence of light, whereas hydroxylamine does not generate any NO under these conditions. Supplementation with 200 mM of the NO donors SNP and hydroxylamine evoked dose-related increases in NO concentration (52.0 +/- 6.7 nM, n = 5, and 14.0 +/- 3.8 nM, n = 5, respectively). The increase in NO concentration was significantly greater during SNP than during hydroxylamine delivery (p < 0.001). In contrast, CBF increased similarly under the influence of both NO donors. Electrocorticogram and cortical direct current potential remained unaffected. In conclusion, hydroxylamine is degraded into NO intracellularly and efficiently dilates cerebral blood vessels. SNP, in contrast, generates NO mainly in the extracellular space.

The hippocampus has been shown to exhibit particular vulnerability to ischemia, suggesting the existence of inherent processes leading to neuronal death. Nitric oxide (NO) has been implicated in neurotoxicity due to ischemia. The relationship between regional distribution of NO synthesis induced by ischemia and the areas vulnerable to ischemia remains elusive. In the present study, we explored regional variation in NO synthesis by determining the concentrations of nitrite (NO−2), a major metabolite of NO, in the brainin vivomicrodialysis samples obtained from the hippocampus and the striatum subjected to ischemia. Sprague–Dawley rats were anesthetized with pentobarbital (40 mg/kg, i.p.). Anin vivomicrodialysis probe was implanted into the hippocampus or the striatum. Subsequently, the animals were subjected to forebrain ischemia for 20 min by occlusion of both common carotid arteries and induced hypotension. Forebrain ischemia gave rise to a significant change in NO−2level only in the hippocampus, resulting in an increase to 111.2 ± 5.4 (mean ± SEM) % of the preischemia level. This finding suggests the presence of a regional difference in NO production during ischemia, which may be concerned with the underlying mechanism of ischemic vulnerability.

Fundus photographs enable non-invasive analysis of the status of the microcirculation by directly observing the retinal vasculature. Retinal microvascular abnormalities are important clinical markers of hypertension and arteriosclerosis, but retinal microvascular changes can be observed in older individuals without hypertension. In this study, our goal is to elucidate the effects of aging on fundus vessels in the retinal photograph. We analyzed retinal vessels of 161 healthy volunteers (49.5 ± 18.7 years, range 18-87) using in-house computer-aided measurement system to measure areas and diameters of all retinal vessels across the entire area of a retinal photograph. The vessels were segmented according to color, and then their area, size, length and thickness were measured by image processing. We also analyzed the correlation between total blood vessel area, age and mean arterial blood pressure (MABP). The decrease in total blood vessel area was dependent on both age and MABP. Moreover, decrease in blood vessel area was also correlated with age for the normotensive group. Furthermore, the slope of the regression line for retinal vessel area with MABP was significantly higher in participants aged ≤ 60 years than in those aged over 60 years. Changes in retinal vessel area with aging were observed in both arterioles and venules. In conclusion, we found the significant decrease in retinal vessel area that is correlated well with calendar age. Therefore, we need to carefully apply traditional classifications of fundus examination for hypertensive retinopathy in older individuals.

posterior DMN connectivity normalized in the middle and posterior cingulate gyri but remained in the precuneus and retrosplenial cortex after adjusting for global cortical PiB retention in DLB. Conclusions: Patients with DLB are characterized by increases in the anterior DMN and decreases in the posterior DMN and PVN. This reciprocal change in the anterior and posterior DMN identified in patients with DLB closely resemble the DMN changes observed in AD. Although As load modifies the decreases in the middle and posterior cingulate regions in the posterior DMN, connectivity abnormalities in DLB persist even after controlling for As load. The pattern of posterior DMN and PVN connectivity decreases sparing the middle and posterior cingulate gyri after adjusting for As load is consistent with the pattern of regional hypometabolism typically observed in DLB.

This multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).To identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.The patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.Forty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.

Background:The foveal contour is asymmetrical in the horizontal optical coherence tomographic (OCT) images in idiopathic macula holes (IMHs) successfully closed by pars plana vitrectomy (PPV). The purpose of this study was to compare the parafoveal retinal contour after PPV followed by gas tamponade for IMHs to that after vitrectomy for rhegmatogenous retinal detachment (RRD). Design:Retrospective study. Participants:Eleven eyes of 11 IMH patients and 10 eyes of 10 RRD patients who underwent PPV. Methods: The internal limiting membrane (ILM) was stained with indocyanine green and peeled in the IMH group but not in the RRD group. The postoperative retinal thickness was measured by spectral-domain OCT. Main outcome measures:The parafoveal thicknesses of the operated eyes were compared to the corresponding areas of the fellow un-operated eyes. Results: In the IMH group, the average postoperative thickness of the temporal sector was 312.6 μm and that of the corresponding area of the fellow eyes was 330.2 μm (P

In order to explore further the presynaptic modulation of monoamine release by glutamatergic nerve fibers, we investigated the effects of selective agonists for ionotropic glutamate (GLU) receptors on striatal release of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT). In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed to measure the release of monoamines and metabolites, and also to administer GLU agonists locally in the tissue. l -GLU and its selective agonists (N-methyl- d -aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA)) evoked simultaneous release of striatal DA, NA and 5-HT in a dose-dependent manner. Pretreatment with MK-801 (5 mg/kg i.p.), a noncompetitive NMDA receptor antagonist, selectively suppressed NMDA-evoked monoamine release. The rank order of GLU agonist efficacy in releasing monoamines was different among DA, NA, and 5-HTergic terminals: AMPA = KA > NMDA for DA release, AMPA > NMDA = KA for NA release, and NMDA = AMPA = KA for 5-HT release. In conclusion, presynaptic ionotropic GLU receptors exist extensively on monoaminergic terminals including not only catecholaminergic (DA and NA) but also indoleaminergic (5-HT) terminals in the rat striatum. Their subtypes include both NMDA subtype and AMPA/KA subtype, and show a differential distribution among these three monoaminergic terminals and a differential contribution to facilitating monoamine release.

We investigated the effects of selective glutamate (Glu) agonists on the release of monoamine neurotransmitters and their implication in the enhanced monoamine release in cerebral ischemia. In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed and the release of excitatory amino acids (Glu and aspartate (Asp)) and monoamines (dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT)) was measured by high-performance liquid chromatography with an electrochemical detector. (1) Forebrain ischemia by 4-vessel occlusion generated significant correlations between the Glu and Asp levels and the DA, NE and 5-HT levels ( r = 0.922 ∼ 0.967, P n = 6). (2) l -Glu and its selective agonists (N- methyl- d -aspartate ) (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA) evoked a simultaneous release of striatal DA, NE and 5-HT in a dose-dependent manner (P ‘ ANOVA , n - 8) . The maximal monoamine release evoked by the Glu agonists showed different magnitudes in the order of DA >> NE > 5-HT (118-, 16- and 9-fold from the baseline levels by 62.5 mM l -Glu, respectively). Each Glu agonist exerted a different magnitude of transmitter release and the order of agonist efficacy was different among NE, 5-HT and DA release: AMPA = KA > l -Glu = NMDA for DA release, AMPA > l -Glu = NMDA = KA for NE release, and l -Glu = NMDA = KA = AMPA for 5-HT release . In conclusion, both presynaptic NMDA and AMPA/KA receptors regulating the transmitter release exist widely on the monoaminergic (DA, NE and 5-HT) nerve terminals in the rat striatum, with a variety of receptor subtypes and variation in the agonist efficacy. Their implication in the augmentation of monoamine release in cerebral ischemia was suggested.

A novel spectrophotometric nitrite ( NO − 2 ) nitrate (NO − 3 ) assay system for a small quantity (5 μl) of dialysate sample obtained by in vivo brain microdialysis was developed based on the diazotization reaction. The system has the advantages of in vivo consecutive measurement, high precision, good reproducibility, technical simplicity, relatively short resolution time (2.5–20 min), and wide availability. The NO−3 level in the rat striatum was found to be 3 times higher than the NO−2 level. A nitric oxide (NO) synthase inhibitor, N G -nitro- l -arginine methyl ester, reduced striatal NO − 2 citrulline formation in a dose-related manner and increased arginine, indicating that the tissue NO−2 level detected by this assay system adequately reflects the striatal NO synthase activity.