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Biomedical subjects

M Wakakura

Publications and source records attributed to M Wakakura.

At least 37 records · Page 2Linked to original sources

[Incidence of acute idiopathic optic neuritis and its therapy in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG)].

Data on the incidence of and treatment for acute idiopathic optic neuritis were obtained by questionnaire sent to departments of ophthalmology, university hospitals, and general hospitals throughout Japan. Inquiry was made as to the number of cases which developed idiopathic optic neuritis from April 1992 to March 1993 along with their clinical features. The response rate was 53.6%. There were a total of 550 cases, and the male to female ratio was 1:1.22. Patients 14 to 55 years old were 65.9%; bilateral involvement: 28.2%; recurrence: 18.6%; positive past history of the other eye; 7.5%. Assuming the answering rate to be 100% and two thirds of the patients to be included, annual incidence of this disease (the annual number of patients) was determined to be 1.62 for an adult population of 100,000 (1.03 cases/100,000 people). Tochigi, Tokyo, Kanagawa, Hyogo, Wakayama, Okayama, Yamaguchi, Tottori, Shimane, Ehime, and Fukuoka showed an annual incidence exceeding 2.0/100,000 adults. At more than 95% of all medical institutions questioned, patients with optic neuritis were usually treated with systemic corticosteroids. Oral corticosteroid therapy, which was shown in a recent study in USA to be contraindicated, was still being used at 15% of the institutions.

Acute Disease↗

[Possible role of the AMPA/KA receptors in cultured Müller cells].

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)/KA (kainate) receptors have been demonstrated in cultured Müller cells in a study on cytosolic free calcium ions ([Ca2+]i). The action of these receptors may be expressed under pathological rather than physiological conditions. 1. Critical concentration in response to AMPA was determined in retinal neurons and Müller cells. At 0.05mM AMPA, in all neurons and in only a limited number of Müller cells (20%) cytosolic calcium transients occurred. 2. The level of lactate dehydrogenase (LDH) and the change in [Ca2+]i following AMPA administration were measured before and after exposure to 0.5mM KA. Neither morphological change nor leakage of LDH could be detected after 24 hours. When AMPA was administered, the responsive cell number was higher for KA-exposed cells than for control cells. Müller cells may be concluded to resist neurotoxic agents and may possibly be involved in the survival mechanism of retinal neurons.

Animals↗

Cytosolic calcium transient increase through the AMPA/kainate receptor in cultured Müller cells.

The intracellular concentration of free calcium ions ([Ca2+]i) following administration of glutamate agonist was monitored for retinal Müller cells cultured from adult rabbits using a fluorescence microscope equipped with a video camera system. The calcium concentration was imaged with fura-2. The transient increase of [Ca2+]i was observed following the administration of L-glutamate (3 mM), kainate (0.07-7 mM) and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 0.07-7 mM), but not N-methyl-L-aspartate (NMDA, 0.7-7 mM) in Mg(2+)-free medium. The AMPA/kainate-induced increase of [Ca2+]i was blocked by the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or low concentrations of external calcium. High K+ solution induced a slight but definite increase in [Ca2+]i which was blocked by nifedipine, a voltage-dependent calcium channel blocker, at 100 microM, suggesting that L-type calcium channels are present in cultured Müller cells. The AMPA-induced transient increase of [Ca2+]i was not blocked at the same concentration of nifedipine. There must be an influx of calcium ions through non-NMDA AMPA-kainate receptors in Müller cells. In the retina, glutamate receptor-linked events are no longer considered as specific to neurons.

Animals↗

Neuro-ophthalmic aspects of vascular disease.

One of the most susceptible sites to vascular diseases is the optic nerve head. By innovative approaches using morphometry and in situ hybridization, vascular and extracellular characteristics of the human optic nerve head were examined. Nonarteritic ischemic optic neuropathy occurs due to vascular insufficiency within the optic nerve head. Various local and systemic risk factors have been proposed among which smoking and acute hypotension are now included. Anatomically abnormal discs such as the small optic disc, tilted disc, and optic nerve drusen are recognized as "disks at risk" and hyperopia may be an additional predisposing factor. Ocular, neurological, and vascular disorders due to giant cell arteritis were reviewed. Intravenous high-dose methylprednine should be administered in certain cases. Differentiating nonarteritic from arteritic ischemic optic neuropathy is sometimes difficult. Isolated choroidal ischemia or choroidal filling delay may be an indication of giant cell arteritis. Studies have been conducted on the vascular event, amaurosis fugax (transient monocular visual loss), and the results of some of these studies are discussed.

Blindness↗

Heat shock response and thermal resistance in cultured human retinal pigment epithelium.

The heat shock response was examined in cultured human retinal pigment epithelium (RPE) using indirect immunofluorescence. Mild head shock (39.5-40 degrees C for 1 hr) caused no changes in cell morphology and cells continued to produce the intermediate filament proteins, cytokeratin (keratin) and vimentin. In addition, cells subjected to mild heat shock demonstrated the presence of a heat shock protein (HSP-90). After severe heat shock (45.5-46 degrees C for 1 hr) most cells showed marked morphological changes and, in addition, HSP-90 and/or stress-induced 40 kDa protein production was significantly enhanced. The expression of vimentin was relatively well preserved whereas that of keratin was markedly reduced. When the more severe grade of heat shock was preceded by mild heat shock 20-24 hr earlier, the subsequent severe heat shock resulted in less marked morphological change than in cells not preconditioned and, in addition, the expression of both vimentin and keratin was relatively well preserved. Mildly heat shocked cells appeared to gain thermal resistance supporting the theory that the concomitant synthetic capacity for HSP and normal cellular proteins contributes to thermal resistance. In doubly heat shocked cells, however, HSP-90 expression was not enhanced. The discrepancy between the expression of HSP and thermal resistance is discussed.

Aged↗

Critical flicker frequency in acute and recovered optic neuritis.

Multiple occasional changes in critical flicker frequency (CFF) were studied in patients who recovered from optic neuritis. Twenty-five patients (31 affected eyes) with onset visual acuity less than 0.5 and who showed recovered visual acuity exceeding 1.0 were included in this study. Recovery stages were determined individually as follows: T1, initial onset stage; T2, intermediate stage; T3, recovered stage when visual acuity was 1.0 or better; and T4, final follow-up stage. CFF was determined using red, yellow and green illuminated targets in a compact CFF measuring device recently developed at our department. The rates of abnormality were 100% at stage T1 for all colors, and gradually decreased as the stage advanced from T2 to T4. However, the rates of abnormality continued to be high at 67% in stage T3 for the red target and 37% in stage T4 for the red target. The rates of abnormal interocular difference in CFF in 15 unilateral optic neuritis patients were 100% for all colors at stage T1 and decreased gradually with recovery. Slight but definite abnormality of CFF was also noted in the silent eyes of clinically unilateral optic neuritis patients. The rates of abnormal CFF more than 7% in all colors could be detected in T1, T3 and T4. These results indicate that CFF abnormality can be detected even at the stage of recovery in the pathologic eyes and the fellow eyes of optic neuritis patients. CFF was also shown to be a sensitive indicator for detecting visual dysfunction in patients with optic neuritis.

Acute Disease↗

Cerebello-oculo-hepato-renal syndrome with possible mitochondrial dysfunction.

Bilateral retinal dysfunction with optic atrophy was evident in a 26-year-old man along with renal, hepatic and cardiac dysfunction. MRI showed undersized cerebellar vermis. Blood lactate and pyruvate were high, indicating possible mitochondrial dysfunction. In biopsied biceps muscle, some ragged red fibers were identified. In five usually congenital or inherited syndromes, Dandy-Walker, Joubert, Arima, Dekaban and COACH, the symptoms such as hypoplasia or aplasia of the cerebellar vermis with multiple ocular and systemic disorders serve as the basis for differential diagnosis. The present case showed numerous symptomatic similarities and a few specific differences with Arima, Dekaban and COACH syndromes. These three syndromes and the present case were thus given a single designation, cerebello-oculo-hepato-renal syndrome, although the present case was an adult patient with sporadic onset. Some systemic disorders not included in cerebello-oculo-hepato-renal syndrome were also noted in our case and may possibly be explained by mitochondrial dysfunction, as indicated by blood pyruvate and lactate levels and the presence of ragged red fibers in biopsied biceps muscle. The relationship between cerebello-oculo-hepato-renal syndromes and mitochondrial dysfunction is discussed.

Abnormalities, Multiple↗

Rapid increase of intracellular Ca2+ concentration caused by aminoadipic acid enantiomers in retinal Müller cells and neurons in vitro.

The ability of the gliotoxic compounds D,L-, D- or L-2-aminoadipic acid (AAA) to increase selectively the intracellular concentration of free calcium ion ([Ca2+]i) was examined in Müller cells cultured with or without retinal neurons. The monitoring of [Ca2+]i following exposure to 0.06 to 6 mM AAA was performed by a microfluorometry using a fluorescent Ca2+ indicator, Fura-2 acetoxymethyl ester. A rapid increase of [Ca2+]i occurred in the Müller cells following exposure to a relatively low concentration of the L-isomer. This is compatible with the known strong gliotoxicity of this isomer. The D,L- and D-forms of AAA activated neurons at low concentrations and activated the Müller cells at higher concentrations. The D-isomer appears to act selectively on retinal neurons and may be an agonist of an excitatory amino acid receptor. These results indicate that the ability of AAA to elevate cytosolic [Ca2+]i depends on the stereospecificity of the AAA and on cell type.

2-Aminoadipic Acid↗

Immunohistochemical studies of Merkel cell carcinoma of the eyelid.

Merkel cell carcinoma of the eyelid is a rare malignant tumor. Immunohistochemical studies can be helpful in establishing the diagnosis of this tumor. We encountered a case of Merkel cell carcinoma of the eyelid and conducted an immunohistochemical analysis for clarification of its cell properties. The patient in this study was a 78-year-old man who noted a small mass on his right upper eyelid, which was subsequently removed. However, the lesion recurred and progressively enlarged. The results of a biopsy indicated the possibility of a highly malignant tumor. The lesion was removed by orbital exenteration. Merkel cell carcinoma was finally diagnosed by using light and electron microscopy. In immunohistochemical studies, the tumor cells showed both neuron-specific enolase and cytokeratin. Most of the cells were also labeled with antibodies against the protein gene product 9.5, endocrine granule constituent and chromogranin A. However, no neuropeptides were labeled. The properties of the tumor cells appeared virtually the same as those of normal human Merkel cells.

Aged↗

Permanent homonymous hemianopias following migraine.

Two patients with migraine and repetitive visual field defects of homonymous hemianopic type are reported. The visual field defects were confirmed by Goldmann perimetry and automated static perimetry. Neither computed tomography nor magnetic resonance imaging showed abnormal findings. Decreased cerebral blood flow at the left basal ganglion area was the only abnormal finding detected in one patient by 123I-IMP (iodoamphetamine)-SPECT (single photon emission computed tomography), which is applicable to right homonymous hemianopia. A visual field test that includes the current automated static perimetry is important to the diagnosis and the subsequent treatment of patients with migraine, particularly those who have experienced visual negative phenomena.

Adult↗

[Radionuclide study of left ventricular function and regional myocardial perfusion in patients with a DDD pacemaker].

In order to determine the influence of right ventricular artificial pacing on left ventricular function, particularly on diastolic specificity and regional myocardial perfusion, 99mTc multigated blood pool study and 201Tl myocardial SPECT at rest were performed on 12 patients with a DDD pacemaker implanted due to atrio-ventricular block at various degrees and on 7 normal adults without pacemaker as controls. Studies were performed on the pacing group during both ventricular pacing (VP) and atrio-ventricular sequential pacing (AVSP) at a rate of 80 beats/min. Although global left ventricular ejection fraction (LVEF) showed no significant differences between the control group (63.7 +/- 9.1%) and the pacing group, or between during AVSP (57.8 +/- 9.6%) and during VP (55.8 +/- 10.0%), global early diastolic peak filling rate (EDPFR) in the pacing group were significantly lower during AVSP (0.90 +/- 0.52 counts/second/end-diastolic counts) than during VP (1.55 +/- 0.52) (p less than 0.01), which were both found to be lower than those seen in control group (2.37 +/- 0.48 (p less than 0.01). Functional images disclosed regional prolongation of left ventricular ejection time (ET) in septal and apical areas of the left ventricle adjacent to the pacing site in 7 of the 12 patients (58.3%) during AVSP and in 3 of them (25%) during VP, and also revealed regional decrease in EDPFR in the similar areas in all of the patients during both modes, being more remarkable during AVSP than during VP. On 201Tl myocardial SPECT at rest, regional perfusion impairment was observed in septum, apex and the infero-posterior wall on the septal side adjacent to the pacing site in 8 of 10 patients (80%) during AVSP and in 6 of 9 patients (66.7%) during VP. These results suggest that a change in electrical conduction by right ventricular pacing may disturb regional myocardial relaxation, probably resulting in a regional impairment of myocardial perfusion.

Adult↗

[Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy--by 201Tl myocardial SPECT].

201Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r = 0.792, r = 0.785) and Tl score and LVEF (r = -0.634, r = -0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r = -0.756, r = -0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders.

Adult↗

[Cyanide with vitamin B12 deficiency as the cause of experimental tobacco amblyopia].

The visual toxicity of tobacco smoke was studied and demyelination change of retrobulbar portion of the rat's optic nerve with an elongation of a peak latency time of visual evoked potentials (VEP) was demonstrated. Cyanide detoxication incapacity and deficiency of vitamin B12 (B12) have been considered as possible causes of tobacco amblyopia. In order to elucidate an influence of cyanide poisoning and B12 deficiency on the visual system, 12 male Wistar rats were subjected to 5 hour's daily inhalation of cyanide gas for 52 weeks, the concentration of which was adjusted to that of tobacco smoke. Six rats of these 12 were fed with a lacking B12 diet. Another 12 male Wistar rats were controls which did not undergo inhalation of cyanide gas, and half of them were fed a diet without B12. In 2 out of 6 rats with cyanide and inhalation and B12 deficiency, demyelination change could be recognized in the central portion of the retrobulbar optic nerve. The histological change was segmental and significant elongation of the peak latency time of VEP was not recognized. Cyanide gas inhalation at a low concentration was proved to be harmful to the optic nerve under the condition of B12 deficiency, but other toxic elements such as nicotine and carbon monoxide may be important factors to cause the more severe changes of the optic nerve with an abnormal VEP response recognized in the experimental tobacco amblyopia.

Amblyopia↗

Evaluation of viral myocarditis in children by radionuclide method.

Evaluation of viral myocarditis is essential for the clinician to assess the prognosis. In this study, Tl-201 myocardial scintigraphy and Tc-99m gated cardiac blood pool scan were performed in 16 patients with myocarditis diagnosed by clinical symptoms and laboratory findings and these nuclear medicine techniques were followed up for 5 years. Exercise Tl-201 scintigraphy using a bicycle ergometer was performed in 8 patients by SPECT imaging. There were mild to severe persistent defects found in all cases (100%), but pressure rate products showed normal response. The Tl-201 defect ratio improved gradually, but did not change significantly. In the resting Tl-201 image one of 16 patients showed severe multifocal defects. LVEF increased significantly from 1 year to 5 years after onset, while RVEF measured by gated blood pool scans showed slight increases 3 years to 5 years after diagnosis. It was concluded that myocardial perfusion improved only incompletely. Cardiac function (LVEF and RVEF) improved gradually, and pressure rate products were normal. Myocarditis should therefore be followed up in order to assess the prognosis; moreover, the relationship of myocarditis to dilated cardiomyopathy needs to be further studied.

Child↗

Herpes simplex virus 1 infection upregulates stress protein expression in cultured retinal neurons.

The production of a 57K stress protein (StrP) after herpes simplex virus type 1 (HSV-1) infection was examined in cultured neonatal rat retinal cells. StrP expression in individual cells was identified using a monoclonal antibody, TI56. Indirect immunofluorescence of uninfected retinal cultures showed that approximately 40% of cells expressed neurofilament (NF+) and 5% expressed a low level of StrP. Following HSV infection the proportion of NF+ cells decreased while the proportion of StrP positive cells became greater and the intensity of staining increased. The number of cells labelled with a polyclonal anti-HSV antibody increased with time after infection. Retinal neurons in culture can be infected with HSV, after which StrP expression is significantly upregulated.

Animals↗

Ultrastructural pleomorphism in medulloepithelioma of the ciliary body: a comparative study of tumour cells and fetal ciliary epithelium.

A locally aggressive nonteratoid intraocular medulloepithelioma occurring in a two-year-old boy was studied by electron microscopy. For comparison the primitive pars plana region was examined in human fetal eyes obtained at 16, 18 and 22 weeks of gestation. The tumour was polymorphic with neural, intermediate and epithelial components. The neural component of the tumour resembled the zonulae adherentes dominant cell junction seen in the apical part of the unpigmented epithelium at 16 weeks, while the well-developed junctional complexes and interdigitations seen in the unpigmented epithelium at 22 weeks resembled those in the epithelial component of the tumour. Intermediate cells which exhibited characteristics of both neural and epithelial components, particularly in the cell junctional features, were found. Pleomorphism in nonteratoid medulloepithelioma might be accounted for by the developmental stage at which the tumour is initiated.

Ciliary Body↗

Enhanced ptosis in Fisher's syndrome after Epstein-Barr virus infection.

A 20-year-old woman presented with bilateral ptosis, total ophthalmoplegia, cerebellar symptoms, and hyporeflexia, indicating Fisher's syndrome. She had been diagnosed with infectious mononucleosis 2 months previously. Increased Epstein-Barr virus (EBV) titer was noted, and the Epstein-Barr virus-associated nuclear antigen (EBNA) became positive during the clinical course. Apparent light-near dissociation of the pupils was noted and accommodation was intact. During pharmacological tests with topical application to the eye by sympathomimetic or parasympathomimetic drugs, the pupils showed no supersensitivity, indicating possible central disorder. Enhanced ptosis was noted in each eye and this condition was aggravated by manually lifting the eyelids. The recovery latency time of this enhanced ptosis was approximately 180 ms, indicating a central polysynaptic process to possibly be the cause. Although this condition is considered specifically associated with peripheral neural or muscle diseases, the present case would indicate a central disorder as a possible mechanism.

Accommodation, Ocular↗