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Biomedical subjects

Toshiaki Abe

Publications and source records attributed to Toshiaki Abe.

At least 55 records · Page 3Linked to original sources

Autosomal dominant macular degeneration associated with 208delG mutation in the FSCN2 gene.

OBJECTIVE: To assess the clinical and genetic characteristics of 2 Japanese families with autosomal dominant macular degeneration (ADMD) associated with a 208delG mutation in the retinal fascin (FSCN2) gene. DESIGN: Case reports with clinical findings and results of fluorescein angiography, electroretinography, kinetic visual field testing, and DNA analysis. SETTING: University medical center. RESULTS: The 208delG mutation in the FSCN2 gene was identified in 14 members of 4 Japanese families with autosomal dominant retinitis pigmentosa and in 5 members of 2 Japanese families with ADMD. The characteristic features associated with this mutation led to 2 different phenotypes, autosomal dominant retinitis pigmentosa and ADMD. CONCLUSIONS: The 208delG mutation in the FSCN2 gene produces not only autosomal dominant retinitis pigmentosa but also ADMD in the Japanese population. This mutation is relatively common in Japanese patients with autosomal dominant retinal degeneration and showed clinical variability. CLINICAL RELEVANCE: Autosomal dominant retinitis pigmentosa and ADMD can be caused by the same 208delG mutation. We suggest that mutations in the FSCN2 gene can lead to a spectrum of phenotypes.

Adolescent↗

Bilateral central retinal artery occlusion in Churg-Strauss syndrome.

PURPOSE: To describe a rare bilateral central retinal artery occlusion in a patient with Churg-Strauss syndrome. DESIGN: Observational case report. METHODS: A 68-year-old Japanese man with Churg-Strauss syndrome developed sudden vision loss in both eyes. Medical history included bronchial asthma, elevated eosinophils, and aortic regurgitation. RESULT: Central retinal artery occlusion was diagnosed by retinal whitening, a cherry-red spot, and delayed arteriovenous transit time on fluorescein angiography. Corticosteroids, cyclophosphamide, and anticoagulant therapy altered the hypereosinophilia and mononeuritis multiplex, but no visual recovery occurred during the following 2 years. CONCLUSION: Bilateral central retinal artery occlusion can occur in Churg-Strauss syndrome. Patients with this diagnosis should be carefully followed.

Aged↗

Comparative study of cathepsins D and S in rat IPE and RPE cells.

To investigate differences between activities related to phagocytosis in iris pigment epithelial (IPE) and retinal pigment epithelial (RPE) cells, an aspartic protease, cathepsin D (cat D), and a cysteine protease, cathepsin S (cat S), of IPE and RPE were studied. IPE and RPE cells were isolated from Long Evans rat eyes. The origin of the isolated cells was determined by pigmentation and cytokeratin labelling. The mRNA expressions of cat D and cat S in cultured IPE or RPE cells were investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Enzyme activities of cat D and cat S in IPE or RPE cells were measured by using specific fluorogenic substrates, MOCAc-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)D-Arg-NH2 and Z-Val-Val-Arg-MCA, respectively. Western blot analysis of both proteins was also performed. The cultured cells, both of IPE and RPE cells were pigmented and showed positive labelling with an anti-cytokeratin monoclonal antibody. The cat D activity in RPE cells was 37 times that in IPE cells. The cat S activity in RPE cells was four times that in IPE cells. On the other hand, mRNA expression levels of cat D in RPE cells were at the same level with IPE cells, cat S mRNA expression in RPE cells were 10 times that in IPE cells. These results were also correlated with the Western blot analysis. In this study, we measured the characteristic expressions of cat D and S in IPE and RPE cells for the first time to compare their lysosomal activities. IPE cells have the lysosomal activities like RPE cells, however, the function of lysosomal activity in IPE cells is beneath RPE's. These results indicated that the ability of ROS digestion in IPE cells was not same as RPE cells.

Animals↗

Interleukin-1beta and barrier function of retinal pigment epithelial cells (ARPE-19): aberrant expression of junctional complex molecules.

PURPOSE: To examine the effects of interleukin (IL)-1beta on the resistance and permeability of the tight junctions of cultured retinal pigment epithelial cells. METHODS: A human RPE cell line (ARPE-19) cultured on microporous filter-supports was used. IL-1beta and monoclonal anti-IL-1beta antibody-treated IL-1beta (mAbIL-1beta) were added to the standard culture medium. Transepithelial resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells to sodium fluorescein, horseradish peroxidase, and inulin was measured. The expression of the occludin and claudin was determined by real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot analysis. RESULTS: A significantly greater decrease of TER occurred in IL-1beta-supplemented medium than in standard medium plus mAbIL-1beta after several days of stimulation. A significantly greater increase of sodium fluorescein, horseradish peroxidase, and inulin permeability occurred in IL-1beta-supplemented medium than in standard medium. The expression of the occludin gene and some types of claudin genes was observed. The expression of occludin was downregulated and that of claudin-1 upregulated more in IL-1beta-supplemented medium than in standard medium by real-time PCR, immunohistochemistry, and Western blot analysis. CONCLUSIONS: The tight junctions of ARPE-19 cells are altered by IL-1beta supplementation either directly or through other factors activated by IL-1beta. The downregulation of occludin and upregulation of claudin-1 may have participated in the dysfunction of the RPE tight junctions in these in vitro experiments.

Biological Transport↗

Surgical strategy for anterior sacral meningocele.

A 25-year-old male presented with an anterior sacral meningocele (ASM) manifesting as repeated urinary tract infections. Surgical correction was completed by simple ligation of the thecal sac next to the ostium via sacral laminectomy, and the thickened filum terminale was sectioned. A 22-year-old female presented with an ASM manifesting as transient difficulty in micturition. Subsequent to sacral laminectomy, the thickened filum terminale was sectioned. However, an aberrant nerve root over the ostium made simple ligation hazardous, so that transdural suture around the ostium was carried out. Complete obliteration was confirmed 5 months after the surgery. Magnetic resonance (MR) imaging could clearly demonstrate the involvement of neurologically important structures. Surgical strategy for ASM based on neurosurgical considerations is proposed, because of the frequent association of caudal spinal cord anomaly as well as presacral mass lesion. Intraoperative assistance systems such as endoscopy for cyst content examination and neurophysiological monitorings are recommended. Several months follow up with MR imaging is required to confirm successful surgical correction.

Adult↗

Microscopic measurement of the facial nerve root exit zone from central glial myelin to peripheral Schwann cell myelin.

OBJECT: The authors have attempted to define the exact borders of the root exit zone (RExZ) of the facial nerve, measure the distribution of myelin histologically, and examine the relationship between contact vessels and the RExZ. METHODS: Seventy-five facial nerves were obtained from brainstems excised from 44 adult patients at autopsy. The arteries and veins associated with the facial nerve were counted and measured. The facial nerves, associated vasculature, and adjoining portions of the brainstem were then removed en bloc. These tissues were serially sectioned and stained, and a photomicrograph of each section was obtained. The distribution of myelin on each section was measured from the upper edge of the supraolivary fossette, and the relationship between contact vessels and the RExZ examined. The lateral transitional zone of the facial nerve began 8 mm distal to the upper edge of the supraolivary fossette (root exit point [RExP]) and had a mean length of 1.9 mm. The root detachment point (RDP) of the facial nerve at the medial side was located very close to the beginning of the medial transitional zone. In more than 80% of the nerves that were examined, vascular structures compressed the central glial myelin of the nerve. CONCLUSIONS: The authors propose the use of the terms "RExP," "RDP," and "transitional zone," instead of RExZ, which cannot be well defined. The RDP appears to be a good landmark for use during microvascular decompression.

Adolescent↗

[Solitary fibrous tumor of the fourth ventricle: case report].

A rare case of solitary fibrous tumor, located wholly within the fourth ventricle, is reported. A 57-year-old male presented with headache and nausea. The preoperative magnetic resonance images revealed a well circumscribed mass in the fourth ventricle that exhibited a low intensity on T1-weighted images and homogeneously enhanced with gadolinium. Vertebral angiogram revealed a tumor stain supplied from the choroidal branches of the posterior inferior cerebellar artery. The tumor was totally resected through a midline suboccipital approach. Histologically, the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Immunohistochemical staining demonstrated vimentin and the CD34 positivity of tumor cells. Solitary fibrous tumor is a newly described entity, which should be considered in the differential diagnosis for dural-based lesions.

Cerebral Ventricle Neoplasms↗

[Progressive brain injury].

The aim of this study was to evaluate the clinical manifestations and prognostic factors of progressive brain injury following trauma. We reviewed the records of 779 patients with head injury who had an admission Glasgow Coma Scale of 9 or more; 70 (7.0%) developed progressive brain injury as evidenced on serial CT scans. Of these 70 patients, 19 (27.1%) had a subdural hematoma, 19 (27.1%) an epidural hematoma, 16 (22.9%) a cerebral contusion, 13 (18.6%) an intracerebral hematoma, and 3 (4.3%) a diffuse brain swelling. Three months after injury, 36 (51.4%) patients died, 2 (2.9%) were left in a vegetative state and 23 (32.9%) had a favorable outcome. The appearance of progressive brain injury was associated with patient age, admission Glasgow Coma Scale, injury mechanisms, skull fracture and hemorrhagic lesions on the initial CT scan. Patients with the extracerebral lesions deteriorated 4 hours after injury, whereas those with intracerebral lesions deteriorated 8 hours after injury. The outcome based on Glasgow Outcome Scale was significantly associated with age, type of intracranial lesion, Glasgow Coma Scale following deterioration, the mechanism of injury and surgical treatment. It is concluded that early repeated CT scan is indicated in patients with risk factors of developing progressive brain injury.

Adult↗

[Two cases of lymphocytic infundibuloneurohypophysitis].

We report two cases of lymphocytic infundibuloneurohypophysitis (LIH). A 32-year-old male and a 13-year-old male were admitted to our hospital because of a sudden occurrence of the diabetes insipidus (DI). MRI of both patients showed the disappearance of hyperintensity of the posterior pituitary in T1WI, pituitary stalk swelling and enlargement of the pituitary gland, with homogeneous enhancement by gadolinium. We thereby diagnosed LIH, so neither patient was operated on, but both were followed-up conservatively. We reviewed 51 cases of LIH. The patient's ages ranged from 4 to 74 years (mean 45.4 years). Based on the initial symptoms, DI was found in all cases. Almost all these cases revealed characteristic MRI findings similar to those in our cases. The mean follow-up period was 3.1 years. The rate of disappearance of radiological abnormalities was 56.2%, but only 13.7% of DI improved. If we encounter a patient presenting with idiopathic DI whose MRI is strongly suggestive of LIH, and barring the necessity of an urgent operation, careful conservative treatment is advised.

Adolescent↗

[Reye syndrome and drug induced encephalopathy].

Reye syndrome, characterized by acute encephalopathy, selective liver damages, a fatty degeneration in visceral organs and miserable prognosis, is probably caused by various drugs, especially antipyretic such as acetylsalicylate. The incidence of the disease has been decreased by prohibition of administration of aspirin for children with high fever, especially caused by influenza infection in western countries, also in Japan. The pathophysiology of the disease has extensively studied, however, still being unknown to be dissolved. Our previous study of lipid analysis of brain from experimental measles encephalitis revealed an increase of cholesterol ester and decrease of sphingomyelin. As cholesterol ester is synthesized from cholesterol and fatty acids catalyzed by acylCoA-acyltransferase(ACAT), ACAT activity can be increased in the experimental animal brain. In the present report, ACAT m-RNA could not be expressed in control brain but in the experimental animal brain, so ACAT may play a role in pathogenesis of Reye syndrome.

Animals↗

Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway.

To study whether nipradilol, which is used as an ophthalmic solution for the treatment of glaucoma, has a cytoprotective effect, we investigated its effect on the apoptosis induced by serum withdrawal in PC12 cells. Nipradilol has alpha1- and beta-adrenoceptor-blocking and nitric oxide (NO)-donating properties. We also investigated the effects of timolol, prazosin and S-nitroso-N-acetylpenicillamine (SNAP) on PC12 cell death. Serum withdrawal from PC12 cells resulted in apoptosis, and the survival rate was decreased in a time-dependent manner. The addition of nipradilol to the medium showed a cytoprotective effect on PC12 cell death in a dose-dependent manner, but timolol and prazosin did not. We measured caspase-3 activity to clarify the mechanism of the inhibition of apoptosis in the presence or absence of dithiothreitol (DTT). The caspase-3 activity could be reactivated by DTT. In addition, to investigate the relationship of the cGMP-dependent pathway to the nipradilol-induced cytoprotective effect, we tested the effect of the protein kinase G inhibitor KT5823. KT5823 partially reversed the nipradilol-mediated cytoprotective effect. These results indicate that the cytoprotective effect of nipradilol in PC12 cell death was due to the caspase-3 inhibition mediated by NO-related S-nitrosylation and activation of protein kinase G.

Animals↗

Neuroendoscopic placement of Ommaya reservoir into a cystic craniopharyngioma.

INTRODUCTION: Total removal of the tumor is the most acceptable therapeutic modality in the management of craniopharyngioma; however, there are innumerable factors that can upset treatment plans. Unresectable lesions are often treated with gamma knife surgery (GKS). Reduction of the cystic volume is necessary, to decrease the area to be treated with GKS. An Ommaya reservoir system is usually placed during open surgery or by stereotactic access. MATERIALS AND METHODS: The authors use a neuroendoscope for safer and less invasive placement of the Ommaya reservoir into deep-seated cystic lesions. The cystic component is aspirated, and the Ommaya reservoir tube is precisely guided and placed into the cyst cavity under neuroendoscopic control with a newly developed two-burr-hole technique. This neuroendoscopic procedure could make it easier to reduce cystic volume prior to GKS as the final procedure. This technique may also be used for instillation of chemotherapeutic agents and for repeat aspirations, making the achievement of cystic control more likely. This type of neuroendoscopic management is a safe and effective procedure and could be considered as an alternative management technique for some stubborn cystic craniopharyngiomas.

Catheterization↗

Intratumoral injection of dendritic and irradiated glioma cells induces anti-tumor effects in a mouse brain tumor model.

Malignant astrocytoma is the most common primary brain tumor in adults. The median survival of patients with malignant astrocytomas (high-grade astrocytomas) is about 1-2 years, despite aggressive treatment that includes surgical resection, radiotherapy and cytotoxic chemotherapy. Therefore, novel therapeutic approaches are needed to prolong survival. We investigated antitumor immunity conferred by the intratumoral injection of dendritic (DC) and irradiated glioma cells (IR-GC) in a mouse brain tumor model. Intratumorally injected DC migrated to the lymph nodes and elicited systemic immunity against autologous glioma cells. In a treatment model, intratumoral injection of DC and IR-GC prolonged the survival of brain tumor-bearing mice. Efficacy was reduced when studies were performed in mice depleted of CD8(+) T cells. Administration of DC or IR-GC alone had no effect on survival of brain tumor-bearing mice. CTL activity against glioma cells from immunized mice was also stimulated by coadministration of DC and IR-GC compared with the controls. These results support the therapeutic efficacy of intratumoral injection of DC and IR-GC.

Animals↗

Elevated immunoreactive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders.

To clarify possible involvement of adrenomedullin in the pathophysiology of inflammation of eyes, we measured immunoreactive-adrenomedullin concentrations in the aqueous humor and plasma obtained from 14 control subjects and 56 patients with uveitis or vitreoretinal disorders. Immunoreactive-adrenomedullin levels in the aqueous humor were significantly elevated in patients with active uveitis, proliferative vitreoretinopathy and proliferative diabetic retinopathy, as compared with control subjects. The plasma immunoreactive-adrenomedullin levels were not significantly correlated with the aqueous humor levels. These findings suggest that adrenomedullin produced locally in the eyes is involved in the pathophysiology of uveitis and some proliferative vitreoretinal disorders.

Adrenomedullin↗

Effects of glioma cells on maturation of dendritic cells.

We investigated whether glioma cells affected the maturation of dendritic cells (DCs). First, DCs phenotypes were analyzed using FACScan. Incubation of both human and mouse immature DCs with glioma cells altered their expression of cell surface molecules, whereas expression of cell surface molecules by mature mouse and human DCs was not affected by exposure to glioma cells. Subsequently, phagositosis was assessed by uptake of FITC-dextran. Coculture with glioma cells did not inhibit phagositosis of either mature or immature DCs relative to the controls. We also analyzed the concentration of IL-12 secreted by mature DCs using enzyme-linked immunoabsorbent assay (ELISA). IL- 12 production by DCs was inhibited by coculture with glioma cells. However, stimulation with lipopolysaccharide restored the production of IL- 12 by both human and mouse DCs. These data suggest that glioma cells suppress the maturation of DCs.

Animals↗